WO2008137795A1

WO2008137795A1 - Cardiac output measurement devices and methods

Info

Publication number: WO2008137795A1
Application number: PCT/US2008/062569
Authority: WO
Original assignee: Icu Medical, Inc.
Priority date: 2007-05-03
Filing date: 2008-05-02
Publication date: 2008-11-13

Abstract

In certain embodiments, a device (10, 10', and 10') for measuring cardiac output of a patient includes a probe (14, 14', 14', 414, 514, 614, 714, 814, 914, 1014, 1114) having an energy producing element (20, 120) and an energy sensing element (22, 122) in spaced relation to one another. In some embodiments, the energy producing element is upstream from the energy sensing element, and can be located at a distal end of the probe. The probe can include one or more mixers (130, 1170) and/or one or more spacers (180) between the energy producing element and the energy sensing element. The probe can include one or more positioning members (140, 520, 670) configured to orient the probe within a blood vessel and, in further embodiments, substantially center the probe within the blood vessel. In some embodiments, the probe is configured to be introduced into a radial artery.

Description

CARDIAC OUTPUT MEASUREMENT DEVICES AND METHODS

RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S. C. § 119(e) of U.S. Provisional Application No. 60/915,898, filed May 3, 2007, titled CARDIAC OUTPUT MEASUREMENT DEVICES AND METHODS, and U.S. Provisional Application No. 61/014,743, filed December 18, 2007, titled CARDIAC OUTPUT MEASUREMENT DEVICES AND METHODS. The entire contents of each of these applications are hereby incorporated by reference herein and made a part of this specification.

BACKGROUND

Field

[0002] The present inventions relate to devices and methods for acquiring data regarding the cardiovascular system of a patient. More specifically, the present inventions relate to devices and methods for acquiring data regarding cardiac output and, in some arrangements, other parameters. Description of Related Art

[0003] The monitoring of cardiac output is a common diagnostic technique used to evaluate the heart function and fitness of a patient. Cardiac output is sometimes defined as the volume of blood pumped by the heart over a period of time and is typically expressed in units of liters per minute (L/min.). Multiple techniques exist to measure or estimate cardiac output. However, the existing methods suffer from one or more disadvantages, including lack of precision, discontinuous or interrupted data collection, high risk of infection, and significant discomfort and inconvenience to the patient.

[0004] One method of measuring cardiac output is known as thermodilution. This method involves producing a temperature change at one point in a blood vessel and measuring the temperature of the blood at a second point in the vessel. The measured change in temperature at the second point provides an indication of the blood flow volume through the vessel. In practice, thermodilution devices and methods have generally been used within a catheter lodged in a patient's blood vessel. Such catheters may include a heating element and a temperature measurement element. A thermodilution catheter is sometimes advanced through the vessel so that it resides at least partially in a heart chamber.

[0005] The heating element produces a temperature change in the blood flowing past it within the vessel. The temperature change is measured by the temperature sensing element, usually located in the catheter, at a point in the blood vessel downstream from the heat producing element. As used herein, the term "upstream" refers to the direction from which blood flow originates within a blood vessel, and "downstream" refers to the direction where blood flow is going within a blood vessel. The temperature change and the quantity of heat introduced to the blood are utilized to determine the blood flow rate within the vessel through a mathematical relationship.

[0006] Although certain conventional thermodilution methods can be relatively accurate in some applications and circumstances, such methods have many shortcomings. For example, if pulmonary artery thermodilution catheters remain within the patient for an extended period of time, the risk of infection becomes significant. It has been estimated that the cost of treating infections caused by pulmonary artery thermodilution catheters can be many times the combined cost of the catheter and the implantation procedure. Furthermore, while the pulmonary artery thermodilution catheters are in place, the mobility of the patients may be significantly restricted. In addition, the presence of a pulmonary artery catheter for an extended period of time is likely to be uncomfortable for the patient because the diameter of the catheter is typically relatively large in comparison with the diameter of a blood vessel. The large size of the catheter can also cause trauma, damage, and other interference within the vessel by contacting internal tissues and impeding blood flow.

[0007] Another method for determining cardiac output involves monitoring a patient's "whole body oxygen consumption." In this method, a first probe is generally placed within an artery of the patient and a second probe is placed within a vein of the patient. The oxygen content of the arterial blood is compared with the oxygen content of the venous blood in order to estimate the body's overall oxygen consumption. The whole body oxygen consumption estimate is then used to estimate the cardiac output. This method has many disadvantages as well. The method typically depends upon several assumptions about the patient's overall body characteristics and also involves averaging several blood parameters. The body's oxygen consumption is not a fixed value, but tends to fluctuate, even if cardiac output remains constant. Accordingly, the use of whole body oxygen consumption to estimate cardiac output may lead to undesirable errors and delays in the reporting of cardiac output events. Although the individual arterial and venous probes used in this method may be smaller than in the typical thermodilution method, multiple access points are generally required in order to collect data from both an artery and a vein.

SUMMARY

[0008] Some embodiments provide a blood data acquisition component with an energy producing element, a temperature sensing element, elongate electrical leads connected to each of these elements, and one or more coatings (such as electrical or thermal insulator coatings) surrounding at least a portion of the elements and/or leads. In certain embodiments, a catheter body is generally not required to support the electrical components or lead wires. As a result, the cross-sectional dimensions of the portion of the device inside of the patient can be greatly reduced in comparison to typical pulmonary artery thermodilution catheters. In addition, smaller blood vessels can be utilized, such as the radial artery, for example. Furthermore, the risk of infection can be greatly reduced because the portion of the blood measuring component that passes through the skin of the patient can be much smaller than in a typical thermodilution method. In such an arrangement, the device can be implanted for relatively long periods of time with minimized risk of infection and discomfort to the patient. Moreover, the patient's pain upon insertion and the discomfort of prolonged usage can be significantly diminished. In other embodiments, a catheter or other coating of suitable size and configuration can be used to deliver, support, protect, cover, contain, and/or communicate blood or other fluid to the data acquisition components or elements disclosed herein.

[0009] In certain embodiments of a cardiac output measuring device, the blood data acquisition component or probe includes an element for delivering energy or matter, such as, for example, an energy producing element. In some embodiments, the device includes a first pair of lead wires configured to transmit electric current through the energy producing element. The device also can include a temperature sensing element and a second pair of lead wires configured to transmit electric current through the temperature sensing element. At least one coating can be configured to electrically insulate each wire of the first and second pairs of lead wires from one another. The coating(s) can provide electrical insulation of the lead wires, energy producing element, and/or temperature sensing element. The coating(s) can also impart a desired degree of stiffness to the blood data acquisition component to achieve a particular positioning or orientation of the component within the blood vessel. The coating(s) can also include one or more substances that produce or enhance antimicrobial or anticoagulant effects. The first and second pairs of lead wires can be secured in an elongate bundle.

[0010] In some embodiments, a device for measuring cardiac output includes a probe that can be connected to one or more controllers configured to calculate cardiac output utilizing information regarding a quantity of energy introduced to the blood within the vasculature by the energy producing element and a change in temperature of the blood detected by the temperature sensing element. Herein, the term "controller" refers to a device that interfaces with the probe, such as by electrical or wireless communication. The controller may comprise one or more receivers, transceivers, processors, or other electrical components that may perform one or more functions, such as sending one or more signals to the probe, receiving one or more signals from the probe, interpreting signals or data, and computation. The controller may be incorporated into or make use of special or general purpose computers. In some embodiments, a first transceiver is electrically connected to the energy producing element and the temperature sensing element. A second transceiver is electrically connected to the controller. The first transceiver and the second transceiver communicate with one another over a wireless connection to transmit control signals and data signals between the controller and the probe.

[0011] In some embodiments, a method of determining the cardiac output of a patient includes accessing an artery of the patient such as the radial artery. A probe is positioned within the radial artery and is used to introduce a quantity of matter or energy (e.g., a quantity of heat, of heated fluid, of cooled fluid, or of electromagnetic radiation) to the blood within the radial artery. The probe is also used to measure a temperature change within the radial artery. The cardiac output is calculated by the controller based on the quantity of matter or energy introduced and the detected temperature change over time.

[0012] In some embodiments, a probe for measuring cardiac output includes an element for delivering a quantity of energy or matter (referred to for convenience as a quantity delivery element) and an energy sensing element in spaced relation to one another. In some embodiments, the quantity delivery element is configured to be positioned upstream from the energy sensing element within a blood vessel, and can be located at a distal end of the probe. In some embodiments, the probe includes one or more mixers, and in further embodiments, includes one or more spacers, between the quantity delivery element and the energy sensing element. The mixers and/or the spacers can be configured to disrupt laminar blood flow and provide relatively uniform blood temperatures across a cross-sectional area of the blood vessel near the energy sensing element. The probe can include one or more positioning members configured to orient the probe within a blood vessel and, in further embodiments, substantially center the probe within the blood vessel.

[0013] In some embodiments, a probe for measuring cardiac output includes a quantity delivery element and an energy sensing element. The probe can include one or more extensions configured to orient the probe within a blood vessel and, in further embodiments, substantially center the probe within the blood vessel. The one or more extensions can be configured to permit the probe to move within the blood vessel in a first direction more easily than in a second direction. In other embodiments, the one or more extensions can be configured to permit the probe to move within the blood vessel in the first direction about as easily as in the second direction. In some embodiments, the first direction is a proximal direction and the second direction is a distal direction. The probe can include a sheath configured to retain the extensions in a compressed state. In some embodiments, the sheath can be removed when the probe is positioned within a blood vessel, thereby permitting the extensions to expand and position the probe. In further embodiments, the sheath is separable into two or more portions.

[0014] In some embodiments, a probe for measuring cardiac output includes a quantity delivery element and an energy sensing element. The probe can include one or more expansion members configured to transition between a substantially mobile state and a substantially fixed-position state. In some embodiments, the probe includes an actuator configured to move the one or more expansion members between the substantially mobile and the substantially fixed-position states. The actuator can include one or more lines that move relative to a lead body to transition the one or more expansion members between the substantially mobile state and the substantially fixed-position state. The lead body can house the energy sensing element. In other embodiments, the actuator includes a core that moves relative to a sheath. In some embodiments, the core houses the energy sensing element.

[0015] In some embodiments, an apparatus for measuring a physiological parameter in a radial artery of a patient comprises an elongate body, a delivery element, a sensing element, and at least one support. The elongate body can be configured to be inserted at least partially into a radial artery upstream from an insertion point in the radial artery and to remain temporarily at least partially inserted into the radial artery. The delivery element can be positioned in proximity to a distal end of the body. The delivery element can be configured to deliver a quantity of matter or energy to blood within the radial artery in proximity to the delivery element. The sensing element can be fixed to the body and spaced from the delivery element at a position proximal to the delivery element. The sensing element can be configured to sense a characteristic of the blood that is changed by the delivery of the quantity of matter or energy. The at least one support can be coupled with the body and can be configured to inhibit contact between the delivery element and a wall of the radial artery while permitting blood to flow through the radial artery.

[0016] In some embodiments, an apparatus for monitoring a patient's cardiac output in a radial artery of a patient comprises a body, an emitting element, a detecting element, at least one positioner, and a controller. The body can comprise a biocompatible material and can be sized for at least partial insertion into a radial artery of a patient. The emitting element can be coupled proximate to a distal end of the body that is to be inserted into the radial artery. The emitting element can be configured to emit energy into blood surrounding the emitting element in the radial artery. The detecting element can be connected to the body at a location that is spaced from the emitting element and is farther from the distal end of the body than the emitting element. The detecting element can be configured to detect a change to the blood caused by the energy emitted by the emitting element. The at least one positioner can be configured to position the body within the radial artery such that the emitting element is spaced from a wall of the radial artery. The controller can be in communication with at least one of the emitting element to drive the emitting element, and the detecting element to acquire data from the detecting element.

[0017] In some embodiments, a method of estimating cardiac output in a patient is provided. At least a portion of an elongate body can be inserted into a radial artery of a patient such that a distal end of the elongate body is upstream of a location where the elongate body is inserted into the radial artery. The elongate body can have an emitter attached in proximity to the distal end and a sensing element attached to the elongate body and spaced proximally from the emitter. The elongate body can be supported from within the radial artery such that movement of the elongate body within the radial artery is inhibited and a substantial portion of the elongate body is spaced from an interior wall of the radial artery. A quantity of energy can be delivered from the emitter to blood at a first location within radial artery. An energy level at a second location within the radial artery can be detected using the sensing element, which can be located downstream from the first location. A value related to cardiac output can be calculated based on the quantity of energy delivered to the blood at the first location and the energy level detected at the second location.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] These and other features, aspects, and advantages of the present inventions are described below with reference to drawings of several embodiments, which are intended to illustrate, but not to limit, the present inventions.

[0019] Figure 1 illustrates a cardiac output measurement device introduced into a blood vessel of a patient for monitoring cardiac output.

[0020] Figure 2 illustrates a portion of the cardiac output measurement device of Figure 1 positioned within the radial artery of the patient.

[0021] Figure 3A is a schematic illustration of a portion of a cardiac output measurement device within a radial artery of the patient.

[0022] Figure 3B is an enlarged schematic illustration of a portion of the cardiac output measurement device of Figure 3A, taken along view line 3B shown in Figure 3A.

[0023] Figure 4 is an enlarged, partial view of a distal end portion of a cardiac output measurement device in which the lead wires are joined by a coating.

[0024] Figure 5 A is a cross-sectional view of a configuration for lead wires in a cardiac output measurement device, taken along view line 5A-5A in an alternative arrangement of Figure 4.

[0025] Figure 5B is a cross-sectional view such as that shown in Figure 5A of another embodiment, or another portion, of a cardiac output measurement device that includes a lead body having multiple lumens.

[0026] Figure 6 is a schematic illustration of another embodiment of a cardiac output measurement device. The cardiac output measurement device includes additional components, such as sensors, to permit the monitoring of other blood parameters.

[0027] Figure 7 is a schematic illustration of another embodiment of a cardiac output measurement device. The cardiac output measurement device is configured for wireless communication with a controller to provide for increased freedom of movement for the patient.

[0028] Figure 8 illustrates a perspective view of an embodiment of a probe configured to be introduced in a blood vessel of a patient. [0029] Figure 9 A illustrates a partial cross-sectional view of the probe of Figure 8 taken along the view line 9A-9A that shows an embodiment of a coiled heating element.

[0030] Figure 9B illustrates a partial plan view of the probe of Figure 8 taken along view line 9B that shows an embodiment of an energy producing element in greater detail.

[0031] Figure 10 illustrates an enlarged view of the probe of Figure 8 taken along view line 10 that shows an embodiment of mixing features in greater detail.

[0032] Figure 1 IA illustrates a partial cross-sectional view of the probe of Figure 8 taken along view line 1 IA-I IA that shows an arrangement of a thermistor and lead wires.

[0033] Figure 1 IB illustrates a partial cross-sectional view such as that shown in Figure HA of another embodiment of a probe that includes separate lumens for housing a thermistor and lead wires.

[0034] Figure 12A illustrates a cross-sectional view of the probe of Figure 8 taken along view line 12A- 12 A that shows an arrangement of two sets of lead wires.

[0035] Figure 12B illustrates a cross-sectional view such as that shown in Figure 12A of another embodiment of a probe that includes separate lumens for housing a first and second set of lead wires.

[0036] Figure 12C illustrates a cross-sectional view such as that shown in Figure 12A of another embodiment of a probe that includes separate lumens for housing a first and second set of lead wires, as well as an auxiliary lumen.

[0037] Figure 13 illustrates a perspective view of an embodiment of a positioning device.

[0038] Figure 14 schematically illustrates a partial perspective view of an embodiment of the probe of Figure 8 positioned within a blood vessel.

[0039] Figure 15 schematically illustrates a cross-sectional view taken along the view line 15-15 in Figure 14 that shows a cross-sectional area of the probe of Figure 8 and a cross-sectional area of the blood vessel.

[0040] Figure 16 schematically illustrates a cross-sectional view taken along the view line 16-16 in Figure 8 that shows a cross-sectional area of the probe of Figure 8 partially circumscribed by a circle representing an inner wall of a blood vessel. [0041] Figure 17A illustrates a partial perspective view of another embodiment of a probe configured to be introduced in a blood vessel of a patient.

[0042] Figure 17B illustrates a partial perspective view of another embodiment of a probe configured to be introduced in a blood vessel of a patient

[0043] Figure 18 illustrates a partial perspective view of an embodiment of mixing features compatible with certain embodiments of the probe of Figure 8.

[0044] Figure 19 illustrates a partial perspective view of another embodiment of mixing features compatible with certain embodiments of the probe of Figure 8.

[0045] Figure 20 illustrates a partial perspective view of another embodiment of mixing features compatible with certain embodiments of the probe of Figure 8.

[0046] Figure 21 illustrates a partial perspective view of an embodiment of mixing features compatible with certain embodiments of the probe of Figure 8.

[0047] Figure 22 illustrates a perspective view of an embodiment of a positioning device having inwardly facing ends.

[0048] Figure 23 illustrates a perspective view of an embodiment of a positioning device having arched arms.

[0049] Figure 24A illustrates a plan view of an embodiment of an introducer compatible with certain embodiments of the probe of Figure 8.

[0050] Figure 24B illustrates a plan view of another embodiment of an introducer compatible with certain embodiments of the probe of Figure 8.

[0051] Figure 24C illustrates a perspective view of another embodiment of an introducer compatible with certain embodiments of the probe of Figure 8.

[0052] Figure 25 illustrates a perspective view of an arm board compatible with certain embodiments of the probe of Figure 8.

[0053] Figure 26 illustrates a perspective view of another embodiment of a probe configured to be introduced in a blood vessel of a patient and that includes an embodiment of extensions for positioning the probe within the blood vessel.

[0054] Figure 27 illustrates a perspective view of an embodiment of a probe that includes another embodiment of extensions for positioning the probe within a blood vessel. [0055] Figure 28 illustrates a perspective view of an embodiment of a probe such as that of Figure 27 that includes an embodiment of a removable sheath configured to hold extensions in a constricted configuration.

[0056] Figure 29 illustrates an exploded partial perspective view of an embodiment of a probe that includes an embodiment of expansion members configured to transition between a substantially mobile state and a substantially fixed-position state.

[0057] Figure 30 illustrates a partial perspective view of the probe of Figure 29 in an assembled state with the expansion members in the substantially fixed-position state.

[0058] Figure 31 A illustrates a cross-sectional view of the probe of Figure 29 taken along view line 31A-31A (shown in Figure 30) that depicts an arrangement of two sets of lead wires and an embodiment of a tension wire.

[0059] Figure 3 IB illustrates a cross-sectional view such as that shown in Figure 3 IA of another embodiment of a probe that includes two tension wires

[0060] Figure 32 illustrates an exploded partial perspective view of another embodiment of a probe that includes an embodiment of expansion members configured to transition between a substantially mobile state and a substantially fixed-position state.

[0061] Figure 33 illustrates a partial perspective view of an embodiment of a probe that includes an embodiment of expansion members in a substantially fixed-position state.

[0062] Figure 34 illustrates a partial perspective view of an embodiment of a probe that includes an embodiment of expansion members in a substantially fixed-position state.

[0063] Figure 35 illustrates a partial perspective view of another embodiment of a probe that includes another embodiment of expansion members in a substantially fixed- position state and further includes an embodiment of extensions at a distal end of the probe for positioning the probe within a blood vessel.

[0064] Figure 36 illustrates an exploded partial plan view of another embodiment of a probe that includes an embodiment of a core and an embodiment of a sheath configured to move relative to the core.

[0065] Figure 37 illustrates an embodiment of an assembly that can include an embodiment of a probe coupled with a variety of connectors. [0066] Figure 38 illustrates another embodiment of an assembly that can include an embodiment of a probe operatively coupled with an actuator.

[0067] Figure 39 illustrates another embodiment of an assembly that can include an embodiment of a probe.

[0068] Figure 4OA illustrates a plan view of an embodiment of a probe that includes an embodiment of expansion members in a substantially fixed-position state.

[0069] Figure 4OB illustrates a plan view of a lead body of the probe of Figure 4OA.

[0070] Figure 41 illustrates a cross-sectional view of the probe of Figure 40 taken along the view line 41-41 shown in Figure 4OA.

[0071] Figure 42 illustrates another cross-sectional view of the probe of Figure 40 taken along the view line 42-42 shown in Figure 4OA.

[0072] Figure 43 illustrates another cross-sectional view of the probe of Figure 40 taken along the view line 43-43 shown in Figure 4OA.

[0073] Figure 44 illustrates an embodiment of an assembly that includes expansion members that are integrally formed with one or more mixers.

[0074] Figure 45 is a schematic diagram of an embodiment of a system for monitoring cardiac output of a patient.

[0075] Figure 46 is a schematic diagram of an embodiment of a system for estimating cardiac output based on temperature sensor data and heater data.

[0076] Figure 47 is a flowchart of an embodiment of a method for estimating blood flow in a patient.

[0077] Figure 48 is a schematic diagram of a model of pulsatile corporeal blood flow.

[0078] Figure 49 is a schematic diagram of a model of time-averaged corporeal blood flow.

[0079] Figure 50 is a schematic diagram of a model of time-averaged corporeal blood flow with vascular resistances divided into subsections. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0080] With reference to Figure 1, in certain embodiments, a cardiac output measurement device 10 is configured for use in monitoring the cardiac output of a patient 12. The device 10 includes a probe 14 connected to a controller 16. The probe 14 is introduced within the vasculature of the patient 12 and is configured to detect certain parameters of the blood within the vasculature of the patient 12. Data collected by the probe 14 is communicated to the controller 16, which utilizes the data to calculate the cardiac output of the patient 12 and/or other desired physiological parameters of the patient 12. Furthermore, the controller 16 can be configured to send control signals to the probe 14, as described in further detail below.

[0081] The probe 14 can be configured to produce a temperature change to the blood within the vasculature of the patient 12, which in some arrangements involves adding heat energy to the blood. The controller 16 can communicate a control signal to the probe 14, such as an electrical current, to activate the probe 14 to introduce a quantity of heat in the blood. The probe 14 can detect the temperature in a localized area in the blood and communicates this data to the controller 16. In some embodiments, the controller 16 uses the data supplied by the probe 14 to calculate the cardiac output of the patient 12 using a mathematical relationship among cardiac output, energy added to the blood, blood flow in the vessel, and temperature changes detected by the probe 14.

