ES2645686T3 - Devices for detecting, controlling, and predicting radiation administration - Google Patents

Abstract

A system for treating a target area in a patient with an irradiation beam, comprising: (a) a tracking assembly configured to track the position of a region of the patient's body that contains the target area and at least one area sensitive to radiation relative to a known reference axis (18) in an external coordinate system; (b) a beam source (108) configured to direct a collimated X-ray beam to the patient's target area along a known beam axis (1400, 1400a, 1400b, 1400c) to intersect with a known treatment axis (19, 2820) defined with respect to the reference axis (18, 2810) in the external coordinate system; and (c) a processor (106, 501) operatively connected to the tracking device and beam source (108), and configured to: (i) determine, from the known position of the body region in the coordinate system external, the coordinates of the target area to be treated and the coordinates of the at least one radiation sensitive patient structure; (ii) during a period in which the beam is being directed along the known beam axis (1400) to intersect with the known treatment axis (19) in the target area, and based on information received from the device follow-up, follow the positions of the target area to be treated and the at least one radiation sensitive structure; (iii) on the basis of the known beam axis (1400) of the collimated beam in the external coordinate system, and the instantaneous positions of the target area to be treated and the at least one radiation sensitive structure, calculate an equivalent of total radiation received in the target area and at least one radiation sensitive structure; and (iv) on the basis of the calculated radiation equivalents of step (iii), control the irradiation beam to ensure that the at least one radiation sensitive structure receives no more than one pre-selected radiation equivalent during the treatment.

Description

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DESCRIPTION

Devices to detect, control, and predict the administration of radiation Technical field

The present description refers to a system for performing a low-energy X-ray therapy procedure guided by the image in the eye of a patient, to systems for planning and controlling said treatments, and stabilization systems for the alignment of the eye useful in procedures ophthalmologists

Background

Macular degeneration is a condition in which the macula light sensing cells, a part near the center of the retina of the human eye, malfunction and slowly stop working. Macular degeneration is the leading cause of loss of central vision in people over fifty. The chemical and histological evidence indicates that macular degeneration is partly caused by or results in an inflammatory process that ultimately causes the destruction of the retina. The inflammatory process can result in the direct destruction of the retina or the destruction through the formation of neovascular membranes that extravalue fluid and blood in the retina, quickly leading to scarring.

Many treatments for macular degeneration aim to stop the neovascular (or "wet") form of macular degeneration rather than geographic atrophy, or the "dry" form of age-related macular degeneration (AMD). All wet AMDs begin as dry AMD. In fact, the current trend in the formation of advanced ophthalmological images is that wet AMD is identified before the loss of visual acuity. Treatments for macular degeneration include the use of medication injected directly into the eye (anti-VEGF therapy) and laser therapy in combination with a targeted drug (photodynamic therapy); Other treatments include brachytherapy (that is, the local application of a material that generates beta radiation).

The exact alignment of a subject's eye is important in several situations. For example, when certain types of eye measurements are taken, it is crucial to know that the eye is in a particular reference position. When a patient's eye cornea is measured before therapeutic treatment, it may be important to repeat those measurements after treatment to determine how much, if anything, the treatment has affected the measurements. In order to achieve that, it must be ensured that the alignment of the eye is in the same position each time the particular measurements are made. Otherwise, the difference in the data before and after the treatment could be due to a change in the alignment of the eye instead of the treatment.

Several treatment and surgery procedures, which typically involve irradiating one or more selected targets in the eye, require that the patient's eye be stabilized or positioned before and / or during the treatment. For example, refractive laser surgery involves removing corneal tissue from the eye with an ultra-fast, ultra-short pulse laser beam to correct refractive errors in a patient's eye. As such, the patient's eye must be stabilized, and either the laser system must be properly and precisely aligned with the patient's eye, or the patient's eye must be properly and precisely aligned with the laser system. The eye is predisposed to saccades, which are involuntary rapid movements of small magnitude. A patient can voluntarily shift his gaze during surgery, and in addition, the stability of the eye position is affected by the patient's heartbeat and other physiological factors.

In order to achieve the objective of maximizing the results while minimizing the risks to the patient during such eye treatment, it is important to eliminate, or at least significantly reduce, as many system errors as possible. This includes inappropriate alignment of the patient's eye with respect to the treatment system. Alignment errors may result from poor system configuration, or from the patient's interaction with the system. As for the patient / system interaction, any voluntary or involuntary movement of the patient's eye during treatment can significantly alter the alignment of the eye with respect to the treatment system. It is therefore necessary to keep the patient's eye stationary during these procedures,

In addition, there is a need to control the distribution of radiation absorption by the eye structures during treatment, so as to ensure adequate dosage to the lesion being treated, and to avoid damaging collateral structures by dispersed radiation.

US2008 / 049896 describes an apparatus and method for determining a target surface distance (TSD) between a target region in a body and a real point of entry of a radiation beam into the body from a radiation source.

WO2007 / 045075 describes a method of treatment with radiation therapy that comprises forming images of a subject and simulating aspects in four dimensions of radiotherapy.

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US2007 / 195929 describes a system and method for evaluating the dose administered by a radiation therapy system using a marker indicating movement.

WO2008 / 124801 describes a radiosurgery system that is configured to administer a therapeutic dose of radiation to a target structure in a patient.

US6134294 describes a device for precision x-ray irradiation of the macular region of the retina of the eye of a patient having a mounting plate mounted on a linear accelerator collimator.

Summary

The embodiments of the systems and methods related to the invention are described in this description. The invention is only defined by the appended claims.

A. Radiotherapy methods:

In one embodiment, a method of treating an injury in or adjacent to the retina of a patient's eye with an external beam radiation device comprises (a) putting the patient's eye in alignment with a known system axis in a system. of external three-dimensional coordinates, and measure the axial length of the eye; (b) from the known position of the system axis and from the measured axial length, determine the coordinates of the lesion to be treated in the external coordinate system; (c) direct a collimated radiation beam along a known beam axis in the external coordinate system to the lesion to be treated; (d) during said addressing, follow the position of the patient's eye with respect to the axis of the known system, to thus follow the position of the lesion to be treated in the external coordinate system; and (e) based on the known beam axis of the collimated beam in the external coordinate system, and the instantaneous position of the lesion to be treated in the external coordinate system, as determined at least in part by the position followed by the eye, calculate an equivalent of total radiation received in the lesion to be treated during treatment.

Said method may also provide that step (b) includes determining the coordinates of at least one radiation sensitive structure in the external coordinate system; step (d) includes monitoring the position of the at least one radiation sensitive structure in the external coordinate system; and step (e) includes, on the basis of the instantaneous position of the at least one radiation sensitive structure in the external coordinate system, calculating an equivalent of total radiation received in the at least one radiation sensitive structure during the treatment; the method also comprising the step of (f) on the basis of the calculated radiation equivalent of step (e), controlling the radiation beam to ensure that the at least one radiation sensitive structure receives no more than one radiation equivalent preselected during treatment.

The method may also provide that stage (a) includes measuring the axial length of the patient's eye by ultrasound imaging, and step (b) includes scaling the measured axial length of stage (a) to an eye model standard human, and determine the coordinates of the lesion to be treated and the at least one radiation sensitive structure of the eye model. Step (a) may include determining the geometric axis of a patient's eye that extends through the center of the limbus and contains a corneal reflex of the patient's eye, and aligning the geometric axis with the axis of the known system; and step (d) may include tracking the angular deviation of the geometric axis of the eye with the axis of the known system. The method may include attaching an eyeglass to the patient's eye, centered thereon so that the geometric axis of the eye corresponds approximately to the axis of the eyeglass, and aligning the axis of the eyeglass with the axis of the known system.

The method may also provide that step (b) includes using the measured optical length of the patient's eye to register the patient with the eye model, and using the coordinates of the lesion to be treated and the at least one radiation sensitive structure in the model to determine its coordinates in the external coordinate system. Step (d) may include tracking the position of the axis of the eyepiece with respect to the axis of the system, so as to follow the positions of the lesion and radiation sensitive structures in the external coordinate system. The eye model may include a virtual medium by which the attenuation of a radiation beam along a known path through the model can be determined; and step (e) may include determining the spatial accumulation of radiation received in the macular region of the eye based on the known intensity of the collimated beam, the instantaneous positions of the patient's eye, and the attenuation of the beam through the virtual medium at along known routes in the eye.

The method may also provide that step (e) includes mapping a spatial amount indicative of a total radiation distribution in the eye model, based on the position followed by the patient's eye during a period of addressing a beam of radiation in the retinal region of the patient's eye. The lesion to be treated may be the macula, the at least one radiation sensitive structure may include at least a part of the optic nerve or optic disc of the eye, and step (e) may include calculating the equivalent of total radiation received in the macula and in the optic disc during treatment. The step (f) of controlling the radiation beam may include controlling the radiation beam to make one or more of: (i) achieve a desired dose of radiation in the injury; (ii) avoid exceeding a selected level of radiation dose in the radiation sensitive structure; and (iii) avoid exceeding a selected threshold based on the spatial amount, the threshold indicative of the output based on the eye movement of the beam axis of the selected target.

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The method may also provide that the step (e) of calculating the total radiation equivalent received in the lesion to be treated and the at least one radiation sensitive structure during the treatment, may include determining the sum of increment vectors of time of a parameter indicative of an output based on the eye movement of the axis of the beam of the selected target lesion to be treated. The step (e) of calculating the total radiation equivalent received in the lesion to be treated and the at least one radiation sensitive structure during the treatment may include modulating a predetermined radiation distribution model representing the distribution of the predicted radiation dose that will be received by the patient's tissue from the collimated radiation beam in the absence of eye movement, the modulation based on the movement of the eye followed during the treatment, so that a distribution is determined of radiation dose that takes into account the actual movement of the eye during treatment.

The method may also provide that the step (e) of calculating equivalent total radiation received in the lesion to be treated and the at least one radiation sensitive structure during the treatment may also include sequentially modulating a model of predetermined radiation distribution for a plurality of successive time increments during radiation treatment to determine a cumulative dose distribution during the course of treatment; and step (f) may include (i) comparing the cumulative dose received by a selected non-target anatomical structure with a predetermined dose threshold amount to determine if the threshold has been exceeded and (ii) in the event that the threshold has been exceeded, control the radiation beam control or beam axis to reduce or eliminate the radiation dose additional to the selected non-target anatomical structure.

The method may also provide that step (e) of calculating equivalent total radiation received in the lesion to be treated and the at least one radiation sensitive structure during treatment; it also includes sequentially modulating a predetermined radiation distribution model for a plurality of successive time increments during radiation treatment to determine a cumulative dose distribution during the course of treatment; and in which step (f) includes (i) comparing the cumulative dose received by a selected target anatomical region with a predetermined threshold dose amount to determine if the threshold has been reached, and (ii) in the event of Once the threshold has been reached, control the radiation beam or beam axis to reduce or eliminate the additional radiation dose to the selected target anatomical region.

The method may also provide that the lesion may be a macular lesion, in which the radiation beam is a collimated X-ray beam, and step (c) may include determining the position of the patient's macula in the coordinate system. of treatment from the position of the known eye and the coordinates of the macula in the external coordinate system, and determine a treatment axis in the external coordinate that intersects the patient's macula. Step (c) may include directing a collimated X-ray beam along each of at least two different known treatment axes in the treatment coordinate system in a region of the patient's retinal macular region. Step (f) may include controlling the x-ray beam to administer approximately equal doses of radiation to the patient's macula along each of the different known treatment axes.

The method may also provide that step (f) includes turning off the beam that is being directed in the patient's eye when the position of the patient's macula, according to the monitoring of stage (c), relative to the axis of the beam, is greater than a predetermined threshold distance. Step (f) may include directing the beam in front of the patient's macular region until the spatial accumulation of radiation mapped in the eye model's macula reaches a predetermined dose level.

B. Radiation therapy systems:

In one embodiment, a radiotherapy system for treating a target area in a patient with an irradiation beam comprises: (a) a tracking assembly for monitoring the position of a patient's body region that contains the target area and at less a radiation sensitive area with respect to a known reference axis in an external coordinate system; (b) a beam source for directing a beam of irradiation to the patient's target area along a known treatment axis in the external coordinate system; and (c) a processor operatively connected to the tracking device and beam source; the operating processor to: (i) determine, from the known position of the body region in the external coordinate system, the coordinates of the target area to be treated and the coordinates of the at least one structure of the sensitive patient to radiation; (ii) during a period in which the irradiation beam is being directed along the treatment axis to the target area, and based on the information received from the tracking device, track the positions of the target area that it will be treated and the at least one radiation sensitive structure; (iii) on the basis of the known beam axis of the collimated beam in the external coordinate system, and the instantaneous positions of the target area to be treated and the at least one radiation sensitive structure, calculate a total radiation equivalent received in the target area and at least one radiation sensitive structure; and (iv) on the basis of the calculated radiation equivalents of step (iii), control the irradiation beam to ensure that the at least one radiation sensitive structure receives no more than one pre-selected radiation equivalent during the treatment.

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The system may comprise a tracking assembly that includes (i) an image forming device for recording an image of a region of the patient's body that contains natural landmarks or fiduciary markers that define a geometric axis of the region from which images have been formed and (ii) an image detector operatively connected to the image forming device to convert the recorded image into a digital image composed of pixels of known coordinates, and the processor may be operatively connected to the detector to determine the coordinates of Geometric axis pixels of the body region and step (ii) of the processor operation includes using the pixel coordinates of the geometric axis, relative to known pixel coordinates of the reference axis, to track the position of the body region of the patient with respect to the reference axis.

Eye systems. The system can be configured to treat an ocular lesion, in which the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, the points of Natural references of the eye that define its geometric axis are the center of the limbus and a first corneal reflection, and the beam source produces a collimated X-ray beam. The system may alternatively include an eyeglass adapted to be placed in the patient's eye, centered on it so that the geometric axis of the eye corresponds approximately to the axis of the eyeglass, and a detector to determine the coordinates of the axis of the eyeglass in the external coordinate system, and the processor may be operatively connected to the detector to determine the axis coordinates of the eyepiece and step (ii) of the processor operation includes using the coordinates of the axis of the eyepiece, with respect to the known reference axis coordinates, to follow the position of the patient's eye relative to the reference axis.

The system can be configured so that the tracking system is operative to capture a plurality of time-sequenced images of the body region and its reference points during the treatment method, and the processor is operative to determine axis coordinates. geometric of the region of the body for each of the plurality of images, and in step (ii) determine a time-dependent change in the coordinates of the target area to be treated and the at least one radiation sensitive structure. The system can be configured so that the processor is operative to carry out, in step (iii) the generation of a total equivalent radiation map covering the target area and the at least one radiation sensitive area in the body region of the patient, and in step (iii), determine from the total equivalent radiation map, the radiation equivalent received at any time during the treatment by the target area and at least one radiation sensitive area.

The system can be configured so that the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, and the processor is operative, to carry carried out in step (iii) the generation of a map of total equivalent radiation covering the target area and at least one area sensitive to radiation in the region of the patient's body, and in step (iii), determine from total equivalent radiation map, the radiation equivalent received at any time during treatment for the eye injury and at least one radiation sensitive area.

The system can be configured so that the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, and the processor includes a model of the human eye through which the coordinates of the lesion that is It will be treated and the at least one radiation sensitive structure can be determined, when the patient's eye is superimposed on the eye model. The eye model in the processor may include a virtual means by which the attenuation of a radiation beam along a known path through the model can be determined, and the processor is operative to determine from the known intensity of the beam and the length of the radiation path through the virtual medium in the eye model, the amount of radiation that is received by the retina in the eye model.

The system can be configured so that the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, in which the processor is operative, by the determination of the position of the ocular lesion in the external coordinate system, to determine a treatment axis in the treatment coordinate system that intersects the lesion. The processor may be operative to determine at least two different treatment axes in the treatment coordinate system, and to control the radiation beam to administer approximately equal doses of radiation in the lesion along each of the different known axes. . The processor is operative to turn off the beam that is being directed to the patient's eye when the distance between the position of the patient's injury, as determined in operation (d) (ii), and the intersection of the beam axis in the retina, is greater than a predetermined threshold distance. The processor can be operative to direct the beam in front of the patient's retinal region until the spatial accumulation of radiation mapped in the lesion of the eye model reaches a predetermined dose level.

C. Machine readable code for system operation:

Monitoring One embodiment includes a code readable by operating machine in an electronic computer included in a radiotherapy system that is operative to monitor the total radiation dose received at a target site during the course of treatment in which the target site is irradiated with a radiation x collimated The code can be operative to carry out the steps that comprise: (a) defining, in an external coordinate system, the

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coordinates for (i) a reference axis, (ii) a radiation beam axis, and (iii) the target site which, when a body axis that has a known relationship with the target site aligns with the reference axis, puts the radiation beam in the center of the target area, (b) receive from a body tracking device, information in progress during the course of the radiation treatment on the position of the body axis with respect to the reference axis, (c ) from the information received in step (b), and from the known intensity of the beam in the radiation beam, calculate the spatial distribution of radiation received in the region of the target site during the course of treatment, and (d ) use the spatial distribution of radiation calculated in step (c) to monitor the total radiation dose at the target site during the course of treatment.

The machine-readable code can be configured to carry out stages in which the target area includes the eye injury, the body axis is the geometric axis of the eye, and the information received from the body tracking device is in the form of ocular images from which the geometric axis of the eye can be determined. The eye can be irradiated during the course of treatment by a collimated x radiation beam directed to the target site along at least two different beam axes. The machine-readable code can be configured to carry out stages in which an eyepiece is centered in the eye such that an axis of the eyepiece corresponds approximately to the geometric axis of the eye, and the information received from a device of Body tracking is in the form of information about the position of the eye gland. The machine-readable code can also be operative, in step (a) to determine the coordinates, in the external coordinate system, of the optical disc of the patient's eye, based on a known spatial relationship between the lesion of the optical disc , and also operative in step (d) to use the spatial distribution of radiation calculated in step (c) to monitor the total radiation dose in the optical disk during the course of treatment.

Control. One embodiment includes a code readable by operating machine in an electronic computer included in a radiotherapy system that is operative to control the treatment of an eye injury by exposing the lesion to a beam of radiation x collimated. The code may be operative to perform the steps comprising: (a) using information received from an eye tracking system to determine an eye's geometric axis in an external coordinate system, (b) with the eye's geometric axis aligned with a reference axis, determine the coordinates of the lesion in an external coordinate system, (c) from the coordinates of the ocular lesion determined in step (b), determine a beam axis that intersects the injury with the patient's eye in a defined position with respect to the reference axis, and (d) control the position of an x-ray beam source to position the beam along the axis of the beam determined in step (d).

The machine-readable code can be configured to carry out stages in which the information received from the eye tracking system is an ocular image from which the geometric axis can be determined by determining the center of the sclera and a corneal reflection from the eye image. The machine-readable code can be configured to carry out stages in which an eyepiece is centered in the eye so that an axis of the eyepiece corresponds approximately to the geometric axis of the eye, and the information received from a device Body tracking is in the form of information about the position of the eye gland.

The machine-readable code can be configured in which step (c) can also include the determination of two or more beam axes that intersect the lesion with the patient's eye in a defined position relative to the reference axis. The computer may be operatively connected with a robot beam source device to position the beam along a selected beam axis, and step (d) may include acting on the robot device to move the beam axis during the course of the treatment, from one beam axis to another determined in step (c).

Tracing. One embodiment includes a code readable by an operating machine in an electronic computer in a treatment system to treat a lesion of a patient's eye by directing a collimated radiation beam along a beam path to the lesion and including, operatively connected to an eye tracking device that includes an eye contact member configured to connect the eye and having visible fiduciary markers, and a camera configured to capture an electronic image of the eye. The code can be operative to execute effective instructions to perform the steps comprising: (a) aligning the camera with a known position and / or orientation with respect to a treatment system coordinate system (system coordinates) in which the camera It is directed to the eye as it is connected to the contact member; (b) capture an image of the eye as it is connected to the contact member; (c) identify one or more pixels of the image that represent the location of an axis of the contact member; (d) determine from the image data that the axis of the eye line is aligned with a known position and / or orientation with respect to the coordinate system; (e) determine from the image data the location of the center of the limbus in the coordinate system; and (f) determine a deviation from the location of the center of the limbus to a known position and / or orientation of the eye's eye.

The machine-readable code can be configured such that step (e) of determining the location of the center of the limbus includes: (i) determining a part of the image including all or a portion of the exposed part of the limit of the limbus, and identify the locations in the image corresponding to the image of the limit of the limbus; (ii) determine a mathematical representation of a form of "best fit" corresponding to the locations of the limit of the limbus; and (iii) calculate a "best fit" form center so that the location of the

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limbo center The code may also include the steps of: (g) recording the positions and / or orientations determined in the stages (a-d) of one or both of the contact and limb member in a virtual informatic eye model; (h) calculate the position of an ocular anatomical structure in the coordinate system based on the registered eye model; and (i) control the at least one operational aspect of the collimated radiation beam in response to the calculated position of the ocular anatomical structure.

D. Method executed by computer for non-ocular and ocular target tracking:

One embodiment includes a method executed by computer for use in a radiation treatment device including an information processor and a body tracking device operatively connected to the computer processor, the tracking device including a contact member with the body configured to connect the surface of a patient's body part that includes a radiation treatment target, and a camera configured to capture an electronic image of the body part. The processor may be effective in executing instructions for performing the steps comprising: (a) determining an initial position and orientation of the body part, based on: (i) determining the alignment of the contact member as it is connected to the body to have a known orientation with respect to an anatomical axis of the body part and a known position with respect to the surface of the body contacted; and (ii) determine the alignment of the contact member as it is connected to the body with the radiation treatment device to have a known initial position and orientation in a coordinate system of the radiation treatment device; (b) determine an initial position of the treatment target in the coordinate system of the radiation treatment device, on the basis of determining the relative position of the treatment target relative to the contact member; (c) electronically capture a plurality of images sequenced over time including the contact member while connected to the body during the administration of radiation treatment; (d) process the images in the computer processor to determine one or both of an orientation and a position of the contact member in a coordinate system of the radiation treatment device at the time of capturing each image; and (e) determine for each image, from the orientation and / or position of the contact member at the time of image capture, the change from the orientation and / or initial position of the contact member in the coordinate system of the radiation treatment device; and (f) determining for each image, the change from the initial position of the treatment target in the coordinate system of the radiation treatment device, to track the sequential movement of the treatment target; and (g) control at least one aspect of the radiation treatment based on the sequential movement tracking of the treatment target.

In certain embodiments, the computer-executed method provides that the body part includes a treatment target is selected from the group consisting essentially of a part of the brain, spinal cord, a breast, musculoskeletal tissue, vasculature, abdominal and gastrointestinal lesions . In alternative embodiments, the computer-executed method provides that the body part is an eye, in which the treatment target includes a part of the retina, and in which the contact member includes a lens element that is in contact. With the surface of the eye.

E. Completion of additional or alternative methods and devices:

Several embodiments that have aspects of the invention are part of the written description and drawings of this application.

Virtual simulated model. In one embodiment, a method of treating a patient with radiation emitted from a radiation source, comprises in any operational order the steps of: a) providing a simulated model that includes a representation of the patient's anatoirna; b) record the simulated model with radiation beams projected virtually from a virtual radiation source and simulate dose deposition in the simulated model; c) simulate the movement of the simulated model while saving the record between the simulated model and the virtually projected radiation beams; d) register the simulated model with a subject that receives radiation, and register the radiation beams projected virtually with a radiation source that treats the subject; e) record the movement of the patient with the movement of the simulated model in the simulation; f) determine, from the model as recorded with the patient, at least one dose of radiation absorbed by the treated tissue during the time of treatment.

The simulated model may include an anatomical representation of one or more structures of an eye, such as target regions of the treatment (areas or volumes that are planned to receive radiation dosage), for example, a part of a retina. The model may also include the representation of non-target anatomical structures (areas or volumes that are planned to have the radiation dose minimized or eliminated), for example, an optical disc, an optic nerve and an eye lens; and adjacent anatomical structures, for example, volumes through which the radiation beam propagates and attenuates, both before reaching a target region, and beyond a target region.

A simulated model can be modified on the basis of one or more measured anatomical features of the patient, such as by scaling a simulated eye model with respect to a measured eye dimension, for example, the axial length of an A mode ultrasound. alternatives, the formation of medical images can

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register, overlap and / or scale to the model and be included to provide specific patient content. For example, a fundus image of a patient's retina (optionally scaled) can be superimposed on a retinal representation in the model to allow the characteristics in the images to be superimposed on the characteristics of the model, such as data from the target region planned for treatment. in relation to a visible lesion, the optical disc, and the like.

A simulated model can be registered or correlated with a patient's measured movement to determine a corresponding virtual movement of the model. In addition, a real radiation source can be registered or correlated with the model to correlate the radiation emission configuration of the radiation source with the virtual movement of the model. Thus, a real radiation dose to anatoirna can be determined by reference to the model, in which the model includes anatomical representations and radiation source, by determining a virtual movement of the model correlated with real or detected patient movement. Embodiments that have aspects of the invention may also include modifying the radiation treatment in response to the determined radiation dose, such as by automatic or manual reduction or shutdown of the radiation emission; or by automatic or manual reorientation of the radiation source.

In exemplary embodiments of methods and devices that have aspects of the invention, an algorithm for determining the movement of a point in a retina comprises: from an image of a fiduciary marker in one eye, correlating the position of the fiduciary marker with a structure in the retina The correlation can be performed by a mathematical transformation, such as a trigonometric transformation. The mathematical transformation can be done in a software program. The algorithm may further comprise detecting a subsequent image after a period of time and correlating the new position of the fiduciary marker with respect to the first position, and a corresponding error function can be created or generated. The algorithm may also comprise detecting more than one fiduciary marker and correlating with more than one coordinate of the retina. The position of the fiduciary marker can be placed or recorded in an external coordinate frame, such as the system reference frame of a radiotherapy treatment device.

Eye stabilization system. An embodiment having aspects of the invention comprises an eye contact device (eyepiece) to secure a patient's eye in a selected position, such as can be used cooperatively with an eye stabilization and alignment device, as described in co-invented priority applications, particularly No. 12 / 103,534 filed on April 15, 2008 and No. 12 / 027,083 filed on February 1, 2008. In one embodiment, the eye or eye grin contact device comprises , in operative condition, (a) a lens body having an internal concave contact surface adapted to face the front surface of a patient's eye so that it covers at least a part of the cornea, an external surface that includes one or more mounting locations, and a transparent window part arranged to allow, when in an operative position, the visualization of an inner part of the eye through the co line (b) a support member that can be mounted on a base; and (c) two or more joints pivotally mounted to the support member and connecting to a lens body mounting location, the configured joints form an assembly that supports the lens body in front of the eye. In certain embodiments, the eyepiece also comprises an adjustment mechanism that connects at least one joint and configured to provide adjustment of the range and / or resistance of at least one degree of pivotal freedom of the lens body relative to the support member.

The window part may have at least one optical property selected from the group consisting of a selected transparency, a selected refraction, a selected magnification, a selected filtration, a selected polarity, and a selected marker pattern. The eyepiece can also comprise a port in fluid communication with the contact surface by means of which a negative pressure can be applied between a patient's eye and the contact surface, to stabilize the position of the eye relative to the contact device. The eyepiece may further comprise a pressure mechanism operatively connected to the contact device connector to press the contact device with the eye in front of the eye with sufficient force to hold the contact device in front of the eye.

Eye alignment. In exemplary embodiments of methods and devices that have aspects of the invention, a patient's eye can be aligned and stabilized for diagnostic or therapeutic purposes, such as radiotherapy treatment. In exemplary embodiments of a method for aligning an axial anatomical axis of a patient's eye with a coordinate system of a medical device, the method may comprise: (a) connecting the anterior surface of the eye with a contact lens member, having contact lens member a defined axis; (b) align the lens with the eye so that the lens axis intersects the center of the eye blade and so that the lens axis has a known orientation with respect to the corneal surface at the center of the cornea to define an axial anatomical axis of the eye; and (c) align the axis of the lens with a coordinate axis of the medical device, so that the coordinate axis of the medical device has a known orientation with respect to the axial anatomical axis of the eye.

The step (b) of aligning the lens with the eye may include: (i) electronically capturing one or more images including the eye and the lens member; (ii) process the image in a computer processor to determine the location of the axis of the lens member with respect to the location of the limbus; and (iii) adjust the position of the lens member relative to the eye until the axis of the lens substantially intersects the center of the eye blade. The sub-stage

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(ii) image processing to determine the location of the lens member may include: A. processing the image to determine the location of the center of the contact lens in a coordinate system; B. process the image to determine the location of the center of the limbus in the coordinate system; and C. compare the location of the center of the contact lens of the center of the limbus in the coordinate system to determine the difference in location, if it exists.

In an embodiment in which the lens member includes one or more reflective fiduciary markers that have a known location relative to the contact surface of an eye of the lens member, the sub-step (a) of determining the location of the center of The contact lens may include: (i) electronically detecting a contrast image of each fiduciary marker to define a set of respective fiduciary marker data; (ii) mathematically determine the center of each fiduciary marker data set; (iii) from the known location of the fiduciary markers with respect to the contact surface of an eye compute the location of the center of the contact surface of the eye in the coordinate system. In one embodiment, the sub-step (b) of determining the location of the center of the limbus may include 1. electronically detecting a limit of contrast between the sclera and iris to define a set of limit data; 2. Mathematically adjust the geometric shape to represent the limit data set; and 3. compute the center of the geometric shape in the coordinate system.

In one embodiment, the step (c) of aligning the lens axis with a coordinate axis of the medical device may include: (i) electronically capturing one or more images including the lens member as it is connected and aligned with the eye; (ii) process the image in an information processor to determine one or both of an orientation and a position of the lens member in the coordinate system of the medical device; (iii) adjust one or both of the orientation and position of the lens member with respect to the coordinate axis of the medical device until the coordinate axis of the medical device has a known orientation with respect to the axial anatomical axis of the eye. The method may also include: (d) determining a coordinate axis of distance from the medical device to the contact lens member as it is connected and aligned with the eye; wherein the distance determination includes (i) electronically capturing one or more images including the contact lens member as it is connected and aligned with the eye; and (ii) process the image in a computer processor to determine the distance.

Eye movement In exemplary embodiments of methods and devices that have aspects of the invention, the movement of a patient's eye can be measured or monitored for a diagnostic or therapeutic purpose, such as radiotherapy treatment. In exemplary embodiments of a method of monitoring the movement of a patient's eye in a coordinate system of the medical device, the method may comprise: (a) determining an initial position and orientation of the eye, including: (i) connecting the anterior surface of the eye with a contact lens member; (ii) align the contact lens member with the eye to have a known orientation with respect to an anatomical axis of the eye and a known position with respect to the surface of the contacted eye; and (iii) align the contact lens member with the medical device to have a known initial position and orientation in the coordinate system of the medical device;

The method may further comprise: (b) electronically capturing a plurality of time-sequenced images including the contact lens member while maintaining the connection and alignment of the contact lens member with the eye; (c) process the images in an information processor to determine one or both of an orientation and a position of the contact lens member in the coordinate system of the medical device at the time of capture of each image; and (d) determine for each image, from the orientation and / or position of the contact lens member at the time of image capture, the change from the orientation and / or initial position of the contact lens in the coordinate system of the medical device, to track the sequential movement of the eye in the coordinate system of the medical device.

Target movement: In exemplary embodiments of methods and devices that have aspects of the invention, the movement of a patient's eye can be used to infer the movement of a tissue or other target region in the eye, for a diagnostic or therapeutic purpose. , such as radiotherapy treatment. In exemplary embodiments of a method of monitoring the movement of a patient's eye, the method may further comprise: (e) determining the position of the target tissue relative to the anatomical axis and surface of the contacted eye; and (f) after step (a) of determining an initial position and orientation of the eye, determining an initial position of the target tissue in the coordinate system of the medical device; (g) determine for each image, from the change from the orientation and / or initial position of the contact lens, the change from the initial position of the target tissue in the coordinate system of the medical device, to track the movement sequential target tissue in the coordinate system of the medical device.

The method may further comprise: the step of changing at least one operational parameter of the medical device in response to a change from the initial position of the target tissue. For example, when the medical device is an external radiation beam treatment device configured to treat the patient by emitting a collimated radiation beam directed at the target tissue; The change in the operational parameter may include one of (i) redirecting the collimated radiation beam to follow the movement of the target tissue and (ii) interrupting the emission of the beam after a threshold of movement of the target tissue.

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Tissue propagation: Exemplary methods and devices that have aspects of the invention may include a radiation therapy treatment plan that provides propagation of a beam of external radiation to target tissue, in which the passage through the tissue affects the characteristics of the make. In exemplary embodiments of a method for treating a patient with an external radiation beam from a radiation source, the radiation beam emitted to propagate along a tissue path to reach a region of target tissue in the patient's body , the treatment carried out according to a radiotherapy treatment plan specifying anatomically the tissue path, the method may comprise (a) selecting one or more input parameters (P1, P2 ... Pi,), the selected input parameters from human anatomical measures, other human measures, and other specific characteristics of the person; (b) characterize the variation with respect to the selected parameters in a human population that includes the patient, the variation correlated with the tissue path length (PL) for the radiotherapy treatment plan; (d) determine a mathematical function and / or calculation algorithm that effectively expresses a relationship between the selected parameters and the tissue path length (PL = f (P1, P2 ... Pi); (e) determine values of the Selected parameters (P1, P2 ... Pi,) for the patient; (f) using the mathematical function and / or calculation algorithm, determine PL for the patient (PL0); (g) modify or adjust one or more aspects of the radiotherapy treatment plan based on the determined value PL0; and (h) treat the patient according to the modified or adjusted treatment plan.

Radiation dose mapping: In exemplary embodiments of methods and devices that have aspects of the invention, movement of a region that includes target tissue in the eye can be used to track radiation dose deposition to anatomical structures. In exemplary embodiments of a method of monitoring the movement of a target tissue or other region in a patient's eye, the method may further comprise: (h) providing a virtual radiation dose distribution model representing a dose distribution of radiation treatment to a tissue region that includes the target tissue; and (i) determine, from the dose distribution model and from the determined movement of the target tissue, a modified dose distribution model that takes into account eye movement.

A dose distribution that takes into account eye movement can be used to trigger changes in the radiotherapy operation. For example, the method may further comprise: (j) defining a geometric parameter in a coordinate system of the tissue region that includes the target tissue, the geometric parameter characterizing a reference location of an increase in radiation dose time of the model provided in step (h); (k) define an accumulation vector by providing a sum of vectors of the geometric parameter in a coordinate system of the tissue region that includes the target tissue; (l) perform steps (h) and (i) for an image sequenced in the time captured according to step (c) to determine a dose distribution with modified time increment and a respective value of the geometric parameter for the increase of weather; (m) add the geometric parameter for increasing the time to the accumulation vector; (n) compare the value of the accumulation vector at one or both of magnitude and direction with one or more predetermined threshold values to determine if the value exceeds the threshold; (o) in the case where the value in step (n) exceeds a threshold, interrupt the emission of the radiation beam. (p) repeat steps (l) to (o) for a plurality of images sequenced in time. The geometric parameter may have a linear relationship or a non-linear relationship (for example, quadratic) with a change from the initial position of the target tissue.

When the target tissue includes a part of the retina of a patient's eye, and the geometric parameter the difference in the location for each time sequence of a centroid of the dose distribution in a plane of the retinal surface with respect to an initial location of the centroid of the dose distribution.

Alignment method by imaging: In exemplary embodiments of a method that has aspects of the invention, an algorithm for aligning a part of a patient's body with a radiation device comprises: (a) defining a normal axis for the part of the body (for example, locating fiduciary markers on the body part); (b) align the normal axis with a pixel in a camera image visualizing the body part; and (c) joining the pixel in the camera image with a coordinate frame of a robotic positioning system thus joining the normal axis of the body part with an axis of the robotic positioning system.

The algorithm may further comprise determining the distance between the body part and the robotic positioning system in which the distance is measured along the normal axis. When the body part is an eye, the normal axis can be defined by detecting fiduciary markers in a device that contacts the eye, such as adjacent to the eye blade. A treatment target on the retina, such as the macula, can be located relative to the normal axis by a measure of axial eye length.

In exemplary embodiments of a method that has aspects of the invention for aligning a patient's eye with a coordinate system of the medical device, the device may be provided to include an eyepiece device configured to connect the eye and a camera configured to capture an electronic image of the eye, the ocular crane having visible fiduciary markers and the camera attached to a computer processor. The method may include: (a) aligning the camera with a known position and / or orientation with respect to the coordinate system of the medical device in which the camera is directed to the eye as it is connected to the eyepiece; (b) capture an image of the eye as it is connected to the eyepiece; (c) identify one or more pixels of the image that represent the location of the central axis of the eyeglass; (d) determine from the image data that the

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central axis of the eye gma is aligned with a known position and / or orientation with respect to the coordinate system of the medical device; (e) determine from the image data the location of the center of the limbus in the coordinate system; and (f) determine any deviation from the location of the center of the limbus to a known position and / or orientation of the eye gma.

The method may also include (i) that the camera is aligned co-axially with a main axis of the medical device's coordinate system ("Z axis"); (ii) that the processor is programmed with software code that acts on the camera image data in the computer memory, to perform calculations and algorithms based on the image data, and determine the distances at pixel scale between locations in an image ("distance in the image"); and (iii) that the eye gma includes at least three fiduciary markers in known position relative to a central axis of the eye gma. The method may also provide that step (c) of identifying a pixel includes: (i) determining the part of the image that includes a first fiduciary marker ("fiduciary marker 1"); (ii) determine a geometric center of the fiduciary marker image area; (iii) select a pixel that represents the center of the fiduciary marker; and (iv) determine a pixel of the image that represents the central axis of the eye gma based on the known position of the first fiduciary marker.

The method may also provide that: (i) the step, of determining that the central axis of the eye gma is aligned, is repeated with respect to one or both of a second fiduciary marker ("fiduciary marker 2") and third fiduciary marker ( "fiduciary marker 3") to select a pixel representing the center of the respective fiduciary marker; and also includes:

(ii) calculate a horizontal center-to-center distance ("X") in the image between fiduciary marker 1 and each of fiduciary markers 2 and 3;

(iii) predict, from the known position of the fiduciary markers in the eye gma, the relative distance in the image from the fiduciary marker 1 to one or both of the fiduciary markers 2 and 3 corresponding to the horizontal alignment of the central axis of the eye gma with the Z axis ("without horizontal inclination");

(iv) compare the distances calculated in (ii) with the predicted distances in (iii) to determine if the ocular gma has no horizontal inclination;

(v) calculate a vertical shift ("Y") in the image between fiduciary marker 1 and one or both of fiduciary markers 2 and 3;

(vi) predict, from the known position of the fiduciary markers in the eye gma, the relative displacement Y from the fiduciary marker 1 in the image of one or both of the fiduciary markers 2 and 3 corresponding to the vertical alignment of the central axis of the eye gma with the Z axis ("without vertical inclination");

(vii) compare the displacements calculated in (v) with the displacements predicted in (vi) to determine if the ocular gma has no vertical inclination;

(viii) determine if the pixel representing the central axis of the eye gma is located in the center of the camera image; and (ix) determine if (iv), (vii) and (viii) are true, that the eye gma is aligned with the Z axis of the device.

The method may also provide that step (e) of determining the location of the center of the limbus includes: (i) determining a part of the image including all or a portion of the exposed part of the limit of the limbus, and identifying the pixel locations corresponding to the image of the limit of the limbus; (ii) determine a mathematical representation of a "best fit" form corresponding to the pixel data of the limit of the limbus; and (iii) calculate the center of the "best fit" form to determine the location of the center of the limbus.

The method may also include the steps: (g) recording the positions and / or orientations determined in the stages (a-d) of one or both of the eye gma and limbus in a virtual informatic eye model. (h) calculate the position of an anatomical structure of the eye in the device coordinate system based on the registered eye model.