[0082] Figure 2 illustrates one method of placing the probe 14 within the vasculature of the patient. In the illustrated arrangement, the probe 14 is introduced into the radial artery 18 of the patient 12 in the region of one of the patient's wrists. The radial artery 18 is conveniently accessible for placement of the probe 14. Many other suitable blood vessels can also be used, including arteries and veins, as well as heart chambers, if desired. For example, in some arrangements, the probe 14 may be configured for use in the brachial artery or femoral artery.

[0083] The probe 14 can be introduced into the radial artery 18 through the skin of the patient 12 at an access point P. In the illustrated arrangement, the probe 14 is advanced within the artery 18 after insertion in a direction toward the heart of the patient 12. In other words, the probe 14 is advanced upstream within the artery 18 in a direction opposite of the direction of blood flow within the artery 18, which is indicated by the arrow A in Figures 2 and 3 A. In other embodiments, the probe 14 can be configured to be advanced within the blood vessel in the direction of blood flow. In such embodiments, the relative positions of energy producing elements and temperature sensing elements on the probe 14 can be modified, as explained in greater detail below.

[0084] Figure 3 A illustrates an end of the probe 14 within the radial artery 18 of the patient 12. As described above, the probe 14 preferably includes an energy producing element 20 and an energy sensing element 22. The energy producing element 20 is configured to introduce a certain amount of energy into the blood within the artery 18. In some embodiments, the energy producing element 20 is configured to introduce heat into the artery 18 and includes a heating coil 24, and the energy sensing element 22 is configured to measure temperature. The probe 14 can be adapted to introduce other suitable types of energy into the blood. Furthermore, other suitable types of heat producing devices may be used.

[0085] In the illustrated arrangement, lead wires 26A and 26B are connected to opposing ends of the heating coil 24, respectively. The lead wires 26A, 26B can extend through the artery 18 and outside of the patient 12 at the access point P. The lead wires 26 A, 26B are connected to the controller 16 by any suitable connection to permit electrical communication between the heating coil 24 and the controller 16. In some embodiments, the lead wires 26 A, 26B and the heating coil 24 can be constructed of a single wire, which may be a single filament wire or a multifilament wire. The lead wires 26A, 26B and heating coil 24 can be constructed of the same or different materials. Any suitable material or combination of materials known to those of skill in the art can be used in the fabrication of the heating coil 24 and lead wires 26A and 26B, such as nickel or platinum, for example.

[0086] In some embodiments, the temperature sensing element 22 comprises a thermistor, or a thermally-sensitive resistor. The thermistor may be a positive or negative thermistor. The resistance of a positive thermistor increases with an increase in temperature and the resistance of a negative thermistor decreases with an increase in temperature. A thermistor is desirable for its simplicity. In other embodiments, the temperature sensing element 22 can comprise a thermocouple. Other suitable temperature sensing devices can also be used. [0087] The temperature sensing element 22 includes a pair of lead wires 28A and 28B, which extend from the thermistor 22, through the artery 18, and exit the patient 12 at the access point P. The lead wires 28 A and 28B are connected to the controller 16 by any suitable connection to permit electrical communication between the thermistor 22 and the controller 16. The lead wires 28 A and 28B may be comprised of any suitable material, or combination of materials, for transmitting a signal from the thermistor 22 to the controller 16, such as nickel or platinum, for example. The lead wires, 26A, 26B, 28A, 28B, either individually or in pairs, can be coated with electrically and/or thermally insulating material 29.

[0088] As illustrated in Figure 3 A, the energy producing element 20 can be positioned upstream in the blood flow from the temperature sensing element 22. When the end of the probe 14 is oriented upstream from the access point P (as illustrated in Figure 3A), the energy producing element 20 is located further from the access point P than the temperature sensing element 22. When the end of the probe 14 is oriented downstream from the access point P (not shown), the energy producing element 20 is located closer to the access point P than the temperature sensing element 22.

[0089] The probe 14 can include other components (not shown in Figure 3A), such as additional heating coils 24 (or other energy producing devices), additional thermistors 22 (or other temperature sensing devices), fluid lumens for sampling, infusion, or measurement, fiber optic cables, and/or saturated venous oxygen sensors (e.g., when the probe 14 is adapted for use in the venous environment). For example, an additional thermistor can be positioned nearer the heating coil 24 to detect a temperature of the blood near the heating coil 24. Such data can be used, for example, to estimate, or to verify, the quantity of heat introduced to the blood by the heating coil 24.

[0090] Furthermore, in some arrangements, an additional heating coil may be provided as a "dummy load," which would preferably be positioned outside of the blood vessel 18. The dummy load can be connected to at least one of the lead wires 26 A or 26B and can be activated inversely of the heating coil 24; when the heating coil 24 is on, the dummy load would be off and vice- versa. As a result, the electrical current through the lead wires 26A and 26B would be constant to reduce the opportunity for error in the temperature measurement caused by heat from the lead wires 26A, 26B affecting the thermistor 22. [0091] As illustrated in Figures 3 A and 3B, an introducer 30 may be used to provide access to the radial artery 18. The introducer 30 can be initially introduced through the wall of the artery 18 with the assistance of a needle positioned partially within the interior of the introducer 30 (not shown). The needle has a sharp tip that extends beyond an end of the introducer 30 for piercing the wall of the artery 18. The needle preferably defines an internal passage, which permits the probe 14 to be passed therethrough and into the artery 18. The needle can be subsequently withdrawn, and the probe 14 and introducer 30 remain. In the illustrated embodiment, the introducer 30 is slightly wider than the combined widths of the coated lead wires 26 A, 26B, 28 A, 28B. In other embodiments, the introducer 30, or at least the portion thereof positioned outside of the body during use, can be substantially larger, e.g., at least about 1.5 times, at least about 2 times, at least about 2.5 times, at least about 3 times, at least about 3.5 times, at least about 4 times, at least about 4.5 times, or at least about 5 times larger, than the combined widths of the coated lead wires 26 A, 26B, 28 A, 28B, to facilitate manually inserting and manipulating the introducer 30 without the need to increase the size of the lead wires. The introducer 30 can comprise a multiple-section, or peel-away, needle, which is configured for separation into two or more portions or halves to permit the introducer 30 to be removed from the probe 14 once the probe 14 has been inserted into the artery 18. Because it separates into two or more portions, the introducer 30 does not have to be sized to pass over any connectors at the end of the probe 14. However, in alternative arrangements, other suitable methods of introduction of the probe 14 to the blood vessel 18 may be used.

[0092] With reference to Figure 4, at least a portion, and preferably a substantial portion of the length of the lead wires 26 A, 26B and 28 A, 28B is covered and/or surrounded by a coating 32. The coating 32 can insulate the lead wires 26A, 26B and 28A, 28B from one another and from the patient 12. The coating 32 can provide electrical insulation and, in some arrangements, can provide at least some amount of thermal insulation. Furthermore, the coating 32 can provide some structural support for the lead wires 26A, 26B and 28A, 28B to help keep the ends of the probe 14 located near the central portion of the blood flow and to maintain a desired spacing and/or orientation between the heating element 24 and the temperature sensing element 22. The lead wires 26A, 26B and 28A, 28B can be spaced from each other as shown in Figures 4 or 5, or the lead wires 26A, 26B and 28A, 28B can be positioned adjacent to each other, or in other suitable spacing arrangements. The coating 32 can be constructed from any suitable material selected to provide the desired properties and/or provide a desired degree of stiffness or column strength for the probe 14. Examples of materials that may be suitable in some applications are various polymers, silicone, epoxy, and/or other adhesives.

[0093] The coating 32 material may also include materials with therapeutic properties, such as agents with one or more specialized functions, such as disinfectants, antimicrobials, antithrombotics, and/or anticoagulants. In some examples, the coating 32 may include sodium nitro-prusside; heparin; AlphaSan® RC 2000 (available from Milliken Chemical of Spartanburg, South Carolina); PolySept® (available from PolyChem Alloy of Lenoir, North Carolina); compounds with silver ions such as, for example, silver sulfadiazine, silver nitrate, silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver laurate, silver oxide, silver palmitate, silver protein, and silver allantoinate; compounds with copper, gold, zinc, and/or one or more lanthanides; biguanides, including chlorhexidine and its salts (e.g., chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate); polymyxin; tetracycline; aminoglycosides, such as, for example, tobramycin and gentamicin; rifampicin; bacitracin; neomycin; chloramphenicol; miconazole; quinolones, such as, for example, oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin; penicillins, such as, for example, oxacillin and pipracil; nonoxynol 9; fusidic acid; cephalosporins; any suitable combination thereof; and/or other materials designed to avoid clotting, reduce infection risks, and/or encourage regrowth of damaged tissue. Similarly, each of the catheters, probes, extensions, and/or other structures disclosed herein (or a portion thereof) can be coated or formed with such materials.

[0094] When heparin is included in the coating 32 and/or other portions or components of the probe 14, the heparin can be applied as an outer layer, such as, for example, by dipping or spraying, and can be bound to one or more surfaces of the probe 14, such as an outer surface of the coating 32. In some embodiments, the heparin is exposed to blood when the probe 14 is within a vessel of a patient, and can be substantially resistant to washing off or otherwise separating from the portion of the probe 14 to which the heparin is bound. Certain methods of heparin binding (or "heparin immobilization") can be achieved via PhotoLink® Technology, available from SurModics, Inc. of Eden Prairie, Minnesota.

[0095] In some embodiments, the coating 32 can terminate prior to the thermistor 22, such that the thermistor 22 is external of the coating 32 and, accordingly, is disposed directly within the blood of the artery 18 to sense changes in temperature of the blood. The coating 32 may terminate prior to the heating coil 24 such that the heating coil 24 is directly in contact with blood. However, if desired, the coating 32 may encapsulate the heating coil 24 and/or the thermistor as illustrated by the dashed lines of Figure 4. In such an arrangement, the coating 32 (or at least the portion of the coating 32 covering the heating coil 24) can permit heat to be passed from the heating coil 24 through the coating 32 and to the blood within the artery 18. Such an arrangement may inhibit clotting of the blood on the heating coil 24 and/or disruption of the blood flow, for example. The portion of the coating 32 covering the heating coil 24 can be constructed of a different material than the remainder of the coating 32. Furthermore, in certain arrangements, the coating 32 may include multiple materials or multiple layers in accordance with the desired properties of the probe 14.

[0096] With reference to Figure 5A, in some embodiments, the lead wires 26A, 26B and 28A, 28B are bundled so as to be relatively compact in a plane transverse to the longitudinal axis of the probe 14. As noted above, the coating 32 can surround all of the lead wires 26A, 26B and 28A, 28B and separate them from one another. However, in some embodiments, there is no cannula or lumen defined within the probe 14. Accordingly, the radial dimension of the probe 14 can be determined primarily by the diameter of the lead wires 26A, 26B and 28A, 28B (and other components, including additional lead wires or other elements) and the desired thickness of the coating 32 (including multiple coating layers). As a result, the cross-sectional width of the probe 14 can be less than the cross- sectional size of typical thermodilution catheters and, in some embodiments, is only a fraction of the cross-sectional size of such catheters. For example, in certain embodiments, the individual or combined widths of one or more of the lead wires 26 A, 26B, 28 A, 28B (with or without coatings) can be similar in size to a human hair, e.g., less than about 20 μ, less than about 50 μ, less than about 100 μ, less than about 200 μ, or somewhat larger than a human hair, e.g., less than about 400 μ, less than about 1400 μ, or less than about 800 μ. In the illustrated embodiment, the cross-sectional width of the combined, coated lead wires 26A, 26B, 28A, 28B is substantially smaller than the diameter of the radial artery (e.g., about one-tenth the size). Thus, by way of example, if the radial artery diameter is about 1.5 mm, then the cross-sectional width of the combined, coated lead wires 26 A, 26B, 28 A, 28B is about 150 μ. In other embodiments, the proportion of the cross-sectional widths of one or more of the lead wires 26 A, 26B, 28A, 28B (with or without coatings) to the radial artery diameter can be smaller, e.g., less than about 1/10, or larger, e.g., between about 1/10 and about 1/4, less than about 1/4, between about 1/4 and about 1/2, or less than about 1/2. As with all quantities provided herein, other sizes and proportions within and outside of these ranges can also be used. In some embodiments, the volume of blood between the vessel wall and the heating element 24 and/or the temperature sensing element 22, and any associated coatings, does not include any other structures associated with the probe 14 to impede or otherwise interfere with blood flow. Accordingly, in some embodiments, the probe 14 can be implanted with less discomfort to the patient, reduced risk of infection, less blood flow turbulence, reduced risk of blockage or clotting in blood flow, and/or reduced risk of trauma or interference with the vessel wall and other body structures and/or tissues (which can be especially desirable if the probe 14 is advanced to a position near or inside of the heart), in comparison to conventional thermodilution catheters. These advantages, either alone or in combination, can permit the probe 14 to remain within the patient for a much longer period of time, in some embodiments, and hence cardiac output may be continuously monitored with diminished discomfort and without interruption for a much longer period of time.

[0097] The coating of the probe 14 may take on a number of suitable arrangements. As illustrated in Figure 5 A, each of the lead wires 26A, 26B and 28A, 28B may be coated individually, as indicated by a dashed line in Figure 5A and labeled with the reference number 34. The individually coated lead wires 26A, 26B, and 28A, 28B may then be secured to one another, for example by the coating 32. In such an arrangement, the coating 32 may extend the entire length of the probe or may be provided intermittently to secure the coated lead wires 26A, 26B and 28A, 28B together.

[0098] As illustrated in Figure 5 A, the probe 14 may take on a variety of cross-sectional shapes. For example, the shape may be determined by the general shape of the bundled lead wires 26 A, 26B and 28 A, 28B and, thus, may vary with the number of lead wires present. Such an arrangement of the coating 32 is illustrated in solid line in Figure 5A. As alternatively illustrated by a dashed line, the coating 32 may be configured to provide the probe 14 with a desired cross-sectional shape, such as the generally circular shape illustrated, regardless of the general shape of the bundled lead wires 26 A, 26B and 28 A, 28B. The coating 32 (or coating 34) may be applied to the lead wires 26A, 26B and 28A, 28B by any suitable method. For example, the coatings 32 or 34 may be applied by dipping, spraying, deposition, extrusion, shrink-fit or any other suitable process.

[0099] Figure 5B illustrates another embodiment of the probe 14. In certain embodiments, a lead body 35 comprises a coating 32, a sheath, or a catheter. The lead body 35 can be formed in any suitable manner, such as, for example, by various forms of extrusion and molding. The lead body 35 can be constructed from any material suitable for providing the desired properties of the probe 14. For example, in some embodiments, the probe 14 is sufficiently stiff in a longitudinal direction to permit a portion of the probe 14 to be inserted in a downstream location of the vessel and to be urged to an upstream location therein. In further embodiments, the probe 14 is sufficiently compliant to bend or deform laterally in order to follow a contour of the blood vessel during insertion. In some embodiments, the lead body 35 comprises any of a variety of plastics (e.g., thermoplastic polyurethane) or silicones, which, in further embodiments, can be biocompatible. For example, in some embodiments, the lead body 35 comprises Estane® thermoplastic polyurethane (e.g., ETE60DS3 NAT 022), available from Noveon, Inc. of Cleveland, Ohio. The lead body 35 (or a portion thereof) can be formed with or coated with materials with therapeutic properties as described herein.

[0100] In some embodiments, the lead body 35 defines a plurality of lumens 36 which can define any of a variety of cross-sectional shapes, such as, for example, circular, semicircular, or polygonal. In some embodiments, the lead body 35 defines three lumens 36A, 36B, 36C. In some embodiments, each of the lead wires 26A, 26B includes an individual coating 34 and is within the lumen 36A. In further embodiments, each of the lead wires 28 A, 28B includes an individual coating 34 and is within the lumen 36B. In some embodiments, the lumen 36C (or, in other embodiments, multiple lumens 36C) can permanently or temporarily house a lead wire, can be used for blood sample withdrawals, can be used to monitor blood pressure, and/or can include one or more sensors or other blood data acquisition devices. Other uses of the lumen 36C are also possible.

[0101] In various embodiments, the lead body 35 can define more or fewer lumens 36 arranged in different configurations. For example, in some embodiments, the lead body 35 defines only two lumens 36A and 36C, and each of the lead wires 26A, 26B, 28A, 28B is disposed in the lumen 36 A. In other embodiments, the lead body 35 can include one or more lumens for fluid transfer.

[0102] In use, the device 10 can be utilized to monitor the cardiac output of the patient 12. The introducer needle 30 is used to access the radial artery 18 of the patient 12. The probe 14 is introduced through the introducer needle 30 into the radial artery 18. Once the probe 14 is positioned within the radial artery 18, the introducer needle 30 may be withdrawn and, desirably, separated into two portions or otherwise removed from the probe 14.

[0103] The probe 14 may be connected to the controller 16, which is configured to provide operating signals to the probe 14 and receive data signals from the probe 14. The controller 16 provides a signal to operate the heat producing element 20 such that a desired quantity of heat is introduced to the blood within the radial artery 18. The temperature sensing element 22 then senses the temperature of the blood within the radial artery 18 at a point downstream from the heat producing element 20. The temperature sensing element 22 sends a signal corresponding to the temperature to the controller 16. Using the known change in temperature imparted to the blood and the resulting change in temperature at the point downstream from the heat producing element 20, the controller 16 uses an appropriate algorithm to determine the cardiac output, or volume flow of blood per unit of time.

[0104] Due to the relatively small cross-sectional dimension of the probe 14, in some embodiments, the probe 14 may be left in place within the radial artery 18 for an extended period of time to permit continuous monitoring of the cardiac output of the patient 12 without significant patient discomfort or risk of infection. This represents an improvement over the pulmonary artery thermodilution catheters of the prior art, which tend to have significant discomfort and costs associated with related infection rates and limited mobility of the patient. [0105] Figure 6 illustrates another embodiment of a device 10' comprising a probe 14'. The probe 14' is similar in some respects to the probe 14 and, therefore, like reference numerals are used to denote like components, with the exception that a prime (') is added. The probe 14' also includes an energy producing element 20' and a temperature sensing element 22'. The probe 14' also includes additional components or sensors that may be used to monitor other physiological parameters of the patient 12. One such sensor can be a blood gas sensor 40, which can be configured to monitor one or more of common blood gas values, such as oxygen saturation, partial oxygen, partial carbon dioxide and bicarbonate. Although illustrated as a single sensor, the illustrated sensor 40 may be comprised of multiple sensors. The controller 16' (not shown) may be configured to receive data from the blood gas sensor 40 and, preferably, compute both directly measured values and those values that are calculated from the directly measured values.

[0106] In some arrangements, the device 10' may include one or more fiber optic probes 41 (one shown) to measure additional blood parameters, such as oxygen or partial O₂, for example. In such an arrangement, the fiber optic probe 41 may also provide some degree of stiffness, or column strength, to the probe 14'. Accordingly, in some embodiments, the coating 32 (see Figure 4) may be provided largely for an insulation function such that the thickness of the probe 14' may be minimized. Furthermore, additional sensors 42 may also be provided to detect other physiological variables of the blood, such as the blood pH level, for example.

[0107] Figure 7 illustrates another embodiment of a device 10" comprising a probe 14". The device 10" of Figure 7 is similar in some respects to the device 10 of Figures 1-5 and, accordingly, like reference numerals indicate like components, with the exception that a double prime (") is added. In the device 10", a transceiver 50 is electrically connected to the probe 14" and is configured to communicate with a transceiver 52 of the controller 16". Preferably, the transceiver 50 and transceiver 52 communicate over a wireless connection, which may follow a suitable communication protocol, such as a Bluetooth communication protocol, for example. However, other suitable types of wireless communication may also be used.

[0108] With such a system, control and data signals may be communicated between the probe 14" and the controller 16", through the transceivers 50, 52, such that the device 10" may operate substantially as described above. Advantageously, the device 10" generally affords the patient 12 more mobility relative to the controller 16" for increased comfort and convenience. As will be appreciated, either of the transceivers 50, 52 may be replaced by a transmitter or receiver, as appropriate, if only one-way communication is necessary or desired. Furthermore, in some arrangements, operational functions of the controller 16" and probe 14" may be otherwise separated, or performed by additional system components, as may be desirable.

[0109] Figure 8 illustrates another embodiment of a probe 114. The probe 114 can resemble the probes 14, 14', and 14" in many respects, thus like features are identified with like numerals (without primes) incremented by 100. In some embodiments, the probe 114 can be configured to operate with any of the controllers 16, 16', or 16" described above, or with any other suitable controller. In some embodiments, the probe 114 is substantially elongate and is configured for insertion in a blood vessel of a patient, such as a radial artery. In many embodiments, the probe 114 is sufficiently stiff in a longitudinal direction to permit a portion of the probe 114 to be inserted in a downstream location of the vessel and to be urged to an upstream location therein. In further embodiments, the probe 114 is sufficiently compliant to bend or deform laterally in order to follow a contour of the blood vessel during insertion. In various embodiments, the probe 114, or portions thereof, can comprise any suitable material, which can be can be formed with or coated with materials with therapeutic properties, as described herein.

[0110] In certain embodiments, the probe 114 comprises a quantity delivery element 120, which can comprise, for example, an energy producing element and/or a fluid delivery element, as further discussed below. The quantity delivery element 120 can be configured to deliver a quantity of any suitable substance, energy form, and/or other entity to produce a temperature change. In various embodiments, the quantity delivery element 120 is configured to deliver an amount of electromagnetic radiation, heat, and/or heated or cooled fluid to a blood vessel of a patient. For convenience in describing some embodiments depicted in the figures, and not by way of limitation, the quantity delivery element 120 may at times be referred to hereafter as an energy producing element.

[0111] The probe 114 can further include an energy sensing element 122, one or more mixers 130, and/or one or more positioning devices 140. In some embodiments, the probe 114 comprises a sheath, catheter, or lead body 150 at a proximal end thereof and a guiding tip 155 at a distal end thereof. The probe 114 can be configured to deliver energy to blood flowing past the upstream end thereof via the energy producing element 120 and to sense a thermal property of blood flowing past the energy sensing element 122 at a more downstream location.