Eye contact device and eyelid retractor: In an exemplary embodiment of an eye contact device having aspects of the invention for use in a system to secure a patient's eye in a selected position, the device comprises: ( a) a lens body having an internal concave contact surface adapted to face the front surface of a patient's eye to cover at least a part of the cornea, an external surface that includes one or more mounting locations, and a transparent window part arranged to allow, when in an operative position, the visualization of an internal part of the eye through the cornea; (b) a support member that can be mounted on a base; and (c) two or more joints pivotally mounted on the support member and connected to a lens body mounting location, the configured joints form an assembly that supports the lens body in front of the eye.

The device may also include an adjustment mechanism that connects at least one joint and configured to provide adjustment of the range and / or resistance of at least one degree of pivoting freedom of the lens body with respect to

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to the support member. The window part may have at least one optical property selected from the group consisting of a selected transparency, a selected optical refraction, a selected magnification, a selected optical filtration, a selected optical polarity, and a selected marker pattern.

In an exemplary embodiment of an eyelid retractor device having aspects of the invention, the device comprises: (a) a spoon-like hook that connects the assembled eyelid configured to maintain an eyelid without damaging it; (b) an elastic tension member (for example, an elastic tape or tube) attached to the spoon-like hook and attached to an insurer base member (for example, a clip or other joint), the tension member being adjustable both in tension as the direction of application of the tension with respect to the eye. The tension adjustment may include altering the length of the tension member (for example, a conventional strip adjustment, Velcro adjustment, or the like) or may include altering the location of the insurer base member (such as by attaching a clip to a location different). The tension member may include a tension release mechanism (such as a magnetic release). The insurance base member can be configured to join a subject's clothing or the subject's body.

X-ray collimator with movable elements: In an exemplary embodiment of collimator having aspects of the invention to produce a collimated X-ray beam treatment, the collimator comprises: (a) a collimator body configured to be supported in operative association with an x-ray source assembly that has an x-ray source; (b) a collimator axis that defines the direction of propagation of the x-ray beam; (c) an outlet opening of the collimator supported with respect to the body of the collimator to determine one or more transverse features of the X-ray beam; (d) either or both of the collimator body and the outlet opening of the collimator include one or more elements that affect a beam configured to produce a collimated x-ray beam directed to intersect the treatment target of a subject's body, so that at least one of the elements that affect a beam is movable to adjust a physical parameter of the x-ray beam.

In one embodiment, the element affecting the beam may include one or more of the following: (i) an extensible body part configured to alter the distance of the opening from the X-ray source; (ii) a movable part configured to alter the position of the aperture with respect to the X-ray source, to alter the direction of the beam axis; (iii) a movable part configured to alter the rotational position of the opening relative to the collimator axis; and (iv) a movable opening element configured to be adjusted to change one of the diameter of a beam and the transverse shape of a beam.

In one embodiment, one or more movable elements are mounted on one or more actuators configured to move the elements during the course of the X-ray treatment, the actuators controlled by an effective tracking controller to detect a movement of the treatment target during the treatment; the effective controller for controlling the actuators to adjust a physical parameter of the X-ray beam to substantially maintain the intersection of the beam with the treatment target in the case where the target moves during treatment.

It should be understood that in general, when a method of treatment having aspects of the invention is described herein, the concept of the invention includes embodiments of a device for performing the method, and embodiments of software or machine-readable code effective for carrying out the method by means of an information processor operatively connected to said device embodiment.

These and other objects and features of the invention will be more fully appreciated when the following detailed description of the invention is read in conjunction with the attached figures.

Brief description of the figures

FIGURES and associated descriptions are provided to illustrate embodiments of the description and not to limit the scope of the description. Throughout the figures, reference numbers are reused to indicate correspondence between referenced elements. The FIGURES are in simplified form and not necessarily to scale. Referring to the description of the present specification, only for purposes of convenience and clarity, the directional terms, such as upper, lower, left, right, up, down, above, above, below, below, in the background , and in the front they are used with respect to the attached figures. Such directional terms should not be considered as limiting the scope of the invention in any way.

The drawings generally illustrate embodiments of methods and devices that have aspects of the invention, except when specific features of the drawings are specifically defined as being from the prior art. Thus, the drawings are an integral part of the written description of the inventions herein. The figures can be summarized as follows:

FIG. 1A is a perspective view of an embodiment of an X-ray treatment system that has aspects of the invention.

FIG. 1B is a plan view of the embodiment of the treatment system of FIG. 1A, which also shows system processors and operator devices, represented as installed in an exemplary console.

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FIGS. 2A-B illustrate perspective views of the contact device or eyepiece having aspects of the invention in several cases of alignment with an axis of the system.

FIGS. 3A-B and 4 represent parts of an exemplary radiotherapy system that includes an alignment and stabilization subsystem of the eye and X-ray source collimator having aspects of the invention.

FIGS. 5 and 6 represent embodiments of a consisted X-ray positioning system to treat the eye.

FIG. 7 represents an anatomical addressing method for radiotherapy, which represents a cross section of a patient's eye;

FIG. 8A is a schematic view of an image of fundus in a patient's retina, showing the anatoirna and geometna of the retina.

FIG. 8B is a perspective view of a virtual model of an eye, including a registered retinal image, such as an OCT image of a patient.

FIG. 9 is a front view of an eye as seen aligned with a system reference axis and representing stereotactic x-ray beam treatment geometry.

FIG. 10 represents results of an experiment in which three beams were focused on the back of an eye using a robotic system.

FIG. 11 represents a simulated eye model that includes a virtual representation of most of the ocular anatomy shown in FIG. 7, including the relationship between different anatomical features and eye geometry.

FIG. 12 shows an X-ray collimator system including the physical parameters that affect the characteristics of the radiation beam, as applied to a simplified anatomical representation of the anatomy of FIG. eleven.

FIG. 13A is a graph showing the results of a Monte Carlo computational simulation for the absorption of X-ray energy in a configuration generally similar to that of FIG. 12.

FIG. 13B shows a plot of dose intensity measured at retinal depth for an X-ray / collimator configuration comparable to that of FIG. 13A.

FIG. 14 shows an example of the mapping using a 3D laser scanner to determine points in the three-dimensional space of the surface of several corpse eyes.

FIG. 15A is a plot of the tissue path length versus axial length from data as shown in FIG. 14.

FIG. 15B is a graph of tissue path and axial length derived from ultrasound mode A of seven examples of corpse eyes.

FIG. 16 illustrates a top view of an embodiment of a system for controllable positioning and / or stabilization of the eye of a subject for therapeutic treatment.

FIGS. 17A-B illustrate top views of an embodiment of a system for connecting the eye of a subject.

FIG. 18A-D represents perspective views of the contact device with the attached control arm having aspects of the invention.

FIG. 19 schematically illustrates an eyepiece device for use in an eye stabilizer system that has aspects of the invention having fiduciary markers.

FIGS. 20A-G schematically illustrates an eyepiece device for use in an eye stabilizer system that has aspects of the invention, and that has molded fiduciary markers, and a method for determining image recognition orientation.

FIG. 21A is a flow chart illustrating a method of using the system to stabilize and position an eye for treatment.

FIGS. 21B-E are schematic illustrations of the eye of a patient associated with an embodiment of the treatment system, which shows particular stages described in FIG. 21A.

FIG. 22 represents an embodiment of an eyeglass having aspects of the invention connected to an eye that has an embodiment of an eyelid retractor.

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FIG. 23 represents an alternative embodiment of an eye gma having aspects of the invention connected to an eye that has an alternative embodiment of an eyelid retractor.

FIGS. 24A-D illustrate an ocular gma shown in FIG. 23, the device having a pattern of fiduciary markers, the gma for use in an eye stabilizer system having aspects of the invention, shown in contact with an eye and representing the method for determining alignment.

FIGS. 25A-B illustrate the effect of inclination on the position of fiduciary markers of the eye gma of FIG. 24.

FIGS. 26A-E are graphs that show eye movements measured experimentally with an embodiment of a system for controllable positioning and / or stabilization of the eye.

FIGS. 27 and 28A-B are flow charts that illustrate the acquisition and processing of data.

FIGS. 29A-B are two plan views of an eye gma included in an eye stabilizer system that has aspects of the invention, shown in contact with an eye during X-ray treatment, illustrating the effect on the retinal position of the movement of the eye.

FIGS. 30A-B are two plan views of an eye gma that has aspects of the invention in contact with an eye during X-ray treatment, illustrating the effect on the retinal position of the eye's rotational movement.

FIGS. 31A-B are views illustrating from a frontal perspective the movement shown in FIGS. 30A-B.

FIGS. 32-36A-B are diagrams representing the transformation procedures that have aspects of the invention for converting detected input signals related to eye movements (see FIGS. 29-31) into corresponding movements of a beam point relative to the retina.

FIG. 37A-B are graphs illustrating a dose map of 3 stereotactic beams of retinal dose measured by radiometna in a simulated eye or model.

FIG. 37C is a dose distribution graph prepared by a Monte Carlo numerical radiation transport simulation used in conjunction with a characteristic model of human anatoirna derived tissue revealed in imaging by CT scan.

FIGS. 38A-B represent a method of confirming an exemplary radiotherapy treatment plan that has aspects of the invention using radiographic measurements in the eye of a corpse.

FIGS. 39A-E are graphs illustrating the retinal movement determined from the eye movement measurements shown in FIGS. 16A-E, and showing the effect on the dosage of radiation absorbed in the retina.

FIGS. 40A-H are graphs that illustrate the retinal movement determined from the eye movement measurements, and that illustrate a method to prevent unplanned radiation dosing in the retina by controlling the inactivation ("gating") of the source of X-rays and realignment of the stabilizing system of the eye.

FIGS. 41A-D are graphs illustrating alternative inactivation control methods based on retinal movement determined from the eye movement measurements.

FIGS. 41E-H are graphs that show the operation of retinal follow-up and control controls of X-ray inactivation during patient treatment.

FIGS. 42A-H are graphs that illustrate the retinal movement determined from the eye movement measurements, and that illustrate a method to correct the patient's flickering during treatment, to control the radiation dosage in the retina.

FIGS. 43A-C illustrate an embodiment for tracking retinal movement by altering the path of the beam using a movable collimator exit plate.

FIGS. 43D-G illustrates an embodiment of a collimator assembly having aspects of the invention, which has a variable collimator length.

FIGS. 43H-K illustrate alternative embodiments of collimator assemblies that have aspects of the invention, which has a variable collimator aperture diameter.

FIGS. 44A-D illustrate a gma device for use in an eye stabilizer system that has aspects of the invention, the gma having a window or transparent stop that allows retinal imaging during treatment.

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FIGS. 45A-C illustrate eye gma devices that have a window or transparent part; and which have an adjustable support arm structure comprising a plurality of joints.

FIGS. 46A-C illustrate two exemplary embodiments of elastically bonded eyelid retractors that have aspects of the invention, and a release of magnetic stress.

FIGS. 47A-C illustrate an alternative embodiment of an eyelid retractor.

FIGS. 48A-D illustrate a further alternative embodiment of an eyelid retractor having aspects of the invention.

FIG. 49 is a schematic structure diagram of an LSLO embodiment, configured for retinal imaging.

FIGS. 50A-B are an elevation view and a plan view respectively of an exemplary optical arrangement of an LSLO instrument.

FIG. 51 illustrates an exemplary LSLO optical housing.

FIG. 52 illustrates an exemplary radiotherapy system that has aspects of the invention that an imaging system has including an image forming instrument of the retina such as an LSLO.

FIG. 53 illustrates an exemplary radiotherapy system that has aspects of the invention for treating a non-ocular target while tracking a contact member attached to the body.

FIG. 54 illustrates an exemplary radiotherapy system that has aspects of the invention, generally similar to the embodiments shown in FIGS. 1-6, but which has an eye tracking system that uses corneal reflections for alignment.

FIGS. 55A-C illustrate schematic side views of an anterior part of an eye in three orientations with respect to an embodiment of an alignment system having aspects of the invention, which represents a method that uses the dimensioning of the blade to define the reference axis.

FIG. 56 is a diagram of an exemplary method having aspects of the invention, showing a sequence of successive data processing steps used to identify the limbic limit and the limbic center.

Detailed description

The following description is related to the content found in priority requests, in particular US applications No. 12 / 103,534 filed on April 15, 2008; No. 12 / 027,069 filed on February 1, 2008; and No. 12 / 100,398 filed on April 9, 2008; each of which is incorporated by reference, to which the reader is directed for description and additional examples. In particular, these applications describe alignment and stabilization devices of the eye that have aspects of the invention, and methods for their use. In addition, these applications describe ocular radiotherapy methods devices, and methods for planning treatments that are relevant to the following description.

I. Definitions

The following terms have the following definitions herein, unless otherwise indicated.

An "injury" refers to a localized area of diseased or disturbed tissue. An "ocular lesion" may refer to a retinal or non-retinal lesion, and a retinal lesion may refer to any localized pathology associated with the retina, including macular degeneration, such as wet and age-related macular degeneration at which the lesion is associated with the macula, lesions associated with tumors or with vascular abnormalities, drusen, including drusen of the optic disc, diseases of the optic disc, lesions associated with inflammation, such as Smdrome de Behcet, lesions associated with hereditary diseases, such as Watanabe Hereditary Hyperlipidemia , and lesions associated with viral, bacterial, or parasitic infection, such as lesions associated with infection, such as lesions associated with Trypanosoma infection.

A "radiation sensitive structure" refers to an area of normally healthy tissue or structure that is close to an injury, and is at risk of loss of function due to radiation overexposure, for example, by a collimated X-ray beam . An example is the optical disc, which is close to the macula in the retina of a patient's eye.

An "external coordinate system" or "treatment coordinate system" refers to the coordinate system in which the coordinate positions of various components of a treatment system, such as an eye gma, a tracking system, and a Beam radiation axis can be determined and their positions with respect to each other are known.

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A "patient axis" refers to an internal axis defined by the natural points or fiduciary reference markers in the patient, and which can therefore be used in the monitoring of the patient's position by an adequate monitoring system in the system of external coordinates. An exemplary patient axis is an ocular "geometric axis" defined as a line that extends through the center of the limbus and through the center of a corneal reflection, for example, the first reflection produced from the cornea when illuminated by a source of light.

An "ocular crane axis" refers to an axis defined by an ocular crane in the external coordinate system. Ideally, an eyeglass is centered on the patient's eye so that the geometric axis of the eye in the patient coordinate system aligns with the axis of the eyebrow in the external coordinate system. This can be done, for example, by focusing the eye gland on the eye, for example, with respect to the eye blade.

A "reference axis" or "system axis" refers to an axis that has known coordinates, and defined in the external coordinate system. As will be seen below, the reference axis can be defined by the axis of a given patient in a defined body position, so that the position of the body can be followed by the movement of the body axis relative to the reference axis. For example, if the region of the patient to be treated is a retinal structure, such as the macula, the patient's eye is initially placed in a position preferably immobilized with the patient facing forward. The geometric axis of the eye is determined in this position, and the coordinates of the geometric axis in the external coordinate system then define the reference axis. The reference axis can be thought of as the axis that forms the reference frame to transform the internal body coordinates in the external coordinate system, by matrix transformation, in which the transformation is determined according to a measured variation of the body axis with respect to the reference axis Alternatively, when the position of the eye is followed by monitoring the position of an eyeglass in the eye, the reference axis can be defined by the axis of the eyeglass when the patient is initially placed in a position preferably immobilized with the patient. looking straight ahead The axis of the eyepiece then becomes the reference frame to determine the position of the eye relative to the reference axis.

The "axial length" of the eye is the distance along the geometric axis of the eye between the front part of the cornea and the back of the retina. This distance can be measured by ultrasound according to known methods.

A "standard eye model" or "human eye model" refers to a geometric model of the eye that is constructed from a large population of human eyes. This model will have its own coordinate system in which the coordinates of the eye structures of interest, including the macula and optical disk, are known.

A patient's eye is "scaled to a human eye model" by aligning a known ejo of the patient's eye, for example, the geometric axis, with the same axis in the model, and scaling the model so that the length Axial model matches the measured axial length of the patient, in effect, overlapping the model in the patient's eye. Once the model has been superimposed on the patient's eye, the internal eye structure coordinates of the model can be assigned to the patient's eye, to define internal eye coordinates of the patient's eye structures. These internal coordinates, in turn, can be transformed into the external coordinates of the known transformation between the geometric axis of the patient's eye with the reference axis. Thus, by tracking the geometric axis of the eye with respect to the reference axis, the coordinates of the geometric axis in the external coordinate system are known, and from these known coordinates, the coordinates of internal ocular structures in the coordinate system can be determined external. The eye model may contain a "virtual medium" that simulates the characteristics of attenuation of the radiation of the medium, for example, human vitreous, in the real eye.

A "sum of time increment vectors of a parameter indicative of an output based on the eye movement of a beam axis of the selected target to be treated" is determined by the steps of (i) at successive points of time, for example, intervals of tenths or hundredths of a second during the course of radiation treatment, using the position followed by the eye to determine the instantaneous coordinates of the target in the external coordinate system, (ii) from the position known of the radiation beam axis in the external coordinate system, determine the position of the radiation beam relative to the position of the target, (iii) using the positions determined in (ii) calculate a vector that represents the magnitude and direction of the position of the beam with respect to the position of the target, and (iv) add these vectors over time.

A "collimated beam of radiation" refers to a beam of radiation x that has been collimated, for example, by passage through a narrow gauge filter.

"Radiation equivalent" refers to a radiation dose received at a position at or near an injury, and determined by integrating the instantaneous radiation dose of that position over the total exposure time. Alternatively, "Radiation equivalent" may refer to an integral parameter based on the radiation beam geometry and time history, in which the integral parameter can be correlated with an equivalent radiation dose based on the beam properties. known radiation. For example, when a beam has a constant dose rate (for example, Gy / sec), the relationship between beam duration and radiation dose at a point that intersects the beam can be a simple linear relationship, allowing a parameter to be used. time-position integral (sometimes referred to as "Accumulation Factor" herein) as a

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equivalent of a cumulative radiation dose in a geometric location (for example, in monitoring and control or "inactivation control" of the beam).

A "tracking assembly" refers to several tracking devices for image formation and / or coordinates in the external coordinate system that can be used to track the position of a region of the body, for example, the eye of a patient. When the region of the body is being followed by natural features of the body, for example, when the eye of a patient and the eye is being followed by determining the position of a geometric axis of the eye, the tracking system may include (i ) a camera for the formation of images of the region of the body that is being followed, (ii) a light source of the region from which illuminated images have been formed, and (iii) a detector in which the image of the Camera can be represented as a digital image. When the region of the body is being followed by applied fiduciary markers that may well emit or reflect signals related to the position, such as an ocular frog fiduciary marker consisting of one or more reflectors to reflect an external beam or beams, such as beams electromagnetic or ultrasonic, the tracking system includes the fiduciary marker (s) applied to the body, and element or elements that respond to the external signal to detect the emitted or reflected signals and determine from the signals, the position or positions of the of fiduciary markers in the external coordinate system. A tracking system can include elements of both image formation and signal response. For example, in the case of tracking the position of the eye by means of an eye gland attached to the eye, the tracking system may include an imaging system to form images of the eye and fiduciary markers attached, such as fiduciary marker of the frog. eyepiece and a fiduciary marker tracking device.

"Code readable by operating machine in an electronic computer" refers to software or wired instructions used to control the logical operations of the computer. The term computer or processor refers to an electronic computer or its specific logical processor hardware. The machine-readable code is included in a tangible medium, such as a hard disk or hardwired instructions.

II. Radiotherapy system

In a general aspect, the invention includes a system for treating a target area in a patient with an irradiation beam. The system includes a tracking assembly for tracking the position of a region of the patient's body that contains the target area and at least one radiation sensitive area relative to a known reference axis in an external coordinate system. A monitoring system for monitoring the movement of a patient's eye, based on only the natural features of the eye, is detailed in the VIIC Sections and with respect to FIGS. 54-56. A tracking system for monitoring the position of the eye, by tracking an eye-centered eyeglass, is detailed in Sections IV and V. A beam source is also included in the system to direct an irradiation beam. to the patient's target area along a known treatment axis in the external coordinate system, as detailed in the IIC Section below. A processor in the system (described below with reference to the IID Section) is operatively connected to the tracking device and the beam source is operative to carry out operations to:

(i) determine the coordinates of the target area and structure or structures of the patient sensitive to radiation during the course of treatment;

(ii) calculate the coordinates of the target area and the structure or structures sensitive to radiation during the course of treatment;

(iii) on the basis of the known beam axis of the collimated beam in the external coordinate system, and the instantaneous positions of the target area to be treated and the at least one radiation sensitive structure, calculate a total radiation equivalent received in the target area and at least one radiation sensitive structure; Y

(iv) on the basis of the calculated radiation equivalents of step (iii), control the radiation beam to ensure that the at least one radiation sensitive structure receives no more than one radiation equivalent preselected during the treatment.

FIG. 1A is a perspective view of an exemplary embodiment that has aspects of the invention of an X-ray treatment system 10 for treating eye diseases. FIG. 1B is a plan view of the embodiment of the treatment system of FIG. 1A, which also shows associated system processors 501 and operator input / output devices 502-503, representing as installed in an exemplary operating console 500. FIGS. 2-6 illustrate alternative or additional aspects of the system 10.

With reference to FIG. 1A, the system is shown with a simulation of the head of a patient 31 connected to a head-chin fastener 160 and head 161, the head aligned in the treatment position. The system 10 includes a module for the generation of radiotherapy or X-ray source assembly 420, for example, comprising one or more X-ray tubes 112, each having a collimator to produce a firmly collimated X-ray treatment beam. System 10 includes a radiation therapy control module that preferably includes an interface monitor 502, processing module 501, operator input devices 503 and a power supply (not shown). The system includes a training module of

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400 images, which may include one or more cameras and associated light sources, such as LED or low power lasers. The processing module, and machine-readable code used to control various module operations, will be described later in Section IID. The module is also referred to herein as a processor and an electronic computer.

The system 10 comprises an alignment and / or stabilization module of the eye including an eye contact device or eyeglass 625 having aspects of the invention, which is further described with respect to FIGS. 2 and 16, among other places. In the example shown, the alignment and / or stabilization module of the eye is configured for use with the system 10, although it can additionally be used in a useful manner independently of the system 10. The eye stabilization device may further comprise sensors or auxiliary devices. motion detection or cameras to assist in the administration of radiation to a patient.

In the embodiment shown, the system 10 includes an automated positioning system (APS) 115 to move and direct the assembly of the X-ray source 420 (including the X-ray tube 112 and collimator 118) to direct a treatment beam to a target from one or more selected addresses. The additional description of system 10 appears below.

FIG. 1B illustrates a particular embodiment of an operating console 500 that has aspects of the invention, suitable for housing the components of the system 10 and for providing its effective and safe operation in the treatment of the patient. It should be understood that the intercom components of the system 10 can be mounted in a variety of different architectural configurations, and the components can be distributed remotely and / or integrated with other devices. For example, the components shown in FIG. 1B in a "tabletop" type assembly (eg, X-ray source positioning system 115) can alternatively be supported in a ceiling or wall mounting configuration, or they can be mounted on trolleys with wheels, or the like. Similarly, alternative embodiments of the system 10 that have aspects of the invention can be optimized to reduce the size, weight and volume to allow the integration of the components into one (or a few) physical modules, for integration into other medical systems. , and / or to provide portability.

The exemplary operating console 500 provides seat 506, 507 for the patient and one or more operators, and may also include shielding against supplementary radiation 508a, b between the operator and the assembly of the X-ray source 420. The system cameras of image formation 410 (for example, one or more CCD or other electronic image capture devices) communicate with computer processors 501 of system 10. Processors 501 communicate with operator monitor 502 and operator input devices, such as keyboard 503. The console also houses one or more computer processors 501, operator input / output / monitor devices 502a-503a, and 505 interconnections to various system components, such as the imaging system 420, positioning system 115 and assembly of the 420 X-ray source.

It should be understood that the elements of the computer processor, and input, output, monitor, memory and / or control components can be distributed, included and / or joined in a number of alternative arrangements by means known in the electronic art, and the arrangement shown in FIG. 1B is exemplary. Also, the intercommunication of the electronic elements of the system 10 can be wireless, and alternatively certain functions of the processor, memory and / or I / O can be performed remotely or over a network.

For example, supplementary presentation and control devices that communicate with the processor 501 can be positioned to assist or interact with an operator or doctor while working near the patient (for example, before the emission of the x-ray beam). An auxiliary presentation / input device 402b-403b is shown adjacent to the eyepiece 600 positioner, for example, to assist an operator in the connection and alignment of an eyepiece (110 in FIG. 2) in the eye of a patient, and / or adjusting the positioner 115 and the x-ray source 420 in an initial treatment position.

In addition, various sensor elements may be included in the components of the system 10 in communication with the processor 501 to provide information, monitoring and security functions. For example, the chin-head fastener assembly 160 may include a right-left pair of handles 163 for the patient to grip, helping to keep the patient's torso and shoulders in perpendicular alignment with respect to the eyepiece 110. Handles may include a force or contact sensor to monitor that the patient is in the correct position. Similar sensors may be included in the head fixation 161, for example, to monitor the position and / or movement of the head. Said safety / monitoring sensors can produce trigger signals to alert an operator and / or can be used to control the activation or interrupt the emission of X-rays during treatment. In another example, light intensity and / or spectral sensors (not shown) can be positioned in system 10, and configured to automatically control the lighting elements of the imaging system 400 (e.g., lights 405,406) to maximize Image recognition performance, as well as other operational parameters.

The console 500 comprises a power assembly / accessories 509 that may include a power supply, power regulators, high voltage source and / or other accessories necessary for the operation of the x-ray tube 112. A number of types should be indicated. commercially available alternatives of X-ray tubes or sources

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(as well as specialized tube designs) can be included in the assembly of the X-ray source 420 without departing from the invention. A high voltage X-ray power supply / source may be a relatively large unit that is most conveniently housed separately from the assembly of the movable X-ray source 420. In the example shown, the conduits 425 lead from the power assembly. / X-ray accessories 509 on the console 500 through the crane reel 426 to connect to the x-ray tube 112. The crane reel 426 is configured to support the ducts 425 when moving the assembly of the X-ray source 420 during the operation of the system, as further described herein.

Additionally, many commercially available X-ray tubes are designed to use liquid cooling to increase the output capacity. The power supply / accessory assembly 509 and the ducts 425 may optionally include coolant connections and / or an integrated coolant / cooler supply, to supply coolant to the X-ray tube 112. Optionally, assembly 509 may include batts or a non-interruptible power supply (UPS) of sufficient capacity to allow the system 10 to complete a radiotherapy treatment regardless of the power line.

The exemplary operating console 500 provides seat 506, 507 for the patient and one or more operators. System 10 can be configured to minimize dispersed x-ray radiation. However, as a radiation safety practice, the console 500 may include shielding against supplementary radiation 508a between the operator's seat position 507 and the assembly of the X-ray source 420. The shield may optionally include a radio window -pack 508b (for example, which comprises a transparent silicate glass including heavy nuclei such as lead) to allow direct observation of (and reconfirmation to) the patient during X-ray emission. Said operator station configuration allows monitoring close to the patient during irradiation treatment, and promotes easy access for direct patient assistance when radiation is not being emitted. Alternatively or additionally, observation cameras (not shown) can be mounted to allow an operator and / or physician to monitor the patient during treatment through electronic monitors.

IIA Alignment and stabilization module of the eye

FIGS. 2A-2B illustrate perspective views of an exemplary embodiment 625 having aspects of the invention of a contact device or eyepiece and alignment and stabilization module of the eye configured for use with the system 10 (additionally it can be used independently of system 10). This can be used in conjunction with the head-chin support device 160, which includes a head support or support 170 to stabilize the subject's head, and includes a chin rest 172.

FIGS. 2A-2B and 3A-3B represent an exemplary embodiment of an image-based method for aligning the eye of a patient 30 and connected eyeglass 110 with the coordinates of the radiation therapy system 10, using a laser beacon 150 to align the eye with the 800 laser alignment system. Optionally, the alignment mechanism also directly aligns a treatment system, such as a radiation therapy system (not shown) in which the radiation therapy system directs its energy towards the eye in relation to the alignment system. . The beam of the laser pointer 810 (which is collinear with the therapeutic beam in some embodiments) is emitted from the laser system 800 through an opening of collimator 820 and is reflected from the surface of the mirror that directs beam 230 of the device contact 110. In the case of non-alignment shown in FIG. 2A, the beam of the laser pointer 810 will not be reflected from the surface of the mirror 230 collinearly with the opening of the collimator 820, but will be off-axis, as shown by the reflection beam 830. The orientation of the laser system 800 and / or the contact device 600 can be adjusted manually or automatically by direct visualization of the location of the reflection beam 830 or by sensors that detect the location of the reflection beam 830 and adjust the laser system 800 to set the laser reflection beam 830 in alignment. FIG. 2B shows a case where the laser pointer is in fact aligned, the beam of the laser pointer 810 is reflected, and the laser reflection beam 830 is substantially collinear with the beam of the laser pointer 830. See the description with respect to FIGS. 3A-3B with respect to the geometry of the mirror 230 and angular alignment of the eyepiece 110. FIGs. 2 and 3A represent a laser beacon 403 mounted to project coaxially with an image detection camera of system 401.

Alternatively or additionally, the alignment of the eyepiece 110 with a coordinate axis of the system can be determined by image capture and recognition methods. See the embodiments of device and method described herein with respect to FIGS. 3A-3B and the sections with the legend "Image formation subsystem" and "Example of eye and eye chart measurements based on images". In addition, the description of the image processing and recognition methodology herein is applicable to detect the deflection of the laser beacon 150 (403 in FIG. 3A) of the mirror 230, and measure any alignment errors thereof. For a further description of laser beacon alignment, reference is made to Requests No. 12 / 027.083 filed on February 1, 2008; No. 12 / 027,094 filed on February 1, 2008; No. 12 / 027,069 filed on February 1, 2008.

The eye positioning assembly 600 is used to position the eye contact device or eyepiece in a selected orientation. The contact device 110 can be attached to a control arm 180 in the positioning assembly 625, which is fed into the groove 610 of the steering mechanism 600. In some

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embodiments, the contact device 110 of the system can be attached to a coupling component to keep the eye in place.

The eye gma device 110 is preferably disposable so that a separate contact device 110 (eg, disposable) is used for each subject and / or use. Alternatively, the contact device 110 may not be disposable and treated, for example, with anti-infective agents, before being used in the eyes of multiple subjects. The steering mechanism 600 is fixed to the base 620 through the connector 640, which can be robotically controlled or manually controlled, and has a known coordinate system. In one embodiment, the steering mechanism 600 is fixed in a known or predetermined location, with respect to the head positioning system (not shown) and / or the subject's eye (not shown) and / or the positioning system of the radiotherapy device The button 630 allows free manual positioning of the contact device 110 in and / or out of the slot slot 610. The control arm 180 is fully connected to the steering mechanism 600 and is fixed in a known, or predetermined, location it allows the subject's eye to be fixed in a known, or predetermined, location when the contact device 110 connects the eye. Although not shown, the eye positioning device may include the operating internal position sensors to detect the position of the arm end 110 in the external coordinate system, according to the movement of the arm in a and direction.

Note that the eyepiece support arm 180 is illustrated in the examples shown as extending mainly in the "X" direction of the ordinates of the system. It should be understood that alternative embodiments of module 625 may have eye gma 110 in support from below or above in the Y direction, or from the Z direction, or combinations thereof. The module of eye gma and alignment and stabilization of the eye 625 is further described with respect to FIG. 16 et seq.

IIB X-ray source and positioning system

FIGS. 3A-3B and 4 represent the X-ray source and collimator (112 and 118 in FIG. 1) having aspects of the invention, shown in FIG. 3A as aligned in position for the treatment of the retina of one eye. FIG. 3A shows the head of a patient including the cross section of an eye in the vertical symmetry plane of the eye, shown in association with the imaging system 410, and an X-ray source assembly comprising an X-ray tube 112 and collimator 118. FIG. 3B is a detailed perspective view of the system components shown in FIG. 3A together with parts of the positioning system 115 (see FIG. 5), illustrated in association with a simulated eye of a patient 30 coupled with the eye gma 110. FIG. 4 is a longitudinal cross-sectional view of collimator 118 and a part of the x-ray tube 112. FIG. 5 is a perspective illustration of an embodiment of a positioning system 115 having aspects of the invention, in this example an automated positioning assembly with 5 degrees of freedom, shown supporting X-ray tube 112 and collimator 118 in association with a simulated eye 30. FIG. 6 represents embodiments of a motion control system in which collimator 118.

As shown in FIGS. 3A and 3B, the assembly of the X-ray source 420 is aligned in position for the treatment of the retinal target 318 of one eye 30. For clarity and simplicity of the illustration, the example of FIGS. 3A and 3B, shows the assembly 420 aligned in the vertical plane including the treatment axis 2820 with an upwardly directed X-ray beam axis 1400. This corresponds roughly to the example beam 1400b as shown in FIG. 9, so that the value of the azimuth angle 0 is 180 degrees. The polar angle (angle between the treatment axis 2820 and the beam axis 1400) is shown as approximately 30 degrees. It should be noted that the orientation of the beam 1400 can be selected and adjusted to fit a particular treatment plan method that has aspects of the invention, and it is not necessary to restrict it to any of the orientations shown in these examples.

FIG. 3A shows components of the image formation / data acquisition system 410 including data acquisition devices that function to track and / or identify the position of the eye 30, its anatomical structures (eg, the eye blade), and / or an eye gma 110. In the example shown, the data acquisition devices comprise one or more cameras (for example, the camera 401 located aligned with the geometric axis of the eye 2810, the camera 402 aligned off-axis, or both ). The cameras can be sensitive to visible and / or non-visible wavelengths (for example, IR) and can include filters configured to fine-tune the sensitivity at certain wavelength ranges. Alternatively or additionally, the data acquisition devices may comprise non-light emitters and detectors, such as ultrasound transducers / generators, radio frequency devices and the like. A number of types of fiduciary markers, transponders and / or mirrors can be included as system components to enhance the function of the data acquisition system. Also, radiation emitters may be included, such as lights, lasers, LEDs and the like.

In certain exemplary embodiments, the imaging system 410 comprises an off-axis camera configured to measure the position of the eye gma 110 and the eye relative to the Z axis (distance from the system), optionally assisted by one or more lights 406 (for example, visible or IR LED). An axis camera 401 is included, configured to determine the alignment or compensation of the eye 30 and / or eye gma 110 with the axis 2810. Similarly, one or more lights 405 (eg, LED) can be included to assist the camera 401

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In certain embodiments, the eyepiece 110 includes an axially perpendicular mirror, and the imaging system 410 includes an axial collimated light pointer 403 (for example, including a diode laser, beam splitter, and camera filter) aligned to reflect from the mirror to be received by the camera 401, allowing the determination of the axial alignment (or difference in alignment) of the eyepiece 110 with respect to the axis 2810.

In alternative embodiments described in detail herein, the eyepiece 110 includes a geometric pattern of highly reflective fiduciary markers, and camera 401 is configured to form images of the pattern, the camera in communication with a system processing unit programmed to determine the alignment (or alignment difference of the eyepiece 110 relative to the axis 2810.

IIC Image formation system

FIGS. 3A and 3B illustrate a particular example of an image forming system 410 that has aspects of the invention. In operation, the image formation system 410 can be configured for several functions, most of which can be performed automatically using image processing and pattern recognition, including:

1. Alignment of the eye 30 with the eyepiece 110.

■ Monitor and assist in the initial positioning of the eyepiece 120 lens by the doctor (presentation and grna).

■ Confirm the alignment of the eyepiece 110 (can be automatic).

■ Monitor and measure the relationship of the lens of the eyepiece 120 with the patient's limb 26, it can be done automatically using image processor and pattern recognition (it can be automatic).

■ Measurement and verification to identify the center of the lens and the limbus in x-y (can be automatic).

■ Locate and measure the grind I in depth z (can be automatic).

■ Measure the orientation of the eyepiece in angular space (can be automatic).

2. Verification of the input position 311 of the X-ray beam 1400.

■ Identify and calculate the position of the laser point 1410 indicating the scleral entry of the X-ray beam and relation to the limbus 26 (it can be done automatically, and it can also be verified by the operator before the X-ray emission).

■ The algorithm used can be based on the analysis of the image formation of the limit of the limbus 26 compared to the center of the limbus. In an example of a treatment plan, the center of the X-ray beam is placed approximately 4 mm from the limit of the limbus, the diameter of the beam being approximately 3.5 mm, so that the edge of the beam is approximately 2.25 mm more beyond the limbus (beam 1400 crosses the region of pars plana to reach target 318 at or near the fovea, and thus minimizes the dosage in the lens.

3. Treatment monitoring (inactivation control)

■ Continuous spatial monitoring x-y-z-0 of the eyepiece 110.

■ Continuous measurement of limbo position x-y (can be automatic).

In the example shown in FIGS. 3A and 3B, the imaging system 410 comprises two cameras. The cameras can be intercommunicated with computer processors (not shown) of system 10, for example, via USB connectors. Illumination (for example, LED lights) can be controlled by signals from computer processors. The cameras include:

1 Main system camera X-Y 401 (on axis)

■ Located along the center axis of the Automated Positioning System (APS).

■ Show live images to the doctor at video speed (30 Hz).

2 Z range camera (off axis)

■ Mounted above the system axis.

■ Angled down to get a perspective view of fiduciary markers 1-3 of eyepiece 110.

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Lights 405, 406 and 407 provide safe, regulated light levels coordinated with the imaging procedures, so that the imaging applications are insensitive to ambient light conditions. These functions include:

■ Illuminate the field of vision for the Main System Camera x-y to see the patient's eye.

■ Direct the light along the path of each camera on the retro-reflective fudiciary targets to monitor Gma I

■ illuminate the lower limit of the blade 26 to enhance the contrast for the detection of the blade.

■ Mark the X-ray entry point with a laser point that has aligned with the X-ray source.

Please see the description below regarding FIGS. 21A-21E and the example with the legend "Example of measurements of the eye and eye guide based on images" for a further description of the methods of use of the imaging system 410.

Collimator 118 is positioned near the patient's eye, to allow acceptable penumbra as well as a firmly collimated radiation beam as described in US applications No. 12 / 103,534 filed on April 15, 2008; No. 12 / 027,069 filed on February 1, 2008, indicated above. In certain embodiments, the diameter of the outlet opening of the collimator is between about 1 mm and about 4 mm so that the size of the point on the back of the retina is about 2 mm to about 7 mm.

FIG. 4 represents a schematic cross-sectional view of a part of an X-ray source assembly 420 of system 10. Laser pointer 1410 travels through a beam splitter 1220 and exits the collimator with its center aligned with the radiation beam . In the example shown, the 1420 x-ray anode has a larger dimension between about 0.1 mm and about 5 mm and can be placed at a distance L of the retina from about 50 mm to about 250 mm, and preferably from about 100- 200 mm, and more preferably about 150 mm. The maintenance of the anode 1420 at said distance from the retina in one embodiment allows to maintain a low penumbra. The radiation beam 1400 is administered through collimator 118, and its divergent path enters the eye approximately in the pars plana region, missing important structures of the anterior chamber such as the lens and the cornea. In the example shown, the lens of the eye gma 110 contacts the sclera and / or the cornea of the eye.

As shown in FIGS. 3A and 4, collimator 1405 is preferably collinear with the collimated beam of light, 1410, which can act as a pointer to indicate the point in the eye through which radiation enters the eye 1300. In some embodiments, the position The image pointer is used to track the source of radiation therapy vis-a-vis an image recognition system that identifies the position of the pointer with respect to an ocular structure (for example, the limbus) and the radiotherapy device is then move on the basis of the image (for example, to a region farther away or closer to the eye blade). In some embodiments, the doctor visualizes the position of the laser pointer relative to the limbus and manually adjusts the source of the x-ray in position.

The light pointer 1410 (for example, a laser beam emitted from a source, such as a diode laser, fiber-coupled gas laser, or the like) is coupled to a collimator 1405, or behind collimator 1405, so that the pointer of light 1410 is coincident with the x-ray beam 1400; the light pointer 1410 may indicate the position 311 on the surface of an eye through which the radiation source enters by tracking angles of incidence of the collimator and x-ray beam. The cameras of the imaging system 410 can track point 311 and image processors can be used to confirm this position to a user, or to trigger automated controls, if position 311 were outside an accuracy threshold, according to a treatment plan

As illustrated in FIG. 3A, for convenience certain dimensions relevant to the collimation of the beam and treatment anatoirna can be identified as L0, L1, L2 and L3, where:

L0 is the total distance from the anode of the X-ray source 1420 to a treatment target 318 (for example, macula or fovea);

L1 is the distance from the anode of the X-ray source 1420 to the plane of the opening of the outlet of collimator 1405;

L2 is the distance from the plane of the opening of the outlet of the collimator 1405 to the beam point of the surface of the fabric 311 (eg, surface of the sclera at or near pars plana); Y

L3 is the length of the path of propagation of the x-ray beam in the tissue to reach the treatment target, the distance from the beam entry point in the tissue 311 to the treatment target 318.

In an exemplary eye treatment plan having aspects of the invention, the outlet plane of collimator 1405 is typically at a distance L2 of about 1 cm to about 12 cm from the point of

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entry of beam 311 in the sclera. However, in alternative embodiments, the collimator may be configured to be in contact with the surface of the adjacent eye or face, and may include a suitable resilient or padded biocompatible contact surface. The distance D can be selected as a middle term between the objective of minimizing the penumbra of the beam 1400 in the retina, and avoiding interference and discomfort of the patient, for example, due to space limitations when working near the face. In certain embodiments, a robot positioner with greater degree of freedom (DOF), high range of motion can be used to position the X-ray tube 112 and collimator 118, which can be programmed and / or controlled to maneuver to avoid interference with objects and parts of the patient's body. See, for example, robotic surgical control systems with a high degree of freedom as used in the CyberKnife® robotic radiosurgery system (Accuray, Inc. Sunnyvale, CA) and da Vinci® minimally invasive surgical system (Intuitive Surgical, Inc., Sunnyvale, CA). However, da Vinci is not autonomous and requires an expert surgeon to move his arms. The Cyberknife is in fact autonomous. However, the linear accelerator that moves around the patient weighs more than 1 ton and cannot move close enough to the patient to deliver X-ray beams to the eye. In addition, the system does not include an eye stabilization system to allow alignment with the eye.

However, alternatively and advantageously, a limited range of motion positioner (see 115 in FIGS. 5-6) can provide greater precision and accuracy of radiotherapy, particularly when moving a single DOF to stereotactically reposition the source X-ray 112 for sequential beam treatment applications, for example, minimizing positioning error, vibration and dynamic effects. In addition, a real or at least conceptual danger of robotic systems with a high degree of freedom that employs energy beam treatment is the large possible range of beam paths (for example, after a failure of the control system), and problems of associated risk, regulatory complexity, and high costs of end-user installation and site modification.

In one example, L2 is selected to be approximately 55 mm and L0 is selected to be approximately 150 mm, suitable for use with APS 115 shown in FIG. 1A and further described in FIGS. 5-6. See, for example, the embodiments described in US application No. 12 / 100,398 filed on April 9, 2008 indicated above.

In many embodiments, only a small part of the movement is required from the 112 x-ray source to treat a retinal disease, such as macular degeneration and / or diabetic macular edema. In these embodiments, six degrees of freedom can be applied to the X-ray source 110, but the range of each degree of freedom may be limited. Because each treatment dose is relatively short and applied over a small distance, the robot can be sacrificed in speed and path distance for a smaller size.

Alternatively, multiple X-ray sources can be used, for example, which have a fixed relationship between each other, to supply multiple stereotactic beams for treatment. However, embodiments employing an APS as shown in FIGS. 1-6 can be more compact, lightweight, and less expensive, and avoid the limitations of excessive equipment space that works near the face.

FIGS. 5 and 6 represent embodiments of a constricted X-ray positioning system for treating the eye (for example, as included in APS 115). The positioning system 115 is represented. The translation in the X-Y-Z movement is shown and in angular orientations O and 0. This positioning system is customized for close treatment and to treat the eye. The range of motion along each degree of freedom is limited and the positioning system 155 administers x-rays to the eye. The X-ray source 112 can be positioned relative to the eye, which can be followed, in some embodiments, with a contact member 110 and module 625.

Note that the image-forming support 412 (see also FIG. 3B) is shown in this example by projecting from stage XYZ 416, so that the image-forming system (410 in FIG. 3b) can be independently supported. of the actuators Oy 0 413 and 414 respectively, but may be positioned by stage XYZ 416 so that it is in alignment with the geometric axis of the eye 2810 or treatment axis 2820, for example. However, it should be noted that all or parts of the imaging system 410 may be supported either together or independently of any of the degrees of freedom of the positioning system 115, without departing from the invention. For example, one component of the imaging system 410 (for example, a camera) can be mounted directly on the tube 112, while other components are mounted at stage XYZ 116, and other components are mounted and positioned independently of all 5 DOF of the exemplary positioning system 115, for example, by an independently operated and controlled robotic support, or the like.

FIG. 6 represents embodiments of a motion control system in which collimator 118 moves through the positioning system around the tip of a cone with x-rays converging at a focal point in the eye, such as the macula. The distance along the center of the cone to the collimator is constant for an angle O since it refers to the angle that the collimator 118 forms with the treatment axis 2820. The distance from the edge of the collimator to the focal point is constant for any O or 0. Because the movement system is sharply built around an axis, the error is very small in terms of positioning and movement.

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In some embodiments, the distance L0 from the anode of the X-ray source 1420 to the retinal target 318 may be from about 200mm to about 50mm, and in an embodiment described in detail herein, this distance (L0) may be approximately 150 mm. In some embodiments, the distance from the end of the collimator (aperture 1405) to the center of focus 318 in the retina (L2 + L3) may be from about 120 mm to about 160 mm, and in an embodiment described in detail herein. , this distance (L0) can be about 40 to about 60 mm.

The angle O may change depending on the prescribed or desired distance. In some embodiments, the angle O is variable and can be changed depending on the desired input position of the beam in the eye. However, to achieve the desired movement around the focus point, the collimator moves around the edge of a cylinder so that the collimator can emit radiation from points at a constant angle to the target. Said movement allows the positioning system to position the collimator and the x-ray tube exactly along an arc. This unique degree of freedom after positioning makes the therapy efficient and precise.

In the exemplary embodiment of positioning system 115 shown in FIG. 5, the system comprises a base (421 in FIG. 1A). Note that the base 421 is shown as a table mount type base, but may alternatively be supported by other known mounting structures for medical devices, such as raised mounts, cantilever wall mounts, wheelbarrow mounts, retractable mounts or folded, or similar.

In this example, the base 421 supports a proximal stage XYZ 116 which has three linear actuators with mutually perpendicular sequential support, which in turn support a more distal rotary actuator 0 414 having a rotation axis parallel to the Z axis, which at its It also supports a rotational actuator even more distal O that adjusts the polar angle with respect to the Z axis. The assembly of the most distal X-ray source 420 is supported by the actuator

0. This exemplary positioning arrangement shown can be operated in several alterative ways. However, it is particularly well adapted to a stereotactic mode of operation in which the degrees of freedom X, Y, Z and O are adjusted and fixed with respect to the treatment axis 2820 and target 318, and subsequently the light source assembly X 420 is repositioned by actuator movement 0 414 to successive positions of the treatment beam, as shown in FIG. 6. Alternative embodiments of the positioning system 115 for assembling the X-ray source 420 having aspects of the invention have a different order proximal to distal of the degrees of freedom shown, and may have more or less than 5 degrees of freedom.

IID System computer and machine readable code

The processor in the system can be a conventional microcomputer that has keyboard and mouse input devices, a monitor display output device, and a computer interface that operatively connects various system components, including the assembly or tracking device of the system. eye, a robotic arm that controls the position and thus the orientation of the beam of the beam source, and optionally, an arm that is mechanically linked to the eyepiece, to carry out the different functions of the system.

As applied to the treatment of an eye injury, such as macular degeneration, these functions are found in one of four general areas: (1) target alignment, (2), treatment plan, (3) target position monitoring during the course of treatment, and (4) control of the radiation beam, including position, duration, and intensity of the beam, to achieve a desired radiation dose at the target and to avoid or minimize potentially harmful effects on nearby radiation sensitive structures . These four functions will now be considered separately from the system designed to treat an eye injury, such as macular degeneration. Although the stages in the algorithm are described with respect to a method for treating retinal lesions, such as macular degeneration, and with respect to the monitoring of the geometric axis of the eye, it will be appreciated how the algorithms can be adapted for radiation therapies that involve different targets, or when Other axes of body targets are used. It will also be appreciated that the machine-readable code for executing the individual functions will preferably be part of an integrated software or hardware system that encompasses all functions.

IID1a. Target alignment, not eyepiece

This algorithm, which is discussed and illustrated in another section of applications, particularly in VIIC Sections and with respect to FIGS. 54-56, follow the general steps described below.

1. With the patient placed in a desired position, and looking straight ahead, an imaging system records an image of the patient's eye, including corneal reflections of an external light source;

2. The image is converted into a digital image consisting of a matrix of N x M pixels. Based on the known position of the imaging system in the external coordinate system, the pixels in the matrix correspond to known coordinates. in the external system;

3. Standard or commercially available components of the image formation system and image processor can be adapted and used, such as, for example, as provided by Edmund Optics, Inc. of

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Barrington, NJ (for example, Edmund Optics-1312, a CMOS progressive scanner with dimensions of 1280 x 1024 pixels) and The MathWorks, Inc. of Natick, MA (for example, Toolbox 6.2 Image Processor). The image processing system analyzes the image to identify the limbo and first corneal reflection, based on pixel values scanned in the matrix and identification of variations in localized pixel value that are consistent with the structures that are being identified, that is , on the basis of limits of image structures characterized by expected changes in pixel values at a certain limit location in the image;

4. Pixel coordinates in the limbus and first corneal reflection are used to calculate the derived reference points, such as the center of the limbus, and the resulting pixel values are used to assign external system coordinates to an axis, for example , the geometric axis of the eye, defined by the structure;

5. Knowing the external coordinates of the geometric axis of the eye, and the distance between the camera and the eye, the three-dimensional coordinates of the eye are assigned in the external coordinate system;

6. The coordinates of the eye axis of step 5 in the external coordinate system are then used to determine the coordinates of the external system of the target structure, for example, the macula and optionally, any other structures of interest, such as nearby radiation sensitive structures. This can be done using known spatial relationships in a standard eye model between the position of the ocular axis, for example, geometric axis, at its point of intersection with the retina, and the positions of the macula and other structures, for example, the disc optical, in the retina;

6 '. In one embodiment, step 6 is carried out by aligning the geometric axis of the patient's eye with the geometric axis of the eye model, and scaling the model to the patient's eye by the known axial length of the patient's eye, so to superimpose the model in the patient's eye. Based on the known coordinates of the structures selected in the model, the coordinates of the same structures in the patient's eye can then be assigned and transformed to the external coordinate system; Y

7. Knowing the coordinates of the patient's target lesion in the external coordinate system, the program now determines the position and orientation of a beam axis that passes through the sclera, slightly above or below the mean line of the eye, and intersects the center of the target lesion. A robotic arm that carries the beam source can be activated to place the beam along the calculated beam axis.

IID1b. Alignment of the target with eye guide

This algorithm, which is discussed and illustrated in another section of the applications, particularly in Sections IV-D and VI-F and FIGS. 21-26, follow the general stages described below.

1. With the patient placed in a desired position, and looking straight ahead, and with an eyeglass centered on the eye, for example, centered on the limbus, an imaging system records an image of the patient's eye, and analyzes the digital image, as in the previous stages 2 and 3, to confirm the positioning of the eye guide in the center of the eye.

2. With the patient facing forward, the information from the monitoring system is used to calculate the external coordinates of the eye guide;

3. Knowing the external coordinates of the eye guide, and matching the coordinates of the contact parts of the eye guide and the eye, then the three-dimensional coordinates of the eye are assigned in the external coordinate system;

4. The eye coordinates of step 3 in the external coordinate system are then used to determine the coordinates of the external system of the target structure, for example, the macula and optionally, any other structures of interest, such as structures sensitive to the nearby radiation, according to step 6 in the previous algorithm; Y

5. The determination of the position and orientation of the beam axis is now carried out as in step 7 above. IID2. Treatment plan

This algorithm is discussed and illustrated later in Section IIIB and FIGS. 8-14 following.

1. From known coordinates of the patient's target area, for example, retinal injury, as determined from one of the above alignment algorithms, determine at least two axes of treatment beam path directed from a source of a radiation beam x collimated through the patient's sclera beyond the limbus and directed to the lesion in the patient's retina,

2. Calculate from a model of an eye superimposed on the patient's eye (see step 6 'in the first previous alignment algorithm) the path distance of each beam through the eye along each beam axis;

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3. Knowing the path distance of stage 2, and the attenuation factor associated with the beam path through the middle of the eye, calculate a total expected beam attenuation for each treatment beam axis from the point of entry into the Diana;

4. From the known radiation beam intensity settings, including intensity and spectral beam characteristics, the desired total known radiation dose, and the calculated beam attenuation through the eye along the known beam axes , calculate a duration time of the total effective beam, when directed to the target, to produce the desired dose; Y

5. Divide the total length of the beam between the two or more beams.

II D3a. Monitoring of the position of the absolute target during treatment

The following two tracking algorithms are discussed and illustrated in Section V.G and FIGS. 29-36. Both are designed to track eye movement during radiation treatment, and to convert eye movement into a spatial map of radiation received in the region of the target area, including any radiation sensitive structures. This first algorithm operates through the construction of a spatial map of radiation exposure with respect to the absolute retinal positions in the region including and around the lesion of the target area.

Steps 1-4 of the algorithm are carried out at regular intervals, for example, every tenth of a second, during the course of treatment, that is, when the target lesion is being exposed to the radiation beam.

1. Receive information from the tracking device on the position of the geometric axis or axis of the eyepiece;

2. Compare the coordinates of the eye axis of stage 1 with the known coordinates of the system axis;

3. From the variation of the coordinates in the eye and reference axes of stage 2, calculate the retinal coordinates of the beam axis, that is, the coordinates of the external system to which the beam axis intersects the retina ;

4. From the calculated retinal coordinates of stage 3, and the known radiation equivalent on the retinal surface, calculate an instantaneous radiation equivalent received at the calculated retinal coordinates;

5. Using the cumulative instantaneous radiation equivalent values calculated in step 4, construct a spatial map of the radiation equivalent over an area of the retina that has received radiation; Y

6. At periodic intervals, for example, every tenth of a second, monitor the total radiation equivalent received on the target and any radiation sensitive structures.

II D3b. Monitoring of the fluctuations of the target position during treatment

This second algorithm operates to construct an eye fluctuation map during the course of treatment, from which the radiation distribution can be calculated as a function of the distance from the target area, for purposes of monitoring the total radiation received in any time in the target area and at known distances from the target area.

Steps 1-4 are carried out at regular intervals, for example, every tenth of a second, during the course of treatment, as before.

1. Receive information from the tracking device on the position of the geometric axis or axis of the eyepiece;

2. Compare the coordinates of the eye axis of stage 1 with the known coordinates of the system axis;

3. From the variation of the coordinates in the eye and reference axes of stage 2, calculate the retinal coordinates of the beam axis;

4. From the calculated retinal coordinates of stage 3, calculate a vector between the target and the position of fluctuation measured instantaneously of the beam at that time point;

5. Use the accumulated fluctuation vectors to construct a vector map sum of fluctuation;

6. From the vector map sum of fluctuation, calculate the total radiation distribution as a function of distance from the target area;

IID4. Radiation beam control (inactivation control function)

This algorithm acts on information of the treatment plan algorithm and on information of a tracking algorithm, such as one of the two algorithms thus considered, to control the intensity, duration, and time of the beam from the radiation source, and the orientation of the beam axis.

1. At each point during irradiation along a single beam axis, compare the total radiation equivalent received in a radiation sensitive structure of one of the two previous tracking algorithms with the maximum radiation equivalent allowed in the structure of that beam axis;

2. If the total radiation equivalent of stage (1) is above a threshold level established during treatment plan 5, terminate the exposure to the beam along that axis; otherwise go to stage 3.

3. If all beam axes of the treatment plan have been exploited, terminate the treatment; otherwise go to stage 4.

4. If the total radiation equivalent in the radiation sensitive structure is below the threshold, continue to irradiate the target;

10 5. Repeat steps (1) - (4) until a value above the threshold is reached in a structure sensitive to the

radiation or a desired radiation equivalent is reached on the target for that beam axis;

6. Have all the treatment axes been exploited? If not, direct the robot arm that controls the position of the beam source to the next beam axis position; If so, then finish the treatment.

ME. Method of radiotherapy treatment

In one aspect, the invention can be used in a method of treating an injury in or adjacent to the retina of a patient's eye with an external beam radiation device. In a first stage, the patient's eye is aligned in alignment with an axis of the known system in an external three-dimensional coordinate system, and the axial length of the eye is measured. The details of these stages are provided in the MIA-MIC Sections below, in which the eye is aligned on the basis of natural features or reference points of a patient, and in Section IV, regarding the use of a crane eyepiece to align the patient's eye.

From the known position of the system axis and from the measured axial length, the coordinates of the lesion to be treated in the external coordinate system are determined, and a collimated radiation beam along an axis of you have known in the external coordinate system in the lesion to be treated. The details of these steps, which are preferably carried out by processor in the system described above, are described in Section IID above.

During the course of the treatment, and in particular, during the period in which the injury is being exposed to external beam radiation, the position of the eye is followed with respect to the axis of the known system, thus allowing the tracking of the position, it is that is, coordinates of the lesion to be treated in the external coordinate system. The details of the processor operations to carry out this stage are also detailed above in Section IID.

Based on the known beam axis of the collimated beam in the external coordinate system, and the instantaneous position of the lesion to be treated in the external coordinate system (as determined at least in part by the position at which the eye has been tracked), the processor system operates to calculate an equivalent of total radiation received in the lesion to be treated during the treatment.

In a preferred embodiment, the method is designed to deliver a desired radiation dose in the target lesion, but without exposing one or more radiation sensitive structures close to the lesion to a dose of harmful radiation, that is, a dose that could adversely affect the functioning of the structure. For example, in the case where the retinal lesion is the macula of the patient's eye, one of the radiation-sensitive structures is the optical disc. The method in this embodiment includes determining the coordinates of at least one radiation sensitive structure 40 in the external coordinate system; for example, the optical, monitoring the position of the structure or structures sensitive to radiation in the external coordinate system; and on the basis of the instantaneous position (s) of the radiation sensitive structure (s) in the external coordinate system, calculate an equivalent of total radiation received in the at least one radiation sensitive structure during the treatment. The details for carrying out these steps substantially follow those used for the determination of the total radiation received in the target injury, according to the processor operations detailed above in Section IID.

IIIA Eye alignment

FIG. 7 represents a method of anatomical addressing for radiotherapy. The central or geometric axis 2810 of the eye can be defined approximately by the eyeglass 2860 (or alternative methods of alignment of the eye), 50 which in some cases is a lens that conforms to the curvature of the front part of the eye. The geometric axis 2810 of the eye 30 may be defined as intersecting perpendicularly to the surface of the cornea 35 in the center of the blade 26. In some embodiments, the geometric axis 2810 may be the treatment axis, or a different treatment axis may be defined 2820. In the example shown, the treatment axis 2820 is offset vertically and / or laterally and is generally parallel to the geometric axis 2810, intersecting fovea 318 of eye 55 (approximately the macular center). In one embodiment, the angle O is adjusted so that the x-ray beam

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1400 travels to the eye at a point adjacent to the edge the blade 26 in the front of the eye, for example, near the flat pars, to have a clearance "c" from the blade to the center of the beam entry point of approximately 2 to 6 mm).

The central axis, in some embodiments, may be the axis that is perpendicular to the center of the cornea or limbus and extends directly posterior and anterior to the cornea and the center of the retina, as previously discussed. In some embodiments, the central axis is the treatment axis, around which a radiotherapy device can rotate; This axis can also be referred to as the system axis. In some embodiments, the treatment axis 2820 may be a line parallel to the central axis 2820 and compensate the geometric axis 2810 for a distance 2850.

The treatment axis can intersect the retina in the macula or the center of an injury to be treated. The axis 2820 can be any axis in any orientation with respect to the central axis 2810, the axis 2810 being continuously identified by the rail 2860. The length of the path 2830 (also indicated as "L3") is a distance of the path followed by the beam of rays X during the propagation from the tissue surface to the treatment target, and it is helpful to predict the dose at the intersection of the retina, since there will be energy attenuation by the time the x-rays reach the retina and, to some degree, this attenuation will depend on the length of the propagation path in the tissue of the 2830 beam. The length of the path in the tissue for a selected planned treatment procedure can be correlated with a measure of the patient's eye, most conveniently with the axial eye length, as described further herein in detail with respect to FIGS. 14 and 15A-15B.

The optic nerve points in the medial direction (towards the middle line) when traveling behind the eye. In addition, it has been demonstrated by the inventors herein, that the typical path of the optic nerve is also inferior (down or caudal) with respect to the eye when traveling behind the eye. The example of a multi-beam stereotactic treatment plan for macular irradiation that has aspects of the invention, as depicted in FIG. 9, takes into account the path of the optic nerve to minimize the dose of radiation absorbed to this structure. Reference is made to Application No. 12 / 100,398 filed on April 9, 2008; and No. 12 / 262,031 filed October 30, 2008 for additional description.

FIG. 8A is a schematic view of a fundus image in the retina of a patient that shows an example of a treatment plan for AMD. The effect of the axis displacement in the retinal treatment region can be observed, the geometric axis 2810 is deviated from the treatment axis 2820 (centered on the fovea). The dimensions that define the relationship with the optical disk are also shown, since the treatment plan preferably ensures a low dosage to this structure. FIG. 8A below illustrates data from a study of several normal volunteers in which the intersection of the geometric axis with the retina was determined and related to the distance to the fovea and the optic nerve. In some embodiments, only one displacement geometry is used for all patients. Alternatively, a scaled displacement geometry can be used based on one or more specific parameters of the patient, such as axial eye length, for example, determined by an A or OCT mode ultrasound. Averages and maximums and mmimos are shown for the measures represented. Also shown is a triangular diagram that summarizes the average displacement data to deflect the axis of treatment of the geometric axis :, x = + 1.16 mm temporarily, ey = - 0.47 mm caudal, and as shown and described further to FIG. 21D. The inventors of the present specification have demonstrated from the clinical data that an exemplary treatment plan with radiotherapy that has aspects of the invention and deviations of the treatment axis incorporated in or near these values accurately predicts the center of a target macular Reference is made to Application No. 12 / 100,398 filed on April 9, 2008; and No. 12 / 262,031 filed October 30, 2008 for additional description.

It has been found that the average displacement values shown resulted in surprisingly small errors in the population studied, a maximum error of 0.20 mm in the horizontal direction and 0.08 mm in the vertical direction. Thus, when the intersection of the geometric axis 2810 with the retina is identified using lane 2860, the fovea or a nearby lesion can be taken as the target. A treatment plan can therefore be developed. For example, a known point on the lens located in the front part of the eye can be determined and then the axial length can be used to locate the inner limit of the retina. After locating the point (either virtually by a model or visually through an imaging device) in the retina in which the axis of the lens in the eye intersects the retina, any point along the target can be taken of the retina such as the center of an injury by the radiation positioning system.

FIG. 8B is a perspective view of a virtual model of an eye 30, including a registered retinal image 350, such as an optical coherence tomography (OCT) image, a fundus camera image, or another medical image of a patient. In this example, the eye model 30 is shown as aligned with a Z axis of the radiotherapy system, which is collinear with the geometric axis 2810 of the eye. The axis 2810 intersects perpendicularly to the cornea 35 at a central point defined by the center of the blade 26, the axis extending through the eye to the retinal pole 340. An XY coordinate plane for the eye model 30 is shown centered on the axis. Z tangent to the cornea at the corneal center 35 (see the example of alignment method described with respect to FIGS. 21A-21E).

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A subsidiary retinal reference plane X'-Y 'is defined centered on the pole 340 (in typical patients, the plane of the retinal surface X'-Y' may be substantially parallel to the corneal plane X-Y). An ophthalmological retinal image can be incorporated into the eye model 30, such as an OCT 350 image, for example, by capturing an electronic image of a patient to be treated, and geometrically recording the image data with the model (aligning the image data with the retinal plane X'-Y '). A convenient scale factor for sizing the image data to the eye model is the axial length of the eye AL, the distance from the anterior corneal center 35 to the surface of the retina at the pole 340, which can be measured non-invasively by a ultrasonography in ultrasonic A mode.

As described further with respect to FIGS. 8A and 21E, a treatment axis 2820 can be defined by deviations of pole 340 (8x, 5y in the coordinate plane X 'and Y'), the treatment axis intersecting the retina at a treatment center 318. By means of the incorporation of a specific retinal image of the patient 350 in an eye model 30 and registration of the image congruent with the geometry of a radiotherapy treatment plan (for example, as shown in FIGS. 8A and 9), can be visualized by a doctor the relationship between the treatment axis 2820 and the patient's retinal injury. The parameters of the radiation target of the treatment plan can either be confirmed or modified, in preparation for treatment.

FIG. 9 is a front view of an eye as seen aligned with a reference axis system 18 (temporal right, nasal left), and representing a stereotactic x-ray treatment beam geometry, as described in FIG. 7. Once the reference axis 18 is identified (for example, geometric axis 2810), the treatment can be carried out by a device oriented with respect to axis 18. Alternatively, a different axis 19 can be defined with respect to axis 18, for example , by a displacement of the distance dy and dx, so that the axis 19 intersects the treatment target 318 positioned outside the axis relative to the axis at axis 18. The axis 19 can be called the "treatment" axis. On the basis of direct geometry, the device 312 can now be positioned such that its beam axis 311 intersects the treatment axis 19 on the tissue target 318. The axis 18 can be used to define one or more correlated geometric axes in the system. of external coordinates, and to define one or more additional intersection points with respect to beam 311. Note that for the treatment targets that are on the reference axis 18, the deviation "d" may be approximately zero, and for administered treatment through or to the cornea, the angle "O" can approach zero. The illustrated example is of an embodiment in which the alignment system is coupled with a treatment system adapted for orthovoltage X-ray treatment of a region of the retina generally including the macula.

FIG. 9 can be correlated with FIGS. 7 and 11, which provide a generally comparable cross-sectional view of an eye, shown in association with a treatment system. As shown in FIG. 9, although a single beam axis 1400 can be used, a plurality of beam axes can be defined in which two or more treatment beams are aimed at stereotactically targeting target 318. The treatment axis 19 can be chosen to intersect a selected target 318 in the eye, and be used as a reference to orient two or more treatment beams that are aimed at stereotactically targeting the target 318.

In the example of FIG. 9, the treatment axis 19 is chosen to intersect a selected target 318 in the eye, and are used as a reference to orient three projected treatment beams along three different beam axes 1400a, 1400b and 1400c, defining the axes of do so that each one hits target 318 from a different direction. Multiple beams can be projected simultaneously, or sequentially, with intermediate periods without treatment if desired. Also, multiple beams can be provided by multiple treatment devices positioned separately. However, a preferred embodiment employs a single treatment device 312 (for example, a collimated orthovoltage X-ray source), which is sequentially repositioned by the positioning device 310 to administer treatment in sequential doses along each of a plurality of beam axes, such as axes 1400a-c (1400a, 1400b and 1400c). The beam axes each have a different respective entry point on the surface of the body (311a, 311b and 311c respectively) and each follows a different tissue path that results in target 318. Also, each beam follows a path of different tissue for any propagation beyond the target 318. In this way, the treatment beam dosage that penetrates the tissue away from the target 318 can be minimized with respect to the dosage received on the target 318.

Note that the number of stereotactic beam paths selected (for emission either sequentially or simultaneously) can be selected from a considerable range to achieve the treatment objectives. FIGS. 9-10 illustrate an example of a 3-beam pattern (1400a-c), and the device embodiments described in detail herein (eg, FIGS. 5-6) can conveniently administer said pattern in sequence. However, alternative devices that have aspects of the invention may have multiple sources of X-rays and / or collimators configured to administer said pattern simultaneously. In other alternatives, the treatment objectives can be achieved with a single beam path 1400. In more additional alternatives, the treatment objectives can be achieved with a number of beams that exceed three (for example, 1 to n beams).

In more additional embodiments, a beam path 1400i can move stereotactically continuously during X-ray emission over a beam path in the sclera (or other body surface) that has a range

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or selected range, so that although the region of entry for radiation spreads along the surface path to reduce the local dose of tissue, at the same time the target region receives a concentrated dose as in the target 318, reaching the path of the moving beam an effective focus in the target region.

In general, when the stereotactic beam pattern is described herein as "one or more beams," "a plurality of beams," or "at least one beam," these expressions include treatment configurations in which a collimated beam. it moves continuously or incrementally over a range of stereotactic position selected during radiation emission to achieve an equivalent treatment target that has a radiation dose at the focused or concentrated target.

The beam axis 1400 (or for multiple beams, each of the axes 1400a-c) can be selected to follow a tissue path that avoids vulnerable structures or tissues that are far from the target 318, so that the received dosage is minimized for these tissues. For example, in the treatment of the macula for macular degeneration, axes 1400a-c can be selected to administer a selected dose of treatment beam (for example, a selected dosage of absorbed X-ray energy) to a target 318 at or near of the retina 340, centered on the macula 342 while minimizing the radiation absorbed by the optic nerve 350, the lens, and the like. In the example shown, three beam axes 1400a-c are defined, corresponding to three rotational angles around the treatment axis 0a, 0b, 0c, so that the beams directed towards the rear eye enter the body on the surface of the anterior sclera 17 at points 311a, 311b and 311c, each entry point a selected distance beyond the limbus 26. Said orientation of the beams can prevent or minimize absorption by the lens and other structures in the eye, by appropriate selection of the paths of the beams.

As illustrated in FIG. 9 one or more axes of the beams (for example, 1400a, 1400b and 1400c) are defined so that each beam axis is on a conical conceptual surface and whereby each beam intersects the apex of the cone. The cone can be defined as having its conical axis the treatment axis 19 with the apex provided on the target 318. In this example, the treatment axis 19 is defined parallel to the reference axis 18, which has deviations x and defined in a perpendicular plane by "dx" and "dy" respectively (for a treatment target that intersects the reference axis the deviations are zero). Once the treatment axis 19 is defined, the base 34, the angle of the apex ("O" in FIG. 7), and the rotational positions of the shafts 1400a-c relative to the axis 19, can be adjusted to provide so much intersection. of the beam at approximately target 318 as well as to provide entry points 311a-c located at a desired position of the body surface.

In an example of an orthovoltage x-ray treatment for macular degeneration, the dx and dy deviations are selected to define a treatment axis 19 centered on the macula, the angle O is selected to provide intersection of the beams 1400a-c in the macular surface, and base 34 is selected to provide entry points at surface 311a-c in a region of the anterior lower sclera beyond the limit of limbus 26. In this example, an X-ray beam source can be positioned by the positioning device (see 115 in FIGS. 1 and 5) so that a collimated beam is projected from a distance from the selected X-ray source to form a beam having a characteristic width at the entrance to the tissue "w" . Note that although a treatment beam can also project through an eyelid or other tissue near the eye, the eyelids (in this case the lower eyelid) can conveniently retract to expose an additional area of the anterior sclera 17.

Note that, in the most general case, the treatment axis 19 does not need to be parallel to the reference axis 18, and the target 318 can be located with respect to axis 18 by other analytical methods including a separately defined treatment axis. On the other hand, a real or at least conceptual danger of robotic systems with a high degree of freedom that use energy beam treatment is the large possible range of beam paths (for example, after a control system failure), and the associated risk problems, regulatory complexity, and high costs of end-user installation and site modification.

FIG. 10 represents results of a procedure in which three beams were focused on the back of a simulated eye model using the robotic system 10 described above, and represents a chromic film after the administration of superimposed x-ray desktop 100 keV at a 3250 target site. A simulated surgical radio model was used in which an eye model was placed in the eye socket. The film was placed on the back of the eye model and the x-rays were administered to a target representing the macula. The region of 3275 x-ray beams is shown in its region of overlap in which the dose is 24 Gy. The optic nerve 3260 is shown lateral to the superimposed set of beams at a scaled distance from the center of the superposition. There is a rapid cauda of isodosis 3273, 3277 lateral to the region of overlap 3275 and very far from the optic nerve 3260. Notably, the isodosis represented in region 3265 is in fact between about 1% and about 10% of the dose (0.24 Gy - 2.4 Gy) at treatment point 3275. These data are a consequence of the geometry of the superimposed beams as well as the fine collimation of the beams; they are the physical proof of the ability of finely collided overlapping orthovoltage x-ray beams to create well-defined treatment regions. Due to the difference of 10-100 times in the dose of treatment with respect to the dose in the optic nerve, fractionation is not required, and the full dose can be provided to the treatment region in a session with minimal concern about damage. to important structures, such as the optic nerve. These overlap regions can be optimized and / or placed elsewhere in the eye that is determined by the treatment plan system and depends on the energies of the beam, collimation, and filtering. The grade

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Overlap is also, to a degree, determined by the system parameters. For example, the treatment of the entire region of the retina for macular degeneration may be different from that for tumors or for hemangioma.

IIIB Eye models and treatment plan

The information as described with respect to FIGS. 7-10 can be used to construct a virtual or simulated eye model that has aspects of the invention (for example, using software and interfaces with an information processor). The eye model can represent the eye to be treated and related anatoirna.

As used herein, "eye model" or "eye model" refers to any representation of an eye on the database, such as, without limitation, an anteroposterior dimension, a lateral dimension, a translimbal distance, limbal-limbal distance, the distance from the cornea to the lens, the distance from the cornea to the retina, a viscosity of certain eye structures, a thickness of a sclera, a thickness of a cornea, a thickness of a lens, the position of the optic nerve with respect to the treatment axis, the visual axis, the macula, the fovea, a neovascular membrane, a curvature of a cornea or a retina, a curvature of a scleral region, and / or a dimension of the optic nerve. Such data can be acquired through, for example, imaging techniques, such as ultrasound, laser scanning ophthalmoscopy, optical coherence tomography, other optical image formation, image formation with a match, image formation in combination with a laser pointer for scaling, CT scanning with or without contrast, and / or T2, T1, or functional magnetic resonance imaging with or without contrast. Said satos can also be acquired through keratometna, refractory measures, retinal fiber optic layer measurements, corneal topography, direct calibrator measurement, etc. The data used to produce an eye model can be processed and / or presented using a computer.

As used herein, the term "modeling" includes, without limitation, creating a model. The eye model is a virtual model that matches the anatomy of the eye with the coordinate system of the radiotherapy device 10. The eye model can be based on the geometry of the eye structures and can be derived with parametric data and mathematical formulas to generate the model. Alternatively, eye geometries are derived from cross-image formation, such as from CT or MRI scans. With the defined treatment axis and the defined ocular anatomy, the coupling device can contact the ocular surface and join the radiotherapy device through the eye model. The radiotherapy device can then be positioned on the basis of the eye model.

The model can be based on the generalized human eye anatomy, and can be based on the specific ocular anatomy of the patient. Although human eye geometry is clearly variable in patient populations, appropriate adjustments and modifications can be made to a generalized eye model taking into account one or more specific patient measurements, so that the anatomy of the eye of the eye is accurately represented. a particular patient For example, a virtual eye model can conveniently and economically include a global structure based on the generalized human eye anatomy, which can then be adjusted or scaled by measurements taken from a patient to be treated, such as a measure of a mode A ultrasound of the axial length of the eye, routine diagnostic test used in ophthalmology (a biomet by ultrasound in mode A with ultrasound can provide, for example, the central or axial length of the eye from the corneal surface anterior to the retinal surface ).

FIGS. 11 and 12 schematically represent exemplary embodiments of virtual or simulated models of a human eye 30 and adjacent structures, as can be defined digitally using conventional software tools, monitors and input / output devices (or using alternative graphic or representation modes). A virtual model can include multiple components, which include different representations of the same anatomical structures. For example, in the embodiment shown in FIG. 11, the eye model includes a virtual representation of most of the ocular anatomy shown in FIG. 7, including the relationship between different anatomical features and eye geometry.

FIG. 12 shows a model 1451 of a 1440 X-ray collimator system including the physical parameters that affect the characteristics of the radiation beam, as applied to a simplified anatomical representation of the anatomy of FIG. 11. However, unlike FIG. 11, model 1440 of FIG. 12 is simplified, so that the surface of the sclera 17 is represented as a perpendicular flat surface 1430, and the surface of the retina 1435 is also represented as a plane perpendicular to the beam axis 1400.

Also note that "emission point" 1420 is represented in FIG. 12 as a flat surface of a defined transverse dimension perpendicular to the beam path 1400, and represents an idealized X-ray emitting surface that emits photons through collimator 118. Actual X-ray devices may have an X-ray emitting source that It has a number of alternative forms, orientations and configurations. For example, the target of an electron beam that emits X-rays from a linear accelerator source can be material with a high atomic number aligned on the path with the electron beam and that has an output plane that can be substantially perpendicular to the collimated X-ray beam 1400. Alternatively, the target anode material of a commercial orthovoltage X-ray tube may comprise a substantial angle surface of the collimated X-ray beam 1400, the output X-rays being emitted through a window (for example, Be thin sheet) oriented

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in a generally transverse direction with respect to the cathode beam that affects the surface of the anode. The anode material may be formed to have a flat surface, or a truncated conical surface in the case of a rotating anode. To simplify the model 1440, the effective X-ray emission point 1420 from the perspective of the aperture 1405 can be represented as a defined diameter disc oriented perpendicularly to the beam 1400 and which emits uniformly X-rays of a given initial spectrum. For convenience, said emission source 1420 is referred to herein as an "anode" or "anode point" without loss of generality.

Also, opening 1405 is represented in FIG. 12 as a single circular opening, but it does not need to be circular and does not need to comprise a single opening. See, for example, the collimator embodiments described in No. 11 / 873,386 filed on October 16, 2007. When the outlet opening of a collimator and / or the radiation beam point projected on a tissue surface or target plane it is not circular (elliptical, rectangular, elongated, irregular or similar), the diameter can be conveniently considered to be a geometrically selected characteristic dimension, such as maximum width, a major or minor axis, a medium width or the like.

A model such as FIG. 12 allows convenient modeling of the spectral change of photon energy as the beam propagates from the anode to the treatment target. The initial spectrum emitted by the point of the anode 1420 can pass through a filter 1423 that displaces the spectrum at a higher average photon energy by absorbing photons with predominantly lower energy. The effective filter 1423 may comprise any device structure material in the beam path (inherent filtration, for example, an X-ray tube window, a laser beacon deflection mirror, aperture coating, or the like) and any material of additional filter positioned for this purpose (for example, one or more aluminum plates of a selected thickness mounted in a selected position along the axis of the collimator 118).

A filter for penetrating radiation is often characterized by its scaled absorption properties with respect to layers of half value or thickness of half value (HVL), related to the mean free path of a photon or particle. An HVL can be defined as the specified material thickness that reduces the intensity of a particular input radiation spectrum that enters the material in half. However, it is not necessary for a filter element to be an integral HVL and can be of any selected thickness. Also, it is not necessary that a filter element be of a single or uniform material. For example, the filters may have a series of layers, such as layers in decreasing order of atomic number such as layers of tin, copper, and aluminum in the direction of propagation. Although the examples described may have filters of a uniform transverse thickness or composition, in alternative embodiments, a filter may not be uniform with respect to the cross section of the beam, so that a spectral variation from one side of the beam to another occurs (with cradle shape), variation radially around a center, or other variable distribution.