[0112] In some embodiments, the probe 114 is used to continuously monitor the cardiac output of a patient using a thermodilution technique. In certain of such embodiments, a relationship between the power delivered to the energy producing element 120 and the resultant rise and/or drop of blood temperature downstream, as measured by the energy sensing element 122, is used to calculate the cardiac output. Accordingly, in many embodiments, it is desirable that the temperature of blood near (e.g., proximate or adjacent to) the energy sensing element 122 be relatively uniform such that a relatively accurate bulk, or average, blood temperature measurement can be obtained. As further described below, in some embodiments, the axial separation and/or radial alignment of the energy producing element 120 and the energy sensing element 122 can affect the accuracy of bulk blood temperature measurements obtainable by the energy sensing element 122. Additionally, the accuracy of the bulk blood temperature measurements can be affected by mixing of heated and unheated blood, which can occur between the energy producing element 120 and the energy sensing element 122.

[0113] With continued reference to Figure 8, in certain embodiments, the tip 155 is configured to guide the probe 114 through a blood vessel during insertion and/or placement of the probe 114. The tip 155 can be substantially cylindrical and can have a rounded or beveled end (not shown). Other shapes and configurations are also possible. The tip 155 can comprise a relatively soft material and can be configured to contact an inner sidewall of a blood vessel substantially without causing harm thereto (e.g., the tip 155 can be substantially atraumatic). In some embodiments, the tip 155 comprises polyurethane or the like. In some embodiments, the tip 155 comprises Tecoflex® (e.g., EG-80A-B20) available from Noveon, Inc. of Cleveland, Ohio. In various embodiments, the tip 155 is joined to or integrally formed with the lead body 150. In certain of such embodiments, the tip 155 can be overmolded, shrink- fitted to, deposited on, or otherwise applied to the lead body 150. [0114] In some embodiments, the tip 155 can protect at least a portion of the energy producing element 120 during insertion of the probe 114 into the blood vessel. For example, the tip can be sized to prevent tissue, through which the probe may be advanced, from damaging the energy producing element 120.

[0115] The tip 155 can be relatively short or can be substantially elongate with a longitudinal length larger than a width (e.g., a diameter) thereof. In various embodiments, the length of the tip 155 is greater than about 0.025 inches, such as between about 0.025 inches and about 0.750 inches, greater than about 0.100 inches, such as between about 0.100 inches and about 0.500 inches, or greater than about 0.150 inches, such as between about 0.150 inches and about 0.300 inches. In some embodiments, the width of the tip 155 is between about 0.5 French (i.e., 0.5 F) and about 6.0 F, between about 1.0 F and about 4.0 F, or between about 2.0 F and about 3.0 F. In other embodiments, the width is no less than about 0.5 F, no less than about 1.0 F, no less than about 1.5 F, or no less than about 2.0 F. In still other embodiments, the width is no more than about 6.0 F, no more than about 5.0 F, no more than about 4.0 F, or no more than about 3.0 F. In some embodiments, the width is about 2.0 F, about 2.1 F, about 2.2 F, about 2.3 F, or about 2.4 F. For any of the foregoing dimensions, and for any other values described herein, other values outside of the listed ranges and/or different from the values specifically recited are also possible.

[0116] With reference to Figure 9 A, in certain embodiments, the energy producing element 120 comprises a core 160; a conducting layer, resistive heater, or heating element 162, such as, for example, the heating coil 24; and/or an outer casing 164. The core 160 can comprise any suitable material for providing structure to the heating element 162, and may include a dielectric material such as, for example, polyurethane or the like. In some embodiments, the core 160 is flexible and thus can permit lateral deformation of the heating element 162. In other embodiments, the heating element 162 is structurally self-supporting, and thus the core 160 can be substantially empty.

[0117] In certain embodiments, the heating element 162 is capable of producing heat as electrical current flows therethrough. The heating element 162 can comprise an electrically conductive material, such as, for example, a metal or metal alloy, disposed on or around the core 160. In some embodiments, the heating element 162 comprises a coiled wire. [0118] The length and/or width of the heating element 162 can affect the bulk blood temperature sensed by the energy sensing element 122. In some embodiments, relatively longer and/or relatively wider heating elements 162 can produce relatively more uniform bulk temperatures at or near the sensing element 122. Additionally, in some embodiments, it is preferable to not heat blood that passes near (e.g., proximate or adjacent) the heating element 162 above a targeted maximum temperature at which damage to blood cells might occur. The length and/or width of the heating element 162 can also affect the amount of temperature change measurable at the sensing element 122 without exceeding the targeted maximum temperature at or near the exterior surface of the heating element 162. In some embodiments, relatively longer and/or relatively wider heating elements 162 can produce relatively larger temperature changes at the sensing element 122 without exceeding the targeted maximum temperature.

[0119] In some embodiments, the heating element 162 is substantially elongate (see, e.g., Figure 9B), and thus can have a length that is larger than a transverse width (e.g., a diameter) thereof. In various embodiments, the length of the heating element 162 is from about 0.10 inches to about 3.00 inches, from about 0.25 inches to about 1.50 inches, or from about 0.75 inches to about 1.25 inches. In some embodiments, the length is no less than about 0.25 inches, no less than about 0.50 inches, no less than about 0.75 inches, or no less than about 1.00 inches. In other embodiments, the length is no more than about 3.00 inches, no more than about 2.00 inches, no more than about 1.50 inches, no more than about 1.25 inches, no more than about 1.00 inches, or no more than about 0.90 inches. In certain embodiments, the length is about 0.75 inches, about 1.00 inches, or about 1.25 inches.

[0120] In some embodiments, the width of the heating element 162 is substantially constant along the length of the heating element 162, whereas in other embodiments, the width varies between an upstream end and a downstream end of the heating element 162. The width of the heating element 162 can be the same as or similar to any of the widths described above with respect to the tip 155. In some embodiments, the tip 155 and the heating element 162 comprise substantially the same width, and in others, the respective widths are different. Other configurations of the heating element 162 are also possible. [0121] In some embodiments, the outer casing 164 comprises a layer of insulation which can substantially electrically shield the heating element 162 from blood passing nearby and/or provide a more biocompatible interface between the heating element 162 and the blood. In various embodiments, the outer casing 164 comprises heat shrink tubing, polyolefin, polyester, or urethane adhesive. In some embodiments, the outer casing 164 comprises Airthane Pet - 75D/1, 4BDO. In some embodiments, the outer casing 164 and at least an outer layer of the tip 155 comprise a unitary piece of material.

[0122] Figure 9B illustrates an embodiment of the energy producing element 120 with the outer casing 164 removed. In certain embodiments, the core 160 comprises the lead body 150 and the heating element 162 includes wire 165, such as bifilar wire, wound or otherwise disposed around the lead body 150. In certain of such embodiments, a distal end 166 of the wire 165 is soldered so as to connect both branches of the wire 165 in series with each other. In some embodiments, the wire 165 is soldered to, integrally formed with, or otherwise connected to the lead wires 26 A, 26B.

[0123] In some embodiments, the wire 165 and/or the leads 26 A, 26B are sized between about 30 AWG and about 50 AWG. For example, in some embodiments, the wire 165 comprises about 46 AWG bifilar wire and the leads 26 A, 26B comprise about 40 AWG or about 41 AWG single strand copper wire. In some embodiments, the wire 165 and/or the leads 26A, 26B are insulated with a heavy or quadruple build poly-nylon material, which can be alcohol resistant. In various embodiments, the resistance of the wire 165 and the leads 26A, 26B is between about 5 ohms and about 50 ohms, between about 10 ohms and about 30, or between about 10 ohms and about 20 ohms. In some embodiments, the resistance is no less than about 5 ohms, no less than about 10 ohms, or no less than about 15 ohms, and in other embodiments, the resistance is no more than about 30 ohms, no more than about 20 ohms, no more than about 15 ohms, or no more than about 10 ohms. Other sizes and resistance values of the wire 165 and the leads 26 A, 26B are also possible.

[0124] With reference to Figure 10, in certain embodiments, one or more mixers 130 (which can also be referred to as disruptors, agitators, etc., in various embodiments) are positioned between the energy producing element 120 and the energy sensing element 122. In some embodiments, each mixer 130 comprises one or more flow directors 172, such as fins, bumps, protrusions, or flow directors 172, configured to direct or redirect blood flow, which can thereby mix heated and unheated blood.

[0125] In certain embodiments, each mixer 130 is substantially elongate and can comprise a body 170 having one or more flow directors 172 extending therefrom. In some embodiments, the body 170 is substantially cylindrical, although other configurations are possible, such as, for example, polygonal prisms. The body 170 can be substantially hollow and can be positioned over and/or adhered to the lead body 150, or can be formed with the lead body 150 as a unitary structure. In some embodiments, the body 170 and/or flow directors 172 are formed directly on the lead body 150 via extrusion, shrink fitting, or any other suitable method. In some embodiments, each flow director 172 is joined at a base thereof with one or more neighboring flow directors 172 such that the mixer 130 does not comprise a body 170.

[0126] In some embodiments, each mixer 130 comprises substantially the same length, and in other embodiments, the length of one or more of the mixers 130 can be different from one or more of the remaining mixers 130. In various embodiments, the length of one or more of the mixers 130 is between about 0.5 millimeters and about 5.0 millimeters, between about 1.0 millimeters and about 4.0 millimeters, or between about 2.0 millimeters and about 3.0 millimeters. In some embodiments, the length is no greater than about 5.0 millimeters, no greater than about 4.0 millimeters, no greater than about 3.0 millimeters, or no greater than about 2.0 millimeters. In other embodiments, the length is no less than about 0.5 millimeters, no less than about 1.0 millimeters, no less than about 1.5 millimeters, or no less than about 2.0 millimeters. In some embodiments, the length is about 1.2 millimeters, about 2.0 millimeters, about 2.25 millimeters, or about 2.5 millimeters.

[0127] In some embodiments, the body 170 of each mixer 130 comprises substantially the same width (e.g., diameter), and in other embodiments, the width of one or more of the mixer bodies 170 can be different from one or more of the remaining mixer bodies 170. In various embodiments, the width of one or more of the mixer bodies 170 can assume any of the widths described above with respect to the tip 155.

[0128] In some embodiments, each flow director 172 comprises substantially the same height, as measured between an exterior surface of the body 170 of a mixer 130 and a maximum radial extent of the flow director 172. In other embodiments, the height of one or more of the flow directors 172 is different from one or more of the remaining flow directors 172 of the mixer 130. In still further embodiments, a height of one or more of the flow directors 172 varies along a longitudinal length of the mixer 130. In various embodiments, a height of one or more flow directors 172 is between about 0.001 and about 0.050 inches, between about 0.005 inches and about 0.040 inches, or between about 0.010 inches and about 0.030 inches. In some embodiments, the height is no greater than about 0.050 inches, no greater than about 0.040 inches, no greater than about 0.030 inches, no greater than about 0.020 inches, or no greater than about 0.010 inches. In other embodiments, the height is no less than about 0.005 inches, no less than about 0.010 inches, no less than about 0.015 inches, or no less than about 0.020 inches. In some embodiments, the height is about 0.010 inches, about 0.015 inches, or about 0.020 inches.

[0129] In some embodiments, one or more of the flow directors 172 comprise wall-like structures having substantially smooth surfaces that meet at an angle. In other embodiments, one or more of the flow directors 172 are substantially rounded and/or substantially smooth and thus do not comprise any angled surfaces. In various embodiments, one or more of the mixers 130 comprise no less than about 2 ridges, no less than about 5 ridges, or no less than about 10 ridges. In other embodiments, one or more of the mixers 130 comprise no more than about 20 ridges, no more than about 15 ridges, or no more than about 10 ridges. In some embodiments, the flow directors 172 spiral about an exterior surface of the body 170 of a mixer 130. The spiraled flow directors 172 can define an arc about the body 170, as viewed along a longitudinal axis of the body 170, of no less than about 15 degrees, about 30 degrees, about 45 degrees, about 60 degrees, about 90 degrees, about 180 degrees, or about 360 degrees; no more than about 15 degrees, about 30 degrees, about 45 degrees, about 60 degrees, about 90 degrees, about 180 degrees, or about 360 degrees; or about 15 degrees, about 30 degrees, about 45 degrees, about 60 degrees, about 90 degrees, about 180 degrees, or about 360 degrees. Any of the sizes, shapes, dimensions, or orientations of any of the features of the mixers 130 can be altered to achieve a desired degree and/or pattern of mixing of heated and unheated blood.

[0130] In some embodiments, one or more of the mixers 130 comprise flow directors 172 that spiral clockwise, as viewed from the distal end of the mixer 130, and one or more of the remaining mixers 130 comprise flow directors 172 that spiral counterclockwise. In further embodiments, adjacent mixers 130 comprise flow directors 172 that spiral in opposite directions, which can result in greater mixing of heated and unheated blood, as compared with some embodiments comprising flow directors 172 that spiral in a uniform direction.

[0131] For example, in some embodiments, the flow directors 172 of a given probe 114 may direct blood flow in a first direction only. Accordingly, in certain of such embodiments, blood heated by the heating element 162 may generally follow a spiraled path around the probe 114. If the heating element 162 does not heat blood passing by it in a uniform manner, some streamlines of heated and of relatively unheated blood may develop. In certain embodiments, the streamlines can affect the accuracy of temperature measurements obtainable by the energy sensing element 122. For example, the energy sensing element 122 could be located in a streamline of either heated or unheated blood, resulting in bulk blood temperature measurements that are either too high or too low, respectively. However, in some embodiments that comprise flow directors 172 that spiral in alternating directions, such streamlines are not likely to form and/or are more likely to be disrupted, which can yield more uniformly heated blood at or near the energy sensing element 122.

[0132] With continued reference to Figure 10, in certain embodiments, the probe 114 comprises one or more spacers 180 between adjacent mixers 130. In certain embodiments, the spacers 180 are substantially hollow pieces that are positioned over and/or adhered to the lead body 150. In other embodiments, the spacers 180 comprise portions of the lead body 150 between adjacent mixers 130. Accordingly, the spacers 180 can define gaps between the mixers 130. The spacers 180 can include surface structures and need not be smooth as shown. In some embodiments of the probe 114, there are no spacers between the mixers 130.

[0133] In certain embodiments, the spacers 180 can enhance mixing of heated and unheated blood. For example, in some embodiments, the spacers 180 permit blood that is urged to flow in a first direction by a first set of flow directors 172 to continue flowing in that direction over a relatively longer distance before being urged to flow in a different direction by an adjacent set of flow directors 172. Additionally, in some embodiments, the spacers 180 can have smaller widths (e.g., diameters) than the widths of the mixers 130 (e.g., the combined width of the bodies 170 and the flow directors 172). Accordingly, in some embodiments, the spacers 180 expose relatively flat faces of the mixers 130, which can further disrupt or agitate flow of the blood.

[0134] In some embodiments, each spacer 180 comprises substantially the same length, and in other embodiments, the length of one or more of the spacers 180 can be different from one or more of the remaining spacers 180. In various embodiments, the length of one or more of the spacers 180 is between about 0.5 millimeters and about 3.0 millimeters, between about 1.0 millimeters and about 2.0 millimeters, or between about 1.1 millimeters and about 1.5 millimeters. In some embodiments, the length is no greater than about 3.0 millimeters, no greater than about 2.0 millimeters, or no greater than about 1.5 millimeters. In other embodiments, the length is no less than about 0.5 millimeters, no less than about 1.0 millimeters, or no less than about 1.2 millimeters. In some embodiments, the length is about 0.8 millimeters, about 1.0 millimeter, about 1.25 millimeters, or about 1.50 millimeters. The spacers 180 can assume any of the widths described above with respect to the tip 155. The lengths and widths of the spacers 180 can be altered to achieve a desired degree of mixing of heated and unheated blood.

[0135] In certain embodiments, the mixers 130 and, in further embodiments, the spacers 180 can serve to reduce the distance between the energy producing element 120 and the energy sensing element 122. For example, in many instances, blood flow within a blood vessel is substantially laminar, thus diffusion constitutes the primary mode of heat transfer between blood heated by the energy producing element 120 in certain embodiments that do not comprise mixers 130 and/or spacers 180. Accordingly, heat imparted by the energy producing element 120 to passing blood results in a rise in the bulk blood temperature at a relatively long distance downstream.

[0136] However, as described above, in some embodiments, the mixers 130 and the spacers 180 disrupt the laminar blood flow such that heated and unheated blood is mixed, thus producing a more uniform bulk blood temperature at a distance that is relatively closer to the energy producing element 120. In some embodiments, such mixing permits the energy producing element 120 and the energy sensing element 122 to be in closer proximity, thus reducing the length of the portion of the probe 114 that is inserted in a patient. In various embodiments, the distance between a proximal end of the energy producing element 120 and the energy sensing element 120 is between about 1.0 inches and about 5.0 inches, between about 1.5 inches and about 4.0 inches, or between about 2.0 inches and about 3.0 inches. In some embodiments, the distance is no less than about 0.5 inches, no less than about 1.0 inches, no less than about 1.5 inches, or no less than about 2.0 inches, and in other embodiments, the distance is no greater than about 4.0 inches, no greater than about 3.5 inches, no greater than about 3.0 inches, no greater than about 2.5 inches, or no greater than about 2.0 inches. In further embodiments, the distance is about 1.75 inches, about 2.0 inches, or about 2.25 inches.

[0137] In various embodiments, the probe 114 comprises relatively few or includes no mixing features between the energy producing element 120 and the energy sensing element 122. For example, in some embodiments, the probe 114 comprises mixers 130 that have relatively short or otherwise relatively less aggressive flow directors 172, comprises relatively few mixers 130 and/or spacers 180, or comprises no mixers 130 or spacers 180. Certain of such embodiments can be relatively easier to insert into a blood vessel, but can be less effective, or relatively ineffective, at disrupting laminar blood flow and/or mixing heated and unheated blood. Accordingly, in some embodiments, the probe 114 defines a larger space between the energy producing element 120 and the energy sensing element 122, thereby permitting blood heated by the energy producing element 120 to more generally mix with unheated blood over a greater distance before being sensed by the energy sensing element 122. In some embodiments, various parameters of the probe 114 (including, e.g., the distance between the energy producing element 120 and the energy sensing element 122 and/or the size, configuration, and/or number of mixing features) are optimized to permit relatively easy insertion of the probe 114 and to achieve a relatively uniform bulk blood temperature near the energy sensing element 122 when the probe 114 is in use.

[0138] In some embodiments, the distance between the proximal end of the energy producing element 120 and the energy sensing element 122 can be relatively longer. In various embodiments, the distance is between about 2.0 inches and about 6.0 inches, between about 3.0 and about 5.5 inches, or between about 3.5 and about 5.0 inches. In some embodiments, the distance is no less than about 2.5 inches, no less than about 3.0 inches, no less than about 3.5 inches, no less than about 4.0 inches, or no less than about 4.5 inches. In other embodiments, the distance is no greater than about 5.5 inches, no greater than about 5.0 inches, or no greater than about 4.5 inches. In some embodiments, the distance between the proximal end of the energy producing element 120 and the energy sensing element 122 can be about as large as or larger than the length of the energy producing element 120, or larger than about twice the length of the energy producing element 120, or larger than about three times the length of the energy producing element 120. In some embodiments, the energy sensing element 122 can be closer to the proximal end of the probe 114 than to the energy producing element 120.

[0139] With reference to Figure HA, in some embodiments, the energy sensing element 122 comprises a thermistor 190 configured to measure the bulk or average temperature of the surrounding blood. In some embodiments, the thermistor 190 is mounted or otherwise attached to an exterior surface of the lead body 150. In some embodiments, a layer of tubing 192 (e.g., shrink tubing) envelops or substantially covers the thermistor 190 and at least a portion of the lead body 150, thereby positioning the thermistor 190 adjacent the lead body 150 in substantially fixed engagement.

[0140] In certain embodiments, the thermistor 190 is spaced from the lead wires 26A, 26B by at least a portion of the lead body 150. In some embodiments, the lead wires 26A, 26B extend through the lead body 150, the mixers 130, and the spacers 180, and are electrically coupled with the heating element 162. In certain embodiments, the lead wires 26A, 26B resist electrical current therethrough and thus can heat up when power is delivered to the heating element 162. The heat so generated can result in thermal cross-talk between the lead wires 26 A, 26B and the thermistor 190, which can affect the temperature measurements obtained by the thermistor 190. Accordingly, in some embodiments, it is desirable to thermally insulate the lead wires 26 A, 26B from the thermistor 190 and/or blood flowing nearby. In some embodiments, each of the lead wires 26A, 26B comprises a separate coating 34, which can provide electrical insulation between the lead wires 26A, 26B and/or thermal insulation between the lead wires 26 A, 26B and the thermistor 190. In further embodiments, thermal cross-talk between the lead wires 26 A, 26B and the thermistor 190 can be substantially accounted for by signal processing algorithms.

[0141] Figure HB illustrates another embodiment of the probe 114. In certain embodiments, the thermistor 190 is positioned within the lead body 150. For example, in some embodiments, the lead body 150 defines a thermistor lumen 193 and a heating coil lumen 194. In certain embodiments, a portion of the lead body 150 is removed to form an opening 195 in the lead body 150, or the opening 195 is otherwise formed in the lead body 150, to provide access to the thermistor lumen 193. The thermistor 190 can be inserted into the thermistor lumen 193 via the opening 195. In some embodiments, epoxy 196 or some other suitable substance can be injected or otherwise added to the thermistor lumen 193 to secure the thermistor 190 in place and/or to substantially seal the opening 195. In some embodiments, the epoxy 196 provides the lead body 150 with a substantially smooth outer surface. The thermistor 190 can be encapsulated by or substantially covered with a coating, such as, for example, a polyimid microsleeve, that can provide a protective layer between the thermistor 190 and the epoxy 196. Other arrangements are also possible.

[0142] In certain embodiments, a width (e.g., a diameter) of the thermistor 190 can be smaller than an exterior width (e.g., an outer diameter) of the lead body 150. Accordingly, in some embodiments, the entire body of the thermistor 190 can be relatively close to an axial center of the lead body 150 and, in further embodiments, can be relatively close to an axial center of the probe 114. In some embodiments, a relatively small size and/or a relatively centered position can permit the thermistor 190 to be in thermal communication with relatively well-mixed blood and thus more accurately sense the bulk blood temperature. In various embodiments, the width of the thermistor is no greater than about 0.030 inches, no greater than about 0.020 inches, no greater than about 0.015 inches, or no greater than about 0.010 inches. In some embodiments, the width is between about 0.005 inches and about 0.015 inches, or is between about 0.005 inches and about 0.010 inches.

[0143] In some embodiments, the thermistor 190 has a rated zero-power resistance (without lead wires) of between about 10 kΩ and about 20 kΩ, including about 14 kΩ, when measured at about 37° C. In some embodiments, the tolerance of rated zero- power resistance is between about ±0.5% and about ±3.0%, and in some embodiments, is about ±0.5%. Thermistors suitable for some embodiments are available from Semitec USA Corporation of Babylon, New York.

[0144] With reference to Figure 12A, in certain embodiments, the lead body 150 can resemble the coating 32 and/or the lead body 35 described above. In certain embodiments, lead wires 26 A and 26B coupled with the heating element 162 and lead wires 28 A and 28B coupled with the thermistor 190 extend through the lead body 150. The lead wires 26A, 26B, 28A, 28B can be coupled with one or more controllers, such as the controllers 16, 16', 16", at a proximal end of the lead body 150 via any suitable connector or other connection interface.

[0145] In certain embodiments, the lead body 150 extends to the distal end of the probe 114, and thus in some embodiments can be covered by the heating element 162 and/or the tip 155 (see Figure 8). In further embodiments, flow directors 172 (see Figure 10) extend from the lead body 150 at one or more locations between the heating element 162 and the thermistor 190. Accordingly, the lead body 150 can replace the mixer bodies 170 and/or the spacers 180 described above. The flow directors 172 can be adhered to the lead body 150 or they can be integrally formed in the lead body 150. The lead body 150 can be formed by any suitable process, such as, for example, by dipping, spraying, deposition, extrusion, or shrink- fitting.

[0146] Figure 12B illustrates another embodiment of the lead body 150. In some embodiments, the lead body 150 defines the thermistor lumen 193 (as described with respect to Figure 1 IB) through which the lead wires 28A, 28B can extend. In some embodiments, the lead wires 28A, 28B are sized between about 30 AWG and about 50 AWG. In some embodiments, the lead wires 28A, 28B comprise a bifilar nickel conductor with a polyester- imid insulation, and in other embodiments, comprise a bifilar nickel alloy 200 with heavy isomid insulation. In further embodiments, the lead wires 26A, 26B extend through the heating coil lumen 194. Other configurations are also possible. For example, in some embodiments, the lead wires 26A, 26B, 28A, and 28B extend through a single lumen. In various embodiments, the lead wires 26A, 26B, 28A, 28B are coupled with any suitable electrical connector or connectors at the proximal end of the lead body 150.

[0147] With reference to Figure 12C, in some embodiments, the lead body 150 defines one or more auxiliary lumens 197. The one or more lumens 197 can be sized and configured to accept any suitable component or device, such as any of the components or sensors described above. For example, the one or more lumens 197 can be sized and configured to accept a guidewire, an optical fiber, a pressure transducer, and/or a blood gas, glucose, pH, and/or other sensor or blood data acquisition device. In some embodiments, at least a portion of a lumen 197 is configured to be in fluid communication with blood in a vessel. One or more lumens 197 can be configured for withdrawing blood samples from a patient. In some embodiments one or more lumens 197 can be used to monitor blood pressure (e.g., via a column of liquid disposed in a lumen 197).

[0148] The one or more lumens 197 can extend substantially throughout the length of the probe 114. For example, in some embodiments, a lumen 197 extends through the tip 155 of the probe 114 and defines an opening at the distal extent of the probe 114. In other embodiments, a lumen 197 extends only through a portion of the lead body 150 and may define an opening at a position proximal of the thermistor 190 to a position that is more proximal of the thermistor 190 (e.g., at the proximal end of the lead body 150).

[0149] In some embodiments, the lead wires 26A, 26B, 28A, and 28B and the one or more lumens 197 extend along substantially opposite longitudinal regions of the lead body 310. In other embodiments, the lead wires 26 A, 26B, 28 A, and 28B are arranged around the one or more lumens 197. Other configurations are also possible.

[0150] With reference to Figure 13, in certain embodiments, a positioning device 140 (which can also be referred to as a positioner, a centering element, an anchoring device, and/or a spacing device, in various embodiments) comprises a plurality of fins, extensions, protrusions, casings, or arms 200. In some embodiments, the positioning device 140 further comprises a sleeve 205 from which the arms 200 extend. The arms 200 and the sleeve 205 can comprise a unitary piece of material or can be joined in any suitable manner. In other embodiments, the positioning device 140 does not comprise a sleeve 205. For example, in some embodiments, the arms 200 are joined directly to the lead body 150 or are integrally formed therewith.

[0151] In some embodiments, the arms 200 extend radially from the sleeve 205 and are substantially perpendicular to a longitudinal axis thereof when in a natural, resting, or extended state. In some embodiments, the arms 200 comprise a resilient material such that when deformed (e.g., bent), the arms 200 are biased to return to the extended state. Accordingly, in some embodiments, the arms can be in the extended state prior to insertion of the probe 114 into a blood vessel, can collapse to a deformed or restricted state upon insertion of the probe 114, and can expand toward the natural state after insertion of the probe 114, as described below. In certain embodiments, the arms 200 comprise polyolefin alloy. In further embodiments, the arms 200 comprise radiation grade Amcor Peel Form PF- 100. Many other materials are also possible. [0152] In certain embodiments, the positioning device 140 comprises at least two, at least three, or at least four arms 200. In various embodiments, adjacent arms 200 project from the sleeve 205 in different directions and can define an angle with respect to a longitudinal axis of the positioning device 140. In various embodiments, one or more pairs of adjacent arms 200 define an angle of no less than about 15 degrees, no less than about 30 degrees, no less than about 45 degrees, no less than about 60 degrees, no less than about 90 degrees, no less than about 120 degrees, or no less than about 180 degrees. In some embodiments, one or more pairs of adjacent arms 200 define an angle within a range from about 30 degrees to about 180 degrees, from about 45 degrees to about 135 degrees, from about 60 degrees to about 120 degrees, or from about 60 degrees to about 90 degrees. In some embodiments, the positioning device 140 comprises multiple pairs of adjacent arms 200 that define substantially identical angles. For example, in some embodiments, the positioning device 140 includes three arms 200, each of which extends from the sleeve 205 at approximately 120 degree angles with respect to the other two arms 200, and in other embodiments, the positioning device includes four arms 200, each of which extends from the sleeve 205 at approximately right angles with respect to two adjacent arms 200.

[0153] In some embodiments, each arm 200 is substantially identical to the remaining arms 200 of the positioning device 140, which can aid in centering the probe 114 within a blood vessel. In other embodiments, one or more of the arms 200 differ from the other arms 200, such as with respect to size, orientation, or material composition, which can result in positioning of the probe 114 at an off-centered position within the blood vessel. In various embodiments, the length of each arm 200, as measured from an outer diameter of the sleeve 205 to a maximum radial extent of the arm 200 when in the extended state, is between about 0.075 inches and about 0.175 inches, between about 0.90 and about 1.50 inches, or between about 1.00 inches and about 1.25 inches; no less than about 0.075 inches, about 0.100 inches, or about 0.110 inches; no greater than about 0.175 inches, about 0.150 inches, or about 0.115 inches; or about 0.111 inches.

[0154] A width of the arms 200 in a direction transverse to the longitudinal axis of the positioning device 140 can be relatively small. In various embodiments, the width of each arm 200 is between about 0.005 inches and about 0.030 inches; no less than about 0.005 inches, about 0.010 inches, or about 0.015 inches; no greater than about 0.030 inches, about 0.020 inches, or about 0.015 inches; or about 0.014 inches. In further embodiments, a thickness of the arms 200 is approximately less than or equal to the width thereof. Accordingly, in some embodiments, a cross-sectional shape of the arms 200 in a plane transverse to a longitudinal length of the arms 200 is substantially rectangular or substantially square. Other cross-sectional configurations are also possible, such as, for example, substantially circular, substantially ovoid, substantially polygonal, etc. In some embodiments, the tips of the arms 200 are rounded and may be relatively soft or relatively compliant to reduce any small risk of damage to the vessel wall that may exist, particularly during insertion or removal of the probe 114.

[0155] With reference to Figure 14, in certain embodiments, the arms 200 of the positioning device 140 are flexible or resilient and can deform (e.g., bend) when the probe 114 is positioned within a blood vessel 210. In certain embodiments, the bias of the arms 200 toward the resting or extended position is weak in comparison with the force applied to the probe 114 to move it into position or to remove it therefrom, such as the force exerted by a health care professional when inserting or removing the probe 114. Accordingly, the probe 114 can be inserted and positioned as desired with relatively little exertion, and can likewise be removed with relatively little exertion. However, the bias of the arms 200 toward the extended configuration can be sufficiently strong to substantially fix or anchor the probe 114, once positioned, such that the probe 114 is substantially fixed relative to the blood vessel 210. The probe 114 can thus be substantially resistant to rotational or translational movement within the vessel 210 due to blood flow or other influences, but adjustable or removable by a healthcare professional.

[0156] The probe 114 can comprise one, two, three, or more positioning devices 140. In certain embodiments, the probe 114 comprises a positioning device 140 at each of an upstream position, an intermediate position, and a downstream position. In some embodiments, the upstream positioning device 140 is at a distal end of the heating element 162, the intermediate positioning device 140 is at a proximal end of the heating element 162 and at a distal end of the mixers 130, and the proximal positioning device is at a proximal end of the mixers 130 and can be proximate (e.g., adjacent to) the thermistor 190. In certain embodiments, each of the positioning devices 140 is configured to position the probe 114 at approximately the center of a transverse cross-section of the blood vessel 210. In other embodiments, the probe 114 comprises positioning devices 140 in only the upstream and the downstream positions.

[0157] Advantageously, the positioning devices 140 can space the heating element 162 from the sidewall of the blood vessel 210 and can substantially align the heating element 162 and the thermistor 190 along a line substantially collinear with or parallel to a longitudinal axis of the blood vessel 210. In certain embodiments in which the heating element 162 is near the sidewall of the blood vessel 210, some of the heat generated by the heating element 162 can be lost to the wall of the blood vessel 210 and surrounding tissue, which can affect cardiac output calculations. Accordingly, some embodiments of a substantially centered heating element 162 can result in more accurate temperature measurements. Additionally, some arrangements in which the heating element 162 and the energy sensing element 122 are aligned can permit the energy sensing element 122 to contact a greater amount of heated blood, which can also result in more accurate bulk blood temperature measurements.

[0158] In some embodiments, the distal and intermediate positioning devices 140 can substantially align the heating element 162 with a longitudinal axis of the blood vessel 210 and with the direction of blood flow through the vessel 210. Such alignment can produce more predictable heating patterns of the blood than may be obtained by other orientations, such as when the heating element 162 is angled with respect to the longitudinal axis of the vessel 210. This can aid in the accurate calculation of cardiac output via data obtained by the probe 114.

[0159] In some embodiments, the positioning devices 140, and more generally, the probe 114, do not introduce excessive impedance to blood flow through the blood vessel 210. For example, the central body of the probe 114 can be relatively small as compared with the inner diameter of the blood vessel 210, and the arms 200 can be relatively thin and thus define relatively large openings between the arms 200 through which blood can pass.

[0160] With reference to Figure 15, in some embodiments, the probe 114 defines a maximum impedance cross-sectional area 230 when the probe 114 is situated within the blood vessel 210. For example, in some embodiments, cross-sections of the probe 114 along various planes that are substantially orthogonal to a longitudinal axis of the probe 114 (e.g., transverse cross-sections of the probe 114) define differently sized areas. In certain of such embodiments, the largest of such cross-sectional areas represents the maximum impedance cross-sectional area 230. In some embodiments, the area 230 represents the maximum cross- sectional area of the probe 114. In other embodiments, the area 230 is larger or smaller than the maximum cross-sectional area of the probe 114.

[0161] In certain embodiments, a plane that comprises the maximum impedance cross-sectional area 230 (e.g., the plane of the page in the illustrated embodiment) can extend through both the blood vessel 210 and the probe 114. In some embodiments, the area 230 within the plane is relatively small in comparison with a cross-sectional area 232 within the same plane that is defined by the inner wall of the blood vessel 210. In various embodiments, the size of the maximum impedance cross-sectional area 230 is no more than about 10 percent, no more than about 15 percent, no more than about 20 percent, no more than about 25 percent, no more than about 30 percent, no more than about 40 percent, no more than about 50 percent, or no more than about 60 percent the size of the area 232.

[0162] With reference to Figure 16, and as described above, in certain embodiments, the probe 114 is distorted from a relaxed state when outside of the blood vessel 210 to a stressed state when inside of the blood vessel 210. In other embodiments, the probe 114 is in a stressed configuration when outside of the blood vessel 210 and is in a relaxed or unstressed configuration when inside of the blood vessel 210. In some embodiments, the probe 114, or portions thereof (e.g., one or more positioning devices 140), can change shape between the relaxed state and the stressed state such that certain transverse cross-sectional areas of the probe 114 are sized differently when inside of the blood vessel 210 than when outside of the blood vessel 210. Accordingly, in some embodiments, the probe 114 can define an extracorporeal maximum impedance cross-sectional area 234 that differs from the maximum impedance cross-sectional area 230 described above. In some embodiments, the maximum impedance areas 230, 234 correspond with cross-sections taken along different planes through the probe 114, and in other embodiments, both maximum impedance areas 230, 234 correspond with a single cross-sectional plane through the probe 114.

[0163] In various embodiments, the area 234 is larger than, smaller than, or the same size as the area 230 of the probe 114. In some embodiments, the area 234 represents the maximum cross-sectional area of the probe 114 when the probe 114 is located outside of the blood vessel 210. In other embodiments, the area 234 is larger or smaller than the maximum cross-sectional area of the probe 114 when the probe 114 is located outside of the blood vessel 210.

[0164] In some embodiments, a portion 235 of the area 234 can be circumscribed by a circle 236 representing the inner wall of a blood vessel 210 into which the probe 114 is to be inserted. The circle 236 can be defined by a diameter that represents an average diameter of an inner wall of the blood vessel 210. For example, in some embodiments, the circle 236 can have a diameter of between about 2.3 millimeters and about 3.0 millimeters, between about 2.3 millimeters and about 2.5 millimeters, or between about 2.6 millimeters and about 2.8 millimeters, and can represent an average diameter of an inner wall of radial artery of a human adult. The portion 235 of the area 234 circumscribed by the circle 236 can be smaller than an area 238 defined by the circle 236. In various embodiments, the portion 235 of the area 234 is no more than about 10 percent, no more than about 15 percent, no more than about 20 percent, no more than about 25 percent, no more than about 30 percent, no more than about 40 percent, no more than about 50 percent, or no more than about 60 percent the size of the area 238.

[0165] In some embodiments, the presence of the probe 114 within the blood vessel 210 results in a decrease in blood pressure. The difference in pressure between a location upstream of the probe 114 and a location downstream of the distal end of the probe 114 can be referred to as a pressure drop at the downstream location due to the probe 114. In some embodiments, a smaller maximum impedance cross-sectional area of the probe 114 can result in smaller pressure drops due to the probe 114. For example, in some embodiments, a probe 114 having fewer and/or thinner positioning arms 200 can result in a smaller pressure drop within a blood vessel. In various embodiments, the probe 114 introduces a pressure drop within the blood vessel 210 of no more than about: 0.25 psi, 0.20 psi, 0.15 psi, 0.13 psi, 0.10 psi, or 0.08 psi. In some embodiments, relatively smaller pressure drops can result in more accurate cardiac output calculations.

[0166] As described above, in various embodiments, the probe 114 can substantially center the energy producing element 120 within a blood vessel, can substantially align the energy producing element 120 and the energy sensing element 122 within the blood vessel, and/or can mix blood heated by the energy producing element 120 with unheated blood by a relatively large amount. These advantages, either alone or in combination, can result in a relatively uniform bulk blood temperature at the energy sensing element 122, can provide a bulk blood temperature that relatively accurately indicates an amount of blood temperature rise due to power delivered to the energy producing element 120, and/or can permit a relatively smaller (e.g., relatively thinner and/or relatively shorter) probe 114 that can be relatively less intrusive and/or painful for a patient and/or less cumbersome for a practitioner to insert and/or position.

[0167] Figures 17 to 24 illustrate various embodiments of certain features of the probe 114. Any suitable combination of the features of the probes 14, 14', 14", and 114 with each other and/or with the features described below is contemplated. Additionally, any suitable combination of any of the devices 10, 10', and 10", or components or features thereof, with each other and/or any of the components or features described below is also contemplated.

[0168] With reference to Figure 17 A, in certain embodiments, the quantity delivery element 120, which can include an energy producing element, comprises an emitter 240 rather than, or in addition to, the heating element 162. The emitter 240 can be located at a distal end of the probe 114, and in some embodiments, can extend through the tip 155. The emitter 240 can comprise a laser, a light emitting diode, an optical fiber, and/or any other suitable device for delivering electromagnetic radiation to blood within a blood vessel. The emitter 240 can be configured to emit radiation at one or more wavelengths that are readily absorbable by blood. Optical components, such as, for example, a diffuser or a reflector, can also be coupled with the emitter 240. In some embodiments, the emitter 240 is configured to emit radiation over a large range of angles with respect to a longitudinal axis of the probe 114, as schematically illustrated by the arrows 245. In other embodiments, the emitter 240 can emit radiation in a substantially collimated beam. In still other embodiments, the emitter 240 irradiates a portion of the probe 114, thereby heating that portion. Blood passing near the heated portion is then heated in a manner similar to that of the heating element 162. In still other embodiments, the emitter 240 comprises a radio-frequency and/or acoustic radiative source. Other arrangements and configurations of the emitter 240 are also possible.

[0169] In certain embodiments, the emitter 240 can substantially reduce or eliminate thermal cross-talk with the thermistor 190. For example, in some embodiments, an optical fiber replaces the lead wires 26A, 26B described above (see, e.g., Figures HA and 1 IB). Accordingly, in some embodiments, radiation delivered through the optical fiber to a distal end of the probe 114 can pass near the thermistor 190 without imparting a significant amount of heat thereto.

[0170] Figure 17B illustrates another embodiment of the probe 114. As shown, the quantity delivery element 120 can define a fluid delivery port 247 rather than, or in addition to, the heating element 162. In some embodiments, the fluid delivery port 247 is located at a distal end of the tip 155, and can further be at an axial center of the probe 114. In other embodiments, the fluid delivery port 247 is located at a side of the tip 155 or can extend through a sidewall thereof. The fluid delivery port 247 can be in fluid communication with a lumen, such as the lumen 197, that extends through the probe 114.

[0171] In some embodiments, a heated or cooled fluid, such as, for example, a saline solution, is delivered to blood within a vessel via the fluid delivery port 247. The energy sensing element 122 can measure a rise and/or drop of blood temperature downstream of the fluid delivery port 247, and the measurements thus obtained can be used to calculate the cardiac output.

[0172] With reference to Figure 18, in certain embodiments, the mixers 130 comprise bodies 250, such as the bodies 170 described above, that are substantially disk- shaped. In some embodiments, the bodies 250 are oriented substantially orthogonally with respect to a longitudinal axis of the probe 114, and in other embodiments, one or more of the bodies 250 are angled with respect to the longitudinal axis. In some embodiments, the bodies 250 can comprise a relatively larger diameter, as compared with the bodies 170, which can make insertion of the probe 114 more difficult. For example, in some embodiments, the bodies 250 comprise diameters slightly smaller than an interior diameter of the blood vessel into which the probe 114 is configured to be inserted. The relatively larger diameter can also result in larger pressure drops, in some embodiments.

[0173] In certain embodiments, the bodies 250 are formed of a resilient material and are thus capable of folding or bending to a retracted or compressed orientation for insertion into a blood vessel and returning to an extended orientation within the blood vessel. In some embodiments, spacers 180 provide sufficient clearance between adjacent bodies 250 to permit distortion of the bodies 250 in a first direction for insertion of the probe 114 and folding in a second direction to permit distortion of the bodies 250 for removal of the probe 114.

[0174] With reference to Figure 19, in certain embodiments, the mixers 130 comprise bodies 260 such as the bodies 250, but shaped substantially as wedges having two substantially flat faces 262 that are angled with respect to each other and a substantially rounded outer face 264 extending from the two angled faces 262. In certain embodiments, the angle between the faces 262 is between about 15 degrees and about 300 degrees, between about 30 degrees and about 180 degrees, or between about 45 degrees and about 90 degrees; no less than about 15 degrees, about 30 degrees, about 45 degrees, about 90 degrees, or about 120 degrees; no greater than about 300 degrees, about 270 degrees, about 180 degrees, or about 90 degrees; or about 45 degrees, about 90 degrees, or about 120 degrees. Other angles are also possible. In various embodiments, any or all of the surfaces of the bodies 260 are curved or rounded.

[0175] In some embodiments, two or more bodies 260 are positioned in a plane transverse to a longitudinal axis of the probe 114. In some embodiments, two bodies 260 are oriented within such a transverse plane on substantially opposite sides of the probe 114. In certain of such embodiments, adjacent pairs of bodies 260 can be oriented substantially orthogonally with respect to each other. Other configurations and orientations are also possible.

[0176] In certain embodiments, the angled faces 262 of a first pair of bodies 260 can direct blood flow inward, or toward a longitudinal axis of the probe 114. In further embodiments, an adjacent pair of bodies 260 oriented orthogonally to the first pair of bodies 260 can redirect the blood flow outward, or toward the sidewall of a blood vessel, thereby interrupting fluid flow and preventing formation of blood flow streamlines. Patterns of alternating inwardly and outwardly directed blood flow can also serve to mix heated blood near the body of the probe 114 with unheated blood flowing nearer the sidewall of a blood vessel. Accordingly, bodies 260 that are offset from each other can provide a relatively large amount of mixing over a relatively short distance.