The filtered spectrum is further "hardened" by upward displacement in the average energy of the photons as it propagates along the path of the L3 tissue of the eye 30 towards the plane of the retina 1435 ("hardened spectrum by tissue"). The intersection of the beam 1400 with the retina 1435 ("retinal target plane") can be represented in this simplified model as a circular center 1441 and a concentric penumbra or margin of "isodosis cafda" 1442. However, in alternative embodiments, the geometna of the beam point (1441, 1442) can be configured not to be circular. See Application No. 12 / 262.031 filed on October 30, 2008, such as FIGS. 8-12 and 22-29 of that request and related description.

It is evident that the relevant anatomical structure can be defined mathematically and geometrically, optionally including convenient simplifications and generalizations, without loss of usefulness in the planning and prediction of radiotherapy treatment.

The characteristics of the radiation beam determined empirically and / or theoretically and the characteristics of human tissue can be correlated with the eye model to allow the modeling of the transmission and absorption of radiation along a path of propagation of the beam. For example, the propagation and absorption of radiation through tissue can be simulated using software such as the Monte Carlo Radiation Transportation Code developed by Los Alamos National Laboratory. As shown in FIG. 11, a virtual model can include a geometric representation of the position of the optic nerve extending later from the optic disc to the retina (in this example characterized by angle n), which is useful for determining the Beam propagation paths that minimize dosing to the optic nerve, such as from the part of radiation applied passing through and beyond a treatment target adjacent to the macula.

In the examples shown in FIGS. 11 and 12, the virtual or simulated eye model 1440, 1450 is configured to represent a narrowly collimated external radiation beam directed to enter an exposed scleral surface 17, such as flat pars 1430, and propagate to the surface of retina 1435 at or near macula 318. See co-invented application No. 12 / 100,398 filed on April 9, 2008 for an additional description of methods that have aspects of the invention for determining suitable beam paths for eye treatments. , and in particular, beam paths that can be used to treat a macular region, while minimizing the absorbed dosage in structures such as the lens and the optic nerve.

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In an embodiment of a treatment plan method that has aspects of the invention, the length of the tissue path of the beam L3 is determined (i.e., the distance of the radiation beam through the tissue from the air inlet point to the treatment target), and the length of the path is used in turn with a radiation transport model to take into account the reduction in the power of the beam and spectral profile when passing through the tissue. This allows the determination of the dosage in the target with respect to the dosing of the kerma beam in air. In the actual treatment, the magnitude of the radiation can then be adjusted to provide a predictable absorbed dosage exactly on the target (for example, by adjusting the duration of the radiation).

As an example, it has been shown in studies conducted by the inventors herein that, for a treatment plan to irradiate the macular region by means of a beam entry point near the pars plana, that the path length in the tissue A wide range of patients can be accurately predicted using a virtual model and a single measure of a mode A ultrasound of the patient's ocular axial length. In fact, a linear approximation can provide good results for a particular treatment plan, such as a formula: PL (mm) = AL (mm) - k; where k is a constant such as about 3. See an additional description with respect to FIGS. 14-15 In addition, patient specific imaging can be incorporated into the eye model, as schematically represented in FIG. 8. In one embodiment, a fundus image of a patient is obtained before treatment with radiotherapy, the image can then be scaled in proportion to a patient's measurement such as the ocular axial length, the image being aligned and superimposed on the virtual model.

An eye model can be used in treatment planning, as depicted in FIG. 9, such as by determining a treatment axis 19 with reference to a reference radiotherapy system 18, and defining one or more target regions of radiation 318 suitable for the disease being treated. One or more paths of the radiation beam 1400 can also be defined with reference to the model. In the example shown, three stereotactic beam paths 1400a-1400c are planned so that they coincide with the adjacent target region 318 centered on the treatment axis 19. The planned positions / orientation of the X-ray beam 1400 can also be superimposed on the model by correlation of the coordinate system of the model with the planned coordinate system. An image presented to an operator / doctor may include model data; fundus image data scaled and registered (and / or other medical image data); together with geometry data of the planned radiotherapy beam. Among other things, this allows a doctor to confirm that the planned treatment is appropriate for the patient's injury, as seen in the fundus image.

The model can be used to determine specific patient parameters relevant to the propagation of radiation, such as tissue path length along the path of beam 1400 to a target region 318 to apply a radiation dose to a target beam point. 1441 (see FIG. 12). Thus, an eye model that has aspects of the invention can be used to compile a patient-specific treatment plan that accurately predicts radiation dosage levels and distribution in a target region 318 as shown in FIG. . 11, and which accurately predicts the distribution of the radiation dosage with respect to anatomical structures such as lens 36 and optic nerve 32 (see optical disk 3260 in FIG. 10). See for example the retinal dose map of FIGS. 37A-37B. Data from said dose distribution measured radiographically and / or computer simulated can be incorporated and recorded with a simulated or virtual model. The geometry of the planned radiation beam (See FIGS. 9 and 11) can then be included in the model as projected radiation beams virtually 1400 from a virtual radiation source, and used to simulate dose deposition in a target region 318 in The simulated model.

A combination of anode size, anode to target distance and collimator length can be selected by methods that have aspects of the invention for an X-ray source that provides a firmly collimated beam point of approximately maximum intensity, sized for a dimension of the selected target region, and which has sudden definition or decrease in the dosage area around the beam point. A combination of potential of the X-ray tube field and filter dimensions can be selected by methods that have aspects of the invention that provides a favorable ratio of radiation dosage at a scleral entry point to the target region (pre-target absorption or "tissue hardening"), while allowing a rapid attenuation of the dosage of the beam beyond the target region, such as absorption in the orbital cranial bone (post-target absorption). See co-invented application No. 12 / 100,398 filed on April 9, 2008 for an additional description of the characteristics of radiotherapy beams and configuration of X-ray treatment devices that have aspects of the invention. The embodiments have selected parameters that provide characteristics of the radiation treatment beam that are particularly well suited to the treatment of ocular lesions, including retinal injury as occurs in AMD.

FIG. 13A is a graph showing the results of a Monte Carlo computer simulation for the absorption of X-ray energy in a configuration generally similar to that shown in FIG. 12. The computer simulation takes into account the effects of radiation propagation, such as tissue dispersion, on the resulting dose profile through a retinal target. The cross-sectional profile at the dose absorbed to the macula target for an x-ray beam of 100 kVp. A collimator was selected to create a beam point of approximately 4.0 mm, and to simplify the geometric adjustment of MCNP, an incident angle is assumed that is not normally normal. The absorbed dose profile in the center of the macula is shown for a focal point size of 1.0 mm X-ray tube anode, positioned 100 mm from the target, for a central directed dose of 8 Gy. The lines

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Vertical 1441 are placed at a radius of +2 mm and -2 mm, also delineating 80% isodosis in this model. The region ± 2mm approximates the anatomical size of a target region of macular injury of 4mm in diameter. Penumbra 1442 is indicated as limited by 20% isodosis, with low dose or "dispersion" region 1443 adjacent to the penumbra margin.

Monte Carlo (MC) simulations are used to model the absorption of x-rays, dispersion, and dosage to structures in which x-rays affect. An example of a useful tool for this type of analysis is the MCNP Radiation Transportation Code developed by Los Alamos National Laboratory (see DB Pelowitz; MCNPX User's Manual Version 2.5.0, LA-CP-05-0369; Los Alamos National Laboratory , Los Alamos, NM, 2005). Monte Carlo methods are computer algorithms widely used to simulate the behavior of various physical and mathematical systems, and for other calculations. They are distinguished from other simulation methods (such as finite element modeling) by being stochastic, that is, not deterministic in some way. Computer radiation simulations, such as Monte Carlo analysis and the like, are included in embodiments of treatment planning systems that have aspects of the invention, and can be used to assist in the treatment planning in which radiation is involved.

The Monte Carlo simulation can also be used to predict and dictate the feasibility and other elements of the radiotherapy system 10 (for example, collimator optimization and treatment planning schemes); for example, collimation designs, energy levels, and filtration regimes, can be predicted using the Monte Carlo simulation. The results of the Monte Carlo simulation have been experimentally verified and further improved, based on initial MC simulation. In some embodiments of radiotherapy in which the anatoirna, beam energies, and treatment volume are similar, Monte Carlo simulations can be operated once and then the path variables are altered (for example, through ray tracing or other methodology geometric) without the need to repeat the Monte Carlo simulation. For example, the MC simulation can predict the penumbra of an X-ray beam.

In FIG. 13A, the dose coefficient in the central region was estimated to be 7.7 Gy / Gy, in which the reference value of kerma in air is adjusted again to 100 cm from the X-ray source. The abruptness of the target point coffee from the full dose to zero or very low dose is measured by penumbra. The penumbra represents the part of the target that does not "see" the focal point of the entire anode and therefore does not receive the full dose. The sharper the penumbra, the more adjusted and more as the dose can be administered. A measure that can be used to characterize the dose profile and size of an X-ray beam point and the effective penumbra dimension uses isodose contours, conveniently expressed as a percentage of a maximum central region dose.

The penumbra can be given an emphatically convenient definition as the distance between levels of selected dose intensity, such as 80% and 20% of the isodose lines (the 80-20 penumbra) or alternatively the distance between 90% and 10% of isodose lines (penumbra 90-10). The 80-20 penumbra in FIG. 13A is indicated to be less than 1 mm in degree for the 4 mm beam point diameter. Note that the model also shows a dispersed dosage level at 10% less than the maximum dose intensity, extending out beyond the 20% isodose line, decreasing thereafter to a low dosage level (> 1% of the maximum) when the radius is increased from the target.

For comparison and validation purposes, FIG. 13B shows a representation of dose intensity measured at retinal depth for an X-ray / collimator configuration comparable to that of FIG. 13A. In this example, an x-ray film was placed behind a thickness of approximately 20 mm of radiographic simulated material equivalent to "solid water" type water, to simulate the tissue thickness depth of the retina. The optical density of the film, exposed to approximately 10 Gy of absorbed x-ray dose, was mathematically converted into an equivalent absorbed dosage. It can be seen that the general shape of the beam and penumbra point is very similar to that shown in the Monte Carlo simulation of FIG. 13A. However, no bolus of dispersion is immediately observed beyond the penumbra (which is believed to be an artifact) in the measurements, the dosage level falling consistently and rapidly to a low level beyond the isodosis of 20 % ("measured dispersion"). This distinction between the modeled dispersion and the measured dispersion is also indicated in FIG. 13a by a discontinuous line. Note that although the measured penumbra and the dispersion region is characterized smoothly and consistently in the radiographic measurements of FIG. 13B, the central beam point is represented in some way irregularly, apparently due to the exposure of saturation of the film to the maximum dosage.

In embodiments of radiotherapy methods and devices having aspects of the invention, the overall axial length of the eye (distance from the surface of the cornea to the retinal surface) and the length of the path of the bundle tissue (the length of the path of tissue which will be penetrated by the treatment beam in the propagation from the surface to the target) are relevant to important treatment parameters. For example, the length of the tissue path is relevant for (a) the selection of the spectral characteristics of the X-ray input beam such as the determination of the potential of the tube and filters (see Application No. 12 / 262.031 filed on 30 October, 2008), and (b) for a given X-ray treatment beam, the length of the tissue path when the beam is actually administered to a patient determines the dose rate to the target in Gy / min (see pre absorption - target indicated in the eye model of FIG. 11). Similarly, the axial length of the eye and other eye geometry are relevant.

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for monitoring the movement of the retina during the administration of treatment, as further described herein.

Thus, it can be seen that the measurement and / or prediction of the length of the tissue path for the patient allows an accurate calculation of the rate at which radiation is absorbed by the target tissue. In certain embodiments of radiotherapy, for a known dose rate based on the length of the tissue path, the duration of the beam emission (for example, a timer to cut the energy to the tube) is conveniently controlled so that administer a planned dose to the target (for example, one third of the total planned dose for a 3-stereotactic stool procedure).

For this purpose, a series of experiments were carried out to determine the appropriate eye measurements to establish the depth of the target in the retina. A correlation model was established to show the relationship between the length of the path and the axial length of the eye. Using a 3D laser scanner, a device that can precisely map the coordinates on a surface, a series of points in the three-dimensional space of the surface of several corpse eyes is derived.

FIG. 14 shows a typical example of the mapping results of this protocol, which allows the mapping of the shape and contours of the corpse eye with a high degree of accuracy. With this model derived from the eye surface of corpses, axial length and path length, and other anatomical dimensions can be measured directly. The axial length (AL) and the length of the tissue path (L3) are indicated in the beam path corresponding approximately to the beam path shown in FIGS. 7 and 11, directed through the entry point of the sclera 311 to the center of the target 318 (for example, macula or fovea), the beam entering the eye beyond the cornea limbus 35 of the eye 30.

As shown in FIG. 15A, which represents the measurements in a series of seven corpse eyes, the length of the tissue path (PL) and the axial length (AL) can then be correlated or related between st In living patients and study populations, the axial length it can be obtained by an ultrasound in mode A. An ultrasound in mode A is an ultrasonic measure conventionally used in ophthalmology in which the eye's geometry is relevant, such as in the correction of refractive vision. It has been found by the inventors herein that the axial length measured by ultrasound in mode A can be realized in a useful way in the eyes of the corpses of the example and compared with the axial lengths determined from the laser scanner data. In general, this relationship can be conveniently and usefully approximated by a variety of linear or non-linear equations or curve adjustments in which the length of the tissue path is a function of the axial length, or PL = t (AL). In this example data set, this correlation can effectively be represented as a linear function. This can be an equation of the form Y = aX + b, in which Y = length of the tissue path (PL), and X = axial length (AL). An example in which a = 1 and b = -3, the equation is PL = AL - 3, expressed in millimeters (curve 200a in FIG. 15A).

It should be understood that different equations can be used as effective mathematical representations of this data or similar data (for example, PL = AL / 2 + 9.5). Also, these or similar data can be expressed as a non-linear function, such as a quadratic equation or the like (curve 200b in FIG. 15A). Alternative expressions can be used, and additional data (or more specialized data sets) can also be analyzed by the methods shown. For example, said ocular data can be represented by alternative nonlinear functions, or they can be included or carried out by interpolations in query tables instead of function evaluations, and the like. Additionally, anatomical data sets that correlate additional attributes of the patient (age, sex, or the like), can be assembled, and relevant predictive relationships can be obtained for these patient populations. Mathematical relationships that represent this data can be included in the radiotherapy system software 10, and used to predict the path length of the treatment tissue, based on medical measurements and inputs for a particular patient.

In certain alternative embodiments, the functional relationship for tissue path length may be based on more than one anatomical measure, other measurable features of the patient (eg, refractive data), or other patient history data (age, sex, and similar). Advantageously and more generally, the method illustrated in the previous example can be extended to other radiotherapy procedures in addition to its use in ocular treatments for the macula. An embodiment of the method can be summarized as comprising the steps:

(a) select one or more input parameters (anatomical measures, other human measures and / or other specific characteristics of the patient such as age, sex, and the like), such as P1, P2 ... Pi;

(b) characterize the variation in a relevant population of patients with respect to the selected parameters (for example, studies of anatomical variation or other measurement in patient populations, optionally as a function of other specific patient characteristics);

(c) correlate the variation in the population with the path length of the PL treatment tissue for a radiotherapy treatment plan;

(d) determine a mathematical function and / or calculation algorithm that effectively expresses a relationship between the selected parameters and the length of the tissue path, which can have the form PL = f (P-i, P2 ... Pi);

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(e) determine the data for the selected parameters for a specific patient to be treated;

(f) use the mathematical function and / or calculation algorithm to determine PL for a specific patient to be treated (PLo);

(g) modify or adjust one or more parameters of the radiotherapy treatment plan based on the PLo value. (for example, duration or dose of the beam, spectral ene, filtration, collimation geometry, beam orientation, or the like); Y

(h) treat the patient according to the modified or adjusted treatment plan.

The embodiments of the method such as the previous example can be integrated into radiotherapy treatment devices having aspects of the invention, such as including software code effective in controllers of the computer processor of a radiotherapy system, so that the device is allowed treatment carry out one or more of the steps of the method.

In FIG. 15B, for each of the seven eyes of example corpses, the axial length derived from an ultrasound in mode A is shown, together with the value of the laser scanner of tissue path length, and a tissue path length calculated according to the linear formula PL = AL-3. For clarity of the presentation, the seven eyes of the example are ordered by axial length of an ultrasound in increasing A mode. It can be seen that, with minimal dispersion, the results of an ultrasound in mode A are a good predictor of the length of the path. The maximum error introduced by ultrasound mode A in this data is approximately 0.3 mm. It has been shown by the inventors herein that an error of 1 mm in path length introduces approximately 3% error in the calculation of the dose for absorption on a retinal target. Therefore, a 0.30 mm error introduces approximately 1% dose error, which is quite small and clinically acceptable. Based on this discovery, an embodiment of a method having aspects of the invention comprises determining the axial length of a patient's eye by means of a pre-operative A mode ultrasound, and then predicting the length of the tissue path of a patient. treatment beam, and adjust at least one treatment parameter based on the length of the tissue path (eg, time of beam duration).

MIC. Alignment, stabilization and / or eye tracking

FIG. 16 illustrates a view from the top of an embodiment of a system for positioning and / or stabilizing in a controllable manner the eye of a subject for therapeutic treatment. The upper part of FIG. 16 shows a block diagram of a system 100 for carrying out a method that has aspects of the invention. The bottom of FIG. 16 shows an eyepiece module to allow alignment, stabilization and / or monitoring of an eye before and during treatment.

In the illustrated embodiment, the system 100 includes one or more cameras 102 positioned to take pictures of the eye 10 along the geometric axis 810 (or 2810). The camera 102 provides video image data of the eye 10 to a processor 106 and preferably to a monitor 104. Attached to the monitor 104 is an image generator / processor 106, such as a personal computer programmed with available computer-assisted design software. commercially, capable of generating and superimposing geometric images in the image of the eye 10 appearing on the monitor 104, and preferably configured to perform image recognition algorithms using eye images. The processor 106 may also include patient-specific data and images obtained before the operation of the system 100, for example, to be included in images presented, and / or to be used to provide patient-specific geometry for treatment.

The eye contact device 110 may be equipped with a plurality of position indicators that are capable, in combination with detectors located in the external coordinate system, of locating the position of the contact device in the external coordinate system. This type of tool-tracking system has been described for use in image-guided surgery, in which it is necessary to place a movable surgical tool, and also images of the pre-op patient, in a common surgical reference frame that contains the patient. In the present application, the position indicators may be three or more beam direction elements designed to reflect the external positioning beams, for example, microwave beams from known position beam sources to known position beam detectors, determining the position of the contact device by a processor operatively linked to the beam detectors. Alternatively, the beam direction elements in the eye contact device may be equipped with a plurality of LEDs mounted on the device to direct, for example, a plurality of beams to known position detectors to determine the position coordinates of the contact device in the external coordinate system. Such tool registration systems have been described, for example, in U.S. Pat. 7,139,601, 7,302,288, and 7,314,430.

In a third general embodiment, the means for determining the position takes the form of a collimated beam assembly, including a laser light source and one or more optical components, such as a semi-silver mirror, to align the laser beam with the collimated irradiation beam produced by beam source 108; so that the two beams are essentially coincident, along the same axis 810. In this embodiment, the beam positioning assembly moves relative to the patient's eye until the laser beam points directly to the

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Selected target region of the patient's eye, for example, the region of the macula in the central anterior part of the retina. As can be seen, this will place the selected target region of the eye on record with the therapeutic irradiation beam; that is, the laser beam acts as a reference beam that works to put the eye in the same frame of reference (coordinate system) as the irradiation beam.

More generally, the registration and spatial gma of the contact device 110 may be through optical or electromagnetic sensor detection. In general, cameras or other detectors are mounted either in the system, or optionally in the treatment room, and are used to track and record the position of the eye or contact device 110. The cameras or detectors are then able to determine and record the three-dimensional position of the contact device 110 in real time, and therefore the position of the eye as it is positioned. A calibration process can be used to determine the relative spatial position of the contact device with respect to a known reference frame, as well as in combination with optional images. The calibration information can be stored in a reference file on the computer and used by a software program.

The system 100 may also include a processor or control unit that has a graphical user interface to receive instructions from, and present information such as alignment data and system functionality to, a system operator. In addition, the control unit may be in electronic communication with one or more of the other components of the system 100 described above, for example, the motors that control the beam positioning assembly, the motors that control the eye positioning assembly, and sensors, detectors and beam source to determine the position of the eye contact device in the external coordinate system, as described above.

IV. Eye gma and alignment methods. These sections detail features and applications of the eye gma in the treatment system of the invention.

VAT Eye guide devices

FIGS. 17A and 17B illustrate top views of an embodiment of a system for connecting the eye of a subject, the contact device 110 being reversibly coupled and controllable with the cornea 200 and / or limbus and / or sclera 239 of the eye 130 is illustrated schematically The eye 130 includes a cornea 200 and a lens 132 posterior to the cornea 200. The eye 130 also includes a retina 134, which covers the inside of the posterior surface of the eye 130. The retina 200 includes a highly sensitive region, known as the macula, in which the signals are received and transmitted to the visual centers of the brain through the optic nerve 136. The retina 200 also includes a point with a particularly high sensitivity known as the fovea. Eye 130 also includes a ring of pigmented tissue known as iris 138. Iris 138 includes smooth muscle to control and regulate the size of an opening in iris 138, which is known as the pupil. The eye 130 resides in a basin of the eye 140 in the skull and is able to rotate there around a center of rotation.

As contemplated by the present invention, the eye contact member 120 may be comprised of a number of materials well known in the art. Preferably, the eye contact member can be made of a material with attention to biocompatibility. In an exemplary embodiment of the invention, the contact member 120 is composed of poly (methylmethacrylate), or PMMA (eg, Vistracryl®, FDA MAF 1189). Thermoset and / or thermoplastic PMMA are contemplated by the present invention and are supplied by a number of sources, such as Perspex CQ (ICI Derby, England). Teflon and tantalum are also indicated. It is also possible to coat the eye contact member 120 with biocompatible materials if the elements of the eye contact member 120 are not biocompatible. In some embodiments, the eye contact member 120 contains pigments or tempts. In particular embodiments, the eye contact member 120 is coated or impregnated with bioactive substances including anti-inflammatory agents / immunomodulating agents and / or anti-infective agents. The particular eye contact members will contain radiopaque, radioactive, fluorescent, NMR contrast or other reporter materials. The contact member 120 or the complete assembly of the eyepiece 110 can be supplied to a user as a pre-sterilized packaged, disposable unit.

A certain degree of stiffness, or hardness, of the eye contact member 120 is useful in the physical coupling with the eye and with the pivot that joins the control arm as described further in detail below. However, the eye contact member 120 includes, in certain embodiments, a certain degree of flexibility, or softness, so that the eye contact member 120 has a degree of flexibility, but still retains a curved shape in its resting position The internal contour 122 can replicate the curvature of a typical photocoagulation lens in ophthalmological practice (for example, Haag-Streit). In operation, a lubricant (for example, Genteal) can be applied to the lens to keep the eye moist during the procedure. A light vacuum (for example, from about 10 to about 50 mm Hg, and preferably less than about 25 mm Hg) can be applied to the device through a vacuum tube (for example, by a spring loaded syringe device, which it can be clipped to the patient's clothes), and the eyepiece gma 600 positioner can apply a force of pressure against the eye (for example, loaded by spring arm 180). The combination of light vacuum and light pressure force has been demonstrated by the inventors herein that provides adequate stabilization of the eye, while promoting patient comfort. The Gma I can have a separate feature (for example, an axial connection post and splint of the lens 120 to post 222) that allows

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the patient leaves the positioning arm quickly and perfectly as needed (for example, during a sneeze). In this case, the ford and suction cup 120 can remain in the patient in the event of moving out of the positioning arm, allowing an easy re-union.

The eye contact device 110 functions to stabilize the eye in a first position to provide interactive support (eg, stabilization and / or controllable movement) for the eye while the eye is being treated. The contact device 110 includes a suction cup or eye contact member 120 that contacts the eye 130. The contact member 120 may be positioned in the eye in a variety of positions, and is therefore useful in A wide variety of eye treatment procedures. In one embodiment, the eye contact member is at least in partial contact with the cornea 200. In the embodiment illustrated in FIG. 17B, the eye contact member covers a substantial part of the cornea (but does not necessarily touch the cornea). The member 120 can also cover parts of the sclera. The contact member 120 preferably includes a curved structure or "lens" that is substantially centered on the axis 235 and overlying the cornea 200.

The curved contact member 120 is preferably molded with a contact surface of the concave eye that substantially conforms to the anterior surface of the cornea 200 of the eye 130. The contact surface of the contact member 120 preferably has a radius of curvature that is larger about 5 mm. In one embodiment of the invention, the radius of curvature of the inner surface of the eye contact member 120 is approximately 7.38 mm. Also, in a preferred embodiment, the radius of curvature of the outer surface of the eye contact member 120 is preferably 7.38 mm. It will be appreciated that a 1: 1 ratio of the internal and external curvatures minimizes or eliminates energy refraction through the eye contact member 120 in certain embodiments of the invention; In this embodiment, the contact member 120 is always a cup for the eye 130. Alternatively, the internal and external curvatures may be different to allow targeting or diffraction of desired energy when transmitted through the eye contact member 120. In some embodiments, the contact member 120 is produced in a variety of ways, one or more of which may be chosen for a given patient depending on their specific anatoirna.

With continued reference to FIGS. 17 A and 17B, the contact member forms, with a back plate 121 of the contact device, an internal reservoir 122 by means of which a negative pressure (partial ford) is applied to the device, through a ford port 210, It is distributed along the contact surface of the device, as can be seen. The ford port is connected to a suitable ford source through a tube 275. In this embodiment, the ford port 210 is positioned through the eye contact member 120 so that a communication space is formed. air or fluid through the eye contact member 120 to allow air trapped between the eye contact member 120 and the anterior surface of the cornea 200 the eye 130 to be removed reversibly, thereby reversibly connecting the member of contact with the eye 120 with the anterior surface of the cornea 200. In an alternative embodiment not shown, the ford port 210 is connected to the connector 270 which may contain an axis along the hollow lumen 235 through the contact member with the eye 120 so that the air between the eye contact member 120 and the anterior surface of the cornea 200 can be reversibly removed as described above. The ford or suction assistance is useful for locating and adhering the base of the scleral lens in the eye 130 of the subject and securing the contact device 110 to the eye of the subject 130. Once in a desired treatment position, the contact device 110 can be coupled with system 100 during the treatment procedure, as described below. After treatment, the contact device 110 can be decoupled from the system 110 and removed from the subject.

In a preferred embodiment, the negative pressure applied to the eye, for example, a negative pressure of 20-50 mm Hg, is effective to stabilize the position of the eye in the device, that is, substantially prevents the movement of the eye relative to the device, but by itself, it is not enough to keep the device in contact with the eye in the eye. Instead, the contact device is secured in the eye by a pressure force that acts to press the device against the patient's eye, acting in combination with the negative pressure applied to the eye by the device. In the illustrated embodiment, the contact device is secured to the eye by the force of pressure acting through the arm 180, in which the negative pressure applied to the contact device functions to prevent the eye from moving relative to the device. As indicated above, the contact device is typically pressed against the eye with a force of between about 1-25, typically 5-25 grams, by a pressure spring, electromagnetic force, or the like. The advantage of this system is that the negative pressure applied to the eye may be substantially less than that required if the ford was only acting to keep the device in the eye, and this substantially lower negative pressure increases comfort and reduces irritation and deformation of the front part of the eye. The pressure force is illustrated in the figures, for example, FIGS. 2A and 2B, by an arrow 119, which indicates the direction of force action in the figures.

When the eye contact member 120 contacts the eye 130, negative pressure is applied to remove air from between the eye and the contact member, to stabilize the position of the eye 130 with respect to the contact member. A primary ford adjustment is in fluid communication with the air passage. A ford line 275 is connected to the ford port 210. Additionally, a ford pump is in fluid air communication with the ford line 275 to evacuate the trapped air between the eye contact member 120 and the corneal surface. 200. Collectively, ford port 210, line 275, and pump (not shown) constitute a primary ford subsystem. The degree of strength of the ford required to seal may vary, and preferably be monitored from

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a controllable and continuous way, by the system of the invention. In one embodiment of the invention, between about 0.5 mm Hg and about 50 mm Hg are used to provide the effective negative pressure to stabilize the position of the eye relative to the contact member 120. Preferably, the ford is between about 20 mm Hg and approximately 50 mm Hg. More preferably, the applied force is approximately 25 mm Hg and is monitored by pressure sensors and / or by direct monitoring of the ford source. In some embodiments, the pressure is passively maintained, for example, by an air chamber. The air chamber can be produced so that it can apply a given maximum pressure.

It should be noted that the forging pressures described herein are dramatically lower than those used in many forms of the prior art of eye surgery, such as laser radial keratotoirna. This system that has aspects of the invention also avoids the need for temporary paralysis of the eye, and prevents patient discomfort. The contact member 122 can be mechanically pressed by a light force (such as a spring applied to a support arm 180) to hold it against the eye, assisting in maintaining connection with the cornea, without strong suction.

By connecting the contact member 120 with the eye 130, the eye 130 is fixed in a first position, the patient is unable to move the contact member with intra-ocular movements. The contact member can, however, move using the control arm 180; movement through the control arm rotates the eye through the eye contact member. Thus, an embodiment of the invention includes substantially stabilizing the eye 130 in a position selected with the eye contact member 120.

FIGS. 18A-18D represent perspective views of the contact device with the attached control arm having aspects of the invention. As shown in the figures, a preferred embodiment of the contact device 110 includes a pivot joint or connector 220 that accommodates the movement of the pivot between the contact member and the positioning arm 180, when the arm moves the contact device to a desired orientation in the external coordinate system. In one embodiment, the pivot connector 220 is a spherical or ball joint that allows three-dimensional rotation. In the example shown, the positioning arm 180 can be removably coupled to the contact device through a rod arrangement and plug that fixes the end of the arm 180 to a pocket formed in the ball joint 220.

FIGS. 18C-18D show an alternative embodiment in which the contact member or lens 320 is supported from one or more points out of center (for example, by side post 302) so that a central part can be transparent, allowing the formation of retinal images while the eye is connected by the device 312 (for example, by a fundus camera, which can be used as a module in the system 10, or can be separated). With a contact that is transparent in its center, direct retinal imaging can be performed so that instead of fiduciary markers, images of the retinal coordinates and movement can be formed directly. Pivot point 220 is out of center and post 302 is also out of center. The apex 320a of the lens 320 is free to transmit incident and reflected light, allowing the retina and other eye structures to be seen through the lens 320.

IVB Fiduciary eye guide markers

FIG. 19 schematically illustrates an eyepiece device for use in an eye stabilizer system that has aspects of the invention, and that has fiduciary markers in patterns, and a method for determining orientation by image recognition. The figure shows a perspective view of an embodiment of contact device or eye guide 512 including contact member 120, spherical pivot 220, mirror 230 and ford port 210. In this embodiment of the invention, contact device 110 includes one or more fiduciary markers 240, 242, 244, 246, 248 defining the geometry of the contact device 110 or geometric relationships between the contact device 110 and additional components of the system and / or eye as described throughout the memory descriptive The fiduciary markers, in one embodiment of the invention, contribute to the knowledge of the positioning of the eye when the contact device 110 is connected to the eye 130, and a coordinate system is known. The spatial register can be used to record and monitor the three-dimensional spatial position of the contact device 110 with respect to a known reference point.

The example shown of an eye stabilizer system 512 has a reflective mirror 230 attached. As described herein, alternative embodiments do not require a specular surface, and tracking of the image-based eye guide 110 may employ non-specular fiduciary markers. the mirror and center pivot 220 can be replaced with these. For example, as shown in FIGS. 23-25, fiduciary markers may be carried on a horizontal cross arm and pivoting center post, and / or on the lens itself, or (as shown in FIGS. 18C-18D), the lens may be supported by a deviated member or side post, so that visualization can take place through the lens.

In the illustrated embodiment, one or more of the fiduciary markers 240, 242, 244, 246, 248 includes a fiduciary marker locator from which images can be formed. The fiduciary marker locator is localizable using one or more modalities of the imaging system. In this embodiment, the fiduciary marker can be mounted on or on the eye contact member 120, so that it is either flush with, or embedded in, an external surface of the eye contact member 120. However, in alternative embodiments, it is not

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it is necessary that the fiduciary marker be configured for flush mounting or recessed in the contact member 120, and can be mounted to extend from the eye contact member 120. In another embodiment, one or more fiduciary markers are positioned at, within , or on the penimeter of the mirror 230. This allows the mirror 230, together with the contact device 110, to be centered or aligned with respect to the limbus or other ocular structure.

The fiduciary marker may include a liquid or gel housed in a sealed inner cavity. Preferably, the fiduciary marker is a solid. The solid, gel, or fluid may be visible by one or more imaging modalities (eg, MR, CT, etc.). In one embodiment, the fiduciary marker is integrated in the eye contact member itself. The fiduciary marker of image formation is visible and provides a good contrast in the images produced by at least one modality of image formation. In one embodiment, the fiduciary marker of image formation is multimodal (i.e., localizable by more than one modality of image formation), such as using a mixture of different fluids, gels or solids of image formation that are localizable in different modalities of image formation.

In one embodiment, the one or more of the fiduciary markers 240, 242, 244 include a substance that can be seen in a first mode of imaging, while one or more of the fiduciary markers 246, 248 include a substance that can be see in a different second mode of image formation. In one such illustrative embodiment, the one or more of the fiduciary markers 240, 242, 244 includes, or is doped with, a substance that has a high atomic number (Z), such as barium, titanium, iodine, gold, silver , platinum, stainless steel, titanium dioxide, etc. which provides a good contrast in a CT or other x-ray imaging system. In this embodiment, one or more of the fiduciary markers 246, 248 includes gadopentatate dimeglumine, gadoteridol, ferric chloride, copper sulfate, or any other suitable MRI contrast agent, as described in Chapter 14 of Magnetic Resonance Imaging, 2nd ed., Edited by Stark and Bradley, 1992.

In an alternative multimodal embodiment, the fiduciary marker is constructed of a substantially solid plastic or other material that is hygroscopic, that is, capable of receiving and retaining a fluid, such as a formation fluid.

images that can be seen in an image formation system (for example, an image formation system

MRI images or similar). In a further embodiment, the plastic that forms the fiduciary marker is doped or otherwise included a substance that can be seen in a different imaging system, such

such as a CT or other x-ray imaging system. The illustrative examples of

Solid plastics that can be made hygroscopic include, among other things, nylon and polyurethane. The use of a hygroscopic material avoids the complexity and cost associated with the manufacture of a sealed cavity to retain an image formation fluid. Furthermore, by adapting the solid hygroscopic plastic for image formation using a first mode, and by using the image formation fluid for image formation using a second mode, each of the solid and fluid can be customized separately to provide a better contrast for your particular mode of image formation.

In a further embodiment of the fiduciary markers illustrated in FIG. 19, the outer surface of one or more of the fiduciary markers is reflective of light or other electromagnetic energy. Consequently, it can be located by a camera in an optical positioning system that is coupled to a workstation guided by images (for example, during the registration of the subject). An additional function of such fiduciary markers is the calibration of the extent to which the distance between fiduciary markers is used to calibrate the distance over or in the eye. In an example like this, the outer surface of the spherical image-forming fiduciary marker includes light-reflecting microspheres (for example, included in an adhesive that covers the fiduciary marker or eye contact member 120). In another example like this, the outer surface of the fiduciary marker is covered with a tape that reflects the reinforced adhesive light, such as SCOTCHLITE 9810 Reflective Material Multipurpose Tape sold by Minnesota Mining and Manufacturing Co. ("3M"), of Saint Paul , Minnesota.

In one embodiment of the invention, the spherical pivot 220, mirror 230 and / or control arm 180 include one or more fiduciary markers. In an alternative embodiment of the invention, the one or more fiduciary markers are configured to be located by a remote positioning system as well as an imager using one or more imaging modalities. In said embodiment, the outer surface of the eye contact member is configured to reflect the light, as discussed above. Fiduciary markers can still be located advantageously using one or more imaging modalities (for example, MR, CT, or other imaging system that provides 3D images or other images internal to a subject) as well as can be localizable outside the subject, such as using a remote camera or similar component of an optical or other positioning system, for example, which is coupled to a workstation guided by images. In one embodiment, this allows automatic registration of the actual location of the subject's eye (for example, using cameras to locate the light reflective fiduciary markers) for pretreatment of images of the system in which additional fiduciary markers of position formation are positioned. images. This eliminates the need to register the subject's eye by inserting an optically locatable positioning control arm into the contact device, and eliminates the need for another absolute position reference, because the fiduciary markers themselves are optically localizable and Recordable in known locations in pre-treatment images of the system.

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The control arm 180 can be coupled to a workstation guided by images or platform (not shown). In this embodiment, the control arm 180 includes an end that is sized and shaped to allow it to engage the spherical pivot 220. The control arm 180 includes, in this embodiment, a plurality of fiduciary markers 520, 522, 524, 526, 528, 530 that can be located by a camera or other similar device of the optical positioning system. The fiduciary markers 520, 522, 524, 526, 528, 530 in the control arm 180 are positioned in a known spatial relationship between sf and with respect to the upper part of the control arm 180. By recognizing the locations of the markers fiduciary, the optical positioning system is able to compute the location of the upper part of the control arm, which is in a known spatial relationship with the configuration of fiduciary markers. This allows the control arm 180 to be used in conjunction with the optical positioning system to record the subject's eye and to plan and / or further perform the treatment procedure using an image-guided work station. An image-guided computerized processing workstation, which is capable of presenting pretreatment images previously acquired and uploaded to the system. The optical positioning system connected to the workstation includes an infrared light (or other energy source) that provides light that is reflected from the reflective fiduciary markers. This allows the reflective fiduciary markers on the control arm 180 to be located and recognized by the cameras.

IVC Detection of fiduciary marker patterns in the eye guide

FIGS. 20A-20H schematically illustrate an ocular eye device for use in an eye stabilizer system that has aspects of the invention, and which has fiduciary markers in patterns, and a method for determining image recognition orientation. In the exemplary embodiment shown, a pattern of highly reflective fiduciary markers is mounted on the device. In the example shown, this is a pattern of three triangular fiduciary markers (4), comprising fiduciary marker 1 (in the center bar 190) and fiduciary markers 2 and 3 (in lens 120), although other patterns may be used. For example, fiduciary markers may have a surface including a tape reflecting reinforced adhesive light, such as SCOTCHLITE 9810 Reflective Material Multi-Purpose Tape sold by Minnesota Mining and Manufacturing Co. ("3M"), of Saint Paul, Minnesota. Also, other methods can be used to apply or form a reflective surface, such as reflective ink compositions, and the like.

The positioning of the fiduciary markers can be conveniently chosen so that they form a right triangle (90-45-45) when the eye guide is in alignment - perpendicular and coaxial with respect to the center of the system (see FIG. 20B). For two fiduciary lens markers, the 45 degree angle is preferred as a better compromise for horizontal and vertical sensitivity during measurement (i.e., if, for example, a 60 degree angle is selected, it provides a greater horizontal sensitivity, but less vertical). Also the fiduciary lens markers are surrounded by the dark area in order to provide an easier detection.

By means of the center pivot 220, the center fiduciary marker 250 can move in a horizontal and vertical direction relative to the lens fiduciary markers. This movement causes the relationship of the angles in the triangle to change, which provides information on the alignment position, and therefore the patient's eye.