[0177] With reference to Figure 20, in some embodiments, the mixers 130 comprise ridges 270 such as the flow directors 172. The ridges 270 can extend in a direction substantially parallel to a longitudinal axis of the mixers 130. In certain embodiments, a mixer 130 can comprise four ridges 270 extending at approximately right angles with respect to adjacent ridges 270 such that the mixer 130 is substantially X-shaped. Other numbers and configurations of the ridges 270 are also possible.

[0178] In certain embodiments, adjacent mixers 130 are rotated with respect to each other such that their respective ridges 270 are substantially offset from each other. For example, in some embodiments, an X-shaped mixer 130 can comprise ridges 270 that are offset with respect to an adjacent X-shaped mixer 130 by an angle of no less than about 15 degrees, no less than about 30 degrees, or no less than about 45 degrees. Other offset angles are also possible. Additionally, any of the disclosed mixers 130 can be configured to reduce shear rates and/or localized stagnant flow within a blood vessel which might otherwise result from introduction of foreign object into the blood vessel and could potentially result in damage to blood cells and/or clotting.

[0179] With reference to Figure 21, in some embodiments the probe 114 does not comprise mixers 130, but rather, comprises a helical or coiled section 280. In some embodiments, the coiled section 280 extends between the heating element 160 and the thermistor 190. The coiled section 280 can comprise a lead body 285, such as the lead body 150, through which the leads 26 A and 26B run to the heating element 160. In further embodiments, the helical or coiled section 280 comprises the heating element 160. For example, a heating element 160 that comprises a tightly coiled wire can additionally be coiled in a larger helical pattern. In certain of such embodiments, the helical heating element 160 can contact a greater amount of unheated blood than can a relatively straight (although tightly coiled) heating element 160 of approximately the same length. In other embodiments, the probe 114 comprises a coiled section 280 and one or more mixers 130. For example, the one or more mixers 130 can be disposed on the coiled section 280.

[0180] As illustrated in Figure 22, in some embodiments, the positioning device 140 comprises arms 290. Each arm 290 can comprise a tip 292 that extends radially inward when the arm 290 is in an extended configuration. Accordingly, the tip 292 is configured to not contact the sidewall of a blood vessel during insertion or removal of a probe 114.

[0181] As illustrated in Figure 23, in some embodiments, the positioning device 140 comprises arms 300 that extend from a sleeve 305, such as the sleeve 205. Each arm 300 can define a substantially arched shape with respect to the sleeve 305. In some embodiments, the arms 300 comprise substantially smooth outer surfaces. In certain embodiments, the arms 300 are substantially rounded or substantially tubular. In some embodiments, the arms 300 are configured to compress, retract, fold, distort, or deform to a reduced size when the probe 114 is inserted in a blood vessel and to decompress, extend, unfold, or return to a natural state within the blood vessel. In some embodiments, a smooth, rounded portion 307 of the arms 300 contacts an inner wall of the blood vessel to position the probe 114.

[0182] With reference to Figures 24A-24C, in certain embodiments, the probe 114 is inserted in a blood vessel of a patient, such as a radial artery, via an introducer. The introducer can comprise any suitable variety known in the art or yet to be devised, and can be similar to the introducer 30 described above.

[0183] Figure 24 A illustrates an embodiment of a suitable introducer 330 that comprises a separable sheath 332 configured for insertion in a blood vessel. The sheath 332 can include one or more extensions or wings 334, which can project laterally from the sheath 332. In some embodiments, the sheath 332 includes one or more separation lines 335, such as frangible sections or areas of relatively weaker or relatively thinner material. The separation lines 335 can extend substantially in a straight line along a longitudinal length of the sheath 332, and can define a path along which the sheath 332 can be separated. In some embodiments, the wings 334 provide convenient surfaces graspable by a user to aid in separating the sheath 332 into two or more portions.

[0184] In some embodiments, a removable portion 336 is sized to fit within the sheath 332 (see Figure 24A). The removable portion 336 can include a needle 337, which can be pointed or otherwise configured to pierce a portion of skin, tissue, and/or a vessel wall of a patient. In some embodiments, the needle 337 is substantially hollow. In some embodiments, the removable section 335 can include a connector 338 configured to couple with any suitable medical connector. For example, the connector 338 can include a Luer interface. In some embodiments, the connector 338 is in fluid communication with the needle 337 such that one or more items (e.g., a guidewire) can extend through the needle 337 and the connector 338 and/or such that blood can be removed through the needle 337 via the connector 338. [0185] In certain embodiments, a method of inserting the probe 114, or a distal portion thereof, into a vessel of a patient includes use of the introducer 330. In some embodiments, an incision is made to provide access to a blood vessel of a patient, and in further embodiments, an incision is made in the blood vessel. The needle 337 then can be introduced into the blood vessel via the one or more incisions. In other embodiments, the needle 337 is introduced into the blood vessel directly (e.g., without first passing through an incision).

[0186] In some embodiments, the needle 337 and the sheath 332 are advanced into the blood vessel. The removable portion 336 can then be removed from the sheath 332, and may be discarded. In some embodiments, the distal end of the probe 114 is advanced through the sheath 332 into the blood vessel, and can be urged upstream within the blood vessel. The sheath 332 can then be pulled back over the proximal portion of the probe 114 (e.g., the lead body 150) and removed from the blood vessel. In some embodiments, the wings 334 are rotated distally to cause the sheath 332 to separate, and can be pulled away from each other to fully separate the sheath 332 and thus remove the sheath 332 from the probe 114.

[0187] Figure 24B illustrates another embodiment of a suitable introducer 330' that can be used in placing the probe 114 within a blood vessel of a patient. The introducer 330' can include a sheath 332 having one or more wings 334, and can include a removable portion 340. In some embodiments, the removable portion 340 includes a dilator 341. The dilator 341 can define a lumen (not shown) sized to receive a guidewire 342.

[0188] In certain embodiments, a method of inserting the probe 114, or a distal portion thereof, into a vessel of a patient includes use of the introducer 330'. In some embodiments, the guidewire 342 is inserted in a blood vessel of a patient. The introducer 330' can then be advanced over the guidewire 342 into the blood vessel. In some embodiments, the guidewire 342 and the dilator 341 are removed from the introducer 330' and may be discarded.

[0189] In some embodiments, the distal end of the probe 114 is advanced through the sheath 332 into the blood vessel, and can be urged upstream within the blood vessel. The sheath 332 can then be pulled back over the proximal portion of the probe 114 and removed in a manner such as described above. [0190] Figure 24C illustrates another embodiment of a suitable introducer 330" that can be used to situate the probe 114 within a blood vessel of a patient. The introducer 330" can include a sheath 332, and can include a removable portion 340 such as described above. The introducer 330" can further include a valve 344 in fluid communication with the sheath 332. The valve 344 can comprise a hemostasis valve configured to substantially prevent blood from exiting the introducer 330" from a proximal end thereof. In some embodiments, the valve 344 is coupled with a fluid line 345, which in turn can be coupled with any suitable medical connector 346. In some embodiments, the medical connector 346 comprises one or more Luer connectors, and can further include a stopcock configured to permit selective communication between any of the one or more Luer connectors and the fluid line 345. Various other arrangements of the valve 344 and the fluid line 345 are also possible. For example, in some embodiments, the valve 344 may include two or more fluid lines 345, each of which is capable of providing access to the blood of a patient.

[0191] In certain embodiments, a method of inserting the probe 114, or a distal portion thereof, into a vessel of a patient includes use of the introducer 330". In some embodiments, a guidewire, such as the guidewire 342 (see Figure 24B) is inserted in a blood vessel of a patient. The introducer 330" can then be advanced over the guidewire 342 into the blood vessel. In some embodiments, the guidewire 342 and the dilator 341 are removed from the introducer 330" and may be discarded. In some embodiments, the valve 344 substantially prevents blood from exiting the introducer 330" through a proximal opening of the valve 344 (not shown) from which the dilator 341 is removed.

[0192] In some embodiments, the distal end of the probe 114 is advanced through the valve 344 and the sheath 332 into the blood vessel, and can be urged upstream within the blood vessel. In some embodiments, the sheath 332 remains within the blood vessel during use of the probe 114. In various embodiments, the connector 346 can be coupled with any suitable device for collecting blood (e.g., a syringe), and blood can be collected via the valve 344 while the probe 114 is within the vessel. In further embodiments, the connector 346 can be coupled with any suitable device for monitoring blood pressure, either instead of or in addition to being coupled with a blood collecting device, and blood pressure can be measured when the probe 114 is within the vessel. In some embodiments, data gathered by the probe 114 and data gathered by the blood pressure monitoring device are both used in an algorithm for determining the cardiac output of the patient, as further described below.

[0193] Other arrangements for introducing the probe 114 into the blood vessel of the patient are also possible. In some embodiments, the probe 114 is inserted into the blood vessel via a lumen of a catheter (not shown) that is already in place within the blood vessel. For example, in some embodiments, the probe 114 can be threaded through an open lumen of a radial artery catheter that comprises one or more additional lumens for other devices or sensors. In further embodiments, the catheter may be inserted into the blood vessel via a valve assembly. Any suitable valve assembly can be used such as, for example, a hemostasis valve, a Toughy-Bourst valve, or any other suitable adaptor, connector, or valve.

[0194] With reference to Figure 25, in certain embodiments, an arm board 350 is used to inhibit movement of the probe 114 relative to the arm 352 of a patient once the probe 114 has been inserted. The arm board 350 can comprise any suitable variety known in the art or yet to be devised. In some embodiments, one or more straps 354 are used to secure the arm board 350 to the patient. In some embodiments, the palm of a patient's hand is oriented away from the arm board 350. Devices other than armboards can also be used.

[0195] In some embodiments, the probe 114 is packaged in a kit with items suitable for use with the probe 114. In some embodiments, the kit includes one or more of an introducer (such as any of the introducers described above), a guide wire, a valve assembly, and an armboard, each of which can be used in manners such as those described above. In some embodiments, the kit includes a local anesthetic and/or other suitable medication or compound for preparing an incision site. For example, in some embodiments, the kit comprises a quantity of lidocaine. The kit can include a scalpel for creating an incision, such as an incision through which the introducer can be advanced into a blood vessel. Similarly, the kit can include a suture for closing an incision.

[0196] In some embodiments, the kit includes instructions for using the probe 114. For example, the instructions can instruct a user of the kit to perform, and/or how to perform, one or more of the methods described above and/or one or more of the following tasks in any suitable order: prepare an entry site, such as an incision site or an area to be punctured by a needle of an introducer, through which the probe 114 can be introduced to a blood vessel (such preparation can include sterilization, application of lidocaine, and/or any other suitable method); create an incision, such as by use of a scalpel; create an incision in a blood vessel (e.g., a radial artery) of a patient, such as by use of a scalpel; insert an introducer into the blood vessel, such as through an incision or over a needle; expand the blood vessel by use of a dilator; couple a valve assembly with the introducer; insert a guidewire into the blood vessel via, for example, the introducer and/or the valve assembly; insert the probe 114 into the blood vessel via, for example, the introducer, the valve assembly, and/or a separate radial artery catheter; remove the guidewire from the blood vessel; remove the introducer from the blood vessel; separate the introducer into two or more portions; secure an arm board to the patient; obtain measurements via the probe 114; remove the arm board from the patient; remove the probe 114 from the blood vessel; and/or close the incision site, such as by use of a suture. The instructions can also instruct the user of the kit to perform other tasks.

[0197] Accordingly, a variety of methods are possible for using certain embodiments of the probe 114. For example, some methods include preparing an insertion site at which the probe 114 can be introduced into a blood vessel (such as, for example, a radial artery) of a patient. In some procedures, an area of the patient's wrist is sterilized and/or anesthetized, and an incision is made in the wrist area to provide access to the radial artery. In some methods, an incision is also made in the radial artery. An introducer can be inserted through the incision site into the radial artery. In other embodiments, an introducer (such as the introducer 330) is inserted into the radial artery without first creating an incision in the artery and/or the wrist area of a patient, as described above.

[0198] In some procedures, a dilator is inserted into the radial artery with the introducer and then removed, and in other procedures, a dilator is not used. Similarly, in some procedures a guidewire is inserted into the radial artery, and in other procedures, a guidewire is not used. The probe 114 can be inserted into the radial artery through the introducer, and in some embodiments, is inserted over the guidewire. In some embodiments, the positioning devices 140 are bent or deformed as the probe 114 is inserted in the artery. The probe 114 can be urged in an upstream direction within the artery, and in further embodiments, one or more positioning devices 140 can contact an inner surface of the sidewall of the blood vessel as the probe 114 is advanced within the artery (see Figure 14). The probe 114 can be positioned as desired, and in some embodiments, the one or more positioning devices remain in contact with the sidewall of the artery. [0199] In some embodiments, the guidewire is removed before insertion of the probe 114, and in other embodiments, the guidewire is removed from the radial artery after the probe 114 is in position. The introducer can be removed from the radial artery, and in some embodiments, is separated into two or more portions to be removed from the probe 114 as well. An arm board can be secured to the patient to inhibit movement of the probe 114 relative to the incision site.

[0200] In various embodiments, the probe 114 is coupled with a controller, such as any of the controllers 16, 16', or 16" described above (see Figures 1 and 7). In some embodiments, the controller delivers signals (e.g., various amounts of electrical current) to the quantity delivery element 120, which can heat blood in the vicinity of the quantity delivery element 120. The energy sensing element 122 can obtain information regarding temperature at a downstream location from the quantity delivery element 120. The information thus obtained can be delivered to the controller. In some embodiments, the controller can utilize the information obtained from the energy sensing element 122 in combination with data regarding the one or more signals delivered to the quantity delivery element 120 to calculate the cardiac output of the patient and/or other desired physiological parameters of the patient. For example, in some embodiments, an algorithm is applied to the data regarding the energy sensing element 122 and the energy producing element 120 to calculate the one or more parameters of interest. In some embodiments, the cardiac output of the patient is calculated continuously.

[0201] In further embodiments, blood pressure information is gathered and used in connection with information gathered from the probe 114. For example, in some embodiments, the probe 114 is inserted into the blood vessel via the introducer 330", which can be coupled with a blood pressure monitoring device, as described above. In some embodiments, the blood pressure monitoring device gathers information regarding the blood pressure of the patient as the probe 114 gathers other information regarding the blood via the energy sensing element 122. In some embodiments, the information gathered by the blood pressure monitoring device and the information gathered by the probe 114 are delivered to the controller, which can utilize at least a portion of the information thus delivered to calculate the cardiac output of the patient and/or other desired physiological parameters of the patient. For example, in some embodiments, an algorithm can be used to process data received from some or all of the energy producing element 120, the energy sensing element 122, and/or the blood pressure monitoring device to calculate the one or more parameters of interest. In some embodiments, the cardiac output of the patient is calculated continuously using blood pressure data in connection with data obtained via the probe 114.

[0202] In some embodiments, after the probe 114 has been used to gather data, the probe 114 is removed from the radial artery through the incision site. The incision site can be closed in an appropriate manner, such as by use of a suture. The probe 114 can be decoupled from the controller, and in some embodiments, can be disposed of.

[0203] Figure 26 illustrates another embodiment of a probe 414. The probe 414 can resemble the probes 14, 14', 14", and 114 in many respects, thus like features are identified with like numerals. The probe 414 can differ from the probes 14, 14', 14", and 114 in other respects, such as those described hereafter. In some embodiments, the probe 414 includes an energy producing element 120, an energy sensing element 122, and a lead body 150. The probe 414 can further include one or more positioning devices 140. In some embodiments, one or more of the positioning devices 140 include one or more arms, arcs, arches, lobes, spacers, projections, protrusions, or extensions 420.

[0204] The positioning devices 140 can be joined with the probe 414 in any suitable manner. In some embodiments, the extensions 420 are integrally formed with, adhered to, sewn to, or otherwise attached to the lead body 150. In other embodiments, the extensions 420 are attached to any suitable covering, such as heat shrink tubing, which is applied to an outer surface of the lead body 150. Other suitable methods can also be used to form and/or apply the extensions 420.

[0205] In some embodiments, the extensions 420 are configured to bend, deform, or be displaced in a first direction when the probe 414 is advanced into a blood vessel and to bend, deform, or be displaced in a second direction when the probe 414 is removed from the blood vessel. For example, in some embodiments, the extensions 420 contact the interior wall of a blood vessel as the probe 414 is advanced in an upstream direction within the blood vessel, which causes the extensions 420 to bend in a downstream direction. As the probe 414 is removed from the blood vessel, contact with the interior wall of the blood vessel causes the extensions 420 to bend in an upstream direction. In some embodiments, at least a portion of the extensions 420 is configured to contact the inner wall of a blood vessel substantially without causing harm thereto.

[0206] In some embodiments, the extensions 420 provide an opposing force to insertion of the probe 414 into a blood vessel and an opposing force to removal of the probe 414 from the blood vessel that are approximately equal. For example, in some embodiments, one or more extensions 420 when in a relaxed state are substantially symmetrical about a transverse plane that is substantially perpendicular to a longitudinal axis of the probe 414, such that approximately the same amount of force can be used to move the one or more extensions 420 in either direction along a line substantially perpendicular to the transverse plane.

[0207] In some embodiments, one or more of the extensions 420 comprise a shape memory material, such as a shape memory alloy (e.g., a nickel-titanium alloy). In some embodiments, one or more of the extensions 420 are substantially loop-shaped, which can provide structural integrity to the relatively thin extensions 420. Other materials, shapes, and configurations for the extensions 420 are also possible.

[0208] In certain embodiments, one or more extensions 420 project from the body of the probe 414 at different positions along the longitudinal length of the probe 414. In some embodiments, two or more extensions 420 project from the body of the probe 414 at substantially the same longitudinal position. In various embodiments, adjacent extensions 420 located at approximately the same longitudinal position of the probe 414 can define an angle with respect to a longitudinal axis of the probe 414. In various embodiments, one or more pairs of adjacent extensions 420 define an angle of no less than about 15 degrees, no less than about 30 degrees, no less than about 45 degrees, no less than about 60 degrees, no less than about 90 degrees, no less than about 120 degrees, or no less than about 180 degrees.

[0209] In various embodiments, the probe 414 can include one or more, two or more, three or more, four or more, five or more, or six or more extensions 420 projecting in different directions at approximately the same position along the longitudinal length of the probe 414. In some embodiments, the probe 414 includes about fifteen or fewer, about ten or fewer, or about five or fewer extensions 420 projecting in different directions at approximately the same position along the longitudinal length of the probe 414. In some embodiments, the probe 414 can include one or more, two or more, three or more, four or more, five or more, about five or fewer, about ten or fewer, or about fifteen or fewer longitudinal positions at which one or more extensions 420 project from the probe 414. In some embodiments, extensions 420 at one longitudinal position of the probe 414 are offset with respect to extensions 420 at a neighboring position such that the adjacent sets of extensions 420 extend in substantially different radial directions, as shown.

[0210] In certain embodiments, the probe 414 includes an opening or a port 440. The port 440 can be in fluid communication with a lumen of the probe 414, such as the lumen 197 described above (see Figure 12C). Accordingly, in some embodiments, the port 440 provides fluid communication between the lumen of the probe 414 and the interior of the blood vessel. In some embodiments, the port 440 can permit blood to be withdrawn via the probe 414. In some embodiments, the port 440 can permit monitoring of blood pressure within the blood vessel, such as via a column of fluid within the lumen or via an instrument passed through the port 440. For example, an external pressure transducer can be connected to the probe 414 such that the external pressure transducer is in fluid communication with the port 440 to monitor the blood pressure. Other uses of the port 440 are also possible. In other embodiments, the probe 414 does not include a port 440. For example, in some embodiments, the probe 414 is inserted into a blood vessel of a patient via an introducer, such as the introducer 330", such that blood pressure and/or other blood parameters can be monitored without accessing the blood via the port 440.

[0211] Figure 27 illustrates another embodiment of the probe 414. In some embodiments, the probe 414 comprises a plurality of extensions 420 that project outward with respect to a longitudinal axis of the probe 414. In some embodiments, the extensions 420 are attached to heat shrink tubing 445 placed over the lead body 150. In some embodiments, a plurality of extensions 420 project from a portion of the probe 414 that is between the energy producing element 120 and the energy sensing element 122. In some embodiments, the number, size, shape, and/or orientation of the extensions 420 are such that blood heated by the energy producing element 120 is substantially mixed with unheated blood. In some embodiments, there is at least one extension 420, at least two extensions 420, or at least three extensions 420. In some embodiments, the extensions 420 replace and/or supplement the mixers 130 described above. [0212] In some embodiments, one or more of the extensions 420 are lobed, and can be substantially shaped as a loop or half heart as illustrated. In certain embodiments, the extensions 420 are configured to permit the probe 414 to move within a blood vessel more easily in a first direction than in a second direction. For example, in some embodiments, the extensions 420 are substantially angled such that the distal portions thereof are larger than the proximal portions thereof. In certain of such embodiments, the probe 414 can be urged in a proximal direction within a blood vessel more easily than it can be in a distal direction.

[0213] With reference to Figure 28, in some embodiments, the probe 414 includes a sheath 442 configured to retain the extensions 420 in a compacted, bent, folded, or compressed state. In some embodiments, the probe 414 and the sheath 442 can be inserted together into a blood vessel. The sheath 442 can prevent the extensions 420 from contacting an inner wall of the blood vessel during the insertion stage, thereby facilitating insertion of the probe 414 into the blood vessel.