Reference is made to the above description regarding the pattern recognition functions of the imaging system, also illustrated in FIGS. 3A-3B. In summary, fiduciary markers as illuminated with the lights 405 provide an image with high contrast to the axial camera 401. The computer processor 501 can be programmed with suitable software to process the electronic image signals to delineate the image regions corresponding to fiduciary markers (using known image processing algorithms, such as contrast enhancement, filtration, intensity thresholds, edge recognition, and the like). The processor can then define a center of mass for each fiduciary marker image, and locate the corresponding points in a frame of reference coordinates, so that a mathematical representation of the fiduciary marker pattern is created from the perspective of the camera. The mathematical representation then allows the calculation of relevant angles and dimensions, and thus the information of the position and orientation of the eye guide is derived. Note that the scaling information can be used to derive the distance information from the Z axis, alternatively or additionally with respect to the off-axis camera 402 described with respect to FIGS. 3A and 3B. The process can be repeated from sequential camera images at any update rate of the selected position (for example, approximately 1 to 50 Hz) to provide continuous position and movement data.

Once the fiduciary markers have been recognized, and the catheter angles and lengths of the triangle have been calculated, the processor 501 can provide information (for example, through the presentation of images) to the user indicating in which direction to move the eye guide with in order to have it aligned. All three angles and their spatial relationships can be considered in order to provide information to the user, since for people it is easier to understand, and react to, one variable per direction (that is, up / down for vertical, and left / right for horizontal), the angles of the fiduciary lens markers are represented as a relationship for the user - A2 / AI. This provides only one number for the direction of movement. For example in

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an aligned condition the relationship is one because 45/45 = 1; if the mirror is tilted at some angle to the right the relationship could be 48/52 = 0.9231, etc.

In FIG. 20A the angles are identified as a, b and c, in which a is the angle of the fiduciary marker of center 250 with respect to the lens fiduciary markers. Angles b and c are the angles of the left and right. The angles a, b, and c determined by the recognition of the fiduciary marker image. Catheter lengths l1, l2 and l3 can be scaled to confirm the Z position. A pattern height h (or width) can also be defined from detected data representing the distance between fiduciary marker 1 and a line joining markers. fiduciaries 2 and 3. Similarly, pattern widths can be defined (w1, w2). It should be understood that the same data of a detected image can be expressed and organized as a number of alterative sets of geometric parameters as stages in calculations, without departing from the spirit of the invention.

FIG. 20H illustrates the effect of the inclination of the eyepiece 110, the rotation of the center post 222 around the pivot 220, causing the fiduciary marker 1 to move in the opposite direction to the lens 120. The inclination may be horizontal, vertical or combinations of these. Note that the effect of inclination is to cause a ± change in the distance between fiduciary marker 1 and fiduciary lens markers 2 and 3, depending on the direction of inclination (compare h1 not inclined with h2 inclined).

Six cases are illustrated in FIGS. 20B-20G:

FIG. 20B shows the eyepiece aligned with the geometric axis, where a = 90 grad .; b = 45 grad .; and c = 45 grad. This corresponds to the image on the right of FIG. 20H.

FIG. 20C shows the eyepiece positioned upwards (pole tilted upwards relative to the lens), but aligned horizontally, where at <90 degrees; and b = c> 45 grad. This corresponds to an inclination in which the height h increases.

FIG. 20D shows the eyepiece positioned down (pole tilted down), but aligned horizontally, where at> 90 degrees; and b = c <45 grad. This corresponds to an inclination in which the height h is decreased, as shown in the image on the right of FIG. 20H.

FIG. 20E shows the eyepiece positioned to the right (pole tilted to the right), aligned

vertically, where at <90 grad .; b> 45 grad .; and c <45 grad. This corresponds to an inclination in which the

width w1 is decreased and width w2 is increased.

FIG. 20F shows the eyepiece positioned to the left (post tilted to the left), aligned

vertically, where at <90 grad .; b <45 grad .; and c> 45 grad. This corresponds to an inclination in which the

width w2 is decreased and width w1 is increased.

FIG. 20G shows a general case: the eyeglass positioned out of center vertically and horizontally, where at t 90 grad .; and b t c, the values of specific angles determine the orientation This corresponds to a case in which each of h, w1 and w2 differs from the nominal values as shown in the aligned case of FIG. 20B.

Note that the methodology described with respect to FIG. 20A-G can be applied to fiduciary marker patterns distributed in different structural elements of the eyecup 110. See for example the eyecup 110 of FIGS. 23-25. In that example, the fiduciary markers 2, 3 are on an extended crossbar 190 and the fiduciary marker 1 is on a raised center post 222, so that a linear pattern is created when they are aligned. In the case of alignment with the axis of the coordinate system (see FIG. 24D, compare with FIG. 20B), the angles b and c = 0 °, the angle a = 180 ° and the lengths l2 = l3. Note that the effect of the horizontal inclination of the center post 222 (FIGS. 25A and 25B) is to render the lengths l2 and l3 not equal, even when the center pivot of the eyepiece 220 intersects the axis of the system 2810. In the Similar case of vertical inclination (not shown), angles a, b are not zero.

V. Examples of and detailed methods. This section describes several more detailed examples and methods of the system and therapeutic applications described above.

GOES. Therapeutic method that employs an eye crane

FIG. 21A is a flow chart illustrating a method of using the system to stabilize and position an eye for treatment. It should be noted that the described devices having aspects of the invention can be used in a wide variety of ocular treatment methods. FIGS. 21B-21E are diagrams of an eye associated with the radiotherapy system, illustrating examples of stages included in the flow chart of FIG. 21A.

The realization of method 2500 can be summarized as including some or all of the stages:

a) Prepare the eye 2510.

b) Position and secure head 2520.

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c) Position the eye support (eye gma) in the eye of the subject 2530.

d) Apply suction to keep the eye support against the eye 2532.

e) The rapid release of the control arm of the eye contact member 2534 can be provided.

f) Align and stabilize the eye 2540.

g) Position the treatment axis with respect to eye 2550.

h) Position and verify beam axis 2555.

i) Perform the treatment following the eye and / or eye gma 2560.

j) As required, interrupt radiation (inactivation control) on the basis of eye movement 2565.

k) Release the eye from the eye support 2570.

l) Additional or alternative steps may be included (for example, corrective realignment of the eye, or automatic correction of the beam path to follow the movement of the retinal target).

The stages included in FIG. 21A and further illustrated in FIGS. 21B-E are described in detail below:

Stage 2510

Prepare the eye - Preparation of the eye of a subject or patient for treatment that may include administering an anesthetic, tape the upper or lower eyelid, adjust a patch on the opposite eye, measure biometric parameters such as axial length, corneal diameter, etc. Optionally, the eye may dilate, particularly when alternative embodiments of device / method are employed that have aspects of the invention that include integrated retinal imaging optics (not shown) with radiotherapy treatment system 10 (eg, OCT or camera). fundus). Preparation may include applying eye drops that numb the subject's eye. The untreated eye can be covered with a patch, for example, so as to avoid distraction. Scleral clearance can be provided by securing the lower eyelid down with an eyelid retractor as further described herein, or with a tape (see FIG. 2) or eversion of eyelids.

Stage 2520

Positioning and securing the head - After preparation, the subject's head is secured in a suitable position with respect to the system, such as resting head and chin 160 and head fixator 161. The subject's head is positioned on a support for The head and chin rest on a chin rest. The fastener 161 may include strips or the like, and may have an adjustable tensioner, optionally with an attachment or grip that limits the force. This assembly may include an interlock detector of the inactivation control (see Step 2565) to ensure that it remains connected during the radiation emission. Other patient position detectors may optionally be included, such as contact sensitive grips 163.

Stage 2530

Positioning the eye support in the subject's eye - The eye contact member or eye gma 110 is then positioned in the subject's eye. The contact lens of the eye gma 120 and / or the surface of the eye may be coated with a lubricating solution or ophthalmic gel (eg, GenTeal® formulations, produced by Novartis Ophthalmics). In one example, the eye contact member is placed in the cornea by tilting the eye contact member to contact the upper part of the sclera. Upon contacting the eye contact member with the upper scleral region of the eye, the eye contact member bends down to achieve full contact with the eye.

As further shown in FIGS. 11 and 21B, the blade 26 comprises the generally circular limit of the sclera 17 and cornea 35, the blade being substantially in the projected plane 26a. A projected tangent corneal plane 35a parallel to the plane of the blade 26a intersects the center of the cornea 35b very adjacent to the center of the blade 26b. The geometric axis 2810 of the eye 30 can be defined as an axis through the center 26b of the blade 26, perpendicular to the center 35b of the outer surface of the cornea 35, and intersecting the surface of the retina 1435 at the pole of the retina 1436) .

The alignment in step 2530 includes connecting the eye gma 110 with the eye 30 so that the eye gma has a known and measurable orientation and position with respect to the center 26a of the blade 26. In the example shown, the contact part of the gma Eyepiece or lens 120 may be advantageously formed to be substantially circular and concentrically aligned with a central axis of the eyepiece GMA 110a. Similarly, the central axis 110a of the eye gma 110 in the example shown is substantially collinear with the support post of the eye gma 222.

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This simetna conveniently assists a doctor to position the eye support or gma 110 in the eye 30 by visually aligning the lens 120 symmetrically with the blade 26. In this position, the post 222 of the eye gma 110 is aligned with the center of the limbus 26 so as to indicate the geometric axis of the eye. The lens 120 may be transparent, advantageously allowing visual confirmation of the concentric alignment of the edge of the lens 120a in the blade 26 in embodiments where the lens 120 is larger than the blade 26 (i.e., covering an adjacent sclera part 17).

However, it is not necessary for the lens 120 to be circular, and it is not necessary for the eyepiece support post 222 to be collinear with the axis of the eyepiece 110a (see examples in FIGS. 18C-D). As described herein in detail, feature recognition methods based on camera images that have aspects of the invention provide determination by the computer processor of the position of center 26b of blade 26, and localized fiduciary markers. in the eye gma 110 they can be followed in a similar manner to determine the relative position and orientation of the eye gma 110 with the center of the blade 26. These determinations provide a non-visual method for guiding and confirming the alignment of the eye gma 110 with the axis geometric 2810 (see step 2540).

The positioning and alignment of the eye gma can be performed by a doctor while observing both the support and the patient's eye directly, or a computer monitor, or both of these interactively. Alternatively, a processor of the imaging camera of the imaging system 410 can automatically determine the center of the limbus and assist in positioning the support with its center aligned with the center of the blade (see the view of the axial camera of FIG. 21C (2)). In some embodiments, the support is automatically positioned instead of manually by the device operator. Note that at this stage it is not necessary that the positioning system of the X-ray source (see 115 in FIG. 1A) is aligned with the geometric axis 2810, and is shown in FIG. 21B in an arbitrary relative orientation P1.

Stage 2532

Apply suction to keep the eye support against the eye - Once the position of the eyeglass 120 lens or lens is determined relative to the limbus, suction can be applied through the support to juxtapose it to the eye, and ensure the lens coupling to the surface of the eye. With the support firmly attached to the eye, the support (and the eye) can move in position relative to the treatment device at known coordinates in the system. Note that the degree of vacuum suction can be selected, and higher or lower levels can be used. In the embodiments described in detail, it has been shown that a relatively light suction (eg, approximately 25-50 mm Hg), suitably couples the eyeglass lens 120 to the patient's cornea 12. Such modest suction levels can stimulate patient comfort and acceptance of treatment.

Stage 2534

Quick release of the control arm / support of the contact lens of the eye gma - As described above, a quick release is constructed in the contact device in some embodiments of the invention. In the case of an emergency or fatigue, the patient can be released from the support by applying a minimum of force resulting in the release or separation of the contact member with the eye or lens 120 from the rest of the eye gma device 110 In that case, the method stage returns to the previous stage to position and secure the head 2520, or to the stage of positioning the eye gma contact device in the eye of the subject 2530, as indicated in FIG. 21A.

Stage 2540

Align and stabilize the eye - As shown in FIG. 21C (1), the axis of the treatment device and the positioning system is adjusted as necessary to position with respect to the eye to place the positioning reference axis of the X-ray source (system Z axis) in alignment with the geometric axis of the eye. In the figures, the axis of the system when aligned with respect to the geometric axis of the eye 2810 is represented as P2. The movement, indicated in the figure as M (x, y, O, 0), may include movement or rotation of either or both of the patient's head and / or eye, and alternatively or in combination, may include movement or rotation of The components of the treatment system. For example, with reference to FIGS. 1A, B and 2A, B, either one or both of the head, patient's eye and / or treatment system 10 can be moved so that alignment is achieved.

In certain embodiments, the adjustments may mainly include adjustments in the X and Y direction of the eyepiece gma 600 positioner, which may include a manual or electric multi-axis micro manipulator. An auxiliary monitor can be positioned (see 503b in FIG. 1B) to provide a physician with information on the imaging system while operating the eyepiece gma 600 positioner. With the head stable, the movement of the eyeglass 110 in the X and Y direction through the eyepiece gma 600 positioner can be used to rotate the geometric axis of the eye 2810 (for example, rotating the eyeball in the orbit) so that it is parallel to the reference axis of the positioning system 115 (system axis). The movement of the positioning system 115 in the X and Y direction can then be used to place the two axes in collinearity.

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Alternatively or additionally, the system axis can also be rotated to align in parallel with an initial orientation of the geometric axis of the eye 2810. Additional adjustments can be provided to adjust the patient's head to rotational degrees of freedom, such as rotation in the XY plane. . However, it has been shown that providing a comfortable but firm chin head and chin restriction assembly 160 is typically effective in stabilizing the patient's head in a generally level and horizontal orientation. See the examples shown in FIGS. 1-2 including chin rest 172, front support 171 and head fixator 173, preferably used in conjunction with an adjustable patient seat height.

FIG. 21C (2), represents an example of a view as captured using a Z-axis camera (for example, camera 401 in FIGS. 1A and 3A) showing an example of a contact device or eyepiece 110 positioned in the eye of patient 30 (see FIGS. 23-25). The fiduciary marker 1 post of the eyepiece is shown centered on the Z axis and the fiduciary markers 2 and 3 of the left and right support bar are shown horizontally aligned and at the same distance from the fiduciary marker post 1, indicating that the eyepiece is aligned in a parallel and coaxial manner with the axis of the camera. This alignment is automatically confirmed and calculated by the image recognition software of the images captured by the camera by the system processor 501, and said data can be presented as an image superimposed on an image of the camera to the operator (monitor 502). Note that in alternative embodiments employing a Z-axis laser beacon or pointer (403 in FIG. 3A, see also FIGS. 30A-B), the eyepiece 110 may be positioned by coaxial alignment of the reflected laser point.

Observe in FIG. 21C (2) that the contact lens member of the eyepiece 120 is positioned slightly outside the center with respect to the limbus 26 (limit of iris 24 and sclera 17 in the eye of the patient 30). Image processor 501 can also follow the position of the limbus as described herein, and compute a divergence from the center of the limb of the alignment axis Z (indicated as 5x and 5y). This divergence can be automatically compared with a preselected tolerance threshold, and can also be presented to the operator in the camera's image frame.

Stage 2542

In the case where the divergence of the limbus is determined to be unacceptable (either in Step 2540 or at any other stage), Stages 2530 to 2540 may be repeated as shown by the return arrows in the flow chart of the FIG. 21A.

Note that the 501 processor can be programmed to monitor the image data of the eye camera (for example, cameras 401,402) to re-determine the limbo-to-lens alignment on a continuous basis during the treatment, and to determine a condition error (an example of patient interlock diagnosis at step 2565) attached to radiation or X-ray source 420 so that the inactivation control is triggered when a selected alignment threshold is exceeded.

Note that in certain embodiments that have aspects of the invention, a reference coordinate system of a treatment system may have an arbitrary, but known, orientation / position, relative to an anatomical reference of the eye, as shown in FIG. 21B. From this orientation / reference position of the known eye, suitable mathematical transformations can be performed, for example, by a control processor of a robotic positioner, to move an X-ray source to a selected treatment orientation with respect to a target of treatment. However, it is advantageous in ocular radiotherapy devices that have aspects of the invention, to have a major mechanical movement axis of the X-ray source positioning system aligned in parallel with, and preferably collineally with, the geometric axis of the eye . For example, the geometric axis of the eye 2810 may be aligned, as shown by the Z axis of the positioning system 115, which may also be the rotational axis 0. In embodiments described in detail herein and illustrated in FIGS. 21C-E, said alignment method leads to the calibration and precision control of the movement of the X-ray source. With this initial system alignment with respect to the achieved eye anatoirna (FIG. 21C), only a limited set of ranges and subsequent directions of movement are required to carry out a stereotactic treatment plan. For example, these may include a small displacement X / Y to the treatment axis 2820 (step 2550, FIG. 21D), small adjustment O and / or Z to the angle of convergence of the target and limb clearance, and a modest adjustment 0 for each rear beam path (step 2555, FIG. 21E). Said limited and restricted movement serves to minimize the negative mechanical response, uncertainties and vibration, and to maximize accuracy, repeatability, patient confidence and intuitive operation.

Stage 2550

Position of the treatment axis - A radiation therapy treatment plan for an eye condition can be developed by specifying the location of a target with respect to an anatomical reference point such as the macula or fovea as described herein (see also the examples and Description in US No. 12 / 100,398 filed on April 9, 2008.

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In certain embodiments, the X-ray source may be positioned for treatment while maintaining the Z axis of the coordinate system aligned with the geometric axis of the eye 2810, either for central axis targets, or for transformations of robot controls suitable for targets outside. From the axis.

However, in the embodiments described in detail herein, and as shown in FIG. 21D, the Z axis of the system (for example, the Z axis of the X-ray source positioning system 115) can be shifted to realign with the treatment axis 2820 that intersects the center of the treatment target 318. The axis of the Asf realigned system is indicated as P3 in the figure. In this example, a macula lesion is treated by radiation to a target 318 approximately centered on the fovea. An exemplary treatment plan can define deviations from the pole of the retina (intersection of the geometric axis 2810 with the anterior retinal surface), the deviations being defined as X and Y movements in the plane tangent to the retinal pole (dx, dy). The detailed diagram indicates dimensions of deviations taken from fundus images of a representative sample of people, which define mean values of deviations of the fovea of the retinal pole of approximately 1.16 mm and -0.47 mm respectively, although these values are purely exemplary In this example, the X-ray source positioning system 115 moves the specified deviations dx and dy by actuation of the X and Y axis actuators (see FIG. 5), so that the Z axis of the system (transaction without rotation) to intersect the defined target 318.

Stage 2555

Position the beam and verify the clearance of the limbus - FIG. 21E illustrates the movement of the X-ray source to perform an exemplary stereotactic treatment after a displacement of the Z axis of the system to intersect target 318, as depicted in FIG. 21D.

The Z and O axis actuators can be moved to orient the collimator assembly 118 so that the beam axis 1400 intersects the Z axis on the target 318, forming a triangular arrangement (see FIGS. 3A-6). With the Z axis and 0 asf positions set (Z0 and O0 values), the collimator assembly 118 can subsequently be reoriented only using the actuator 0 for selected treatment beam positions (for example, beams 1, 2 and 3 to the values 0i, 02 and 03 respectively) to align the beam axis 1400 to propagate to target 318 and intersect the body surface to respective selected beam entry points (eg, sclera beam points 311). Note that while it is advantageous to re-orient the collimator assembly 118 for multiple beam paths by a single degree of freedom movement, it does not need to be so, and alternative embodiments can be provided for a more complex movement.

The clearance c (of each) X-ray beam 1400 at the scleral entry point 311 can be confirmed both visually by the operator and / or by image recognition by the processor 501. As shown in more detail in the frame image of camera of FIG. 21C (2), a laser beacon 1410 (see FIG. 4) can be aligned along the beam axis 1400 (the intended beam path as set before the X-ray emission) to create a small visible point in the known position sclera with respect to beam 1400 (for example, concentric), the point being found in the frame of the camera. The laser point can be recognized by the processor 501, its calculated position, and compared with the position followed by the limbus 26, to calculate the clearance of the center of the beam at the edge of limbus c. The clearance c can then be compared with a minimum tolerance (optionally also a maximum tolerance). For example, based on a predicted collimated beam radius of approximately 1.5 mm in the sclera, a minimum margin in the selected limbus of 2.0 mm can be determined by a value of c “1.5 + 2.0 = 3.5 mm The beam margin from the limbus can be specified in a treatment plan, for example, from about 1 to about 5 mm. The radius of the X-ray beam in the sclera (for example, from about 0.5 to about 5 mm) can also be predicted, such as by calculating the collimator geometry and / or radiographic measurement as described in detail herein. memory. The clearance c can be adjusted if necessary, for example, by small movements of the X-ray source 420 in the Z and / or O directions.

Stage 2560

Perform the treatment with eye tracking - X-ray treatment can be administered according to the treatment plan, such as a pre-selected configuration, intensity and spectrum of the beam, emitting the beam for a selected time interval to deposit an absorbed dosage desired on the target. Multiple beams can be emitted stereotactically to administer a desired total target dosage, while non-target regions (such as beam entry points in the sclera 311) are exposed to less dosage than that of an equivalent treatment of a single beam.

During the treatment, the position of the eye with respect to the system 10 can be continuously monitored as described in detail herein and the data of the position of the eye thus obtained can be automatically monitored by the processor 501 on a real time basis as the treatment, including the calculation of the movement of the target and other anatoirna of the eye (a variation of resulting dose) based on the data of the monitoring of the movement of the eye. See the description regarding FIGS. 26-36, and detailed description in Co-invented Application No. 61 / 093,092 filed on August 29, 2008 as well as other requests that are

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incorporate by reference. As described below with respect to Step 2565, said eye tracking data and calculations can serve as a basis for the interruption or control of radiation inactivation.

In the embodiments described in detail herein, the X-ray collimator assembly 118 may remain fixed during the X-ray beam emission. However, in alternative embodiments, the positioning system 115 may be configured to provide repositioning. in real time of the X-ray source during the X-ray emission, for example, to compensate for the residual movement of the retinal target during treatment. Alternatively, in certain embodiments, all or some of the actuators described with respect to FIG. 5 for positioning the X-ray source (X, Y, Z, O and 0 of positioner 115) can be used to re-position the X-ray source to compensate for the movement of the retina. Alternatively, additional actuators and / or degrees of freedom may be provided to provide a rapid response, a small range (Vernier) adjustment of the orientation of the X-ray beam (for example, by re-directing the retinal beam point) and / or shaping (for example, responsibly blocking a part of the beam point, such as proximal to the optical disk), to allow rapid adaptation of the beam to compensate for a moving retinal target. Such embodiments are further described in co-invented Application No. 61 / 093,092 filed on August 29, 2008, which is incorporated by reference.

Stage 2562

For a multi-beam path or stereotactic treatment, the method of Steps 2555-2560 may be repeated as indicated by Step 2562 until a desired treatment is completed, for example, for a pattern of three stereotactic beams as described in detail. In the present memory.

Stage 2565

Stop radiation (trigger inactivation control) - During the course of Step 2560 when radiation is emitted along beam path 1400, radiation may be interrupted (control of inactivation of the X-ray source 420) in response to selected criteria, such as threshold values of measured criteria, diagnostic error of discrete system level or failure states, or interlocking of patient level or diagnostic triggers. After triggering the inactivation control, several devices can be used to interrupt the emission of X-rays or the emission of another radiation, as described herein.

Stage 2567

After the inactivation control, a corrective action can be taken as indicated depending on the particular cause of triggering (it may require repeating one or more preceding steps), and the treatment irradiation then restarted until a fraction of the desired beam is administered.

(i) In the motion threshold inactivation control, such as Subsection 1 below, all or parts of the alignment and positioning steps 2540-2455 are generally repeated to bring the center of the beam into alignment with the center of the target, before completing the treatment fraction.

(ii) In some cases, such as the transitory system conditions in Subsection 2 below, the corrective action may involve brief system corrections that do not require repetition of pre-radiation stages 2555 or earlier, and the treatment may be restarted. in step 2560. In other cases, it may not be necessary to completely repeat the positioning actions included in steps 2450-2550, but verification of alignment and position (visually or by image processor) may be desirable before restarting the treatment. .

(iii) if the inactivation control is triggered by decoupling of the blade 26 and eyepiece lens 120, as in the example of Subsection 3 below, the corrective action may include repeating the positioning stages of the eyepiece 2530 and 2354 as well as steps 2450-2550.

Examples of inactivation control criteria may include one or more of:

1. Exceed the threshold of retinal movement. As described herein and in the incorporated applications, eye tracking data can be used to determine one or more discrepancy or error values based on a movement of the target or dose distribution related to movement, such as a maximum displacement of the target, a cumulative displacement vector of the retina, an indicator of the dose distribution, or the like. The error value can in turn be compared on a real-time basis with an inactivation control threshold value to trigger an inactivation control event. Optionally, eye tracking algorithms can be used to track movement or dose with respect to non-target structures, such as the limbus, eye lens, optic nerve and the like, with respective inactivation control thresholds.

(a) In an example embodiment of a movement threshold for a retinal target region, the error value may be the actual scalar magnitude of a sum vector representing cumulative retinal target movement derived from a time-increasing base. (for example, frame rate per frame of the camera or speed of a selected subsample) of the eye tracking data. For example, vector entries may include

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components in the X and Y directions of the plane of the retinal target, indicating the X and Y deviations at each time measured from the center of the beam from the center of the target. The sum vector accumulates these components as directional vector quantities, representing the magnitude scaling the radial distance from the center of the target of the sum vector (square root of the sum of the squares of the components). This magnitude of the sum vector represents the time-weighted cumulative displacement error at the center position of the beam point from the central point of the planned retinal target. The vector can be linear, or alternatively have a quadratic or non-linear distance weighting to emphasize small fluctuations in position (eg, fluctuation or vibration) with respect to greater, continuous displacements. After reaching a pre-selected scalar magnitude threshold, the inactivation (interruption) control of the X-ray source can be triggered.

(b) A "no movement" dose distribution can be determined experimentally and / or informatically calibrated (for example, Monte Carlo simulation and / or radiographic beam spot measurements) representing the dose distribution well in the target region ( for example, surface of the macula) or in any other location of the tissue in or adjacent to the path of the radiation beam. From the distribution of the calibrated dose, a dose distribution with equivalent time increment can be determined for a desired time increase (eg, video frame rate). The movement of the retina or other tissue can then be derived from the eye tracking data as described herein, and said movement data can be used to be modulated with the dose distribution with increased time to make a contribution to increase the time to a cumulative dose distribution that takes into account the movement of the measured eye. Said distribution of the motion-modulated dose can be used to validate or determine a movement threshold value as in 1 (a) above by determining the distribution of the dose at the trigger point of the inactivation control. Alternatively, the distribution of the motion-modulated dose can be used to assess the adequacy of the dose level of the treatment in the planned target region 318.

(c) Alternatively, the distribution of the motion-modulated dose of 1 (b) can be determined on a real-time basis at any desired anatomical location in the distribution, and said dose can be compared with a dose threshold that can be used to trigger Inactivation control. For example, a maximum cumulative dose at the edge of the optical disc can be used to trigger the inactivation control.

(d) Alternatively or additionally, the cumulative dose distribution determined in real time of 1 (c) can be evaluated in the planned target region, and can be used to trigger the termination of treatment to a desired target treatment profile, including effects of the distribution of the dose of the eye related to movement. Examples include triggering inactivation-termination control after (i) reaching a maximum treatment dose level selected at the point of highest dose in a defined target region; (ii) reach a minimum treatment dose level selected at the point of lowest dose in a defined target region; (iii) reach a selected average dose in a defined target region; (iv) a combination of these (for example, reaching at least one selected average dose after achieving a minimum selected low); or similar.

2. Functional diagnostics at the system level. The inactivation control can be triggered by error or failure conditions, such as loss of eye tracking by the system, loss of limbo tracking, or other system-based failure that is considered a justification for interruption of radiation treatment. , for example, due to electronic conditions, camera conditions, lighting conditions, inadvertent blocking or interference with the formation of images, and the like. Alternatively or additionally, processor 501 can determine and monitor a selected number of different diagnostic conditions that can be used to trigger inactivation control, such as X-ray tube parameters, illumination parameters, laser pointer position 1410 followed with respect to limbo (limbo clearance), and the like.

3. Patient level interlocks. Alternatively or additionally, the processor 501 can determine and monitor a selected number of patient-based interlock or diagnostic conditions that can be used to trigger the inactivation control.

(a) These may include specific patient interlock sensor signals, such as indicating disconnection of head restraint fasteners, disconnection of the eyeglass lens assembly (see step 2534); contact sensors of the patient's grip 163 (See FIG. 1A), and the like.

(b) The patient-based condition can also be determined by image processing / recognition of one or more cameras or other remote sensors. For example, the relative positions of the eyepiece 110 and limbus 26 can be continuously monitored during treatment by tracking the camera-based eye and compared against a selected threshold indicating disconnection or decoupling of the eyepiece lens 120 from the eye of the eye. patient (such as sliding the lens over the cornea). An error condition can be determined to trigger the radiation inactivation control. (c) In a further example, the transient "flicker" compensation inactivation control embodiments are described in Co-invented Application No. 61 / 093,092 filed on August 29, 2008. The transient inactivation control embodiments

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they compensate for sudden, brief, large displacements, usually vertical that result from involuntary blinking or jerky eye movements, typically followed by a rapid return to a generally well aligned position of the eye. These eye movements can be detected quickly by image-based eye tracking to trigger a rapid response of radiation inactivation control. The radiation of the treatment can be automatically restarted, either after a set time delay or an automatic realignment confirmation. This "flicker" inactivation control can be used independently or in combination with the retinal threshold threshold inactivation control described in Subsection 1 above.

Stage 2540

Release the eye support - After treatment, the patient can be released from the eyepiece 110 (for example, release of suction by vacuum) and head support 160.

VB Pixel level image alignment methods

In certain embodiments that have aspects of the invention, image recognition and processing can be conveniently and advantageously performed at a digital pixel level of camera resolution based on camera image signals (for example, cameras 401, 402 ), such as a selected video frame that represents an image at a defined image capture time. The method of alignment of the eye of Step 2540 can be applied similarly to the alignment of other anatomical features as a stage that carries out the treatment with a radiation device.

Conventional video frame image data can be stored for processing in a manner known in electronic techniques, such as defining a two-dimensional array of pixel data in a computer memory, in which each element of the matrix is mapped into a particular pixel position of the camera image and in which each element of the matrix is associated with one or a plurality of values that indicate the color and / or intensity of the pixels. For example, 24-bit RBG color-coded pixel values of an array for image dimensions of 1,000x1,000 pixels can be stored. When the image capture is focused and delimited by a specific area of interest, (for example, a part of the patient's face including an eye, eyelids and adjacent skin surface), the pixel position can be mapped to a particular point in the area of interest. For example, when the area of interest is an area of approximately 10 cm x 10 cm of the patient's face, each pixel of a 1 Megapixel image represents approximately a region of approximately 0.1 mm x 0.1 mm, or approximately a resolution of 100 micrometers. A 4 Megapixel image represents approximately a region of approximately 0.05 mm x 0.05 mm, or approximately a resolution of 50 micrometers.

The imaging camera may conveniently align with the axes of the radiotherapy coordinate system (or alternatively, in a known orientation and position with respect to the coordinate system). For example, an axial camera can be aligned so that the optical axis of the camera is parallel to the Z axis of the system, and so that the central pixel of the camera's sensor chip corresponds exactly to the Z axis of the system. For this orientation, the camera "sees" its field of vision in direct relation to the origin of the X-Y plane of the system, as shown in FIG. 21C (2). The deviations and directions of the features with formed images can then be measured in pixel scale in this frame of reference.

Image data storage can continue for subsequent video frames. If desired, image processing and feature recognition can be carried out on a real-time basis in all, or a selected sub-sample, of the captured video frames. The resolution of the camera sensor and image size (for example, conventional CCD image sensor chip), frame capture speed, and other image formation parameters can be selected in consideration of associated optical and mechanical components, to optimize system performance, cost, speed and the like, as is known in electronic techniques.

Referring to the view of the axial chamber shown in FIG. 21C (2), in an example of realization of the sub-method, the processor 501 can be programmed with a suitable software code, acting on the image data in the computer memory, to carry out all or a part of the sub -Stages of an image alignment algorithm, including:

(a) Identify a pixel of the image that represents the central axis of the eyepiece. For example, the processor can:

(i) determine the part of the image including the fiduciary marker center post 1 (for example, contrasting the edge detection);

(ii) determine the geometric center of the area of the fiduciary marker image; Y

(iii) select the pixel that is closest to the center of the fiduciary marker.

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(b) Determine that the eyepiece 110 is aligned with the camera (system Z axis). For example, the processor can:

(i) repeat step (a) with respect to each of the fiduciary markers 2 and 3 to select a pixel that represents the center of each fiduciary marker;

(ii) calculate the center-to-center horizontal distance (X) between each of the fiduciary markers 2 and 3 and the fiduciary marker 1 (for example, number of accounts of the pixels involved);

(iii) determine whether fiduciary markers 2 and 3 are equidistant from fiduciary marker 1 (without horizontal inclination) [* optionally present any magnitude of error to the operator];

(iv) calculate the vertical displacement (Y) of fiduciary markers 2 and 3 of fiduciary marker 1;

(v) determine whether fiduciary markers 2 and 3 are in a horizontal line that includes fiduciary marker 1 (without vertical inclination) [* optionally present any magnitude of error Y and 0 to the operator];

(vi) determine if the pixel representing the center of the eyeglass is located at (0,0) of the Z axis of the image system (central pixel of the camera image) [optionally present any magnitude of error X e And to the operator];

(vii) determine, if (iii), (v) and (vi) are true, that the eyepiece 110 is aligned with the Z axis of the system [* optionally compare with selected tolerance thresholds and present conformity or nonconformity to the operator ];

(c) Determine the location of the center of limbo 26 in the coordinate system.

For example, the processor can:

(i) determine the part of the image including all or the exposed part of the limit of the limbus (for example, contrasting the edge detection) and identify the locations of the pixels corresponding to the image of the limit of the limbus;

(ii) mathematically determine a form with the "best fit" corresponding to the limit limit data, for example, using the limit pixel locations as inputs to determine an equation for a circle or ellipse with the least error function ;

(iii) calculate the center of the shape with "best fit", and identify the pixel of the image closest to the center.

(d) Determine any deviation from the location of the center of the limbus 26 of either or both of the Z axes of the system. For example, the processor can calculate the horizontal (X) and vertical (Y) displacement of the center of the limbus from the pixel representing the Z axis of the system (for example, by counting the vertical and horizontal pixels involved) [* optionally presenting the X and Y values to the operator].

(e) Record the positions and / or orientations determined in the stages (ad) of one or both of the eyepiece 110 and the blade 26 in a virtual eye model, for example, anatomical geometry of the eye stored in the computer memory . For example, the eye model may additionally include specific patient data measured and / or images such as the axial length of the eye, and an OCT or fundus scaled image.

(f) Calculate the position of the retina (or other structures) in the coordinate system based on the registered eye model.

As described above with respect to FIG. 21A, the positioning of the eyepiece 110 with respect to the limb 26 on the surface of the eye can be adjusted until the limbo-to-lens alignment (measured in step (d) above) is reduced to as close to zero as desired. Also, the alignment of the eyepiece 110 with respect to the Z axis of the system can be adjusted (for example, by the positioner 600 in FIG. 1A) until the alignment error of the eyepiece (measured in step (b) above) ) is reduced to as close to zero as desired.

A related method has aspects of the invention, including an algorithm for aligning a body part with a radiation device, can be summarized: (a) defining a normal axis for said body part; (b) aligning said normal axis with a pixel in an image of the camera that visualizes said part of the body; and (c) linking said pixel in said camera image with a coordinate frame of a robotic positioning system thereby linking said normal axis of the body part with an axis of the robotic positioning system.

The algorithm may further comprise determining the distance between said body part and said robotic positioning system in which said distance is measured along said normal axis. The algorithm may further comprise defining a normal stage that comprises locating fiduciary markers in said body part. The algorithm may include that the detection of said fiduciary markers directs said alignment of

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said normal axis, such as when the fiduciary markers are attached to a device that contacts the sclera of an eye, and which may have a contact member adjusted to the eye blade. The algorithm may include that an axial length of an eye be used to define a position in the retina of the eye and said position is used to define movement to a macula from said position.

V.C. Positioning of the eye guide and eyelid retraction

FIGS. 22 and 23 are drawings of a patient's eye showing two different embodiments of an eye gma 110 having aspects of the invention as connected to the eye in an operative position, in this case with the eye substantially as it appears when aligned with the axis of alignment of the eye 2810 of the radiotherapy system 10. The lens of the eye guide 120 is shown approximately centered on the limbus 26, the lens being supported by the arm 180.

In the example of FIG. 22, the eye guide 110 includes one or more reflective fiduciary markers (as further described herein), in this example having two or more fiduciary markers 240 positioned spaced apart between sf in lens 120, and one or more fiduciary markers 250 positioned in the center post crown 222. In this example, the center post can also include a mirror surface 230, which can be used to follow the alignment with a beacon pointer or axial laser beam, as described additionally herein (see also FIGS. 2AB and 29-31). The embodiment of the eye guide shown is of the type used during the acquisition of the eye tracking data of the example shown in FIG. 26A-E, using an eye alignment / tracking system that has a low energy laser pointer centered on the alignment axis 403 (see FIG. 4).

In this example, the lower eyelid is retracted downwards by a retractor or eyelid speculum 320a to expose an area of the sclera for the entry of the treatment beam (see FIG. 46A and related description). The upper eyelid can be mounted on top of the eye guide lens 120, but the cameras of the system can effectively follow both fiduciary marker lenses 240, and detect and compute the image of the limbus (as described further), allowing the positions of each one to be determined automatically (including extrapolations for covered parts shown as dashed lines). Retractor 320a includes a portion similar to a soft, non-abrasive hook 323 comprising a loop of yarn configured to overlap and connect the eyelid. The retractor hook 320a can be supported in several alternative ways (for example, held by hand, held with tape to a support, mounted on a base, an elastic lock, or the like).

FIG. 23 shows the alternative eye guide embodiment 110 as connected to the eye 30 in an operative position. The eye guide shown is of the type described in detail herein and shown in FIGS. 24A-D and 25A and 25B. The lower eyelid in this example is retracted downwards by the embodiment of retractor 320d (see FIGS. 47-48 and related description), which has a hook member similar to a gently curved or non-abrasive saddle-shaped spoon 320c, optionally composed of radiopaque material.

FIGS. 24A-24D illustrate an embodiment of eye guide device 110 having a pattern of fiduciary markers, the guide for use in an eye stabilizer system that has aspects of the invention, shown in contact with an eye and representing the method for determining alignment . In the example shown, the eye guide does not have a mirror surface, but includes 3 fiduciary markers that have a highly reflective material (for example, "Scotchbright"), one at the top of the center post 222 (fiduciary marker 1) , and two in the crossed arm 190 on each side of the center post pivot 220 (fiduciary markers 2, 3).

The arrangement of the fiduciary markers shown allows a transparent lens 120 to lack fiduciary markers, which promotes recognition of the digital image of the limbus. In addition, the eye guide can be followed by the camera's image processor without a collimated and aligned light source (for example, a laser), and can be followed under simple illumination, such as LEDs positioned adjacent to the eye.

FIGS. 24B-24D show a series of perspective views of an embodiment of the eye guide 110 from several different orientations to the point of view, which can be a camera. View B is substantially angular, so that fiduciary markers 1-3 form a triangular pattern 4, which can be measured by image recognition methods. View C is a less angular and has a correspondingly smaller triangular pattern. View D is aligned with the point of view, and shows a line layout, with the right (2-1) and left (3-1) legs between the fiduciary markers. Note that the aligned pattern of View D is very easy to recognize visually by the operator, either directly or as presented in a user interface.

FIGS. 25A-25B illustrate that the rotation of the center post 222 around the pivot 220 will result in a displacement of the fiduciary marker of the center 1 (in X or Y or both), even when the eye guide support arm 190 is perpendicular to the axis Of vision.

IV.D. Alignment Method Example

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As shown in FIGS. 3-5, the imaging system 410 has a known position and orientation with respect to the positioning system of the X-ray source 115 of the radiotherapy system 10 in a global coordinate system. In preferred embodiments, the imaging system is supported to be movable by positioner 115. For example, as shown in FIGS. 3B and 5, the image formation system 410 may be mounted on the image formation support 412, which in turn may be mounted to move in concert with the stage xYz 416 while remaining independent of the actuator O 413 and the actuator 0 414

In an example method using particular embodiments of device and sub-method described in detail herein (for example, as shown in FIGS. 1-2, and 23-25, using the methods shown in FIGS. 21A -21E), the method may include or some of the following:

(a) Initially, the patient is positioned in the head holder 160 of the system 10, with the eyepiece 110 connected and the lens 120 centered on the blade 26.

(b) The imaging system 410 is moved to a position (for example, by the positioner 115 movement X, Y and / or Z) where the retro-reflective fiduciary markers 1-3 of the Grna I 110 can be seen by the imaging system 410 (for example, by cameras 401-402 in FIGS. 3A-3B communicating with a system processor and an operator monitor).

(c) When processing the image data of fiduciary markers in spatial information (see the flow chart of FIGS. 27-28, positioner 115 can be configured to auto-align (or manually) to the center of the crown of the Grna I in X and Y (fiduciary marker 2 of the center in FIGS. 23-25).

(d) The operator then adjusts the angle of the Grna I until it is oriented along the axis of the system as shown in FIG. 21C, for example, by rotation around the pivot of the eyepiece 220 by adjustment of the positioner of the eyepiece 600 along the axes X ', Y' and / or Z '. An additional self-alignment of the X and Y axes of the positioner 115 puts the axis of the eyeglass in co-linearity with the Z axis of the system. In this configuration, the geometric axis of the eye 2810 is collinear with the Z axis of the positioner 115.

(e) The positioner 115 can then be deflected by X and Y to move the Z axis of the alignment system with the geometric axis 2810 to align with deviated treatment axis 2820 (X0, Y0 in FIG. 21E). In an example of a treatment plan, this is a shift of 1.16 mm temporarily (it may be ± X depending on whether the left or right eye is being treated) and -0.47 mm caudal (-Y), as shown in FIG. 21D. Note that this offset can be done alternately before or after the Z0 and O0 settings.

(f) With the eyepiece 110 and the positioner 115 aligned as described, the positioner 115 moves axially along the Z axis until it reaches the selected treatment position (Z0 in FIG. 21 E), and the X-ray source 112 is rotated around the O axis at the selected beam angle (O0 in FIG. 21 E). In this configuration, the laser beacon point 1410 is directed to appear at the entry point of the beam 311 (see FIGS. 3A and 4). The operator can confirm the position of the beam and the clearance of the beam from the limbus 26 by the visual presentation by means of cameras 401-402, and the system 10 can confirm the alignment by processing and image recognition of both the laser beacon and the limbus.

(g) (i) In a preferred treatment practice, the system is maintained in this configuration at four degrees of freedom (X0, Y0, Z0, O0), and additional stereotactic re-positioning of the X-ray source assembly Assembly 420 is confined to rotation around the axis positioner 0 115.

(ii) Note that when the treatment axis 2820 a (X0, Y0) intersects a center of the target of the surface of the retina 318 (for example, center of the macula) and the combination of (Z0, O0) is directed to the beam path 1400 to intersect the treatment axis 2820 in the center of the target, the subsequent rotation around the 0 axis causes the stereotactic beam paths to describe a cone with the apex at the center of the target 318. The combination of (Z0, O0) can also be selected to provide clearance of the blade 26 and lens of the eye 36, to have points of entry in the sclera 311i distributed spaced apart between one another in an approximately circular arc outside but adjacent to the blade 26 (see FIG. 9).

(iii) For example, the first treatment beam may be at an angle of 0 = 180 °. For convenience, an angle 0 of 180 degrees (referenced from 0 ° north) can be referred to as the 6 o'clock position (beam 1 in 01 in FIG. 21E). Other treatment positions can be selected by adjusting angle 0, for example, make 2 in 02 and make 3 in 03, at positions approximately "5 o'clock" and "6 o'clock" (0 "150 ° and 210 °, respectively).

(iv) Alternatively or in combination, the adjustment of other DOFs can be done by directing the beam 1400 to suit an alternative treatment plan.

GO. Example of eye measurements and eye chart based on images.

The exemplary embodiment of the imaging system 410 can be configured to acquire data at a selected rate for each camera, and typically the processor processes and calculates the data at a rate

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of selected update, for example, approximately 10-50 HZ. In one example, a set of direct measurements is made at an update rate of 30 Hz, and is used to calculate an additional set of inferred measurements when the data is updated.

As shown in the example of eye gland shown in FIGS. 23-25, direct measurements are performed automatically using an image processor and pattern recognition software on a frame by frame basis of the camera's video input signals, and includes:

1 X-Y position of the center of the eye blade.

Seen from the main system camera on axis 401.

Locate the anatomical transition between the darkness of the iris and the light of the sclera (margin of limbus 26 in FIG. 9). Defined by the center of mass of the circle with better fit using limbo detection software.

X-Y position of the eyepiece yoke 110 Y (yoke or tie bar in FIG. 23).

Seen from the main system camera 401.

Locate 2 fiduciary markers on coupling bar 190 (fiduciary markers 2 and 3 in FIG. 23). Defined by the center of mass between 2 fiduciary markers (Yoke).

Note that the relative positions of yoke 190 and crown.

X-Y position of the crown of the eyepiece 110.

View from the main system camera 401.

Use infrared light from the IR LED light bank 406, near the axis of camera 401.

Locate the fiduciary marker at the tip of the eyepiece 110 (fiduciary marker 1 in FIG. 23).

Defined by the center of mass of the fiduciary marker (crown).

Position Z of yoke 190 of eyepiece 110.

Seen from the Z-camera off-axis range 402.

Defined by the center of mass between the 2 fiduciary markers in fiduciaries 2 and 3 in FIG. 2. 3).

The calculated measurements are performed automatically using real-time processors as direct averages are updated, and include:

5 Position X-Y of the base lens 120.

(a) This is a projected estimate of the center of the base lens 120 approximately in the same plane as the measurement of the limbus. The inputs include measures 2 and 3 (yoke XY 190 and fiduciary crown marker 1, respectively), which define a longitudinal axis of the eyeglass, which can be extrapolated from the known structural geometry of the eyeglass 110 to determine XY of lens.

(b) Note that the relative XY positions detected of yoke 190 and fiduciary crown marker 1 also define an angle of the axis of the eye gland relative to the coordinates of the system 10 (analogous to "rolling and guiding" of the eye gland 110, designated here as O of the eyepiece).

(c) Note also that the relative vertical positions detected of fiduciary markers 2 and 3 in yoke 190 define an angle of the eyegrow in the XY plane of the system (analogous to the "turn" of the eyewire 110, described here as 0 of the eyepiece). In certain embodiments, this can be largely controlled by the support of the head and chin fasteners 160 and positioner of the eyecup 600, and the value 0 of the eyecup can be small or negligible.

6 Limbo coupling to lens.

■ This is a functional measure based on the relative amount of movement between the X-Y position of the base lens 120 and the X-Y position of the blade 26.

■ Relative movement that exceeds a threshold value (for example, 500 micrometers) can be interpreted as an indication that the base lens 120 has shifted from its original location in the eye alignment or has been decoupled.

the tie bar (computer system markers on a base in

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7 Position X-Y-Z of the retinal target 318.

■ This calculation involves all motion parameters detected to estimate the related movement in the back of the eye, inferred as retinal target movement 318 (See the embodiments of FIGS. 2936).

■ The inactivation control algorithms and criteria are based on these calculations (See the embodiments of FIGS. 39-42).

Observe the flow chart of the eye alignment method and the geometric diagrams of FIGS. 21A-21E with respect to examples of the use of the measurement as described above by computer processors 501 of system 10 (by suitable software) and monitors 503a, b: For example:

■ Measurements 1, 5 and 6 (relative position of the eyeglass lens 120 and limbus 26) can be presented to assist a physician in positioning the eyepiece gma 110 as shown in FIG. 21B as centered on the limbus, and used to automatically confirm the accuracy of the positioning of the eye gma.

■ Measurements 2, 3 and 5a, b (angle of the eye gma and X-Y of the eye gma) can be used to automatically guide and / or direct the movement M (x, y, O, 0) of FIG. 21C to align the geometric axis of the eye 2810 coaxially with the Z axis of the system (the relative values X, Y, O, 0 of the eye gma versus the coordinates and Z axis of the system 10 become closed).

■ Measures 2, 3 and 5 can be used to confirm the accuracy of the X-Y offset of the positioning system 115 from the geometric axis 2810 to the treatment axis 2820, as shown in FIG. 21 D.

■ Measure 4 can be used to confirm the accuracy of the movement of the positioning system 115 to the treatment Z position (Z0) as shown in FIG. 21 E.

All of the above measures can be used to track eye position and retinal position on a real time basis during treatment.

V.F. Example of data extraction from the eye guide and eye movement

FIGS. 26 to 41 refer to measures of eye movement of patients who are connected by an alignment, stabilization and eye tracking system that has aspects of the invention, as depicted in FIGS. 1,2 and 16-26. These aspects also include mechanisms and methods to ensure that any residual movement of the stabilized eye does not prevent radiotherapy from being performed with a dosage distribution adjacent to a target region that remains at the planned parameters.

FIGS. 26 A-E are graphs that show the eye movements measured experimentally with an embodiment of a system to control and / or stabilize the eye of a subject in a controllable manner. In this particular embodiment, the data was acquired using three video cameras mounted in an embodiment of the eye stabilization and tracking system that has aspects of the invention, and using a coaxial 810 laser beacon with a system axis (see FIGS. 2A and 2B) and which is reflected from a fiduciary marker of the ocular gma of the mirror surface 230. Note that the particular camera / image formation configuration used in the example illustrates only one of a range of alternative embodiments comprising cameras and / or other sensor configured to acquire movement data of the nature shown. For example, FIGS. 3A and 3B illustrate an image formation system that employs two cameras, capable of acquiring comparable eye movement data. In the example of FIGs. 26A-26E, for each patient, the video of each camera was processed, frame by frame, in order to extract the desired data. The cameras were configured as follows:

"PSD camera", also referred to as "fine angle data". The coaxial laser beam is reflected from the mirror of the eye gma and is detected by the camera. Although it allows the extraction of high resolution data, this setting can only collect data in a very limited range of +/- 1.25 grad.

"Central chamber" - the data of fiduciary markers of the eye gma; The camera is mounted perpendicular to the patient's eye and can see the lens and mirror of the eye gma, as well as anatomical data such as the position of the limbus.

"Z range" camera - distance data; The camera is able to see the mirror of the eye gma but is mounted on the side of the central axis. The anterior and posterior movement of the eye gma, and therefore of the patient (Z axis) is easily detected exactly.

Fine angle data

The PSD camera is adjusted so that the reflected laser beam is visible as a white (bright) area contrasted on the dark background in the camera view. Each frame of the video is extracted individually, and using a custom algorithm and software, the location and centroid of the laser area is determined. The centroid data is expressed in pixel coordinates (x, y) and using a translated default conversion factor

to the angle in the X direction and angle in the Y direction. The conversion factor is (pre) determined on the basis of the adjustment and calibration data. As a head movement of the known patient was desired during the treatment (i.e., relative movement) each angle in the X and Y direction was subtracted from the data point that was recorded first.

5 Fiduciary marker data

Using custom algorithm and software, each frame of the video of the central chamber was removed, and fiduciary markers were detected on the lens (2) and mirror (1) of the eyepiece. The center of each fiduciary marker is expressed in pixel coordinates (x, y). By design the fiduciary markers form a triangle, therefore, it is possible to calculate angles in a 'fiduciary marker' triangle. The angle formed in the center of the eyepiece 10 mirror is used for vertical determination (angle Y), and the ratio of angles formed by fiduciary markers on the lens is used for horizontal determination (angle X). Relative motion data was desired so that each set of acquired data was subtracted from the first data point. During the study, the location of fiduciary markers was slightly different in each lens, without affecting the method. The fine X and Y angles were matched with the fiduciary markers X and Y and a correlation factor 15 was determined for each patient data set. The correlation factor was determined using the linear equation y = ax + b, in which y is fiduciary marker data, a is pending, x is fine angle data, and b is deviation. The variables a and b were determined using few points from the data set (in the future the whole set will be interrogated).

Distance data

20 The reflection of the laser spot in the eyepiece mirror, as observed by the "Z-range" camera was used to determine distance data. For each frame of the video, the center of the laser spot was detected using custom algorithm and software (see an additional description of the measurements under the caption "Example of eye measurements and eye-based image guidance". Note that in addition to the image-based methods described, the range data can be obtained by ultrasound techniques or other reflected signal techniques.Using 25 predetermined calibration and correlation factors, each detected location was converted from pixels to millimeters.Other image data can be used in instead of the laser point, such as light that hits the eyepiece 110 from a source of LED lights (eg, visible or IR)

The measurements shown in FIGS. 26A-26E are from a typical patient who tolerated the procedure well during the administered period of approximately 300 seconds (5 min.), And are as follows:

30 A. Horizontal X movement of the eye gland and limbus represented together to show their relative movement.

B. Vertical Y movement of the eye gland and limbus represented together to show their relative movement.

C. Horizontal X movement of the eyepiece mirror due to angular deflection around the pivot.

35 D. Vertical Y movement of the eyepiece mirror due to angular deflection around the pivot.

E. Z movement of the eye gland due to eye movement later.

It can be seen that each parameter includes movements in the order of 1 mm or less, and most of less than 0.5 mm, for a substantial period of 5 minutes without any re-alignment procedure.

FIGS. 27, 28A and 28B are flow charts that illustrate the acquisition and processing of data used in this example, and are self-explanatory to one skilled in the art. It should be understood that the algorithms and methods represented are merely an example to demonstrate the functionality of an embodiment of the system, and alternative or additional particular and sub-methods may be included.

The flow chart of FIG. 27 (on two sheets) is a summary of the fiduciary marker detection algorithm used to obtain the data in FIG. 26. The input to the method is a video signal captured by the 45 cameras of the system. The data flow is a loop that processes each frame of the video data, preferably on a real-time basis when each frame is captured. Alternative methods can select particular frames for data calculation (for example, in a timed sequence to support a desired data update rate), for example, in which a higher frame rate is desired for a visual presentation to the user. that is desired for the calculation of data. As can be seen, the output of method 50 is particular calculated values, which in this example are represented as being written as correlated with the particular video frame with the memory media, indicated as "saved file". It should be understood that these output values can be accessed additionally or alternatively directly by electronic processors of the system for additional presentation, calculation or control functions.

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The flowcharts of FIG. 28A and 28B represent additional processing and conversion steps based on the raw data obtained from the video frames, as in the process of FIG. 27.

FIGS. 26A-26E are graphs that show the eye movements measured experimentally with an embodiment of a system to position and / or stabilize in a controllable way the eye of a subject. The measurements can be used as inputs for methods herein to determine the movement of retinal structures of interest during radiotherapy.

V.G. Extrapolation of eye movement to retinal movement, and dosage mapping

The tracking of eye movement as described above can be correlated with a virtual eye model that has aspects of the invention, as described herein to evaluate the movement of a particular eye anatoirna during radiotherapy treatment, for example, the movement of a target retinal region with respect to the path of an x-ray beam during treatment. Said anatomical movement can in turn be used to evaluate the actual absorbed radiation dosage and its distribution in relation to a planned radiotherapy treatment.

It has been shown that low suction levels (for example, 25-50 mm Hg) are sufficient to provide reliable coupling of the eyecup 110 in the eye, to keep the eyecup in a selected position (for example, with the lens 120 centered on the blade 26 in contact with the cornea 12 and the sclera 17).

However, eye movement can still occur on the scale of a fraction of a millimeter to a few millimeters even when the eyepiece 110 and the eyepiece support assembly are substantially nigged and coupled to the eye, and when the Chin and head support assembly 160 provides a firm head support (for example, generally firm chin and forehead members 171, 172 and an adjusted head fixation 161). Sources of residual voluntary or involuntary eye movement include: (a) the eye is movably mounted in the skull, and can move in the orbit and adjacent soft tissue, such as by the eye muscles or head movement; and (b) the skin and soft tissue that covers the skull, face and chin is generally loose and free to move in limits on the underlying bone support, and such movement may allow a small movement of the head, which then applies rotational forces and / or translational to the eye, as the eye tends to follow the movement of the head.

It should be understood that certain methods and stabilization devices of the eye that have aspects of the invention can omit the aggressive measures sometimes used in ophthalmologic and cranial surgery, such as temporary paralysis of the eye, contact eye supports with high suction, grips of the eye. orbital basin, and / or mechanical pinching of the skull. Less aggressive stabilization measures can reduce treatment costs, improve patient acceptance, and reduce treatment time. Average terms can be made in patient comfort, convenience, and cost that favor tolerating a modestly selected level of change in the position / orientation of the eye during treatment versus the absolute prevention of eye movement. Alternative embodiments of methods and devices for monitoring the retinal target, dosage mapping and compensation that have aspects of the invention provide a safe dosage control in which a residual level of eye movement is present during the treatment. In addition, embodiments of methods and devices provide "fault protected" functionality for treatment procedures that have low levels of eye movement.

FIGS. 29-31 graphically illustrate the effect of particular movements of the eye of an eye connected by an eye stabilization system that has aspects of the invention in the movement of the retinal target, including a treatment target (for example, the macula) and a sensitive structure (for example, the optical disk). In each case, a beam of radiotherapy is directed to a region that encompasses at least a part of the macula, and the views show the beam initially aligned on the target, and show the effect of a particular movement out of alignment. The structure of assembly 117 is essentially similar to that shown in FIGS. 17-18.

These figures demonstrate the effects on the retinal dosimetna of the movement of the eye of a real patient during radiotherapy. Data from the anterior eye movement of several patients were collected with an embodiment of an eye stabilization and monitoring system as described herein (but an X-ray source was not present in this test system). These data were analyzed to obtain retinal movement during the 5-minute study period. Using a measured dose map from a stationary model study, the dose in the retina was modulated by the calculated movement to determine the effects on the dosimetna of the macular target and optical disc. The following entries and assumptions were used in this example analysis:

(a) 3-beam superimposed dose map of a simulated radiometric dose study of real model.

(b) Retinal movement calculated on the basis of the measured eye movement.

(c) It is assumed that the eye is solid, without changing shape during the study, and it is assumed that retinal curvature has a negligible effect on dosimetna.

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(d) It is assumed that the eye and head move together to accommodate rotation around the pivot point (220 in FIG. 17), it is assumed that the pivot point (220 in FIG. 17) does not move, and it is assumed that the relative movement of the eyebrow to limbus (decoupling) is around a curvature of the fixed cornea (observe the alternative models described herein).

(e) Geometna and "typical" retinal positions of the macula and optical disc.

(f) It is assumed that the initial tracking alignment is perfect; you make them focused exactly on the fovea.

FIGS. 29A and 29B are two plan views of an eye gland included in an eye stabilizer system that has aspects of the invention, shown in contact with an eye during X-ray treatment, illustrating the effect on the retinal position of the movement of the eye. eye in the Z direction of the system. In this case, a subsequent Z movement (see FIG. 26E) can be seen that the movement of the eye moves to the retina along the Z axis without components of the movement of the retina on the X or Y axis. However, the Eye movement does not result in a relative movement of the beam point on the retina due to the angular alignment of the beam with the retina. In this illustration, the beam point moves relatively in the X direction as shown, for an angular beam from the opposite direction.

It will be clear that the direction of relative motion of the beam point depends on the orientation of the X-ray beam with respect to the Z axis (see angles O and 0 in FIGS. 5-9), and in the general case of an arbitrary angle 0, an eye movement in the Z direction will result in both X and Y components of the relative movement of the beam point in relation to the planned target. It will also be evident that the scale of said relative movement depends on the angle O of the beam with the treatment axis, a small angle O resulting in a relatively small movement of the point of the beam in relation to the movement of the eye on the Z axis. preferred embodiment, the angle O remains constant during stereotactic repositioning, with angle 0 changed for each beam application.

FIGS. 30A and 30B are two plan views of an eye gland in contact with an eye during X-ray treatment, illustrating the effect on the retinal position of eye movement angularly around the eyepiece pivot. In this case, the eye and the lens pivot through a small angular change (see FIGS. 26C and 26D). Note that, although it is assumed that the pivot is still fixed, the eye movement is both in translation and angular orientation. This can be seen to result in a movement of both the fiduciary markers of the eyepiece lens (shown in the X direction, but generally both in X and Y), and in a greater movement of the retinal target in the same direction , due to the longer lever arm pivot to retina relative to the shorter lever arm pivot to lens.

FIGS. 31A and 31B are a comparison between the side illustration of FIG. 29B (reproduced as FIG. 31A) and two front schematic views of a simulated eye, in which FIG. 31Bl shows the frontal projection of the lens movement, and FIG. 31Br shows the frontal projection of the corresponding retinal movement. Note that FIG. 31Bl shows a relatively small movement of the fiduciary lens markers with respect to the movement of the eye body.

FIG. 31Br has a projection of the target retinal geometry, as shown more clearly in the attached detailed view, and shows a retinal beam point b. Note that the movement of the retina in this example moves the optical disk (od) in the path of beam point b, and moves the macula out of the treatment beam point, both unwanted effects with respect to the exemplary treatment plan.

FIGS. 32-36 are diagrams that represent an example of a transformation procedure having aspects of the invention for converting detected input signals related to eye movements (see FIGS. 29-31) into corresponding movements of a beam point with respect to to the retina These figures refer to the example data shown in FIGS. 26A-26E.

Note that the set of input signals is only exemplary, and that alternative modes and measurement detectors can be used without departing from the spirit of the invention. Likewise, the alignment and monitoring system and the set of input signals shown in this example are presented as demonstration of certain inventive principles and aspects, and that alternative modalities and detectors of measurement can be employed without departing from the spirit of the invention. For example, it is not necessary that the alignment of an eyepiece (for example, 110 in FIGS. 17A and 17B) be determined by a beacon that is reflected from a mirror, as shown in FIGS. 2 and 30, but can be determined by a variety of other monitoring methods. In certain embodiments, one or more cameras linked to a paton recognition and processing software can be used to track the movement of fiduciary markers (for example, located on the eyepiece lens, brackets, pivot post or in the eye of the patient), to determine the geometric alignment of the eye and the position of the eye gland in relation to the anatoirna of the eye.

Likewise, particular features of the eye can be followed by said imaging methods regardless of the structure of the eyecup (or without the use of an eye contact member), such as limbo image formation, a Purkinje reflection, a retinal image, and the like. See the examples and description herein with respect to FIGS. 54-56. The position and orientation data of the eye of

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said tracking systems without contact with the eye (for example, values sequenced in time of angles of the geometric axis of the eye and positions X, Y and Z of the eye in a radiotherapy device coordinate system) can then be used to calculate the position and movement of the target in the posterior or middle eye, such as the position of a fovea or macula target, for example, by the methods illustrated and described with respect to FIGS. 2936. For additional examples and description, see co-invented priority requests, such as No. 12 / 103,534 filed on April 15, 2008 and No. 12 / 027,083 filed on February 1, 2008.

FIG. 32 is a diagram of a physical model of a transformation procedure. The figure shows on the left side the eyepiece mounted on one eye with respect to a radiation beam, with indications of input signals detected from fiduciary markers and mirrors on the lens of the eyepiece, pivot post and / or support arm , and input signals of the image formation of the eye blade with respect to the lens. The figure shows on the left side a diagram of the retina as an XY plane, in which a time sequence of the relative movements of the radiation beam point is superimposed, indicating each successive position as Xi, yi, count (xi, y) is a function of the entries.

FIG. 33 is a diagram showing a data flow from individual measurements to intermediate outputs, then to a final output sum. The inputs shown, and the detection methods are described above with respect to FIGS. 26A-26E. The input measurements can be made at a selected acquisition update rate, for example, approximately 10 Hz (or more or less), with the positions increased representing successive data acquisition cycles. As indicated in FIG. 33, the intermediate analysis of the inputs produces for the input cycle:

(1) Values for the displacement of the pivot in the X-Y plane, in turn reduced to corresponding components of the retinal displacement.

(2) Values for the inclined angular components of the eyepiece in the x and y directions, in turn reduced to corresponding components of the retinal displacement by rotation in the pivot-to-retina lever arm.

(3) Values for the movement of the lens of the eyepiece with respect to the eye blade (decoupling), in turn reduced to corresponding components of the retinal displacement; Y

(4) Values for the movement of the eyeglass along the Z axis, in turn reduced to the corresponding relative movement of the point of intersection of the retina with a fixed beam path (a function of the rotation of the beam 0 and beam angle O), which can be expressed as components of retinal motion in the XY plane.

(5) Sum of the intermediate values (1) to (4) to produce output values expressed as components x and y of the relative movement of the radiation beam point on the retina, as depicted on the right of FIG. 32

FIG. 34 schematically illustrates the relationship between the rotation of the eyecup (see FIG. 18) measured as components of the angular change or inclination of the eyecup 0x and 0y (note that in this context, 0 is different from the rotation of the source of radiation 0 in FIG. 5), and deviations of the eye blade from the eyepiece lens, measured as displacements in the x and y directions. The diagrams illustrate the components in the X directions, and the method is similar in the Y directions. Note that in certain embodiments, the eyepiece holder (see FIG. 2) can be configured to be relatively nidged, so that the Pivot of the eye gland tends to remain stationary in the XY plane, and the inclination of the eye gland and limbo movement corresponds to head and eye movement as indicated in the diagrams. In certain embodiments, the eyepiece holder may have hinges to allow a range of motion along the Z axis.

(1) The retinal displacement xo due to the rotation around the pivot of the eyepiece is a function of the pivot lever arm, which is the sum of the pivot distance of the eyepiece to the cornea L and the axial length of the eye D ( retina to cornea) and the angle change: x0 = (D + L) * tan 0x. The vertical component (Y direction) is determined similarly.

(2a) In a modeling embodiment, the 5x retinal displacement due to the movement of the eye with respect to the eye gland, detected as a change in the position of the limit of the limbus with respect to the lens of the eyepiece (uncoupling of the eyecup) it can be modeled as a rotation around a center of rotation that is approximately the axial length of the center of the eye or center of the eyeball, such as the displacement in the retinal center is approximately equal to but opposite the displacement in the cornea (i.e., D, axial “2 R, eye). Consequently, the equal lever arm results in: 5x ~ 1 * (x3 - x4), where x3 and x4 are lens and limbus positions respectively.

(2b) In an alternative modeling embodiment, the 5x retinal displacement due to the movement of the eye with respect to the eyeglass can be modeled as a rotation along the curved surface of the cornea, such that a virtual center of rotation is modeled ( radius of curvature of the corneal surface Rc). This may vary by the patient and is typically substantially shorter than the A of the axial length. Rc can approach

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empirically, for example, D, axial "kc * Rc, where kc is from about 3 to about 4. Consequently, 5x ~ (kc-1) * (x3-x4).

(2c) In a sub-method embodiment, the models of (2a) and (2b) are combined using a weighted factor to determine an effective movement due to relative lens-to-retina movement: 8x "(ke-1) * (x3 -x4), where ke is a constant so that D, axial = ke * Re (effective rotation radius), and ke is selected to be from about 2 to about 4 (for example, ke “2.25). The vertical component (Y direction) is determined similarly.

(3) The combined effect of ocular gma inclination and decoupling movement of the limbus can be determined as the sum of these components in the X and Y directions, such that:

horizontal: Ax = xO + 5X

vertical: Ay = y0 + 5y.

FIG. 35 schematically illustrates the relationship between the movement of the eye and the eye gma in the Z direction and changing the point of intersection of a beam of angular radiation with a retinal target center. The diagram illustrates the component in the Y direction (for a beam angle p in the Y-Z plane), and the method is similar for the components in the X direction where the beam is also angular in the X-Z plane). As can be seen, a 5z offset measured in the ocular gma implies an equal displacement of the retinal target along the Z axis. Although the position of the target in the XY plane is unchanged, there is a relative movement of the "beam point" formed by the beam of angular radiation on the retinal surface, in fact, a displacement of the beam point in the XY plane, in this example indicated as 5y. The trigonometric relationship with respect to beam angle p can be expressed as 5y = 5z * as p.

FIGS. 36A and 36A show details of the formulas for conversion, in this case carried out for each of the three stereotactic beam paths aligned in a common target region, as shown for example in FIGS. 6 and 9. As shown in FIG. 36A, the formulas yield intermediate values that are then added to yield collective horizontal and vertical components. Note that beam alignments are indicated in abbreviated notation as 5 o'clock, 6 o'clock, and 7 o'clock beams, referring to an exemplary treatment plan in which the three-beam rotational positions relative to the treatment axis (angle 0 in FIG. 5) are approximately 150, 180, and 210 degrees from the vertical respectively, while the angle of the beam with the treatment axis O remains constant. Although this has been shown by the inventors herein that it is an advantageous treatment plan to minimize the dose in the optic nerve during the application of a pattern of 3 superimposed macular treatment beams with entry points in flat pars, the positions Alternatives are, of course, possible. As shown in FIG. 36B, the components x and y of relative motion are functions of both angles 0 and O, and thus are calculated with different conversion constants.

As further shown in FIGS. 39-41 the incremental retinal beam point positions determined as described in FIGS. 29-37 can be used to "paint" incremental radiation dose depositions in the representation of the retina in the simulated model. For example, the dosage distribution and irradiation rates for a fixed retinal determined experimentally and / or theoretically (for example, a pattern of distribution speed model in Gy / sec), can be adjusted for the movement of the retina, and the Distribution and dosage levels of the cumulative radiation to the real movement of the retina can be calculated exactly on a real-time basis. As described further below, said distribution of the real-time dose accumulation can be used to modify the radiation treatment in progress. For example, the irradiation can be stopped (inactivation control), the eye-to-source alignment corrected, and the irradiation can be restarted. Alternatively, the radiation source can be actively repositioned to correct any change in retinal alignment (for example, "direct" the source to reduce and zero error function). In another alternative, the irradiation may be temporarily stopped, and restarted when it is determined that the retinal position has been realigned with the patient's movement. This last alternative has been shown by the inventors herein that is convenient and effective for "flickering" effects that can induce brief transient displacements, without greatly affecting the overall alignment of the eye.

FIG. 37A and 37B are graphs illustrating a dose map of 3 stereotactic beams of retinal dose measured by radiometna in a simulated eye or model (by optical density analysis of the exposed film), without eye movement, as described herein. memory, which serves as a basis for comparison for the examples of modulated eye movement shown in FIGS. 39-41. Note that the beam paths are substantially as shown in FIG. 9.

The dose contour map of FIG. 37A shows that the 4 mm target region is completely at 80% isodosis (20 Gy based on a maximum level of ~ 25 Gy). In fact, the area of the 24 Gy isodosis (approximately 96%) is approximately co-extensive with the 4 mm target region. The optical disc is completely beyond the 1 Gy isodosis, and thus receives substantially less than 4% of the maximum dose. Note that while the term "penumbra" is used herein to refer specifically to the distribution of doses from a single collimated beam, it is instructive to observe that the concept

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as applied to a stereotactic multiple beam dose map, and a "penumbra" of 80% -a-20% cumulative isodosis is indicated in FIGS. 37A-B as the range between isodosis 20 Gy and isodosis 5 Gy, based on a maximum dose level of approximately 25 Gy. Note that dose levels may vary substantially depending on the particular treatment plan. For example, a particular treatment plan may provide an average dose level in the retinal target region of less than about 8 Gy; or about 16 Gy; or approximately 24 Gy or more, depending on the specific medical objectives for the treatment. Also, treatments can be repeated at selected time intervals for fractionation purposes.

FIG. 38B is a dose profile represented in a graph corresponding to line B-B in FIG. 37A, which is a transect through the center of the target and the center of the optical disc. This profile provides a clear illustration of the isodose cauda in the "penumbra" region, rapidly decreasing to a low value in the margin of the optical disc.

For comparison purposes, FIG. 37C illustrates the dose distribution in tissue both before and after the retinal plane map of FIGS. 37A and 37B. FIG. 37C is a dose distribution graph prepared by Monte Carlo numerical radiation transport simulation (see the methodology in FIG. 13A) used in conjunction with a characteristic tissue model derived from human anatoirna revealed in CT scan imaging. The mapping of FIG. 37C is a vertically oriented flat cross section taken through treatment axis 2820 (see FIG. 21E), which corresponds to the plane containing a central treatment beam path (beam 1 to 0 = 180 degrees in FIG. 21E). The model includes lens 35 and optic nerve 350 of eye 30, the balloon being surrounded by particular tissue 37 with bone orbit 38, and showing brain tissue 22.

The mapping includes the contribution of the radiation dose 1400a from the central beam 1 as well as the radiation applied in the transverse plane from two stereotactic angular beams (beams 2 and 3 in FIG. 21E,) which are directed to intersect the plane of the mapping only in a region adjacent to the central retina (region of "3-beam overlay" 318a). The Monte Carlo simulation showed the dose level in selected structures as indicated in Table 1 below:

Table 1 - Dose in Selected Structures

 Three Beams Managing 24 Gy to the Macula

 Structure

 Dose (Gy)

 Lens

 0.3

 Optic nerve

 0.7

 Cornea

 0

 Sclera

 25

 Brain

 4

 Orbital Bone

 18

 Taint

 24

The isodose contours of FIG. 37C illustrate three major regions of higher dosage:

(a) the area of the scleral surface 311 (25 Gy), which represents only the single central beam 1, since the angular beam 2 and 3 have distinct and separate input regions;

(b) the region of superposition of the 3 beams 318a (24 Gy in the macula) in which each beam makes an approximately equal contribution; Y

(c) high absorption by comparatively dense orbital bone (18 Gy), which again represents only the central beam. Note that in part due to greater bone absorption and consequently reduced penetration beyond, the residual dose on the surface of the brain is only approximately 4 Gy, rapidly decreasing to the small fraction of one Gy deep.

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FIG. 37C illustrates a method and treatment device having aspects of the invention, for the radiation treatment of a retinal target, including providing a positionable orthovoltage X-ray source configured to emit a firmly collimated X-ray beam, the beam emitted in a path that avoids both the lens and the optic nerve of the eye, the beam being filtered so that the surface dose fraction is minimized with respect to the retinal dose fraction, the beam also has a maximum photon energy low enough to minimize the dose fraction that penetrates deeper than the bone orbit of the skull.

VH Radiometric confirmation of eye alignment and X-ray dose addressing

FIGS. 38A and 38B represent a method for confirming an embodiment of a radiotherapy treatment plan that has aspects of the invention. FIG. 38A illustrates the eye of a corpse 30 that has been fixed in a mount 500, configured to be aligned with the radiotherapy system 10 using a suitable mechanical support (not shown) generally in the manner and orientation shown in FIG. 3B. The assembly 500 positions the corpse eye as, indeed, a simulated eye for the purpose of confirming both the method of alignment of the eye and the dosimetna of the treatment system. FIG. 38A shows that the eye of the corpse 30 has been partially dissected to expose the tissue adjacent to the posterior retina, to allow a reinforcement of the radiographic film 502 to be positioned behind the eye parallel to the retina.

The procedure includes the following: The eye in the mounting 500 with film is mounted in the eye alignment and stabilization system 625 (see FIGS. 2 and 16 for example) by a suitable mechanical support (not shown), and the eye it is aligned using the methodology described with respect to FIGS. 21A-21E, in the same general way as the alignment of the eye of a human patient. The eyepiece (represented by the lens of the eyepiece 2860 in FIG. 38A) is applied to the cornea so that it is centered in the limbus, suction is applied with ford, and the X-ray source 420 moves in the treatment position as shown in FIG. 3B. As with the treatment plan described herein, the X-ray beam is aligned with a treatment axis 2820, which is positioned relative to the geometric axis of the eye 2810 by a predetermined deviation 2850.

A series of three treatment beams are applied to the eye 30 (see FIGS. 9-10), so that the radiographic film 502 adjacent to the retina is exposed to produce an exposed spot 504 indicative of the distribution of the absorbed dose by the Diana. The radiographic film is formulated to produce a visible point that allows a marker pin 506 to be inserted through the film into the eye 30, in this example in the center of the point 504, to record and maintain the orientation of the film 502 as exposed with eye tissue

Eye 30 is then dissected along a retinal section as shown in FIG. 38A to expose the posterior retina, recorded to the exposed film 502. The flattened retina superimposed on the exposed film is depicted in FIG. 38B. The retinal geometry is shown in detail on the left to the left, the retinal dissection shown schematically in the right view of the figure. As can be seen, the exposed film point 504 is substantially centered on the macular target, which covers the 4 mm target region. Point 504 is also substantially separated from optical disk 350. The dosage geometry can be compared with the dose map of the simulated model of FIG. 37A.

The procedure thus confirms the effectiveness of the eye alignment method and ocular addressing methods that have aspects of the invention, by demonstrating that the radiation dose applied is directed to the macular tissue (and avoids the optical disk), as provided for the treatment plans described herein.

Results of studies in patients

FIGS. 39A-39E are graphs showing extrapolated retinal movement based on the eye movement data of FIGS. 26A-26E. The calculated retinal movement was used to modulate the dose map of 3 superimposed beams derived from a model study shown later in FIG. 37A and 37B.

Note that preferably said extrapolations are carried out automatically by a digital processor when the eye movement data is acquired, more preferably in real time. It will be apparent to a person skilled in the art how this can be done without unnecessary experimentation.

FIGS. 39A and 39B show the X and Y components of the actual movement of the patient for a period of approximately 5 minutes. These data are presented as a simulated model for an X-ray treatment procedure (irradiation of human patients was not performed in the acquisition of eye movement data presented in FIGS. 26-41). The duration has been divided into three segments that represent stereotactic beam applications. It has been assumed that the eyeglass is aligned with the coordinate system of the treatment system after each repositioning of the X-ray source, that is, twice for the duration of 5 minutes, indicated as b1, b2 and b3 in the graphics.

The graphs include both complete data (broadband) and 1 second filtering or averaging movement represented on the same axis (narrow central graph). Note that the eye tracking system may have a selectable update rate. In the case of the example, the update rate of the image formation system was approximately 10 Hertz, resulting in approximately 3,000

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samples in the duration of 5 min. In general, the data shows a movement or fluctuation of the sacchaic eye, of high frequency and low amplitude, which tends to disseminate the raw data in a wider band. The short period of filtering makes eye movement trends more evident. In addition, the data in which the retina is treated as flat is calculated.

FIG. 39C is a parametric graph of the data in FIGS. 39A and 39B, and graphically represents the outputs of the retina from the center of the target, in both directions X and Y. It can be seen that almost all movement, weighted by duration, remains in approximately a 0.5 mm radius of the target. .

FIG. 39D is a graph similar to that of FIG. 39C and showing the retinal geometry of the optical disk as well as an indication of a treatment target planned as a 4 mm circle around the center of a target. A center of mass CM was calculated on the basis of retinal movement, weighted by duration in the position, to yield a cumulative indicator of the displacement of the radiotherapy dose application. For convenience, 4 and 6 mm circles are shown around the CM, the 4 mm circle around CM being directly comparable with the 4 mm circle around the center of the target (the equivalent without movement). It can be observed that the displacement of the CM is less than about 0.2 mm, and in the adverse case (displacement towards the optic nerve), it produces little difference in the dosage pattern.