[0214] In some embodiments, the sheath 442 can be removed from the probe 414 once the probe 414 is situated as desired within a blood vessel. In certain embodiments, the sheath 442 is advanced in a proximal direction for purposes of removal, as indicated by arrow 444, and can be separated into two or more portions, as indicated by the arrows 446, at a position outside of a patient. In some embodiments, one or more of the extensions 420 expand to contact a sidewall of the blood vessel once the sheath 442 is removed. The extensions 420 can thereby position the probe 414 at a desired location and/or orientation within the blood vessel. In some embodiments, the extensions 420 substantially anchor the probe 414 such that it resists movement relative to the blood vessel due to passing blood or other influences. In some embodiments, the extensions 420 are configured to bend, fold, collapse, deform, or otherwise be displaced relative to the lead body 150 such that the probe 414 can be removed from the blood vessel by a healthcare professional. As noted above, in certain embodiments, the probe 414 is configured to move more easily in a first direction than in a second direction. Accordingly, in some embodiments, the probe 414 is configured to move more easily in the proximal direction, which can inhibit distal advancement of the probe 414 within a blood vessel and permit relatively easy removal of the probe 414 from the blood vessel. [0215] Figure 29 illustrates an exploded view of an embodiment of a probe 514. The probe 514 can resemble the probes 14, 14', 14", 114, and 414 in many respects, thus like features are identified with like numerals. The probe 514 can differ from the probes 14, 14', 14", 114, and 414 in other respects, such as those described hereafter. In some embodiments, the probe 514 includes an energy producing element 120, an energy sensing element 122, and a lead body 150. In some embodiments, the probe 514 includes one or more expansion members 520, such as baskets, bundles, cages, anchors, positioning devices, or centering features. In some embodiments, the probe further includes an activation member or actuator 530 configured to transition the one or more expansion members 520 between a narrow, compacted, contracted, constricted, collapsed, attenuated, or substantially mobile state and a deployed, activated, expanded, extended, broadened, widened, or substantially fixed-position state.

[0216] In some embodiments, each expansion member 520 is capable of transitioning between the substantially mobile state and the substantially fixed-position state. In some embodiments, the expansion members 520 are relatively narrow (e.g., relatively close to a longitudinal axis of the probe 514) when in the substantially mobile state, and in further embodiments, can define an outer perimeter (e.g., an outer diameter) that is substantially the same as an outer perimeter of the lead body 150. In some embodiments, the expansion members 520 are relatively wide (e.g., relatively distanced from the longitudinal axis of the probe 514) when in the substantially fixed-position state such that at least a portion thereof can contact a sidewall of a blood vessel in which the probe 514 is inserted, thereby substantially preventing the probe 514 from moving relative to the blood vessel due to blood flow or other influences.

[0217] In various embodiments, one or more of the expansion members 520 comprise one or more, two or more, three or more, or four or more strands of material configured to deform (e.g., bend) outward, or away from an axial center of the probe 514, when the expansion member 520 transitions to the substantially fixed-position state. In certain embodiments, the expansion member 520 comprises one or more, two or more, three or more, or four or more filaments, threads, or wires 540, which in some embodiments can be netted, woven, or braided. In other embodiments, the wires 540 substantially do not overlap. For example, in some embodiments, each of the wires 540 substantially defines a plane that is substantially parallel to a longitudinal axis of the probe 514 when the expansion member 520 is in the substantially fixed-position state. In some embodiments, the wires 540 comprise shape memory material such as, for example, a nickel-titanium alloy. Other suitable materials are also possible.

[0218] In some embodiments, the wires 540 are braided such that longitudinal compression of the expansion member 520 (i.e., compression along a longitudinal length of the expansion member 520) causes the expansion member 520 to deploy, dilate, extend, or expand outward (i.e., away from an axial center of the probe 514). For example, in some embodiments, the expansion members 520 are braided in such a manner that longitudinal compression of the expansion members 520 produces a radial displacement or radial bulge of the expansion members 520. In some embodiments, the expansion members 520 are configured to substantially center the probe 514 within a blood vessel when in the substantially fixed-position state. For example, in some embodiments, the expansion members can deform to a substantially circularly symmetric configuration.

[0219] In some embodiments, the expansion members 520 can be at least partially covered in a coating that inhibits or prevents blood clotting. For example, the expansion members 520 can be covered with a silicone coating. In addition or in the alternative, the expansion members 520 may also include any of the materials with therapeutic properties described in connection with coating 32.

[0220] In some embodiments, the expansion members 520 separate adjacent portions of the lead body 150. Wires 540 of the expansion members 520 can be coupled with a portion of the lead body 150 via one or more caps, cuffs, or collars 542. In some embodiments, the wires 540 are integrally formed with the collars 542. For example, in some embodiments, the wires 540 and the collars 542 comprise a unitary piece of material. In various embodiments, a collar 542 is crimped, clamped, or otherwise secured to the lead body 150, and in some embodiments, can press a portion of the wires 540 against an exterior surface of the lead body 150. In further embodiments, the wires 540 are bonded or adhered to the lead body 150 in addition to or instead of being secured by a collar 542. For example, in some embodiments, nitinol wires 540 are placed over a polyimide lead body 150, plastic (e.g., Pebax® plastic) is placed over the wires 540, and tubing (e.g., FEP heat shrink tubing) is placed over the plastic. In some embodiments, the tubing is heated, and optionally may be removed.

[0221] In some embodiments, the actuator 530 comprises one or more lines 545, such as relays, cables, rods, or tension wires, which can extend through a substantial portion of the lead body 150 in an assembled probe 514. For example, in some embodiments, a line 545 is threaded through a lumen of the lead body 150. In some embodiments, the line 545 is coupled with one or more portions of the lead body 150 such that the probe 514 can contract longitudinally due to movement of the line 545. For example, in some embodiments, the line 545 is secured to a distal portion of the lead body 150 and is slidably retained within the lead body 150 along a substantial length thereof. In some embodiments, as the line 545 moves in a distal direction, adjacent portions of the lead body 150 that are separated from each other by an expansion member 520 move toward each other, thereby deploying the expansion member 520, as further described below.

[0222] In certain embodiments, the actuator 530 comprises a proximal grip or handle 550 and/or a distal handle 552. The handles 550, 552 can be formed of any suitable material, such as, for example, metal, plastic, or silicone, and can be configured to be easily gripped by a medical practitioner. In some embodiments, the handles 550, 552 comprise a series of ridges or bumps. In some embodiments, the handles 550, 552 in an assembled probe 514 are at a proximal end of the lead body 150, and can be positioned outside of a patient when the probe 514 is within a blood vessel of the patient. Accordingly, in some embodiments, the handles 550, 552 can be manipulated by a medical practitioner to deploy the expansion members 520 once the probe 514 is in place.

[0223] In certain embodiments, the handles 550, 552 are configured to translate and/or rotate relative to one another in an assembled probe 514. For example, in some embodiments, the distal handle 552 is attached to or extends from an outer sheath or tube 554. In further embodiments, the proximal handle 550 is attached to or extends from an inner rod or tube 556 that is substantially complementary to the outer tube 554 and thus capable of translating and/or rotating within the outer tube 554. In some embodiments, the proximal handle 550 and/or the tube 556 is connected or otherwise coupled with the line 545 such that movement of the proximal handle 550 and/or the inner tube 556 effects movement of the line 545 relative to the probe 514. In some embodiments, the probe 514 includes a spring or biasing member 558 configured to urge the handles 550, 552 toward either the substantially fixed-position state or the substantially mobile state. In other embodiments, the wires 540 provide a sufficient bias toward either the substantially fixed-position state or the substantially mobile state, and/or the line 545 provides sufficient tensile and/or compressive force to the expansion members 520, such that the probe 514 does not include a biasing member.

[0224] In some embodiments, the actuator 530 comprises a switch or lock region 560 configured to secure the probe 514 in one or more of the substantially mobile and the substantially fixed-position states. In some embodiments, the lock region 560 comprises a channel or groove 562 defined by the outer tube 554. In some embodiments, the groove 562 defines a path with a curved portion that can define a proximally extending ledge 563 and a notch 564. In some embodiments, the lock region 560 further comprises a protrusion 565, such as a pin or knob, extending from the inner tube 556. In some embodiments, the protrusion 565 is configured to slide within the groove 562 between a distal end thereof and the notch 564. In some embodiments, the probe 514 is in the substantially mobile state when the protrusion 565 is at or near the distal end of the groove 562, and the probe 514 is in the substantially fixed-position state when the protrusion 565 is near or seated in the notch 564.

[0225] With reference to Figure 30, in certain embodiments, the probe 514 is biased toward the substantially mobile state. For example, in some embodiments, the expansion members 520 are in a relaxed, natural, radially compacted, or resting configuration when in the substantially mobile state. In some embodiments, adjacent portions of the lead body 150 can be moved closer to each other via the actuator 530, which causes the expansion members 520 to move from the substantially mobile state to the substantially fixed-position state. Accordingly, in some embodiments, a biasing, spring, or restorative force arises in the expansion members 520 when they are in the substantially fixed-position state that tends to urge them toward the substantially mobile state. In some embodiments, this restorative force can tend to separate adjacent portions of the lead body 150, thereby urging the line 545, and hence, the inner tube 556 in a distal direction relative to the outer tube 554.

[0226] In some embodiments, the biasing member 558 (see Figure 29) can provide a biasing force in addition to or instead of that produced by the expansion members 520, and can urge the probe 514 toward the substantially mobile state. For example, in some embodiments, the biasing member 558 is coupled with the inner tube 556 and the outer tube 554 such that movement of the handles 550, 552 away from each other creates a restorative force within the biasing member 558. For example, in some embodiments, the biasing member 558 is stretched when the handles 550, 552 move away from each other. Accordingly, in some embodiments, the biasing member 558 can urge the inner tube 556 in a distal direction relative to the outer tube 554 when the protrusion 565 is not seated in the notch 564. As a result, in some embodiments, the protrusion 565 is urged toward the distal end of the groove 562.

[0227] A bias toward a particular operational state of the probe 514 (e.g., toward the substantially mobile state) can affect operation of the lock region 560. For example, in some embodiments, the handles 550, 552 are moved away from each other to overcome restorative forces of the expansion members 520 and/or the biasing member 558 and thus move the protrusion 565 toward the notch 564. In some embodiments, the handles 550, 552 are urged away from each other and simultaneously twisted in order to seat the protrusion 565 within the notch 564. Due to the bias that urges the protrusion 565 distally, the protrusion 565 remains substantially locked in the notch 564.

[0228] In some embodiments, to move the protrusion 565 from the notch 564, the handles are urged away from each other and twisted, thereby moving the notch 564 past the ledge 563 and allowing the protrusion 565 to move to the distal end of the groove 562 under the natural bias of the probe 514. Accordingly, in some embodiments, the lock region 560 can substantially prevent unintended transitioning of the probe 514 between the substantially mobile and substantially fixed-position states. Other arrangements for the lock region 560 are possible, and, more generally, other arrangements of the actuator 530 (with or without a lock region 560) are possible.

[0229] Other arrangements of the probe 514 are also possible. For example, as discussed above, in certain embodiments, the wires 540 of an expansion member 520 are not braided. In some embodiments, the wires 540 are separate from each other and do not touch or overlap. In certain of such embodiments, the wires 540 are biased to deform away from a longitudinal center of the probe 514 when a longitudinal compressive force is applied to the wires 540. [0230] In still other embodiments, the wires 540 are biased toward the substantially fixed-position state, rather than the substantially mobile state. For example, in some embodiments, when the line 545 is moved proximally relative to the lead body 150, the wires 540 are placed in tension as they move toward the substantially mobile state, and when the line 545 is moved distally relative to the lead body 150, the wires return to their natural or substantially fixed-position state.

[0231] With reference to Figure 3 IA, in certain embodiments, the probe 514 includes a single line 545 for transitioning the probe 514 between the substantially mobile and the substantially fixed-position states. In some embodiments, the line 545 is housed within a separate lumen 585, which, in further embodiments, can be substantially centered within the lead body 150. In some embodiments, the lumen 585 and/or the line 545 includes polyimide, Teflon®, or some other suitable substance to provide a relatively small amount of friction between the wall of the lumen 585 and the line 545. In some embodiments, one or more lumens in which the lead wires 26A, 26B, 28A, and/or 28B are housed substantially surround the lumen 585 and/or are at a greater distance from an axial center of the probe 514. Other arrangements for the lumen 585 are also possible.

[0232] With reference to Figure 3 IB, in some embodiments, the probe 514 includes two or more lines 545 A, 545B for transitioning the probe 514 between the substantially mobile and the substantially fixed-position states. In some embodiments, the two or more lines 545 A, 545B are housed within two or more lumens 585A, 585B. In some embodiments, a first line 545 A is within a first lumen 585 A at a first side of the lead body 150 and a second line 545B is within a second lumen 585B at a second side of the lead body 150 that is opposite the first side. In some embodiments, the first and second lines 545 A, 545B can inhibit lateral movement of the probe 514 within a blood vessel when the probe 514 transitions between the substantially mobile and substantially fixed-position states.

[0233] Figure 32 illustrates an exploded view of an embodiment of a probe 614. The probe 614 can resemble the probes 14, 14', 14", 114, 414, and 514 in many respects, thus like features are identified with like numerals. The probe 614 can differ from the probes 14, 14', 14", 114, 414, and 514 in other respects, such as those described hereafter. In some embodiments, the probe 614 includes an insert or core 620 and a cover or sheath 625. In some embodiments, the core 620 is configured to be received within the sheath 625. In further embodiments, the core 620 is configured to translate and/or rotate within the sheath 625. In some embodiments, an outer surface of the core 620 is substantially complementary to an inner surface of the sheath 625. For example, in some embodiments, both the outer surface of the core 620 and the inner surface of the sheath 625 include substantially cylindrical portions.

[0234] In some embodiments, the core 620 includes a tip 155, an energy producing element 120, an energy sensing element 122, and a lead body 150. In some embodiments, the lead body 150 defines cross-sectional area that is substantially the same size between the energy producing element 120 and a position 630 near the energy sensing element 122, and transitions to a larger cross-sectional area at the position 630. For example, in some embodiments, the lead body 150 defines only one lumen, such as the lumen 194 (see, e.g., Figure HB), between the energy producing element 120 and the energy sensing element 122 in which lead wires for the energy producing element 120 are housed. In some embodiments, the lead body 150 transitions to a larger cross sectional area at the position 630 to accommodate an additional lumen, such as the lumen 193 (see, e.g., Figure 12B), in which the energy sensing element 122 and/or lead wires for the energy sensing element 122 are housed. In some embodiments, lead wires for both the energy producing element 120 and the energy sensing element 122 are housed in a single lumen.

[0235] In some embodiments, the lead body 150 includes an auxiliary lumen, such as the lumen 197 (see Figure 12C), that is separate from one or more of the lumens in which lead wires are housed. In some embodiments, the lead body 150 transitions to a larger cross sectional area at the position 630 to accommodate the auxiliary lumen. In some embodiments, the lead body 150 defines an opening or a port 632, such as the port 440, that is in fluid communication with the auxiliary lumen. In some embodiments, the port 632 is at a position distal to the energy sensing element 122. In further embodiments, the lead body 150 includes a thermal inhibitor 634 such as an insulator, block, or stop between the port 632 and the energy sensing element 122. In some embodiments, the thermal inhibitor 634 impedes thermal communication between the energy sensing element 122 and the port 632 and/or the auxiliary lumen.

[0236] In some embodiments, the lead body 150 is coupled with a tube 556, which in further embodiments is coupled with a handle 552. In some embodiments, the tube 556 includes a protrusion 565. In other embodiments, the lead body 150 is coupled directly with the handle 552 and includes the protrusion 565. Other arrangements are also possible.

[0237] In certain embodiments, the sheath 625 includes a sheath body 650. The sheath body 650 can include any suitable material, such as, for example, any of the materials described above with respect to the lead body 35. In some embodiments, portions of the sheath body 650 are separated from each other by expansion members 520. In some embodiments, at least a portion of the sheath body 650 is between the energy producing element 120 and the energy sensing element 122 along a longitudinal length of the assembled probe 614. In certain of such embodiments, the portion of the sheath body 650 between the elements 120, 122 can include mixing features (e.g., any of the mixers 130 described above) and/or spacing, positioning, or centering features (e.g., any of the positioning devices 140 and/or extensions 420 described above).

[0238] In some embodiments, the sheath 625 includes one or more collars 542, which can be configured to move relative to lead body 150 when the sheath 625 is coupled with the core 620. For example, in some embodiments, the collars 542 are substantially cylindrical and define an inner diameter that is slightly larger than an outer diameter defined by the lead body 150. In various embodiments, the sheath 625 includes a handle 550 and/or defines a groove 562. In certain embodiments, the sheath body 650 defines an access port 658. In some embodiments, the access port 658 provides selective fluid communication between the port 632 of the core 620 and the exterior of the probe 614, and in other embodiments, the access port provides continuous fluid communication between the port 632 and the exterior of the probe 614.

[0239] In some embodiments, the sheath 625 and the core 620 function in a manner similar to the actuator 530. For example, in some embodiments, the core 620 functions in a manner similar to the line 545, and can extend through a substantial portion of the sheath 625 in an assembled probe 614. In some embodiments, the core 620 is coupled with one or more portions of the sheath body 650 such that the sheath 625 can contract longitudinally due to movement of the core 620. For example, in some embodiments, the core 620 is secured to a distal portion of the sheath body 650 and is slidably retained within the sheath body 650 along a substantial length thereof. In some embodiments, as the core 620 moves in a distal direction, adjacent portions of the sheath body 650 that are separated from each other by an expansion member 520 move toward each other, thereby deploying the expansion member 520 and transitioning the probe 614 from a substantially mobile state to a substantially fixed-position state.

[0240] In some embodiments, the sheath 625 includes one or more expansion members 520 that substantially surround the energy producing element 120 within a vessel when the probe 614 is in the substantially fixed-position state. Similarly, in some embodiments, one or more expansion members 520 substantially surround the energy sensing element 122 when the probe 614 is in the substantially fixed-position state. Accordingly, expansion members 520 can substantially center one or more of the energy producing element 120 and the energy sensing element 122 within a blood vessel (e.g., substantially align the elements 120, 122 with an axial center of the blood vessel) when the probe 614 is in the substantially fixed-position state.

[0241] With reference to Figure 33, in certain embodiments, one or more of the expansion members 520 define a substantially cylindrical portion 660 when deployed. In some embodiments, substantially all of the substantially cylindrical portion 660 contacts the inner wall of a blood vessel when an expansion member 520 is deployed. In some embodiments, the energy producing element 120 and/or the energy sensing element 122 are approximately at a longitudinal center of the substantially cylindrical portions 660 of respective expansion members 520. Accordingly, in some embodiments, blood flow near the elements 120, 122 can be relatively unaffected by the cylindrical portions 660 of the expansion members 520.

[0242] With reference to Figure 34, in certain embodiments, one or more of the expansion members 520 define two relatively wide outwardly extending portions or lobes 662 when deployed. In further embodiments, one or more of the expansion members 520 include more than two relatively wide lobes 662. In some embodiments, the lobes 662 of one or more of the expansion members 520 are at, near, or adjacent respective distal and proximal ends of one or more of the elements 120, 122. For example, in the illustrated embodiment, an expansion member 520 is at the same longitudinal position as the energy sensing element 122 and comprises a lobe 662 distal to the element 122 and another lobe 662 proximal to the element 122. As shown in the illustrated embodiment, an expansion member 520 is at the same longitudinal position as the energy producing element 120 and comprises a lobe 662 at a distal end of the element 120 and another lobe 662 at a proximal end of the element 120. In some embodiments, the portions of the expansion members 520 located between the lobes 662 are closer to an axial center of the probe 614 than are the lobes 662, and can have a relatively smaller effect on blood flow.

[0243] Figure 35 illustrates another embodiment of the probe 614. In some embodiments, the core 620 includes one or more positioning members 670 (e.g., any of the positioning devices 140 and/or extensions 420 described above) at a position distal the energy producing element 120. The positioning member 670 can be at a proximal end of a tip 155 of the probe 614. In some embodiments, the one or more positioning members 670 inhibit proximal and distal movement of the probe 614 by approximately the same amount. Accordingly, in some embodiments, the probe 614 resists insertion into a blood vessel of a patient by about the same amount as it resists removal from the blood vessel. In some embodiments, the one or more positioning members 670 are configured to disrupt blood flow by a relatively small amount. For example, in some embodiments, the core 620 includes relatively few and/or relatively thin positioning members 670.

[0244] In some embodiments, the probe 614 includes an expansion member 520a at or near a distal end of the sheath 625. In further embodiments, the expansion member 520a, when deployed, does not extend past the proximal end of the energy producing element 120. Accordingly, in some embodiments, the expansion member 520a is downstream of the energy producing element 120 when the probe 614 is in the substantially fixed-position state, and can be configured to not disrupt the flow of blood past the energy producing element 120.

[0245] In some embodiments, the probe 614 comprises one or more expansion members 520b, 520c near the energy sensing element 122. In some embodiments, the expansion members 520b,520 c are separated by a portion of the sheath body 650, which, in further embodiments, substantially envelops, covers, or surrounds a substantial portion of the energy sensing element 122.

[0246] Other configurations of the probe 614 and/or components thereof are also possible. For example, in some embodiments, the sheath 625, rather than the core 620, includes one or more of the tip 155, the energy producing element 120, and the energy sensing element 122. [0247] Figure 36 illustrates an exploded view of an embodiment of a probe 714. The probe 714 can resemble the probes 14, 14', 14", 114, 414, 514, and 614 in many respects, thus like features are identified with like numerals. The probe 714 can differ from the probes 14, 14', 14", 114, 414, 514, and 614 in other respects, such as those described hereafter. In some embodiments, the probe 714 includes an insert or core 720, such as the core 620 described above, and a cover or sheath 725, such as the sheath 625 described above. In some embodiments, the core 720 is configured to be received within the sheath 725, and in further embodiments, is configured to translate within the sheath 725.

[0248] In certain embodiments, the core 720 includes a lead body 150, which can include one or more extensions 420 (described above) for positioning a distal end of the probe 714 within a blood vessel. In some embodiments, the one or more extensions 420 are attached to or otherwise placed over a tip 155 of the probe 714.

[0249] In certain embodiments, the core 720 includes one or more spacing members 730, which can be similar to the extensions 420. In some embodiments, the spacing members 730 are formed of the same material as the extensions 420. For example, in some embodiments, the spacing members 730 include a shape memory alloy that is heat treated to form a desired anchoring shape. In some embodiments, the spacing members 730 include a wire of a nickel-titanium alloy having a thickness of between about 0.001 inches and about 0.005 inches, including about 0.002 inches, in certain embodiments. In some embodiments, a spacing member 730 includes two longitudinally extending base portions 732, which can be adhered to or otherwise joined with the lead body 150 and/or covered with heat shrink tubing. In some embodiments, the base portions 732 are joined by a laterally extending anchoring portion, arm, or protrusion 734. In some embodiments, the protrusion 734 is substantially rounded or curved at least on an end thereof, and is configured to contact a wall of a blood vessel substantially without causing harm thereto.