FIG. 39D is a dose map based on the data in FIG. 39D and uses the data for an X-ray study without movement using a simulated eye (model, model that assumes a perfect alignment, without movement), using the data from the X-ray study to evaluate the distribution of the dose absorbed by the tissue which hinted at the real eye movement of the patient's study. The isodosis contours are shown for gradations from the maximum level (approximately 24-25 Gy), to a lower limit of 20 Gy coffee (80% isodosis), and outer beam point limit of approximately 5 Gy (20% isodosis ), and a lower dispersed limit of 2 Gy.

In an example of a radiotherapy treatment plan that has aspects of the invention, it is desired to maintain a dose of between 25-20 Gy on approximately a 4 mm treatment target centered approximately on the fovea, and maintain less than approximately 5 Gy outside a 6 mm treatment region around the center of the target. In addition, the example of the treatment plan includes avoiding more than one dosage of approximately 2 Gy, and preferably much less, in the optic nerve and optic disc.

It can be seen that the motion-modulated dose map of FIG. 39D achieves the objectives of the treatment plan with realistic patient movement data, by using the eye stabilization system that has aspects of the invention.

SAW. Control and inactivation control algorithms.

This section details several methods and algorithms by which the processor in the system controls the total exposure to the beam, for example, intensity and duration, in response to the position of the eye movement detected during the therapeutic treatment.

VIA. Eye position and exposure control

FIGS. 40A-40H are graphs showing the extrapolated retinal movement of a patient in which a consistent pattern of lateral drift was observed. The eye movement data were of the same nature as shown in FIGS. 26A-E, and acquired by the same methods and with the same eye tracking devices, but in the case of a patient who exhibits a different behavior of eye movement. In these graphs, the same methodology and presentation as in FIGS is generally used. 39A-39E, and the following discussion will focus only on differences.

FIGS. 40A and 40B show the X and Y components of a patient's retinal movement over a period of approximately 5 minutes, divided into three "beams" as described above. It can be seen that there is a tendency to a relatively large displacement in the X direction, due to the movement of the patient's head and the rotation of the eyepiece lens around the pivot point. The vertically deviations are relatively small, but the horizontal deviations of the retina exceeded 1 mm during substantial periods. FIG. 40 C shows a parametric movement graph.

FIGS. 40D-40F are three CM offset graphs made in the manner of FIG. 39D in which FIG. 40D shows the uncorrected drift data, FIG. 40E shows compensated data as described below, and FIG. 40F is a reproduction of FIG. 39D for comparison purposes.

FIG. 40D shows that the CM of the duration of movement of the data in FIGS. 40A and 40B is displaced approximately 0.75 mm from the center of the target, and that the 6 mm circle moves to extend near the optical disk.

FIG. 40E shows that the CM of the duration of the movement after a drift compensation procedure that employs a "time shift" analysis triggers the inactivation control

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(off) of the x-ray source (simulated aqm), followed by realignment of the patient's eye with the axis of alignment of the system. An example procedure includes:

a) Define a time of travel vector in time such that TDM = (Offset from the center) * (Time out of the center). This is less sensitive for short, long journeys than long persistent ones.

b) In exemplary treatment system embodiments, the dose rate is relatively low (approximately 4 Gy per minute) which gives time to respond to deviations by inactivation control.

c) Define an inactivation control threshold for a selected quantity of cumulative TDM, which is the trigger point for the inactivation control. A term of "spring constant" may be included to decrease or adjust the sensitivity. In one example, the threshold is selected to prevent the CM deviation from exceeding approximately 0.2 mm from the center of the target. A higher or lower threshold can be selected.

d) Realign the patient and treated eye to the coordinates of the system (a) after repositioning of the beam, simulated aqm for 1/3 of the treatment period, and (b) after the inactivation control of the X-ray source according to criteria .

e) Restart the treatment, extending the treatment period as needed to obtain a complete treatment dosage.

A comparison of FIGS. 40E and 40F show that the drift compensation procedure (in this case 5 inactivation control events in the 5-minute treatment period) results in a very small CM deviation, and comparable with the data of a patient without drift Systematic

FIGS. 40G and 40H are graphs of uncompensated and compensated dose maps corresponding to the data in FIGS. 40D and 40E. Note that FIG. 40G shows both an untreated area, the 20 Gy isodosis encompassing only marginally one side of the 4 mm target circle, and unplanned doses that exceed 2 Gy to parts of the optical disc. Both of these effects are avoided by the inactivation-realignment control procedure, as shown in steps 2565, 2540 of FIG. 21A.

VIB Motion-based inactivation control algorithms.

The embodiments of methods and devices having aspects of the invention provide a merit figure for the displacement of the "center of mass" of the radiation dosage from the center of a target, on the basis of monitoring the retinal movement with respect to the center of a beam in the X and Y components (nasal-temporal and cranial-caudal respectively). This can be configured to accept small fluctuations from the center of the target, but will avoid persistent large fluctuations, and can be configured to provide increased protection for sensitive structures, such as the optic nerve. Note that alternatively or additionally, embodiments of generally similar methods and devices can be used to follow a radiation beam path with respect to other anatomical structures, such as the cornea or the lens of the eye.

In experiments by the inventors herein, it has been shown that the relevant eye movements are typically found in certain categories: (a) high frequency fluctuation (+/- x and y directions); (b) stationary directional drift for prolonged periods; and (c) fluctuations of great magnitude, of short duration, (for example, blink direction +/- and), generally that do not change the alignment of long duration. Small positive and negative changes without cumulative drift result in a modest "spread" of the beam point, but are typically not problematic.

Linear response algorithms:

Advantageously, with respect to the stationary drift (b), a "center of mass" or CM vector representing the cumulative deviation can be defined, in which the incremental contributions to the sum of the vector have the components:

Qx = x * dt Qy = y * dt

Where

xi = displacement x [mm] at the time of the sample yi = displacement y [mm] at the time of the sample

dt = time [s] between samples (for example, sample rate from about 1 to about 50 Hz)

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Optionally, alternative embodiments may include smoothed data to suppress high frequency "fluctuation" (for example, 1 sec. Average values for a sample rate 30Hz to yield equivalent values of xi, yi for dt = 1 sec).

Additional attributes may include:

CM (sumQx, sumQy) = sum of the operating vector of the components X and Y, where:

■ magnitude is the distance from the center of the target = SQRT (sumQxA2 + sumQyA2)

■ address is the arctan of the angle (sumQy / sumQx).

Inactivation / realignment control criteria = magnitude of the threshold CM = CM * k

■ k is an adjustable constant to define the inactivation control sensitivity: k = "spring constant" [Gy / mm / s].

CMmax = CM for the total treatment time, final sum vector (with or without inactivation / realignment control during treatment).

■ magnitude can define a general beam-target registration (TRE) error.

■ address can be used to analyze the dose at and / or protect particular structures.

In the embodiments described in detail, the re-orientation of the X-ray source / collimator can be done quickly and discreetly by an automated positioner under operator monitoring, and it is preferable to continue treatment with successive stereotactic beams without necessarily realigning the treated eye. regarding system coordinates. In this method of practice, realignment is performed only when inactivation control occurs with the intent of the pre-established displacement vector criteria.

In other alternative embodiments, a separate calculation can be made to reinforce a maximum CM clearance of a vulnerable structure (e.g., separately monitoring the CM component in the direction of the optical disk, with inactivation control at a clearance threshold). Also, additional alternative embodiments may include real-time dose mapping to vulnerable structures (eg, optical disk, cornea, lens, etc.) using the data as depicted in FIGS. 37A and 37B. Inactivation and realignment control can be performed when a dose threshold is reached.

Note that in some commercially available X-ray tubes, a pressure network can be included that provides rapid shielding of the electron flow by field neutralization. In others, the high voltage power supply can be changed to provide an effective inactivation control response.

Nonlinear response algorithms:

In alternative embodiments of methods and devices that have aspects of the invention, a non-linear algorithm can be employed, which provides an adjustable weighting to provide a greater response to large deviations than to small deviations. As with the linear algorithm described above, a modified "center of mass" vector can be defined that represents a nonlinear cumulative deviation factor (AF), where the incremental contributions to the sum vector have the components:

image 1

image2

Where

k = sensitivity constant that scales the components in an adjustable way to optimize the treatment (for example, k = 1 to approximately 5). Note that sensitivity can also be adjusted as a factor in the Inactivation Control Criteria.

Xi = displacement x [mm] in the sample time

yi = displacement and [mm] in the sample time

n = selected exponent (for example, n = 1 to 3, such as 1 for linear, 2 for quadratic, etc.) dt = time [s] between samples

Observe for a quadratic form (n = 2), the weighting of the incremental contribution is proportional to the square of the instantaneous displacement (for example, Qx (2 mm) = 4 * Qx (1 mm)), thus emphasizing the

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Magnitudes with great drift, with less emphasis on minor fluctuations close to zero. To avoid directional ambiguity, the sign with respect to the zero axis of the displacement can be taken into account in a sum vector where n is an even integer, for example, n = 2, where sign (x) = x / | x |, and sof ± 1, such as:

image3

image4

The accumulation factor can be integrated over time as AF (sumQx, sumQy) = sum vector of the components X and Y, where:

magnitude = SQRT (sumQxA2 + sumQyA2), which represents a deviation from the nonlinear target.

direction = arctan (sumQy / sumQx), which is an angle in the x / y coordinates that is in the retinal surface plane.

AF (total or terminal) = final cumulative value of AF at the end of the treatment, can be considered to define a target registration error (TRE) for the treatment.

The inactivation control criterion can be formulated in several alternative ways. In one example, a maximum value for AF deviation (MaxDist) can be selected that can be considered acceptable if it is maintained during the entire treatment period as a constant value (for example, from about 0.1 mm to about 1.0 mm, and preferably about 0.2-0.4 mm), so that the Inactivation Control Criteria = MaxDist * Treatment Time.

An additional or alternative sensitivity factor or constant can be applied to the Inactivation Control Criterion, so that Inactivation Control Criteria = MaxDist * Treatment Time / Sensitivity Factor. For example, the sensitivity of the inactivation control can be made more / less conservative by adjusting the sensitivity factor. For example, the Sensitivity Factor can be approximately 3.

The treatment factor can also be adjusted in response to a typical or medium target registration error (ERT) for a population of patients. Simulated treatments (without radiation with real eye stabilization / monitoring) have been used by the inventors herein to collect patient population data to assist in the establishment of inactivation control criteria. For example, a reasonable conservative MaxDist may initially be established for a treatment plan, which may result in infrequent inactivation control events for an acceptable TRE. Experience in populations may show that improved accuracy in treatment is possible without excessive inactivation control (for example, up to approximately 21-5 inactivation control events per treatment), and thus the Sensitivity Factor can be increased to decrease the mean TRE achieved . Similar adjustments can be made to other computation factors, such as the exponent n.

A strategy to determine a maximum distance or value (MaxDist) for the accumulation factor (AF) is an estimated error analysis. For example, the distance from the edge of the "error-free" beam idealized for a vulnerable structure, such as the optical disk, can be determined from the measured features of the collimated beam and the ocular anatoirna of the typical patient. For example, with reference to FIGS. 37A and 37B, the distance or clearance of the structure from the edge of the penumbra to the edge of the optical disk could be estimated to have an average value of 0.75 mm or 750 micrometers. The probable sources and magnitudes of the potential error can then be identified, including a proposed value for MaxDist. For example, three sources of potential error and a maximum representative magnitude can be considered: (a) centered Gma I lens to limbus (~ 0.4 mm), (b) addressing error of the positioning system (~ 0.4 mm) , and (c) effects of eye movement (~ 0.4 mm). An RMS value from these three sources can be estimated as SQRT (0.42 + 0.42 + 0.42) = 0.69 mm. As this is in the clearance of the 0.75mm structure, the proposed MaxDist value of 0.4mm (400 micrometers) seems reasonable.

Radiation equivalent parameters based on motion.

Note that alternative mathematical and statistical algorithms to those described herein can be used to define cumulative displacement factors and inactivation / realignment control criteria useful for the same purposes of medical treatment, without departing from the invention.

As can be seen in the previous examples, a motion-based parameter, such as the accumulation factor of the addressing error, can be defined, without calculating the absorption of the actual radiation, to function as an equivalent or substitute for the distribution of the dosage of radiation on a treatment target (for example, a defined macular region) or a sensitive non-target anatomical structure (for example, the optical disk). The known radiation properties of a treatment beam (for example, a speed and isodose distribution calculated in the cross section of the beam) can be used to determine equivalence. Thus a dose intensity of the known beam (for example, in Gy / sec at the depth of retinal tissue) can

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used to select a motion-based property reliably associated with the effects of radiation.

A controller of a treatment system based on a software processor can calculate said equivalent radiation based motion parameter (eg, AF in the examples herein) and monitor this parameter against pre-determined numerical thresholds. The movement of a target and / or sensitive structure can be detected directly (see the discussion of FIGS. 49-52); or determined by an extrapolation algorithm based on the overall movement of the eye (as in FIGS. 29-36).

Alternatively, a controller of a treatment system based on a software processor can calculate the actual radiation dose distribution in targets and / or sensitive structures (see methods with respect to FIGS. 37A and 37B), taking into account the effects of eye movement detected. The threshold for inactivation control (or other motion compensation) may be based on specific radiation dose levels.

VIC Examples of inactivation control

FIGS. 41A-41D illustrate an example of embodiments of methods and devices for the control of inactivation and control of dose distribution in response to retinal movement. FIGs. 41A and B are graphs showing the X and Y components of retinal movement respectively. In this case, the alignment and stabilization of the eye was performed, but no irradiation was performed, yielding the movement data of the input eye as shown in FIGS. 26A-26E. A conversion of the retinal movement was performed (see FIGS. 32-36), and an inactivation control control was simulated using a linear algorithm as described above with a trigger sensitivity of approximately 3 (example of inactivation control) and 0 (example without inactivation control). The re-alignment in the example of inactivation control in this patient was simulated by resetting the X and Y offset of the data when the inactivation control threshold was reached, resulting in 1-5 settings as indicated in the figures. Both the "movement without inactivation control" and the "movement with inactivation / realignment control" are shown as indicated in each figure.

FIGS. 41C and 41D are parametric XY graphs that show retinal surface beam traces without inactivation control and with inactivation control, respectively, with respect to the center of the target (0,0), and which also show the optical disk and a target zone 4 mm around the center of the target. In each case, the location of the vector position of the "center of mass" terminal of the beam position (CM) is superimposed, as described above together with 4 mm and 6 mm circles around the CM. As can be seen in FIG. 41C, the terminal CM (also indicated as RArm) without inactivation control is approximately 1.55 mm as indicated by the dimension arrows. In contrast, when the sensitivity of the inactivation control is adjusted to result in 5 inactivation / realignment control events, FIG. 41 D on the basis of the same input data shows a terminal CM of only approximately 0.31 mm, or a reduction of approximately 5 times in the addressing error.

The algorithms and triggering devices of the inactivation control performed by said algorithms (for example, an informatic processor / controller of a radiotherapy system, which communicate an automatic inactivation control signal to an associated X-ray source) have been jointly demonstrated with embodiments of the eye alignment / stabilization system to provide TRE accuracy of less than about 0.5 mm, while performing a maximum of approximately 3-5 inactivation / realignment control events for a substantial patient population.

FIGS. 41E-41H are graphs illustrating additional examples of embodiments of methods and devices that have aspects of the invention for the control of inactivation and control of dose distribution in response to retinal movement. The graphs are arranged in pairs (41E and 41F and 41G and 41H), a pair for each of two subjects that are being treated using a radiotherapy system embodiment according to FIGS. 1-6. Each graph has the same horizontal time axis and each one refers to a unique X-ray beam emission interval in which a macular dose of approximately 5.3 Gy was administered as part of a 3-stereotactic stool treatment by making a total of approximately 16 Gy in the macula.

In each pair of graphs, the upper graph shows the time variable values of the retinal displacement X the treatment axis the system 2820, shown as a light solid line, and the values of the retinal Y displacement, shown as a dark solid line. These values are calculated on the basis of fiduciary marker and limbo tracking signals, as described herein with respect to FIGS. 21-36. In these examples, the data update rate during the treatment was approximately 10 Hz. For presentation clarity purposes without loss of meaning, the displacement data represented in the figures is filtered (averaged point by point over a few data cycles ) to suppress the presentation of high frequency perturbations or fluctuations in the frame by frame data.

In the lower graph of each pair, the Accumulation Factor (AF) is represented as a dark solid line, relative to the left vertical axis as a fraction of the maximum pre-inactivation control criteria threshold

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determined allowed. The total cumulative central X-ray dose with increased time to retinal depth (TD) is shown as the clear solid line, relative to the right vertical axis, in Gy. AF was calculated as a sum of the magnitude of a quadratic displacement vector, as described above. The total cumulative dose is a sum of incremental doses for each time increase during X-ray treatment ("beam time on"). Each incremental dose is based on calibrated properties of the emission of the kerma X-ray tube into air using the measured field potential voltage of the tube and the cathode current of the system. The incremental dose determination includes calibrated propagation of the X-ray spectrum through filters of the collimator and participating ocular tissue at retinal depth, determining the length of the tissue path from the geometry of the beam path as it scales to the eye of the particular patient on the basis of an ultrasound mode ultrasound measurement.

Returning first to FIGS. 41 E and 41F it can be seen that the alignment of the macular center at the start time of the beam shifted a fraction of a millimeter in both directions X and Y (-0.26 and -0.43 mm respectively). The AF graph can be seen that a moderately pronounced angle was initially tilted upwards. During the first 20-25 seconds, the retinal displacement in the Y direction increases while the displacement in the X direction decreases. It will be appreciated that the trigonometric magnitude of the displacement vector (square root of the sum of the squares of the components X and Y) increases during this interval, and this increase is reflected in a pronouncement of the slope of the AF curve. Upon reaching the AF the threshold of inactivation control criteria (AF => 1 * GC) at approximately 29 seconds of beam time on, the system processor triggers the inactivation control of the X-ray source, turning off the tube the source of x-rays

After the inactivation control, the responsible physician realigned the eye and the eyecup with the treatment axis 2820 (X, Y displacements of -0.13 and 0.08 mm respectively), and the X-ray source was restarted Note that the TD line is flat briefly as the emission intensity at the reboot increases over a period of approximately 1-2 seconds. During the rest of the beam emission, the X and Y retinal components remained in a fraction of a millimeter, and the AF curve only had a less steep upward slope, accumulating only at a small fraction of the maximum GC at the time of termination of the beam at approximately 73 seconds of the ignition time, reaching the total dose administered 5.23 Gy.

Going back to FIGS. 41G and 41H it can be seen that the displacement data in this case show a marked and persistent periodicity, particularly in the Y displacement, with a period of approximately 3.5 seconds and an amplitude Y of approximately one third of a millimeter. It is believed that this is largely due to the patient's particular respiratory behavior, which caused slight head and eye movements. For a linear algorithm for the accumulation factor (AF), the periodicity does not affect the AF, while for a quadratic algorithm for the accumulation factor (AF) in which the displacements are weighted with the square of their magnitude (as used in these examples), the periodicity of this nature increases the AF with respect to a non-oscillating curve of the same average value. [Note, in addition to the X and Y retinal displacement curves in FIG. 41G, there are curves for the "distance" L of the retinal target from the center of the beam where L =

2205 J ''

(X + Y) '., And for a "pulse" of X-rays. These are discussed below with respect to an alternative treatment method].

As in the previous case, it can be seen that in FIGS. 41G and 41H, the alignment of the macular center at the start time of the beam shifted in both directions X and Y (-0.10 and 0.53 mm respectively). The AF graph can be seen to rise upward at a pronounced angle, reaching the trigger level of the inactivation control (AF => 1 * GC) after approximately 14 seconds of beam-on time. After the inactivation control, the responsible physician realigned the eye and the eyeglass with the treatment axis 2820 (X, Y displacements of -0.11 and -0.01 mm respectively), and the ray source was re-started X. During the rest of the beam emission, the average tendency of the X and Y retinal components remained small, although as indicated, the amplitude of the periodicity was significant. The AF curve has a modest upward slope, accumulating at approximately 35% of the maximum GC in the beam termination time at approximately 72 seconds of the on time, reaching the total central dose administered 5.19 Gy.

Pulse modulated radiation control.

In the examples described in detail herein, the systems use an X-ray source of substantially constant intensity, so that the cumulative exposure time is generally linear in relation to the absorbed dose in a tissue in the path of the beam . However, depending on the characteristics selected from the X-ray source, either or both of variable intensity beams or pulse modulated beams can be used to apply radiotherapy, without departing from the invention.

As an illustrative example, and going back to FIGS. 41G and 41H, it can be observed that the dical fluctuations in the location of the foveal target due to the patient's respiratory movement (mainly in the vertical or Y direction) place the target intermittently very close to the zero displacement of the center of the treatment beam. FIG. 41G shows a curve of the magnitude of displacement or "distance" L (as a dashed lumen curve) of the retinal target from the center of the beam where L = (X2 + Y2) 0.5, indicating that L is thus always a positive magnitude regardless of whether the components of the vector X and Y are positive or negative.

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The X-ray source 420 can be controlled to emit a beam radiation only when the value of retinal displacement L is less than a selected threshold (for example, 0.25 mm or 250 | j is illustrated), although this was not the procedure of real treatment for the subject in this case. The distance curve is thickened with a dark gray overlay for those parts for which L <250j, indicating an example of alternative treatment in which the X-ray source is modulated to emit radiation only when L is at this threshold.

In radiological technique, very precise X-ray emission or pulse control is known for X-ray tubes, such as for cinematographic and similar radiographic techniques. The rapid change of the X-ray emission from the point of the anode can be obtained, for example, by the use of high voltage change in the secondary circuit of a constant potential X-ray generator; starting and stopping the inverter in a medium frequency generator; or using an X-ray tube with grid-controlled. See, for example, the G-1078 Rotary Anode X-ray Tube controlled by grid by Varian Medical Systems, Inc. Alternatively, controlled physical blocking of the X-ray beam can be performed by a shutter, such as a radio-opaque shutter. fast-acting electro-mechanically directed, for example, mounted on the collimator.

A method of pulse-modulated X-ray treatment having aspects of the invention may include, for example, monitoring (adding) the ignition time of the modulated or "pulsed" beam by the control processor, and continuing treatment with the beam until a desired dose is applied. An inactivation / realignment control criterion may be included, such as a "duty cycle" criterion in which the treatment is interrupted if the percentage of beam ignition time decreases below a selected level for a selected period, such about 50% of the work cycle. Thus, if the eye movement is such that the distance L is continuously beyond the pulse threshold, the eye is re-aligned to provide a useful duty cycle. In the example of FIG. 43G, the inactivation control at approximately 14 seconds would have served as said re-alignment inactivation control, putting the alignment close enough for approximately 50% of the duty cycle.

In additional alternatives, a constant speed and length pulse can be used, in which each of said pulses has a fixed duration, and the pulses are allowed at a selected speed. The system can determine an IR / NO IR decision for each pulse based on the displacement of the current target beam, the pulse being only triggered when the IR criteria are met (for example, L <250j). The duration of treatment can be a pre-determined number of triggered pulses, corresponding to a selected dose.

VINE. Inactivation control controls for flickering movement

FIGS. 42A-42H are graphs showing the extrapolated retinal movement of a patient in which a consistent pattern of involuntary blinking was observed during the simulated treatment, each blinking resulting in a strong, rapid, albeit temporary, eye movement upwards. It should be noted that upward displacements do not tend to increase the dosage in the optical disc, but may result in a sub-treatment of a macular target region.

FIGS. 42A and 42B show the X and Y components of a patient's retinal movement over a period of approximately 5 minutes, divided into three "beams" as described above. It can be seen that there is a large number of vertical fluctuations or very short Y, in some cases exceeding 2 mm, although there is much less movement in the X direction. The eye tends to return to alignment quite quickly after each blink. FIG. 42C shows a parametric motion graph.

FIG. 42D shows that the CM of the duration of the movement of the data in FIGS. 42A and 42B experience only a very small displacement despite the large vertical fluctuations of the movement. However, FIG. 42D shows that the corresponding dose map is most strongly affected due to large-scale deviations (the coffee gradient of the isodosis beam point is highly non-linear), resulting in a vertical "blur" of ascending dose, and a dose loss in the lower part of the treatment region, resulting in a substantial subtreated area (doses of less than 20 Gy in the 4 mm target circle.)

FIGS. 42F-42H show the results of a "flashing" method that has aspects of the invention. The exemplary method includes.

■ Define a parameter to trigger the inactivation control that responds to flickering movements. An example of a trigger parameter is to look for the first large difference from one sample to the next (suitable for an update rate of 10 Hz), for example a difference of approximately 0.5 mm in 1/10 of a second between measurements.

■ Trigger the results in the simple inactivation control of the X-ray source, such as closing the high voltage or HVPS power supply (moderate response), or alternatively activating a cathode pressure grid to prevent electron acceleration (response faster). Any time down / up of HVPS rise can be allowed for dosing mapping and duration of treatment.

■ Wait for a defined period for the patient to realign spontaneously, for example, 3 seconds.

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■ Restart the treatment and optionally add a time without beam to the treatment period.

FIGS. 42F and 42G show the data in FIGS. 42A and 42B after filtering to illustrate the above method, discarding the samples for a waiting period of 3 seconds after triggering. FIG. 42H shows the resulting change in the dose map, which eliminates the effect of dose "blurring".

FRI. Repositioning the X-ray source in real time to follow the retinal movement

In certain embodiments, as an alternative to or in addition to the controls and methods of realignment of the emission of the X-ray source described above with respect to FIGS. 39-42, either or both of the X-ray source (for example, by means of actuators of the X-ray positioner) or the patient's eye (for example, by means of actuators for holding the eye and / or head gland) they can be repositioned and / or reoriented to compensate for the movement of the patient's eye, as detected on a real time basis.

For example, the manual positioner of the eyepiece 600 shown in FIG. 1 may include effective actuators to move the eyeglass automatically under the control of the system processors, in response to retinal movement as detected during treatment. As shown in FIGS. 29-31, just when eye and / or head movements (causing retinal movement) are detected as translation or rotation of the components of the eyecup 110. For example, as shown in FIGS. 29A and 29B, the movement of the relative eye and X-ray beam source on the Z axis of the system (dZ) results in a relative movement of the beam point on the retina (dX), depending on the direction of the relative movement of the orientation particular angle of the treatment beam with the geometric axis of the eye 2810. Similarly, as shown in FIGS. 30A and 30B, the translation of the eye in the X or Y directions with respect to the eyeglass 110 induces rotation and retinal movement in the direction of translation. Conversely, the movement of the eyepiece 110 can be used to induce a compensatory retinal movement, to reposition the retinal beam point with respect to the target.

Movement of the positioner of the X-ray source. In alternative embodiments, the actuators of the positioning system 115 shown in FIGS. 1-6 can be used to reposition the X-ray source assembly 420 to reorient the treatment beam in response to retinal motion as detected during treatment (for example, automatically under the control of system processors). As shown in FIG. 21 E, the path of the X-ray beam 1400 is carried to target 318 by a sequence of movements of the actuators of the positioner 115 to an adjusted position (X0, Y0, Z0, O0), position in which the change of the Rotational variable 0 around the treatment axis 2820 results in substantially no relative movement of the retinal beam point. Conversely, the movement of one or more of the actuators X, Y, Z, and / or O of the positioner 115 can be controlled to re-position the retinal beam point in response to the movement of the patient's eye, as detected in a real-time base, such as acting to move the X-ray source 420 from (X0, Y0, Z0, O0, 01) to (X ', Y', Z ', O', 01). In alternative embodiments, the positioning system 115 may comprise additional actuators configured for fast and precise movement (eg, "small range" Vernier actuators) in addition to primary actuators for one or more of the X, Y, Z, and / or O of the system.

Likewise, the positioning system 115 may comprise additional or alternative degrees of freedom or mechanical axes in addition to the X, Y, Z, and / or O axes of the system, and these can be configured for real-time reorientation of the beam path 1400 in response to retinal movement detected.

Direction of the beam by the lateral translation of the collimator opening. In the example shown in FIGS. 43 A-C, one or more additional degrees of freedom are provided for the structure to move the retinal beam point relative to the initial beam axis 1400. Advantageously, the mass of the X-ray source (weight and inertia) that must be moved for the fine-scale re-orientation of the beam can be reduced by having an actuator configured to reorient only a part of the collimator assembly structure 118 to delimit the beam to a slightly adjusted beam path. In the example shown, it is only necessary to move a very small fraction of the mass of the X-ray source assembly to make small compensatory movements of the retinal beam point, where one or more actuators 119a are configured to connect and move the plate outlet of the collimator 1405b of modest mass, the actuator assembly 118b being arranged adjacent to the distal end of the collimator assembly 118. Typically, a small mass can be repositioned more responsibly and accurately than a relatively large mass, such as total mass of the X-ray source tube 112.

As shown in FIGS. 43A-43C, the opening plate 1405 is supported by the opening assembly 119b (for example, it can be held in position by the supports 119c) and connected by actuators 119a. In the example shown, the plate is supported to move in two dimensions (directions I and J for relative movement di and dj respectively) in a plane perpendicular to the beam axis 1400, but this is not necessarily ast Similarly, the example represents pairs of linear actuators in a parallel "push-pull" arrangement for each direction, but this is purely exemplary. For example, actuator assembly 118b may alternatively provide a degree of rotational freedom (not shown) in addition to a lateral translation of plate 1405b, to provide movement by polar coordinates lateral to axis 1400.

FIG. 43A provides a transverse "ray tracing" beam model similar to that of FIG. 12, with the elements generally identified by the same numbers, and which has identified collimator dimensions

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similarly as L0, L1, L2 and L3. The X-ray tube 112 emits a beam 1400 via the collimator 118 to propagate to the surface of the sclera 1430, penetrating the retinal surface 1435 to form a retinal beam point 1441. The lateral movement of the opening plate 1405b moves the exit opening 1405 through a distance indicated as opening path 1406. Both opening plate 1405b and beam 1400 are both shown in an initial position / orientation (dashed or clear lines) and a displaced position / orientation (solid lines). or dark) as you do 1400 '.

FIGS. 43B and 43C are front elevations of collimator 118, which show the arrangement of linear actuators 119c to plate 1405b, in which Figure B represents an initial position, and C represents a displaced position, where plate 1405b has moved in two directions (di, dj respectively). Since the plate 1405b is mounted at a distance between the anode 1420 and the retina 1435, the path of the opening 1406 results in a path of the respective retinal beam point 1407 that is magnified to a degree. For example, if the aperture 1405 is exactly at the midpoint (L0 = 2 * L1), the path of the beam point 1407 will be twice that of the path of the aperture 1406. Thus a movement of 1mm through the plate 1405b will result in this case in a displacement of approximately 2mm at the point of beam 1441. Observe FIGS. 40A-40H that the retinal movement of a patient with restraint may be of the order of 1-2 mm or less during reasonable treatment periods. For embodiments in which the aperture is close to the scleral surface 1430, the magnification of the movement can be modest.

Observe FIG. 43A that the entry point 311 of the beam 1400 in the sclera 1430 is displaced by a distance comparable to the path of the point of the beam 1407. In the treatment systems described herein, the relationship of the beam point of the sclera 311 can be actively followed by the imaging system and processors, and accurately predicted based on the detection of eye movement. The collimator assembly 118 may include an addressable mirror 1220 '(see laser beacon 1410 and mirror 1220 in FIG. 4) to allow directing a laser beacon with an aligned beam to remain aligned with the beam 1400', to assist in automatic monitoring or by beam shift operator. System processors can be configured (for example, by suitable software) to predict the movement of the sclera beam point 311 to prevent movement of the plate 1405b leading to the sclera beam point 311 at a selected threshold distance of a vulnerable structure, such as the cornea or the lens of the eye (for example, source inactivation control could be used to control the distribution of the retinal dose in this case). In many cases, the movement of point 311 will be far from or at least not towards a vulnerable structure.

In an alternative, actuators 119b comprise one or more electromechanical actuators known in the art. In another alternative, actuators 119b comprise one or more piezoelectric actuators, such as a 2-D piezoelectric actuator. These actuators can be configured to move quickly in a controllable manner (for example, response of the order of milliseconds) over a distance of a few mm with accuracy in the order of a few micrometres.

Axial rotation of the collimator opening. The opening 1405 can move in a degree of axial rotational freedom around the longitudinal axis of the collimator 118, as shown in FIG. 43C, by axial rotation 1408 (dp). Suitable actuators and support bearings (not shown) can be included in the assembly of collimator 118 to achieve this movement, either by rotation of all or a part of collimator 118, or by rotation of a different opening plate 1405b, and these can operated manually and / or by motion control software through the 501 system processor.

Rotation of the opening can be particularly useful when opening 1405 is offset from the collimator axis (as in FIG. 43C), or to align an opening shape with a target in the embodiments (not shown herein) when opening 1405 includes a non-circular opening or opening pattern, such as an elliptical, elongated, or semi-moon opening or the like (see the opening embodiments described in Requests No. 12 / 103,534 filed on April 15, 2008 and No. 12 / 100,398 filed on April 9, 2008, which are incorporated by reference).

For example, robotic positioner 115 of FIGS. 5 and 6 is configured to rotate the X-ray source assembly through an angle 0 to adjust the beam position for successive stereotactic treatment paths. The rotation of the collimator opening in the opposite direction can be used as shown in FIG. 43C to maintain a desired orientation of an asymmetric collimator aperture 1405 relative to target 318 when the X-ray source 112 is repositioned.

Longitudinal extension the collimator. The example of FIG. 43D is shown in the form of an assembly similar to an extensible "zoom lens" of an outlet aperture 1405 in a body of collimator 118 '. The telescopic tube mounting structure shown is only exemplary, and it should be noted that in alternative embodiments it can be done with a substantially different structure without departing from the spirit of the invention. For example, it is not necessary for the outer part 118b to be mounted directly on the base part 118a, but it can be supported independently, the independent support configured to allow movement of the opening 1405 distally and axially out of the anode 1420, to increase the distance L1. In this way, certain embodiments can be made to omit the base part 118a, as when any

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desired beam conditioning components (eg, containment plate, filter, shield against scattered radiation) are provided independently.

Note that an extensible collimator can be included as, in effect, an additional degree of freedom for the positioning of the initial X-ray source, as well as for monitoring the movement of the target during treatment. For example, in certain embodiments of radiotherapy systems that have aspects of the invention, the X-ray source 112 and retracted collimator 118 'can be positioned first in one or more degrees of freedom, for example, in volume XYZ and with a selected polar angle O. The azimuth angle 0 can be selected in sequence for beam position (for example, b1-b2-b3 in FIG. 6). For each beam position, before the radiation emission, but after the positioning of the X-ray source and collimator, the extendable outer part 118b of the collimator 118 'can be extended axially (extension 118c) or "subjected to zoom" to set the outlet of collimator 1405 at a selected distance from the surface of the eye 30. After the emission of radiation, the extendable outer part 118b can be retracted before repositioning the X-ray source and collimator.

Note that collimator 118 ', and / or the system in which it is used, may contain detectors and safety mechanisms that allow a close approach to sensitive tissue. For example, opening 1405 may be covered with compliant, biocompatible material 119 for quilting and protecting the sclera or other ocular structures, which can be molded to conform to an ocular surface, facilitating operation near the face or allowing contact with the eye. sure. Also, proximity sensors and / or servo controls can be used to automatically maintain a selected non-contact clearance of the tissue, and / or to limit any force applied to the tissue contact.

FIGS. 43E and 43F schematically represent a ray tracing model similar to that of FIG. 12, which graphically compares the effect of the collimator extension, illustrating a series of two different examples of the plane collimator's exit distance (L2 + L3 in FIG. 12), with the opening size 1405 and distance anode to target L0 kept constant, FIG. 43E can be considered as representative of a counter value L2a according to FIG. 43D, and FIG. 43F can be considered to be representative of an extended or "zoomed" value of L2b. Note that the values of L0, L1 and L2 and aperture diameter as illustrated are purely exemplary, and these can be varied substantially without departing from the spirit of the invention. The comparison of the two figures shows that the variation in the distance of the opening has an effect on both the width of the penumbra 1442 and the size of the center beam point 1441, both are reduced as the aperture approaches the plane of the target , for a given opening diameter. If desired, opening 1405 can be sized for a selected treatment configuration and remain with a fixed dimension.

Alternatively, the diameter of the opening (and / or shape) can be made adjustable. FIG. 43G shows the same configuration as FIG. 43F ("extended collimator"), but has an enlarged aperture (25% larger in this example) to compensate so that a diameter of the center beam point of the constant target is maintained (4 mm as illustrated). In certain embodiments, the aperture diameter is adjusted to fit a specific treatment plan, for example, based on the dimensions of a patient's macular injury.

Adjustable collimator opening diameter. FIGS. 43H and 43I schematically a distal part of a collimator assembly 118 that has aspects of the invention and that has an adjustable opening, comprising a plurality of movable opening plates (1405a-1405b), arranged to move radially out of the axis of the collimator 118, to increase the effective opening radius. In each figure, the view (1) is a plane or front view of the arrangement of the opening plate, and the view (2) is a longitudinal cross section of the collimator 118. In the example shown, the assembly includes two opposite pairs of opening plates arranged in superimposed, upper and lower parallel layers oriented perpendicularly. In this example, each plate has an almost elliptical opening that serves to define a quadrant of the penimeter of the opening of the opening 1405. A plate support ring 119c is shown schematically (alternative support arrangements may be included) and holds the plates 1405a-b in position at the distal outlet of collimator 118, while allowing lateral sliding movement in a radial dimension for each plate. FIG. 43H illustrates the counter opening (2.5 mm diameter) and FIG. 43I illustrates the dilated opening (3,125 mm).

For each plate, a schematic linear actuator 119a connects the plate to controllably move the plate radially in or out. It should be understood that a wide range of alternative mechanical and electromechanical assemblies can be included as plate actuators, which can be controlled automatically or remotely, or can be manually adjustable.

One of the advantages of orthovoltage radiotherapy is that radiation control components such as collimator aperture plates can be much smaller, lighter and more compact than comparable components used with multi-MeV x-ray treatment devices, due to the reduced penetrating effect of low energy photons. This allows the assembly of a remotely adjustable compact opening assembly that has aspects of the invention in a collimator assembly suitable for use near a patient's face.

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For example, miniature linear motors and actuators are commercially available that provide the exact, remotely controllable actuation for the device of FIGS. 43 H and 43I as well as for devices such as camera lenses, film advance, shutter motion control and the like (eg, piezoelectric linear actuators, by New Scale Technologies, Inc. of Victor, NY, and by Dynamic Structures & Materials, LLC of Franklin, TN). An alternative actuation arrangement may employ cable or gma junction arrangements, or the like as known in mechanical and electromechanical techniques. Note that on the right side of FIGS. 43H and 43I the actuator 119a is mounted directly on the opening assembly 119c, while on the left side, the actuator 119a is mounted at a certain distance from the actuator assembly 119c, mechanically linked to the actuator plate 1405a, b, which it can be by means of a pulley cable, crank, sliding or union cable, conduit cable or other mechanical union known in the art. Springs or other pressure components may be included (see the actuator on the left) to counteract the force of an actuator, to allow reversible movement after relaxation of the actuator, or the movement may be positively directed in each direction (contraction and dilatation).

It can be indicated by comparison of FIGS. 43 H and 43I that the "counter" state of the opening plates 1405a, b (2.5 mm aperture, FIG. 43H) closely approximates a circular opening with only small parts of the opening exceeding the inscribed circle of 2 , 5 mm. The dilated state of the opening plates (3,125 mm aperture, FIG. 43I) has substantially an exactly circular opening, since the positions of the plate arc have that curvature. It is not necessary that the shape of the plates be as shown, the figures exemplifying the principle of the adjustable opening assembly. Also, non-circular adjustable opening aperture forms are possible. Note also that the dimension range of the examples (2.5-3,125 mm) is purely exemplary, and the range may be and substantially less than substantially greater than the example shown.

FIG. 43J illustrates an example of a collimator assembly 118 having adjustable aperture 1405, generally similar to the embodiment of FIG. 43H and 43I, but having a hexagonal plate pattern, on two layers of three plates each layer (1405a and 1405b), in which each plate defines a 60 degree segment of the opening aperture pen 1405. The view (1) shows the contrafdo state (2.5 mm) and the view (2) shows the dilated state (3.125 mm).

FIG. 43K, Views (1) and (2) illustrates an example of a collimator assembly 118 having an adjustable opening 1405, generally similar to the embodiment of FIGS. 43H and 43I, but having a plurality of double interlaced interlocking plates 1405a and 1405b forming a series of four linked layers. The double plates (a greater plurality of sheets is possible) can be operated in the manner of assembly of FIGS. 43H and 43I.

Combined opening movement. The embodiments of FIGS. 43A-43C having a laterally movable opening 1405 can be combined with the embodiments of FIGS. 43H-43K that have the radially adjustable opening diameter, to have a simultaneous (or sequential) lateral opening movement while the opening diameter is used. For example, each plate 1405a, b of the opening assemblies 119c may be supported and actuated to have a complex movement, radially with respect to each companion plate, and collectively laterally (eg, X and / or Y) to produce a lateral movement of a changing opening. Alternatively, an assembly with a discreetly adjustable diameter can be mounted on a laterally movable support, so that the expansion / contraction of the opening can be combined with the overall movement of the support.

VII. Additional realizations This section describes additional embodiments of the eye gma and method of treatment of the invention.

VIIA. Additional embodiments of the eye gma

FIGS. 44A-44D illustrate an eye gma device 110 for use in an eye stabilizer system that has aspects of the invention, the gma having a window or transparent part 300 that allows retinal imaging during treatment (see alternative example in FIGS. 18C and 18D). In the example shown, the lens 120 is supported by one or more posts or extensions 222, which connect a Y-shaped yoke 190 comprising the arms 191, 192. The yoke 190 is mounted on a support arm 180 by a link swivel 223. Arms 191-192 mounted on extensions 222 by pivots 224. Pivots 224 and swivel 223 provide freedom of movement for lens 120 in two perpendicular directions. The window 300 is formed in the center of the lens 120 (which can be completely transparent), to allow an image of the inside of the eye 130 to be obtained while the eye gma 110 is connected to the eye. Vacuum connection 275 communicates out of center in lens 120 and does not obstruct window 300.

FIGS. 45A-45D illustrate an alternative eye gma device 110 for use in an eye stabilizer system that has aspects of the invention, similar in many respects to the embodiment shown in FIGS. 44A-44D. As in the eye gma of FIG. 44, the gma has a window or transparent part that allows the formation of retinal images during treatment, and has a vacuum line to provide suction on the contact surface of the lens. In this example, the lens is supported by two posts, each of which connects a pivot joint, such as a ball joint, to a pole thus connected directly to the support arm, and

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the companion pole linked by a coupling bar and second ball joint mounted on the side of the support arm. The arrangement of these components forms a frame, which can be of an adjustment mechanism, in this case the coupling bar is attached to a sliding and fixing screw assembly, which can be selectively repositioned along the axis of the support arm. The arrangement shown allows the eyepiece to have asymmetric pivot characteristics, whereby the resistance of the pivot can be selected to be different in the X and Y directions.

FIG. 45E illustrates an alternative embodiment similar to that of FIGS. 45A-D, in which the support frame for the lens 120 is rotated approximately 90 degrees. with respect to the support arm 180, so that the lens l2o is at the end of a lever arm around the axis of the support arm 180. The lever arm allows to transmit a pressure or reaction force of the lens 120 on the eye 30 as a torque around the support arm 180. This can be exploited or regulated by means of a torque spring or other actuator in the eyepiece holder (600 in FIG. 2).

Eyelid retractors

FIGS. 46A and 46B illustrate two exemplary embodiments of elastically connected eyelid retractors 320a, 320b having aspects of the invention, generally similar to those used during the acquisition of data shown in FIG. 26A-26E. Each of the retractors 320a, 320b includes a soft and non-abrasive hook-like part 323 configured to overlap and connect the eyelid, the hook being mounted on a handle portion 324. FIG. 46A shows a wire loop type hook and handle part, and FIG. 46B shows a retractor member of the Desmarres type having a soft curved hook-like member.

The part of the handle can be supported in several alternative ways (for example, held by the hand, glued to a support, mounted on a base, or the like), but an advantageous alternative is to connect the handle through a connection part Elastic 325 to a joint 326, such as a spring clip or the like. The connection may comprise a stretchable elastic member, which may comprise an elastic strip, an elastomeric tube or the like. A terminal joint is included to mount the connection on a convenient base, such as a spring clip, elastic fit, or the like. Either or both of the connection length or joint position can be adjusted to provide a selected connection voltage acting on the eyelid. A length adjustment accessory (not shown) may be included in connection 325, such as a friction loop, Velcro adjustment, or the like.

In certain embodiments, the connection is configured to join the patient so that the relationship of union to the eye is relatively constant, despite the movement of the patient. For example, the union 326 may include a spring clip that can clamp the patient's clothing adjacent to the face, such as a shirt collar, buttonhole, pocket, or the like.

FIG. 46C shows an optional tension release adjustment 328, which includes a coupling to limit the force, such as a magnetic or adhesive coupling, the coupling being configured to release if excessive tension is applied to the connection. For example, the coupling may include a pair of adhesion discs 327a, b of ferric oxide composition with magnetically made patterns, each disc fixed to an adjacent elastomeric tube section (upper or lower) 325a, b by a pin inserted in and attached to the lumen of the tube.

FIGS. 47A-47C illustrate an alternative embodiment of the top of an eyelid retractor 320c (A. front view, B. side view, and C. perspective), which has an extended hook portion 323 configured to slide behind the eyelid, and a top surface shaped like a mount. The dimensions shown are purely exemplary.

FIGS. 48A-48D illustrate an additional alternative embodiment 320d, generally similar to that of FIG. 24, and having an enlarged and asymmetrically curved hook part 323, configured to align with the eyelid in a comfortable connection configuration, while covering a substantial part of the eyelid. The complex curvature of the hook part allows you to follow the shape of the eye to minimize the stress of the eyelid to that required to expose the sclera for treatment. As shown in FIG. 48E, the retractor part 323 can be mounted on a handle 324 including a hinge mechanism 329 configured to align the handle with the retraction stress on the eyelid, for example, to relieve the stress of lateral folding on the eyelid due to the alignment of the mounting. The hinge mechanism 329 may be flexible in one or more directions, and may comprise one or more mechanical hinges or live hinges, and may comprise a rotating link and / or ball joint.

The attention is directed to FIG. 23, which shows the embodiment of retractor 320d of FIGS. 48A-48D as operatively connected to the lower eyelid of a patient. The top, curved, curved surface is configured to provide an adjacent scleral x-ray beam point of limit 311. All or a portion of the retractor body 320d may comprise a radio-opaque material to provide effective shielding of the eyelid and tissue. adjacent scattered or scattered radiation during treatment with X-ray beam emission.

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VIIB Additional embodiments of retinal and ocular imaging

In addition to the imaging device used in eye alignment, motion tracking and confirmation of beam position (see FIGS. 3A and 3B), embodiments of the radiotherapy system 10 that have aspects of the invention may include devices of formation of additional or alternative images to provide images of ocular structures such as the retina. For example, the system 10 may include a direct or indirect ophthalmoscope, a slit lamp biomicroscope, a fundus camera, an optical coherence tomography (OCT) system, a laser scanning ophthalmoscope (SLO), a laser scanning ophthalmoscope in lmea (LSLO), an ultrasonic eye imager, and the like.

FIGS. 49-52 illustrate aspects of an exemplary embodiment of a radiotherapy system including an LSLO instrument mounted to obtain images of a patient's eye before, during and / or after treatment. An LSLO is a simple, compact device that scans a laser line focused on the fundus or other ocular structure, and processes the reflected light to form an image.

FIG. 49 is a schematic diagram of a structure of an embodiment of LSLO 700, the boxes of the structure of the stage diagram of an operation process or method of use being also indicative. The figure is taken (with certain modifications) from US Patent 6,758,564. In summary:

(a) Light source 1 (for example, including one or more lasers or LED) provides a point of substantially visible, infrared and / or ultraviolet light source. The light initially propagates in an optical path to the eye 7 (incoming light), and subsequently propagates in an optical path reflected from the eye 7 (reflected light).

(b) Initially, the light from source 1 is received and converts a light line in the generator into line 2 (for example, including one or more lenses, a fixed optical cylinder, or a holographic optical element). The light line emitted from the line generator 2 is received by a beam conditioner 5, which includes beam separator 3 and scan reflector 4.

(c) Beam separator 3 (for example, rotating mirror or rotating prism) and scan reflector 4 are collectively configured so that incoming light and reflected light are made to follow separate paths in the distal part (relative to the eye ) of instrument 700: (i) incoming light propagates between light source 1 and beam conditioner 5; (ii) both incoming and reflected light propagate through an optical interface 6 arranged between the beam conditioner 5 and the eye 7; and (iii) the reflected light is deflected to propagate between the beam conditioner 5 and the linear detector 10.

(d) The eye 7 includes a cornea 20, a pupil 22 and a retina 24, and the region of the inner posterior wall of the eye 7 is generally referred to as fundus 26. The optical interface 6 (for example, an assembly of one or more more lenses) receives and focuses a line of light, the light being scanned by the reflector 4 in a direction perpendicular to the line to move through a part of the eye 7 such as fundus 26.

(e) The eye can interact with the light that affects different ways. The light can pass through the eye in transmission, and may be reflected from some regions of the eye, including the surfaces of the cornea 20 and fundus 26. The structures in the eye 7, such as layers in front of and behind the fundus 26, They can absorb and re-emit part of the light. The properties of transmission, absorption / remission, and reflection of parts of the eye 7 are a function of the wavelength of light and the structure and composition of the parts of the eye.

(f) The light that then returns from the eye 7 to LSLO 700 via interface 6 (collectively "reflected light") includes the reflection and / or absorption-remission of the incoming light line, with possible contribution of the ambient light environmental. The reflected light is received confocally by the optical interface 6, and then it is reflected by the scanning reflector 4 in a synchronized manner with the scanning of the incoming light line, so that the reflected light passes to the optics of the light line. imaging 8. The beam separator 3 may be arranged in the conjugate to the cornea 20, and the scanning reflector 4 may be arranged in the conjugate to the pupil 22.

(g) The image formation line optics 8 reconfigures the light reflected in a line, which passes a linear confocal aperture 9 and affects a linear detector 10. The linear confocal aperture 9 may be positioned to be conjugated to the line of illumination on the retina 24. The linear confocal opening 9 can be designed to prevent light from being confocally received by the apparatus through the linear detector 10. The linear detector 10, which can be a linear CCD matrix detector (for example , a linear matrix of 1 x 512 pixels) or a linear matrix 1 xn CMOS (n is equal to the number of pixels of the matrix), generates electrical signals corresponding to the received image.

(h) The electrical signal processor 11 receives the electrical signals from the linear detector 10, and may include an analog to digital converter (AaD) that converts analog light levels into digital signals, and may include a digital processor (e.g., one or more semiconductor microprocessor chips operatively mounted, or a commercially available personal computer) to receive, store, and analyze the signals, such as by the use of an image freezer.

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(i) The signal processor 11 may be connected to an image capture / presentation module 12, which may include any of a computer monitor, video monitor, an image storage medium, printer or the like. As is well known in the art, power supplies and motors are provided to operate the scan reflector 4, the light source 1, the linear detector 10, and the signal processor 11 and image capture / presentation 12. The Instrument components 700 described can be miniaturized and made compact if desired, and image data can also be transmitted for remote processing, use and visualization.

FIGS. 50A and 50B are an elevation view and a plan view respectively of an exemplary optical design of an LSLO 700 instrument configured to form images of the fundus of an eye, the example having particular elements functionally corresponding to the schematically diagrammatic embodiment in FIG. . 49. In summary:

(A) Light 202 (for example, a 3 mW 830 nm single mode fiber-coupled laser diode) substantially provides a point of light source, which expands to a light line by cylindrical lenses 204, 206, so that the beam remains collimated on a transverse axis, but focuses near the pupil conjugate and then quickly deflects on the other transverse axis. The light line strikes a rotating prism or mirror 208 to be directed to the scanning mirror 210, which is mounted to be moved by an actuator such as a galvanometer motor. The light line is scanned by the mirror 210 and is directed to pass through one or more lenses 212, 214, and 216, which are positioned and / or adjusted to pass the light line through a cornea 218 of a eye 222 and through a non-dilated pupil 220 of the eye to influence as a lmea focused on a fundus of the eye, which includes the retina 222.

(B) The reflected light leaves the eye through the pupil 220 and the cornea 218, passes through the lenses 216, 214, 212, and is redirected by the scanning mirror 210. The redirected path of the reflected light passes around the rotating mirror 208 and passes through the pupil stop 224, then passes through one or more lenses of the lens 226. Images of the laser line are formed by the lenses 216, 214, 212, and 226 confocally to a matrix linear CCD 228 (for example, a digital camera scanning camera). The side view of FIG. 50B shows the separation of the pupil in the small rotating prism mirror 208 (the incoming light is focused on the pupil conjugate) to allow the illumination beam (incoming) to pass to the retina 222 while acting as a stop for reflections corneals in the reflected light. The line 230 is scanned in the retina 222 by the scanning mirror 210 and the reflection is scanned and images are formed to the linear matrix CCD 228.

(C) The linear CCD reading is synchronized with the scanning movement of the mirror 210 and an image is acquired with an image freezer. A focus adjustment for the laser, and rotation and displacement adjustments of the line to align the laser line with the linear CCD matrix can be provided with desvm / tilt mounts, rotary mounts, and commercially available sliding mounts. The confocal system of lmea aligns quickly and optimizes on the length of the matrix. An ophthalmoscopic lens blade 229 that supports the lens 216 can be used to focus the light line in the eye, as well as to correct the ametropia. Thus a rectangular image of the fundus is obtained. The camera body can house one or more circuit cards including signal processor chips, and power and computer cables can be attached to the camera body.

FIG. 51 illustrates an exemplary LSLO 701 optical housing. Optical housing 701 may be provided with a place to house the electronic actuator plates for the SM source module and mirror directed by galvanometer G. The SM source module may contain electronic actuator and multiple sources of S laser diode light of different wavelengths (for example, 532, 670, 780, 830, and / or 905 nm) combined with dichroic beam splitters and / or collimators or L lenses. The illumination light is collimated and disseminated in one dimension with a CL cylindrical lens and it co-aligns with the return path with an optical BC beam combination. The line is focused on the retina with an SL scanning lens and OL ophthalmoscopic lens, and is scanned with a mirror directed by galvanometer G. The retrograde diffused light of the retina is scanned by the galvanometer through the pupil's stop. PS and focuses on linear matrices LA1,2 with the objective of the O detector. The BD beam shift optic separates and displaces the left and right sub-apertures for stereo operation, if desired. The pupil can be transferred to a conjugate between BC and G. The pupil can be divided into three parts: (i) left sub-aperture and (ii) right sub-apertures for stereoscopic imaging, and (iii) BC placed in the center in the pupil conjugate to block the corneal reflections of the detection.

In this example, the beam shift optic or BD beam splitter consists of two identical windows fused at a 37 degree angle. that work to move the beam before the objective of the detector to achieve stereopsis, producing the angle of the windows a lateral separation between the sub-openings in the pupil. The separate sub-aperture beams are directed through the objective of the O detector and pupil division optics to a pair of right and left linear detectors LA1,2. Alternatively, BD the optical beam displacement can be omitted so that the rays originating from the same structure will follow identical paths through the objective of the detector O to a single linear detector LA and do not produce stereoscopic disparity.

Additional description of the principles operating in LSLO and other examples of components, optical parameters and suitable aspects are described in US Patent 6,758,564, and in Hammer, et al .; "Line-scanning laser

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ophthalmoscope "; J. Biomedical Optics (2006) 114, 041126, each of these publications are incorporated herein by reference.

FIG. 52 illustrates an exemplary radiotherapy system having aspects of the invention, generally similar to the embodiments shown in FIGS. 1-6, and having an image forming system 410 'including a retinal imaging tool, such as axially mounted LSLO 700. See the description regarding FIGS. 3A and 3B for the description of common elements. LSLO 700 may be supported by an independent mounting of the positioning system 115 of FIG. 1, or it may be mounted on the positioner 115, to be supported in a suitable configuration of image formation. LSLO 700 can be adjusted by one or both of adjustable optics and an adjustable mount to be supported in an appropriate configuration of image formation and be compatible with the eye tracking optics, as required.

Note that in the case where an axial tracking camera 401 is included, one or both of a translation assembly 702 or an airship / retractable mirror 703 can be included to allow each camera 401 and LSLO 700 to access a path non-obstructed axial (system Z axis) in turn. Alternatively, the imaging system 410 'may omit an axial tracking camera, such as when tracking is performed only by off-axis cameras (for example, including a pair of stereoscopic cameras). It should be understood that an alternative positioning system 115 'can be included optimized to allow the operation of a retinal imaging system and a tracking system together, without departing from the invention.

In an alternative, the actuators of the positioning system 115 'can be used to provide a three-dimensional adjustment of the position of LSLO 700 for the alignment of retinal images. Alternatively or additionally, assembly 702 may provide one or more degrees of freedom (automated or manual) for adjusting the position of LSLO 700, such as X-Y-Z translation and / or angular adjustment of banding and guiding.

In an operational method that has aspects of the invention, LSLO 700 is configured and used to determine retinal alignment with respect to treatment axis 2820 before starting treatment. For example, a retinal image (registered with the radiotherapy coordinate system) can be used to adjust the treatment axis 2820 to intersect an anatomical feature from which selected images of the patient's eye have been formed, such as the fovea (see step 2555 of FIG. 2l A and FIG. 21D).

In another operational method that has aspects of the invention, LSLO 700 is configured and used to capture one or a plurality of retinal images during the course of the X-ray treatment. Such images can be used (for example, by methods of recognition and processing of images similar to those described herein) to directly monitor retinal movement with respect to the X-ray treatment beams, giving rise to the inactivation control or corrective action as needed (see step 2565 of FIG. 21A).

In an additional operational method that has aspects of the invention, LSLO 700 is configured and used to plan a treatment, using adjustable parameters of the assembly of the X-ray source 420 and positioner 115 (e.g., X-ray beam shape, diameter , dose distribution, overlapping beams, and the like) to customize the treatment to an injury of a particular form or distribution, as determined by a retinal image (other alternative or additional modalities to LSLO, such as OCT) may be included.

VIIC Alternative applications of radiation therapy

The methods and devices for monitoring and mapping motion based on images and radiation dose as described herein can be applied to the precision control of radiation therapy beams to other parts of a patient's body, in addition to the examples of treating an eye injury described in detail herein. In particular, in embodiments of the system and method of treatment having aspects of the invention, a contact member having one or more fiduciary markers can be connected or attached to a surface of a part of the patient's body adjacent to tissue that is going to treat The body part can be followed exactly by an image formation system, allowing the extrapolation of any movement of the body to the treatment target. A range of disease conditions can be treated in this way without departing from the spirit of the invention. Examples include radiation treatment administered to targets of the brain, spinal cord, a breast, musculoskeletal tissue, vasculature, abdominal or gastrointestinal lesions, both in humans and animals. Reference is made to U.S. application no. 11 / 956,295 filed on December 13, 2007, which is incorporated by reference herein. In particular, see the description related to FIGS. 13-22 of that request.

FIG. 53 illustrates an exemplary radiotherapy system 6010 having aspects of the invention, generally similar to the embodiments shown in FIGs. 1-6, and configured to administer radiation therapy, such as by directing an orthovoltage X-ray beam firmly collimated through a body surface to a target treatment region 6000 located in the body. The monitoring of the movement of the target and the control of the emission or direction of the radiation can be carried out by methods generally similar to those described herein with respect to FIGS. 32-42, among other sites.

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In the example shown in FIG. 53, the treatment target is a region that includes vulnerable carotid lesions found in a patient's neck. The goal of treatment may be the prevention of restenosis or treatment of hyperplasia, or treatment of vulnerable atherosclerotic plaques present in the vessel. Radiation therapy can be administered in association with the positioning of a stent or other vascular device. Radiation therapy may be combined with pharmaceutical therapy before or after the installation of radiation therapy, such as by administration of compounds described herein, administered locally or systematically to reach the treatment site. In some embodiments, radiotherapy is administered in a fraction of about 10 Gy to about 50 Gy and in some embodiments, radiotherapy is administered in doses of about 5 Gy to about 10 Gy in various fractions, which can be applied through different paths. , as discussed in other embodiments.

The contact member 6110 is connected to the neck surface, such as with a pressure sensitive adhesive, a pincer or strip member, or the like. One or more fiduciary marker elements 6120 are mounted on the surface of member 6110, so that images can be formed by camera 6250 of the image formation system 6240. FIG. 53 represents the administration of x-rays through the skin covering the peripheral vessels 6100 through one or more beams of orthovoltage x-rays 6060 from radiotherapy devices 6050 to regions of peripheral vascular disease 6000.

The contact member 6110 may comprise a shaped or elastic material, or it may comprise a nested material. Alternatively, the contact member 6110 may have a rigid upper part attached to a material that contacts the surface of the shaped skin. In other embodiments, the contact member may be a disposable unit that is conformable in shape at the time of application to the skin, being composed to harden (for example, by a curing resin or the like) in place to provide a platform ngida during treatment. The contact member 6110 may comprise a material that is easily penetrated by orthovoltage radiation, such as a low density polymer layer, or the like. The contact member 6110 may have radiopaque fiduciary elements or markers, allowing convenient location in the formation of x-ray images. The contact member 6110 may be molded to expose parts of the skin at the point of entry of the beam of rays. X.

Alignment and registration of the contact member 6110 with a coordinate system of the treatment device 6050 can be performed with methods and devices such as those described with respect to the FlGS. 3-4 and 17-25, such as by aligning member 6110 to a processing axis 6220 by computer processing of images captured by camera 6250. The position of treatment target 6100 relative to contact member 6110 can be determined by various means, such as medical imaging, CT scans, ultrasound, and the like, to record the position of member 6110 with respect to target 6100. The subsequent movement of the patient resulting in movement of contact member 6110 and target 6100 can determined by monitoring the movement of member 6110 by the methods described in detail herein, suitably adapted to the geometna / anatoirna of the part of the body being treated. The radiotherapy beam energy, beam width, and direction can be chosen according to tissue, disease, and treatment time.

Example of eye tracking without an eye contact member.

FIGS. 54, 55 and 56 illustrate embodiments of alternative exemplary radiotherapy system and method that have aspects of the invention, generally similar to the embodiments shown in FIGS. 1-6, but which have an eye tracking system that employs a training system. of images of the eye that is operative independently of a contact member with the eye, and can be used without a contact member with the eye. In addition to the examples described below, please see the examples, illustrations and description of co-invented priority application No. 12 / 103,534 filed on April 15, 2008.

Alignment of the corneal reflection

FIG 54 shows a schematic view of an alignment and treatment embodiment 300, including a cross-sectional view of a part of the eye taken along the geometric axis. In the example shown, the imager 306 is coupled with a positioning device 310 used to position an ophthalmic treatment device 312, for example, a radiotherapy device. The position of the geometric axis 18, properly located by the alignment system, can be used by positioning the device 310 to direct the ophthalmic treatment device 312 to a tissue target 318, which may or may not be positioned along the axis 18. In In this example, target 318 is positioned as an axis relative to the geometric axis 18.

The system 300 includes an image capture device 302 positioned to form images of the eye 10 along the geometric axis 18. The image capture device 302 provides video image data of the eye 10 to a monitor 304. Attached to the monitor 304 is an image generator 306, such as a personal computer programmed with commercially available computer aided design software, capable of generating and superimposing geometric images in the image of the eye 10 that appear on the monitor 304. In operation, the generator of images 106 superimposes an image on the image of the eye 10 on the monitor 304. The superimposed image has a geometric shape sized and positioned to coincide with a

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distinctive anatomical feature that appears in the image of the eye 10. The selected distinctive anatomical feature must be one that remains unchanged in size, shape and position with respect to the eye 10.

A preferred distinctive anatomical feature is limbo 26, which is circular. Accordingly, as a first stage, an image generator 306 can be operated to position an image of a circle on the image of the blade 26. The imager 306 can then locate the center 30 of the blade 26. Next, the Purkinje 32's first reflex is identified. The light from the light source 308 travels along the path 35, entering the eye 10 through the cornea 12 and is directed through the lens to the retina. A part of the light is reflected at point 32 outside the anterior surface of the cornea 16, identifying the first Purkinje reflex. The alignment of the center of the blade 30 with the first Purkinje reflex 32 defines and allows the exact location of the geometric axis 18 as a reference axis with respect to the external coordinate system.

With the position of the geometric axis 18 properly located, the geometric axis 18 becomes a reference axis, and can thus be used by the positioning device 310 to direct the ophthalmic treatment device 312 towards the eye at a predetermined orientation relative to the geometric axis 18 so that a therapeutic beam, such as a collimated electromagnetic radiation beam 311, can be directed to a predetermined coordinate of the eye 10 to enter the surface of the body (point 324 on the surface of the sclera 17) and propagate to influence a target of the selected tissue 318.

Note that FIG. 54 is a flat illustration of the three-dimensional eye anatoirna, and in general it is not necessary for the beam axis 311 of the device 312 to intersect the reference geometric axis 18 (i.e., axes 18 and 311 can be found, but not necessarily, in a plane). In general, the beam axis 311 can have a selected orientation with respect to the geometric reference axis 18, such as an angle "0" and deviation "d" selected from the axis 18. The device 312 can in fact be angular to intersect any anterior-posterior lmea in the eye.

Once the reference axis 18 is identified, the treatment can be carried out by a device oriented with respect to the axis 18, for example, where a treatment target is located along the axis 18 (see the description regarding the FlG 3B). Alternatively, a different axis 19 can be defined with respect to axis 18, for example, by a displacement of the distance "d", such that axis 19 intersects the treatment target 318 positioned off-axis with respect to axis 18. Axis 19 It can be called the "treatment" axis. On the basis of the direct geometry, the device 312 can now be positioned such that its beam axis 311 intersects the treatment axis 19 on the target of the fabric 318. The axis 18 can be used to define one or more correlated geometric axes in the external coordinate system, and to define one or more additional intersection points with respect to beam 311. Observe for treatment targets that are on the reference axis 18, the deviation "d" may be approximately zero, and for treatment administered to through or in the cornea, the angle "0" can approach zero.

As shown in FIG. 54, in an example of an X-ray treatment with orthovoltage for macular degeneration, the deviation d is selected to define a treatment axis 19 centered on the macula, the angle 0 is selected to provide intersection of the beams 311 on the macular surface and the entry point at the surface 324 in a region of the lower anterior sclera beyond the limit of the limbus 26. In this example, an X-ray beam source may be positioned by the positioning device 310 to project a collimated beam. from a distance from the selected x-ray source to form a beam having a characteristic width at the entrance to the tissue "w". Note that, although a treatment beam can project through an eyelid or other tissue near the eye, the eyelids (in this case the lower eyelid) can conveniently retract to expose an additional area of the anterior sclera 17.

Alignment by limbo dimensioning

FIGS. 55A-55C illustrate another embodiment having aspects of the invention, including schematic side views of an anterior part of an eye in three orientations with respect to an embodiment of an alignment system having aspects of the invention, which represents a method for using the limbo sizing to define the reference axis. In this method, it uses the dimensioning of the blade to define the geometric axis. In this embodiment, as illustrated in FIGS. 55A-55C, a schematic side view of a part of an eye 10 is shown. The alignment system and method in this embodiment of the invention is based on the detection of the maximum area of the blade 26 of the eye of the subject 10. cornea 12 of eye 10 is characterized by an anterior surface 16 and a posterior surface 14 that are concentric with each other, iris 24 extending outwardly to posterior surface 14 of cornea 12. The intersection circle between iris 24 and the surface interior 14 is a distinctive anatomical feature known as limbo 26. Images of the limb of an eye can be easily formed.

As discussed above, an "axis of interest" identified as a reference axis for embodiments of the eye alignment method having aspects of the invention may advantageously, but not necessarily, be the optical axis or the geometric axis of the eye. . The geometric axis 18 in FIGS. 55A-55C, can be determined to be aligned with the external coordinate system of the system 100 when the axis 18 is coincident with the center of the blade 26 when the area circumscribed by the limit of the blade is positioned to achieve its maximum apparent area with respect to the camera 102. In the illustrated embodiment, camera 102 is

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positioned to form images of the eye 10 along the direction 600. The light from the light source 108 travels along the path 35, entering the eye 10 through the cornea 12 and is directed by the lens to the retina. The camera 102 provides video image data of the eye 10 to the monitor 104. Attached to the monitor 104 is an image generator 106. In operation, the image generator 106 generates an image of the blade 26 and presents it on the monitor 104. accordingly, as a first stage, the image generator 106 can be operated to generate a first image of the blade 26 when the eye is in a first position, as shown in FIG. 55A. The imager 106 can then locate the limit of the blade 26.

Next, the first area defined by the limit of the limbus is determined. As shown, FIG. 55A represents the angled eye 10 so that the area 610 defined by the limit of the limbus is smaller than the maximum. The camera 102, or preferably the eye 10, is then positioned in a second position and the imager 106 is operated to generate a second image of the blade 26, as shown in FIG. 55B. The imager 106 can then locate the limit of the blade 26. Next, the second area 611 defined by the limit of the blade is determined. As shown, FIG. 55B represents the angled eye 10 so that the area 610 defined by the limit of the limbus is smaller than the maximum. This process is repeated until the maximum area defined by the limit of the limbus is identified, as illustrated in FIG. 55C, where address 600 co-aligns with the reference axis 18. The detection of the maximum area 612 of 26 indicates that the eye is in alignment with the system, and the reference axis 18 is defined.

Limit Limit Identification

FIG. 56 is a diagram of an exemplary method having aspects of the invention, showing a sequence of successive data processing steps used to identify the limbic limit and limbic center (alternatively or in addition to the methods described herein with respect to FIGS. 21A-E).

As indicated above, the limbic limit is determined in the described alignment methods. The determination of the limbic limit, and the limbic center, can be achieved in a variety of ways. An exemplary method for determining the center of the limbus is illustrated diagrammatically in FIG. 56, which shows the sequence 700 of the successive data processing steps to identify the limbic limit and the limbic center. The input image 710 represents the eye image data with a relatively high resolution that is applied. The first stage of data processing 720 is to average and reduce the input image 710. This can be achieved by convolving the data defining the input image 710 with a low-pass Gaussian filter that serves to spatially average and this way to reduce high frequency noise. As spatial averaging introduces redundancy in the spatial domain, the filtered image is then sub-sampled without any additional loss of information. The sub-sampled image serves as the basis for further processing with the advantage that its smaller dimensions and smaller resolution result in less calculation demands compared to the original input image, full size 710.

The following data processing steps involved in locating the limit of the limbus, and center of the limbus, include the sequential location of several components of the limbic limit. In sequence, step 730 locates the limbic (or outer) limit 732 of the iris. The localization stage can be carried out in two sub-stages. The first sub-stage includes an edge detection operation that is tuned for the expected configuration of high contrast image localization. This tuning is based on the generic properties of the limit component of interest (for example, orientation) as well as specific boundaries that are provided by the previously isolated limit components. The second sub-stage includes a scheme in which the detected edge pixels serve to exemplify particular values for a parameterized model of the limit component of interest.

In more detail, for the limbic limit 732 of step 730, the image is filtered with a gradient-based edge detector that is tuned in orientation to favor almost verticality. Thus, even with occluded eyelids, the left and right parts of the limbus should be clearly visible and oriented near the vertical, when the head is in a straight position. The limbic limit is modeled as a parameterized circle by its two center coordinates, xc and yc, and its radius, r. The detected edge pixels are thinned and then represented in histogram in a three-dimensional space (xc, yc, r), according to the permissible values (xc, yc, r) for a given image location (x, y). The point (xc, yc, r) with the maximum number of votes is taken to represent the limbic limit. Finally, with the limbic limit 732 isolated, the final processing stage 740 includes locating the center 750 of the limbus.

The strategy described above to identify the center of the limbus can be generalized in several ways. For example, representations of the image other than edge detection based on oriented gradient can be used to increase the limits of the iris. Secondly, alternative settings for the iris limit can be used. Finally, the iris limit location can be done without the initial stages of average and subsampling.

From the above, it can be seen how various objects and features of the invention are fulfilled. Although certain aspects and embodiments of the description have been described, they have been presented only as

example, and are not intended to limit the scope of the description. The methods and systems described herein may be included in a variety of other forms, and the components, arrangements, and alternative data acquisition and processing devices may be included or replaced. All publications and patents cited herein describe and present systems and methodologies that may be used in connection with the invention.

Claims (14)

5 10 fifteen twenty 25 30 35 40 Four. Five fifty 55 1. A system for treating a target area in a patient with an irradiation beam, comprising: (a) a tracking assembly configured to track the position of a region of the patient's body that contains the target area and at least one radiation sensitive area relative to a known reference axis (18) in an external coordinate system; (b) a beam source (108) configured to direct a collimated X-ray beam to the patient's target area along a known beam axis (1400, 1400a, 1400b, 1400c) to intersect with a known treatment axis (19, 2820) defined with respect to the reference axis (18, 2810) in the external coordinate system; Y (c) a processor (106, 501) operatively connected to the tracking device and beam source (108), and configured to: (i) determine, from the known position of the body region in the external coordinate system, the coordinates of the target area to be treated and the coordinates of the at least one radiation sensitive patient structure; (ii) during a period in which the beam is being directed along the known beam axis (1400) to intersect with the known treatment axis (19) in the target area, and on the basis of information received from the device follow-up, follow the positions of the target area to be treated and the at least one radiation sensitive structure; (iii) on the basis of the known beam axis (1400) of the collimated beam in the external coordinate system, and the instantaneous positions of the target area to be treated and the at least one radiation sensitive structure, calculate an equivalent of total radiation received in the target area and at least one radiation sensitive structure; Y (iv) on the basis of the calculated radiation equivalents of step (iii), control the radiation beam to ensure that the at least one radiation sensitive structure receives no more than one radiation equivalent preselected during the treatment. 2. The system of claim 1, wherein the tracking assembly includes (i) an image forming device for recording an image of a region of the patient's body that contains natural landmarks or fiduciary markers defining an axis geometric of the region from which images have been formed and (ii) an image detector operatively connected to the imaging device to convert the recorded image into a digital image composed of pixels with known coordinates, and the processor (106, 501) is operatively connected to said detector to determine the coordinates of the pixels of the geometric axis of the body region and the step (ii) of the processor operation includes using the coordinates of the pixels of the geometric axis, with respect to coordinates of the known pixels of the reference axis (18), to follow the position of the patient's body region with respect to the reference axis (18). 3. The system of claim 1, for use in the treatment of an eye injury, wherein the region of the body includes the patient's eye, the target area includes the eye injury, the at least one radiation sensitive structure includes the optical disc of the eye, the natural reference points of the eye that define its geometric axis are the center of the limbus and a first corneal reflection, and the beam source (108) produces a collimated X-ray beam. 4. The system of claim 1, for use in the treatment of an ocular lesion, wherein the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, and the natural reference points of the eye that define its geometric axis are the center of the limbus and a first corneal reflection, which also includes an eyepiece adapted to be placed in the patient's eye, centered in this way that the geometric axis of the eye corresponds approximately to the axis of the eyeglass, and a detector to determine the coordinates of the axis of the eyeworm in the external coordinate system, and the processor (106, 501) is operatively connected to said detector to determining the coordinates of the axis of the eyepiece (110a) and step (ii) of the processor operation includes using the coordinates of the axis of the eyepiece, relative to the known coordinates of the axis of reference rencia (18), to follow the position of the patient's eye with respect to the reference axis (18). 5. The system of claim 1, wherein said tracking system is operative to capture a plurality of time-sequenced images of the body region and its reference points during the treatment method, and said processor (106, 501) is operative to determine the coordinates of the geometric axis of the region of the body for each of the plurality of images, and in step (ii) to determine a time-dependent change in the coordinates of the target area to be treated. and the at least one radiation sensitive structure. 6. The system of claim 5, wherein the processor (106, 501) is operative to carry out, in the step (iii) the generation of a map of total radiation equivalent that covers the target area and the at least one area 5 10 fifteen twenty 25 30 35 40 Four. Five fifty 55 sensitive to radiation in the region of the patient's body, and in step (iii), to determine from the map of total radiation equivalent, the radiation equivalent received at any time during treatment by the target area and at least one radiation sensitive area. 7. The system of claim 6, for use in the treatment of an eye injury, wherein the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, and the processor (106, 501) is operative, to carry out in step (iii) the generation of a map of equivalent of total radiation that covers the target area and the at least one sensitive area at radiation in the region of the patient's body, and in step (iii), determine from the map of total radiation equivalent, the radiation equivalent received at any time during treatment for the eye injury and at least one sensitive area to radiation. 8. The system of claim 1, for use in the treatment of an eye injury, wherein the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, and said processor (106, 501) includes a model of the human eye by means of which the coordinates of the lesion to be treated and the at least one radiation sensitive structure can be determined, when the patient's eye is superimposed on the eye model. 9. The system of claim 8, wherein the eye model in the processor (106, 501) includes a virtual means by which the attenuation of a radiation beam along a known path through the model can determined, and the processor (106, 501) is operative to determine from the known intensity of the beam and the length of the radiation path through the virtual medium in the eye model, the amount of radiation received by the retina in the eye model. 10. The system of claim 1, for use in the treatment of an ocular lesion, wherein the region of the body includes the patient's eye, the target area includes the ocular lesion, the at least one radiation sensitive structure includes the optical disc of the eye, in which said processor (106, 501) is operative, to determine the position of the ocular lesion in the external coordinate system, to determine a treatment axis (19, 2820) in the coordinate system of treatment that intersects the injury. 11. The system of claim 10, wherein said processor (106, 501) is operative to determine at least two different axes of treatment in the treatment coordinate system, and to control the radiation beam to administer approximately equal doses. of radiation in the injury along each of the different known axes. 12. The system of claim 11, wherein said processor (106, 501) is operative to turn off the beam that is directed to the patient's eye, when the distance between the position of the patient's injury, as determined in operation (d) (ii), and the intersection of the beam axis in the retina, is greater than a predetermined threshold distance. 13. The system of claim 1, wherein said processor (106, 501) is operative to direct the beam in front of the patient's retinal region until the spatial accumulation of radiation mapped in the lesion of the eye model reaches a level of predetermined dose. 14. Code readable by operating machine in an electronic computer (501) included in a treatment system according to claim 1 comprising a collimated X-ray source, an external coordinate system, a reference axis (18), an axis of radiation beam, a body tracking device and a body axis, in which the machine-readable code operates to monitor the total radiation dose received at a target site during the course of treatment in which the target site is irradiated with collimated x radiation, to perform the stages that include: (a) define, in the external coordinate system, the coordinates for (i) the reference axis, (ii) the radiation beam axis, and (iii) the target site that, when the body axis that has a relationship known to the target site aligns with the reference axis (18), puts the radiation beam at the center of the target area, (b) receive from the body tracking device, continuous information during the course of radiation treatment on the position of the body axis with respect to the reference axis (18), (c) from the information received in step (b), and from the known intensity of the beam in the radiation beam, calculate the spatial distribution of radiation received in the region of the target site and at least one structure sensitive to radiation during the course of treatment, and (d) use the spatial distribution of radiation calculated in step (c) to monitor the total radiation dose at the target site during the course of treatment and at least one radiation sensitive structure to ensure that the at least one sensitive structure The radiation does not receive more than one pre-selected radiation equivalent during the treatment.