[0250] In certain embodiments, the sheath 725 surrounds a substantial portion of the core 720 in an assembled probe 714. In some embodiments, the sheath 725 includes one or more tension lines or wires 740. In some embodiments, the wires 740 extend from a proximal end of the sheath 725, and in further embodiments, extend along at least a portion of the length of the sheath 725. [0251] In some embodiments, the sheath 725 includes one or more slits, ports, or windows 742, and in further embodiments, includes a separate window 742 to coincide with each spacing member 730 of the core 720. The windows 742 can be substantially aligned with the spacing members 730 along a length of the probe 714.

[0252] In certain embodiments, the sheath 725 is configured to transition the probe 714 between a substantially mobile state and a substantially fixed-position state. For example, in some embodiments, the sheath 725 is configured to position the protrusions 734 of the spacing members 730 near (e.g., proximate or adjacent) the lead body 150 in an assembled probe 714, thereby retaining the probe 714 in the substantially mobile state and facilitating insertion and positioning of the probe 714 in a blood vessel. In some embodiments, separate sets of windows 742 are positioned distal to separate sets of spacing members 730 when the probe 714 is in the substantially mobile state.

[0253] In some embodiments, once the probe 714 is positioned as desired within the blood vessel, the sheath 725 can be retracted to transition the probe 714 to the substantially fixed-position state. For example, in some embodiments, the wires 740 (and hence, the sheath 725) can be urged in a proximal direction such that the windows 742 of the sheath 725 move over spacing members 730. The protrusions 734 can extend through the windows 742 and curl or bend outward to their natural state. In some embodiments, the protrusions 734 extend away from the lead body 150 and contact the wall of the blood vessel when in the substantially fixed-position state.

[0254] In some embodiments, the sheath 725 can be advanced in the distal direction to again cover the protrusions 734 and retain them close to the lead body 150, thus placing the probe 714 in the substantially mobile state for relatively easy removal of the probe 714 from the blood vessel. In further embodiments, the protrusions 734 are configured to bend or otherwise displace in a distal direction due to a proximally directed force imparted on the probe 714 by a medical professional. Accordingly, in some embodiments, the medical professional can remove the probe 714 with relative ease without first transitioning the probe 714 to the substantially mobile state.

[0255] With reference to Figure 37, in certain embodiments, a catheter assembly 800 includes a probe 814 such as any of the probes 14, 14', 14", 114, 414, 514, 614, and 714. In some embodiments, the assembly 800 comprises a primary manifold 820 coupled with the probe 814. The manifold 820 can include one or more paths, conduits, or passageways (not shown) that can extend one or more lumens of the probe 814. In some embodiments, the passageways are relatively close at the distal end of the manifold 820 and can spread to a more spaced apart or fanned out orientation at the proximal end of the manifold 820.

[0256] The assembly 800 can include a primary lead extender 822 coupled at a one end with the primary manifold 820 and at another end with a secondary manifold 824. In some embodiments, the secondary manifold 824 branches into two secondary lead extenders 826, 827. In some embodiments, each of the secondary lead extenders 826, 827 is coupled with an electrical connector 828, 829, respectively. In certain embodiments, the connectors 828, 829 are configured to couple with one or more controllers, such as any of the controllers 16, 16', or 16" (see Figures 1 and 7).

[0257] In certain embodiments, the probe 814 includes a lead body 150, which houses lead wires for both an energy producing element 120 and an energy sensing element 122. For example, the lead body 150 can define one or more lumens such as the lumens 193, 194 (see, e.g., Figure 12B). In some embodiments, the lead wires for the energy producing element 120 extend through the lead body 150, the primary manifold 820, the primary lead extender 822, the secondary manifold 824, and the secondary lead extender 826 to the connector 828. In some embodiments, the lead wires for the energy sensing element 122 extend through the lead body 150, the primary manifold 824, the primary lead extender 822, the secondary manifold 824, and the secondary lead extender 827 to the connector 829. Accordingly, in some embodiments, one or more controllers or other devices may be connected with the connectors 828, 829 to electrically communicate with the energy producing element 120 and the energy sensing element 122, respectively. In some embodiments, the one or more controllers can use information regarding energy delivered to the energy producing element 120 and energy detected by the energy sensing element 122 to calculate the cardiac output and/or other desired physiological parameters of the patient, as described above and/or below.

[0258] In some embodiments an auxiliary extender 830 is coupled with the primary manifold 824. In some embodiments, the auxiliary extender 830 is further coupled with a connector 832. The connector 832 can comprise any suitable medical connector. For example, in some embodiments, the connector 832 includes a Luer connector. In some embodiments, a fluid sampling device or a device for monitoring a blood parameter is coupled with the connector 832.

[0259] In some embodiments, the lead body 150 defines an auxiliary lumen, such as the lumen 197 (see Figure 12C). In some embodiments, the auxiliary lumen is in fluid communication with the auxiliary extender 830 and the connector 832, and thus can be in fluid communication with a fluid sampling device or a device for monitoring a blood parameter via the connector 832. For example, in some embodiments, the connector 832 can be coupled with a pressure monitoring device. The pressure monitoring device can obtain information regarding the blood pressure of a patient. In some embodiments, the information thus obtained can be used in connection with information regarding the energy producing element 120 and/or the energy sensing element 122 to calculate the cardiac output and/or other desired physiological parameters of the patient, as described above.

[0260] Figure 38 illustrates an embodiment of a catheter assembly 900. The catheter assembly 900 can resemble the catheter assembly 800 in many respects, and can differ in other respects, such as those described hereafter. The catheter assembly 900 can include a probe 914, such as the probes 514, 614 described above. For example, in the illustrated embodiment, the probe 914 comprises a lead body 150, one or more expansion members 520, and an actuator 530 such as like-numbered features of the probe 514. The actuator 530 can include a proximal handle 550 and a distal handle 552. The assembly 900 can further include connectors 828, 829, 832 such as like numbered features of the assembly 800.

[0261] In some embodiments, the probe 914 is coupled with a manifold 820. As with the embodiment illustrated in Figure 37, the manifold 820 can include a first passageway (not shown) leading to an auxiliary extender 830, which can be coupled with the connector 832, and a second passageway (not shown) leading to a primary lead extender 822.

[0262] In some embodiments, the manifold 820 includes one or more passageways (not shown) coupled with one or more actuator extenders 920, which in turn can be coupled with the actuator 530. In some embodiments, one or more tension wires or lines 545 extend through the lead body 150 (see Figure 29), through the one or more passageways of the manifold 820, and through the one or more actuator extenders 920 to the actuator 530. In the embodiment illustrated in Figure 38, the assembly 900 includes two actuator extenders 920, each of which surrounds at least a portion of a separate line 545. The embodiment illustrated in Figure 38 thus can be particularly suited for use with a lead body 150 through which two lines 545 extend (see Figure 3 IB).

[0263] In certain embodiments, the proximal handle 550 of the actuator 530 includes one or more extensions 930 that project in a distal direction and the distal handle 552 includes one or more extensions 932 that project in a proximal direction. In some embodiments, the proximal and distal extensions 930, 932 substantially interlock when the actuator 530 is in the substantially fixed-position state. The extensions 930, 932 thus can substantially prevent rotation of the handles 550, 552 relative to each other.

[0264] In some embodiments, the proximal and distal handles 550, 552 are separated from each other to transition the actuator 530 to the substantially mobile state. In some embodiments, transitioning the actuator 530 to the substantially mobile state can provide sufficient clearance between the extensions 930, 932 to permit rotation of the handles 550, 552. In some embodiments, a distal end of the one or more proximal extensions 930 defines one or more proximally extending recesses that receive the one or more distal extensions 932, which thus can substantially secure the actuator in the substantially mobile state. In some embodiments, to transition the handles 530, 532 from the substantially mobile state to the substantially fixed-position state, the handles 530, 532 can be slightly separated, rotated such that the extensions 930, 932 are offset from one another, and urged together.

[0265] In certain embodiments, the catheter assembly 900 is used to determine the cardiac output and/or some other physical parameter of a patient. In various embodiments, one or more of the connectors 828, 829, 832 can be used in any suitable manner, such as those described above with respect to the assembly 800. In some embodiments, at least a portion of the probe 914 is introduced into a blood vessel of a patient via an introducer, such as any of the introducers 30, 330, 330', 330" describe above. In some embodiments, the introducers 330, 330' (see Figures 24 A and 24B) are particularly suitable for use with the catheter assembly 900, as blood collection and/or monitoring can be performed via the connector 832. In other embodiments, the introducer 330" (see Figure 24C) can be used to provide additional access to the blood of a patient. [0266] In some embodiments, a length of a proximal portion of the lead body 150 (e.g., the portion of the lead body 150 between the manifold 820 and an energy sensing element 122) is sized to facilitate insertion of the probe 914 in the blood vessel and/or to provide relatively unencumbered use of the catheter assembly 900. For example, in some embodiments, the length of the proximal portion of the lead body 150 is sufficient to permit a desired portion of the probe 914 to be inserted through the introducer to a desired position within the blood vessel, while leaving enough separation between the insertion point and the manifold 820 to permit the introducer to be readily removed from the blood vessel.

[0267] In certain embodiments, a method of introducing the probe 914 into the blood vessel of a patient includes inserting an introducer (e.g., the introducer 330 or 330') into the blood vessel through an insertion point. In some embodiments, the method can include transitioning the actuator 530 to the substantially mobile state, and in other embodiments, the catheter assembly 900 may already by in the substantially mobile state. The method can include inserting a first portion of the probe 914 through the introducer to a desired position within the blood vessel. The method can include transitioning the actuator 530 to the substantially fixed-position state. In some embodiments, the method includes removing the introducer from the patient over a second portion of the probe 914 while the first portion of the probe remains substantially in the desired position. In further embodiments, the method includes removing the introducer from the probe 914, such as by separating the introducer into two or more pieces.

[0268] Figure 39 illustrates an embodiment of a catheter assembly 1000. The catheter assembly 1000 can resemble the catheter assemblies 800, 900 in many respects, and can differ in other respects, such as those described hereafter. In some embodiments, the catheter assembly 1000 comprises a probe 1014, such as any suitable probe described above. The probe 1014 can house lead wires for an energy producing element 120 and an energy sensing element 122. In some embodiments, the assembly 1000 includes a single connector 1020 coupled with the lead wires for both elements 120, 122. In some embodiments, the connector 1020 can be coupled with a controller, which then can communicate with the energy producing element 120 and/or the energy sensing element 122.

[0269] In some embodiments, the catheter assembly 1000 includes an actuator 530. In some embodiments, the actuator 530 is configured for use with a single hand. For example, in the embodiment illustrated in Figure 39, the actuator 530 comprises a housing 1030 that includes a proximal portion 1032 and a distal portion 1034. The proximal portion 1032 can be sized and shaped to fit comfortably within one or more, two or more, three or more, or four curled fingers of a user. The distal portion 1034 can define a channel 1040. In some embodiments, a button 1042 extends through the channel 1040 and is configured to move within the channel. The button 1042 can be connected to a line 545 of the probe 1014. In some embodiments, in order to transition the actuator 530 between the substantially mobile state and the substantially fixed-position state, the proximal portion 1032 is grasped with one or more, two or more, three or more, or four fingers of a hand, and the thumb of the hand is used to move the button 1042 from one end of the channel to the other. Other suitable arrangements are also possible.

[0270] In some embodiments, such as the embodiments illustrated in Figure 39, the catheter assembly does not include a connector 832 that facilitates access to the patient's blood, while in other embodiments the catheter assembly can include the connector 1020 and a connector, such as the connector 832 (see Figure 38), that facilitates access to the patient's blood. In some instances, it can be desirable to use the assembly 1000 with an introducer or other device that provides access to the patient's blood, such as the introducer 330".

[0271] Figure 4OA is a plan view of an embodiment of a probe 1114. The probe 1114 can resemble the probes 14, 14', 14", 114, 414, 514, 614, 714, 814, 914 in some respects, thus like features are identified with like numerals. The probe 1114 can differ from the aforementioned probes in other respects, such as certain respects described hereafter. In certain embodiments, the probe 1114 can suitably be included in a probe assembly, such as the probe assemblies 800, 900, 1000 described above.

[0272] As shown in Figure 4OA, the probe 1114 can comprise a lead body 150, an energy producing element 120, an energy sensing element 122 spaced longitudinally from the energy producing element 120 along the lead body 150, and one or more expansion members 520.

[0273] In some embodiments, the lead body 150 can comprise one or more lumens and one or more openings, such as those shown in Figures 4OB and 41-43. The lead body 150 illustrated in Figures 41-43 has four lumens 1150, 1160, 1165A, and 1165B. In some embodiments, the lead body can have more than or fewer than four lumens. The lumens can extend longitudinally along all or substantially all of the entire length of the lead body 150, or can alternatively extend longitudinally through the lead body 150 over a distance less than substantially all of the length of the lead body 150.

[0274] Some of the lumens, such as lumens 1150, 1160 can have a characteristic dimension (e.g. diameter) that is larger near one end of the lead body 150 than near another end of the lead body 150. The characteristic dimension can be larger at the proximal end than at the distal end or larger at the distal end than at the proximal end. In some embodiments, the characteristic dimension at the larger end can be at least two, three, four, or more times the magnitude of the characteristic dimension at the smaller end. For example, the lumen 1150 can have a diameter of between approximately 14 thousandths of an inch and approximately 35 thousandths of an inch at the proximal end of the lead body 150 and a diameter of between approximately 5 thousandths of an inch and approximately 20 thousandths of an inch at the distal end of the lead body 150. In one embodiment, the lumen 1150 has a diameter of approximately 17 thousandths of an inch at the location of the cross- section of Figure 41, and a diameter of approximately 10 thousandths of an inch at the locations of the cross-sections of Figures 42 and 43.

[0275] The lead body 150 can have one or more characteristic external dimensions (e.g. an outer diameter) that vary over the length of the lead body 150. For example, the lead body 150 can have an outer diameter that is larger at a proximal end than at a distal end. The outer diameter at the larger end can be at least two, three, four, or more times greater than the outer diameter at the smaller end. In some embodiments, the lead body 150 can have an outer diameter of approximately 42 thousandths of an inch at the location of the cross-section of Figure 41, an outer diameter of approximately 28 thousandths of an inch at the location of Figure 42, and an outer diameter of approximately 24 thousandths of an inch at the location of Figure 43.

[0276] In some embodiments, reductions in one or more characteristic external dimensions of the lead body 150 can provide one or more advantages, which may include, for example, facilitation of access between the lumens, such as lumens 1165 A, 1165B, and an exterior of the device, and facilitation of a generally uniform cross-sectional area along the section of the assembled probe 1114 to be inserted into the patient when in the substantially mobile state. [0277] As shown in Figures 4OB and 42, the lead body 150 can have openings 1132, 1134, 1136, 1138, 1140, 1142, 1144, 1146, 1148A, and 1148B. In some embodiments, a lead body can have more than or fewer than ten openings. Some openings may be ports that permit access between one or more lumens and the exterior of the device during manufacture and/or use of the probe 1114. For example, in the embodiment illustrated in Figures 4OA, 4OB, and 41-43, the openings 1132, 1138, 1140, 1142, 1144, and 1146 can provide access between the lumen 1150 and the exterior of the lead body 150, while the opening 1134 can provide access between the lumen 1150, the lumen 1160, and the exterior of the device, the opening 1136 can provide access between the lumen 1160 and the exterior of the device, and the openings 1148A, 1148B can provide access between the lumens 1165 A, 1165B, respectively, and the exterior of the device.

[0278] In certain embodiments, such as the embodiment illustrated in Figures 4OA, 4OB, the opening 1132 in the probe 1114 can define a port, similar to the ports 440, 632, described above, that permit fluid communication between a blood vessel and the lumen 1150. Thus, in some embodiments, blood can be drawn from a blood vessel through the port 1132 and the lumen 1150 (see Figure 41) to permit blood sampling and/or pressure monitoring, as discussed above. Similar to ports 440, 632, the port 1132 can be located proximal of the energy sensing element 122, and may be spaced from the element 122 so as not to disturb measurements taken by the element 122. In other embodiments, the probe 1114 can include a lumen that extends the length of the probe 1114 to an opening at a distal end of the probe 1114 that can be used to facilitate blood collection and/or pressure monitoring.

[0279] In some embodiments, the energy sensing element 122 can comprise a thermistor. The energy sensing element 122 can be positioned within the lumen 1160 of the lead body 150, as illustrated in Figure 42, near the opening 1136, shown in Figure 4OB. In some embodiments, the opening 1136 can be filled with a urethane adhesive to secure the element 122 near the opening 1136. The element 122 can be connected to lead wires 28A, 28B that extend through the lumen 1160 (see Figure 41) to connect the element 122 with one or more controllers.

[0280] Lead wires 26 A, 26B can connect the energy producing element 120 to one or more connectors, which may be the same as or different than the connector(s) to which the energy sensing element 122 is connected. The lead wires 26 A, 26B can extend from a proximal end of the probe 1114 to a location near the distal end of the probe 1114. For example, the lead wires 26 A, 26B can extend through the lumen 1160, the opening 1134, and the lumen 1150 to a location near the openings 1138 and/or 1140. The opening 1134 can be filled with a urethane adhesive during manufacture to substantially prevent fluid communication between a blood vessel and the lumens 1150, 1160 during use.

[0281] In some embodiments, the temperature of the lead wires 26A, 26B may increase as current is conducted to the energy producing element 120. Heat transfer from the lead wires 26A, 26B to the lead wires 28A, 28B, which are connected to the energy sensing element 122, may potentially interfere with the precision, accuracy, and/or reliability of measurements taken using the energy sensing element 122. To inhibit transmission of heat from the lead wires 26 A, 26B to the lead wires 28 A, 28B, one or both of the lead wires 26 A, 26B and the lead wires 28A, 28B can be insulated. Additionally or alternatively, the lead wires 26A, 26B may extend through a different lumen than the lead wires 28A, 28B over all or a portion of the length of the lead body 150 to inhibit transmission of heat from the lead wires 26 A, 26B to the lead wires 28 A, 28B. In some embodiments, the lead wires 26 A, 26B and the lead wires 28A, 28B can extend through the same lumen over a length of the lead body 150, as shown in Figure 41.

[0282] In some embodiments, a block or stop 1155 (see Figure 40A) is provided within the lumen 1150 to prevent fluid communication between the port 1132 and that portion of the lumen 1150 containing the leads wires 26 A, 26B. The block or stop 1155 can be similar to the thermal inhibitor 634 and can inhibit transfer of heat between the lead wires 26A, 26B and the blood.

[0283] The lead wires 26 A, 26B can be joined to the energy producing element 120 near the openings 1138, 1140. The openings 1138, 1140 can provide access to the lumen 1150 to facilitate connection of the lead wires 26A, 26B to the energy producing element 120.

[0284] In some embodiments, the element 120 can comprise a resistive heating coil, such as the heating element 162, described above, and can be soldered to the lead wires 26A, 26B. The heating coil can extend out of the lead body 150 through the opening 1142, can wind around the lead body 150, and can extend through the opening 1144 and the lumen 1150 to the opening 1146. The ends of the heating coil can be soldered together near the opening 1146. After the heating coil and the lead wires 26A, 26B have been properly positioned and connected, the openings 1138, 1140, 1142, 1144, and 1146 can be filled with a urethane adhesive, such as a urethane epoxy, to maintain the positioning of the lead wires 26 A, 26B and the element 120 and to substantially prevent fluid communication between the lumen 1150 and a blood vessel.

[0285] In certain embodiments, the heating coil can be made of a high-resistance conductor, such as Chromel® or A-Nickel, to promote energy dissipation at the heating coil and, thereby, to reduce the amount of heat generated by electrical conduction through the lead wires 26 A, 26B. As a result, the influence, if any, of the heat generated in the lead wires 26A, 26B on the lead wires 28 A, 28B may be reduced.

[0286] In the embodiment illustrated in Figures 4OA, 4OB, and 43, the energy producing element 120 can be connected to the lead body 150 at a location that has an external dimension (e.g., an outer diameter) that is smaller than at other locations along the lead body 150.

[0287] This smaller external dimension of the lead body 150 may permit the energy producing element 120 to be attached to the exterior of the lead body 150 while maintaining a generally uniform external dimension (e.g., outer diameter) of the probe 1114 along the section of the probe 1114 that is to be inserted into the blood vessel.

[0288] In some embodiments, the probe 1114 can comprise one or more expansion members. In the embodiment illustrated in Figure 4OA, the one or more expansion members 520 include a proximal expansion member 520a and a distal expansion member 520b, each comprising three wires 540. In some embodiments, the one or more expansion members 520 can include one or more, two or more, or three or more wires 540, and can each include one or more collars 542. In some embodiments, a reduction in the number of wires 540 can reduce the maximum impedance cross-sectional area 230 (see Figure 15) of the probe 1114, which can result in a reduction in the pressure drop across a given expansion member and a reduction in the likelihood and severity of clotting.

[0289] As described above, in some embodiments, the wires 540 and the collars 542 can be joined in any suitable fashion, and in further embodiments, can comprise a unitary piece of material. For example, in some embodiments, the wires 540 and the collars 542 can be formed from a substantially cylindrically shaped tube having portions removed therefrom. The tube may comprise a shape-memory material, for example, Nitinol. The wires 540 may be biased toward an expanded configuration, such as that illustrated in Figure 40.

[0290] In various embodiments, the proximal expansion member 520a and the distal expansion member 520b are integrally formed from a unitary piece of material. For example, the proximal expansion member 520a and the distal expansion member 520b can be formed from a substantially cylindrically shaped tube having portions removed therefrom.

[0291] In certain embodiments, one or more expansion members 520 can be integrally formed with one or more mixers, such as the mixers 130 described above, from a unitary piece of material. For example, Figure 44 illustrates the proximal expansion member 520a and the distal expansion member 520b as integrally formed with a mixer 1170 from a substantially cylindrically shaped tube having portions removed therefrom. The illustrated mixer 1170 comprises a plurality of flow directors 1172. The illustrated flow directors 1172 have a generally helical shape and are arranged in three groups, each group having six flow directors 1172. In other embodiments, the flow directors 1172 can be arranged into more than or fewer than three groups, such as one, two, four, five or more groups. Each group can have one or more flow directors 1172. The one or more of the flow directors 1172 of one group can be formed or structured to be separate from those of an adjacent group, if any, or one or more of the flow directors 1172 of each group can be formed or structured to be continuous with those of an adjacent group, if any. One or more intermediate members 1174 can be provided to assist in retaining the flow director(s) 1172 to a probe and/or to facilitate the deployment of a probe and/or to assist in producing a desired shape for the flow director(s) 1172 to assist in thermally mixing the blood. In some embodiments, the flow director(s) 1172 can be configured to transition between an expanded configuration and a collapsed configuration.

[0292] The expansion members 520 can be configured to transition between a substantially fixed-position state and a substantially mobile state. The expansion members 520 are illustrated in the substantially fixed-position state in Figure 4OA. In some embodiments, the wires 540 can be substantially curved or rounded and extend generally laterally (e.g., radially) from the lead body 150 when in the substantially fixed-position state. The wires can be positioned substantially parallel to a longitudinal length of the lead body 150 when in the substantially mobile state.

[0293] The distal expansion member 520b can include a distal collar 542a and a proximal collar 542b. The distal collar 542a can be attached to the lead body 150. The proximal collar 542b can be attached to a tube 1130. The tube 1130 can be free to move relative to the lead body 150. The tube 1130 can have an interior dimension (e.g., an inner diameter) that is slightly larger than an exterior dimension (e.g., an outer diameter) of the lead body 150. The tube 1130 can comprise any suitable material, for example, polyamide.

[0294] The proximal expansion member 520a can include a distal collar 542c and a proximal collar 542d. The distal collar 542c can be attached to the tube 1130. The distal collar 542c and the proximal collar 542d can be free to move relative to the lead body 150. The collar 542d can be attached to one or more lines 545. The lines can extend through the openings 1148A, 1148B and the lumens 1165A, 1165B in the lead body 150.

[0295] The lines 545 thus can transition the expansion members 520a, 520b between the substantially mobile state and the substantially fixed-position state. For example, the expansion members 520a, 520b can be biased toward the substantially fixed- position state. The expansion members 520a, 520b can be moved to the substantially mobile state by moving the lines 545 in a proximal direction. This urges the collars 542b, 542c, 542d and the tube 1130 proximally. Because the collar 542a is fixed relative to the lead body 150, the wires 540 of the expansion members 520a, 520b are placed under tension, and are deformed such that they are closer to the lead body 150 and extend a longer distance in a direction substantially parallel to a longitudinal length of the lead body 150. The expansion members 520a, 520b can be moved from the substantially mobile state to the substantially fixed-position state by urging, or releasing, the lines 545 in a distal direction to allow the wires 540 to move to a natural, or lower energy, state. In other embodiments, the expansion members 520a, 520b can be biased in the substantially mobile state. The lines 545 may also be used to move one or more mixers, such as the mixer 1170 shown in Figure 44, between an expanded configuration and a collapsed configuration. For example, one end of the tube illustrated in Figure 44 may be fixedly attached to the lead body 150 while another end is connected to the lines 545 such that movement of the lines 545 in one direction expands the mixer 1170 (see Figure 44) and movement of the lines 545 in the opposite direction collapses the mixer 1170.

[0296] In some embodiments, the tube 1130 (Figure 40) can be connected to the collars 542 by overlapping the tube 1130 and the collars 542, placing a bonding tube 1128 over the junction between the tube 1130 and the collar 542, placing a heat-shrinkable tube over the bonding tube, and heating the heat-shrinkable tube and bonding tube. As the heat- shrinkable tube and bonding tube are heated, the bonding tube softens and the heat- shrinkable tube shrinks and applies pressure to the bonding tube such that material of the bonding tube seeps into the gap or gaps between the tube 1130 and the collar 542. After the bonding tube has cooled the heat-shrinkable tube can be removed.

[0297] In a similar manner, the collar 542d can be connected to the lines 545 by overlapping the collar 542d and the lines 545, placing a bonding tube 1128 over the junction between the collar 542d and the lines 545, placing a heat-shrinkable tube over the bonding tube, and heating the heat-shrinkable tube and bonding tube. The flow directors 1172 (Figure 44) can be connected to one or more collars 542 or intermediate members 1174 in a similar manner.

[0298] Alternatively, the tube 1130 can be connected to the collars 542 by positioning the tube 1130 and the collars 542 over a mandrel, butting the tube 1130 and the collar 542 against one another, placing a bonding tube 1128 over the abutment between the tube 1130 and the collar 542, placing a heat-shrinkable tube over the bonding tube, and heating the heat-shrinkable tube and bonding tube. As the heat-shrinkable tube and bonding tube are heated, the bonding tube softens and the heat-shrinkable tube shrinks and applies pressure to the bonding tube such that the material of the bonding tube seeps into the gap or gaps between the tube 1130 and the collar 542. After the bonding tube has cooled the heat- shrinkable tube and the mandrel can be removed.

[0299] In some embodiments, the bonding tube 1128 can comprise a thermoplastic elastomer (TPE) or other suitable material. For example, the bonding tube 1128 can comprise poly ether block amide, such as Pebax ®.

[0300] In some embodiments, the lead body 150 and the collar 542a can be connected by a urethane adhesive. In other embodiments, the lead body 150 and the collar 542 can be connected by other adhesives or other attachment methods know to those of skill in the art, such as mechanical joining techniques.

[0301] In some embodiments, the proximal collar 542b of the distal expansion member 520a can be connected directly to the distal collar 542c of the proximal expansion member 520b. In certain embodiments, the proximal collar 542b of the distal expansion member 520a can be integrally formed with the distal collar 542c of the proximal expansion member 520b.

[0302] In some embodiments, the lumens 1150, 1160, 1165A, and 1165B can be occluded at a distal tip of the lead body 150 by a plug 1126 (Figure 40A). The plug 1126 can be the same as or similar to the tip 155, described above. In some embodiments the plug 1126 can comprise a urethane adhesive. The plug 1126 can have an atraumatic shape to avoid damage to the blood vessel.

[0303] Any suitable combination of any of the features of the probes 14, 14', 14", 114, 414, 514, 614, 714, 814, 914, 1014, and/or 1114 with each other is contemplated. Additionally, any suitable combination of any of the devices 10, 10', and 10", or components or features thereof, with each other and/or any of the components or features described herein are also contemplated.

[0304] Additionally, any of the probes 14, 14', 14", 414, 514, 614, 714, 814, 914, 1014, and/or 1114 can be included in the kit described above with respect to the probe 114. The kit can also include a probe assembly, such as any of the assemblies 800, 900, 1000. In some embodiments, the kit includes different or additional instructions for use than those described above. For example, in certain embodiments, the kit includes an embodiment of the probe 414 and also includes additional instructions for removal and/or separation of the sheath 442. In some embodiments, the kit includes an embodiment of the probe 514 and also includes additional instructions regarding use of the actuator 530 to deploy or retract the expansion members 520, such as by separation and twisting of the handles 550, 552. In some embodiments, the kit includes an embodiment of an assembly 800 and also includes instructions regarding the coupling of one or more of the connectors 828, 829, 832 with a controller or a blood sampling or monitoring device.

[0305] Any suitable portion of any of the probes 14, 14', 14", 114, 414, 514, 614, 714, 814, 914, 1014, and/or 1114 can be treated (e.g., coated) with any of the therapeutic agents described above. For example, in some embodiments, one or more portions of the probe 1114 that are configured to be exposed to blood when the probe 1114 is within a blood vessel of a patient can be coated with heparin.

[0306] In some embodiments, a cardiac output measurement device, such as devices 10, 10', and 10" (Figures 1, 6, and 7) can include a variety of hardware and software components. Figure 45 is a schematic diagram of an embodiment of a system 1500 including several hardware components for monitoring cardiac output of a patient. In the illustrated embodiment, the monitoring system 1500 includes a controller 1502, a heating element 1524, a temperature sensor 1528, and cables 1522, 1526 configured to connect the heater 1524 and sensor 1528 to the controller 1502.

[0307] The controller 1502 shown in Figure 45 includes a display 1504, a processor 1506, memory 1508 capable of being accessed by the processor 1506, storage 1510, a heating element driver 1512, data acquisition hardware 1514, an isolation amplifier 1516, a heating element interface 1518, and a temperature sensor interface 1520. However, in some embodiments, the controller can include less than all of the elements illustrated in Figure 45. The controller 1502 can also include other components such as, for example, communications interfaces, other input and output devices, digital signal processors, power supplies and backup power facilities, and peripheral medical equipment. The controller 1502 can be implemented as a single device (for example, a device housed within a unitary enclosure) or as multiple interconnected devices (for example, a general purpose computer connected to an external equipment chassis).

[0308] In some embodiments, the controller 1502 is a transportable system that is sized and configured to be a bedside cardiac output monitor. The controller 1502 can perform several functions related to monitoring cardiac output, including driving the heater 1524, measuring voltage and current through the heater 1524, and obtaining temperature measurements using data from the temperature sensor 1528. In some embodiments, the heater 1524 is a heating element, such as a heater coil 24 (Figure 3A). In some embodiments, the temperature sensor 1528 is a temperature-sensing element 22, such as a thermistor. Persons skilled in the art will recognize that alternative embodiments could employ another suitable heaters and/or temperature sensors. The heater 1524 and temperature sensor 1528 can be attached to a probe, such as any of probes 14, 14', 14", 114, 414, 514, 614, 714, 814, 914, 1014, and/or 1114, configured to be inserted into a patient blood vessel, such as the radial artery.

[0309] In some embodiments, the controller 1502 maintains a log of data in a storage device 1510. The storage 1510 can be any suitable storage medium to which a computer can write data such as, for example, a hard disk drive, an optical storage medium, a magnetic tape device, or a solid state storage device. The data written to the storage 1510 can include temperature measurements; heater voltage, current, resistance, and/or power measurements; cardiac output estimates; and/or data from peripheral instruments connected to the controller 1502.

[0310] In an exemplifying embodiment, the controller 1502 includes a computer running an instrument control system, such as Lab VIEW. Other control systems, including custom control systems, can be used to implement the functionality of the controller 1502. The computer includes a processor 1506 for performing instructions stored in memory 1508. Any suitable processors 1506 and memory devices 1508 can be used. The memory 1508 is a computer-readable medium capable of storing program code and data pertaining to the modules and methods described herein. The controller 1502 can include a display 1504 operatively connected to provide a user interface for communicating information to a user. In some embodiments, the controller 1502 includes other components not shown in Figure 45, such as, for example, an input device, a loudspeaker, specialized processors, interfaces and connectors to other devices, an uninterruptable power supply, and/or other components found on monitoring devices. The components shown in Figure 45 are not an exclusive or exhaustive representation of components that can be part of the system 1500.

[0311] The controller 1502 includes a data acquisition module 1514 that provides hardware for acquiring signals (including analog and/or digital signals) produced by devices connected to the controller 1502. Components of the data acquisition (DAQ) and controller hardware 1514 can be integrated within the computer (e.g., data acquisition may be performed by the processor 1506), connected to the computer via a suitable bus such as a Universal Serial Bus (USB), connected to an equipment chassis, and/or connected via another suitable interface. In some embodiments, the data acquisition hardware 1514 includes an analog-to-digital converter. [0312] An equipment chassis connected to the computer can include an isolation amplifier 1516, a heating element driver 1512, and probe interfaces 1522, 1526 for connecting to probe leads. The chassis can include a power supply configured to drive the heating element 1524 and supply a reference signal. The chassis can measure temperature sensor 1528 output. In some embodiments, wherein the temperature sensor comprises a thermistor, the chassis can provide an excitation signal. In some embodiments, the chassis is a National Instruments SCXI-1000 external card cage or another suitable equipment interface. In some embodiments, the chassis can be integrated with the computer to form a unitary controller 1502.

[0313] The storage 1510 can include a hard drive housed in the same unit as the processor 1506 or an external hard drive. Logging of data from peripheral medical instruments can occur via a serial-to-USB adapter, in the case of serial instruments, or via a terminal block, in the case of instruments that produce analog data streams. In some embodiments, the storage 1510 is a high capacity hard disc drive, such as a drive capable of storing 500 GB of data or more.

[0314] An isolation amplifier 1516 can be used to protect data acquisition components 1514 and reduce noise in acquired signals. In some embodiments, the isolation amplifier 1516 provides an excitation signal to the thermistor 1528. The temperature sensor 1528 (for example, a thermistor) can be connected via a suitable interface 1520 (for example, an isothermal terminal block) to the isolation amplifier 1516. In some embodiments, the isolation amplifier 1516 is a National Instruments SCXI-1121 amplifier with thermistor excitation. The temperature sensor interface 1520 can be a National Instruments SCXI- 1328 isothermal terminal block attached to the isolation amplifier 1516 or another suitable interface.

[0315] In some embodiments, the isolation amplifier 1516 measures the signal produced by the temperature sensor 1528. The isolation amplifier 1516 can also be configured to measure the output current of the heating element driver 1512. The heating element driver 1512 can be connected to the heating element 1524 via a heating element interface 1518. In some embodiments, the heating element interface 1518 is a terminal block, such as a National Instruments SCXI- 1300 terminal block. The differential amplifier 1516 can be used to calculating the current passed through the heating element 1524 by measuring the voltage across a small resistor (for example, a 0.1 Ω resistor) placed in series with the heating element 1524. A small capacitor (for example, a 1.0 μF capacitor) can be used to assist in filtering the signal from the temperature sensor 1528.

[0316] The heating element driver 1512 can include an amplifier assembled inside a breadboard module, such as, for example, a National Instruments SCXI-1181 breadboard module. The heating element driver 1512 can be connected to the controller 1502 via an equipment chassis. In some embodiments, the driver 1512 includes a unity-gain current amplifier to drive a header coil. The amplifier can contain an operational amplifier with sufficient drive output capability. In some embodiments, the drive output capability of the driver 1512 is 1.2 A or another suitable capacity sufficient to efficiently drive the heating element 1524. The driver 1512 can include a current limiter set to limit the output to 0.4 A or another sufficiently small current. In some embodiments, the current limiter is adjustable with a potentiometer or another suitable device. In some embodiments, the driver includes an amplifier circuit connected to a power supply that insures proper operation of an operational amplifier. The amplifier circuit can include a resistor and a capacitor to prevent oscillation. An output of the driver 1512 can include a small resistor to create a voltage drop. The current through the heating element 1524 and the output voltage of the driver 1512 can be monitored by the controller 1502.

[0317] In some embodiments, the heater driver 1512 includes a signal generator. The signal generator can provide a waveform in analog format that determines the drive voltage or current supplied by the heater 1524 over time. In some embodiments, the drive signal to the coil heater is about 5 V in amplitude and has a suitable current, such as 0.25 A. The heater driver can be designed to supply about 0.5 W of power, less than 1 W, or another safe and suitable amount of power.

[0318] In some embodiments, cables 1522, 1526 between the controller 1502 and the probe are used to connect the heating element 1524 and the temperature sensor 1528 to respective interfaces 1522, 1526. The cables 1522, 1526 provide a suitable number of conductors between the controller 1502 and the probe components. In some embodiments, the temperature sensor cable 1526 includes three twisted conductors, two for providing power to the sensor 1528 and one for conducting the temperature signal from the sensor 1528. The conductors can be any suitable gauge, such as, for example, between 22-24 AWG. In some embodiments, the heating element cable 1522 includes two twisted conductors of suitable gauge for supplying power to the heater 1524. For example, the heater cable 1522 can use 20-22 AWG conductors to supply power to a resistive heating coil configured to be used with the probe.

[0319] Figure 46 is a schematic diagram of an embodiment of a system 1550 for estimating cardiac output based on temperature sensor data and heater data. The components of system 1550 are software components that can be used to operate the hardware shown in Figure 45. The system 1550 shown in Figure 45 includes a monitoring application 1556 that allows control of a radial artery flow monitor. The application 1556 accepts temperature data 1552 produced by a temperature sensor 1528 and heater data 1554 relating to the power supplied to the heater 1524 by the heater driver 1512.

[0320] As shown in Figure 46, the monitoring application 1556 can include an interface module 1558, a data acquisition and control module 1560, a data logging module 1562, a heater driver module 1564, and an algorithm module 1566. The modules can be implemented as program code for performing operations executable by a computer processor 1506 or a specialized integrated circuit. The modules can be implemented in a high-level development environment, such as Lab VIEW, as software code compiled to run on a microprocessor or microcontroller, or in another suitable fashion to allow the system 1550 to operate effectively.

[0321] In some embodiments, the interface module 1558 can implement an interface for a user to control the operation of the system 1550 and monitor data produced by the system 1550. In some embodiments, the interface module 1558 includes a clinician interface that displays a trend graph and/or numeric indicator for an estimated flow rate (for example, in the radial artery) and/or continuous cardiac output. In some embodiments, the clinician interface can also include a digital readout for the most recent estimate. Other information displayed can include the measured heater coil resistance (for example, as calculated from measured voltage and current), whether the coil resistance is in an acceptable range, the measured coil power (for example, as calculated from measured voltage and current), whether the coil power is in an acceptable range, the measured probe temperature, and whether the temperature of the probe is in an acceptable range. [0322] The clinician interface can be configured to obtain input from the user, including, for example, the following information: the nominal coil resistance, a desired level for heater power, a time span for the trend graph (for example, 15 minutes), an acceptable range for the heater coil resistance, an acceptable range for the heater coil power, an acceptable range for the probe temperature, a selection of whether the measurement process should be suspended or resumed, and a selection of whether the measurement process should be stopped or started. One or more of these inputs, such as the time span of the trend graph, can have default values such that information need not be entered for each input before every monitoring cycle. The interface module 1558 may require the user to enter values for other inputs, such as the nominal coil resistance and the heater power level, before a monitoring cycle begins. Information can be entered by a keyboard, touch screen, or another suitable input device.

[0323] In some embodiments, the interface module 1558 includes a notes interface that allows a user to input notes before or during a monitoring cycle. The notes interface can include a text window for the user to enter data. The notes interface can be configured to automatically post a time stamp upon posting a note. The notes can be stored in a clinical data directory in a notes sub-directory. The note files can be retrieved from a list sorted chronologically, by caregiver, by patient, or by another appropriate criterion. The notes interface can be configured to automatically post an indication of the status (for example, online or offline) for each instrument connected to the system 1550. The notes interface can display user interface elements to clear the notes window, cancel a current monitoring session, and confirm and post notes to a notes file.

[0324] In some embodiments, the data acquisition and control module 1560 is configured to provide a stimulus signal to the heater 1524 in the probe. In some embodiments, the stimulus signal is a low-frequency sinusoidal signal. The stimulus signal provides a periodic variation in heat deposited by the heater 1524 in the bloodstream. The periodic variation in the heat deposited can be called a stimulus pattern. The stimulus signal can be obtained from a hardware- or software-based signal generator. The signal can be appropriately scaled and/or limited before being passed to the heating element driver 1512. The data acquisition and control module 1560 can consider several criteria when determining whether to scale or limit the signal passed to the heating element driver 1512. The criteria can include the current probe temperature, the current voltage reading, and the nominal heater coil resistance.

[0325] In some embodiments, the power amplitude of the coil signal can be selected by a caregiver, a manufacturer of the system 1550, and/or an algorithm. In some embodiments, the clinician interface includes an interface element that allows the user to set the power amplitude of the coil signal. The data acquisition and control module 1560 can measure and/or calculate voltage, current, and power of the coil signal. In addition, these values can be displayed in trend charts or as a digital indicator. A timed loop structure can be used to encapsulate the process of acquiring data. The timing of the loop can be set by the caregiver, the manufacturer, or an algorithm. For example, an algorithm can provide a sampling rate that is fed into the loop. In some embodiments, a value for the timing of the loop is about 156 milliseconds. During iterations of the loop, data may be acquired from some or all of the available data sources, including the heater data 1554 and the temperature sensor data 1552. A time stamp for each data acquisition can also be created and recorded with the acquired data. The time stamp information can be used to average the values extracted from the data acquisition hardware 1512. The data can also be selected, conditioned, and/or displayed using the time stamp information.

[0326] The data acquisition and control module 1560 can measure temperature in the radial artery of a patient using the temperature sensor 1528 of the probe. In some embodiments, the system 1556 displays a "slow chart" and a "fast chart" for the temperature. In some embodiments, the slow chart and the fast chart are displayed simultaneously in different portions of the display 1504. The slow chart can provide a long term view of the temperature trend and scale to a relatively large range of temperatures and time periods. The fast chart can be synchronized with other charts that display, for example, drive voltage and current. The fast chart can be configured to automatically scale to small ranges of temperature, which can in some instances allow differences less than 0.01⁰C, for example, to be discerned.

[0327] In some embodiments, the data logging module 1562 can implement the collection of data from analog and/or digital data sources. In some embodiments, the data logging module 1562 collects data from multiple sources, such as from the data acquisition and control module 1560 and from a multiple-port serial adapter. Collected data can be stored in data files using an appropriate format. In some embodiments, collected data is stored in spreadsheet files, delimited text files, or compressed data files during device operation. Data can be collected from the probe during a time when the system 1550 detects that the probe is connected. In some embodiments, data is logged once during cycle of the data acquisition loop. In some embodiments, the data logged during cardiac output monitoring includes the time (for example, with format resolution of one millisecond or better), the temperature measurement (for example, with format resolution of 0.01⁰C or better), the coil voltage (for example, with format resolution of 0.01 V or better), and the coil current (for example, with format resolution of 0.001 A or better). In some embodiments, the logged data additionally includes a gain and a phase associated with the data, an estimated flow rate, and a mixing volume. In some embodiments, the mixing volume is the product of the vessel cross section and the distance between the heater and the temperature sensor.

[0328] In some embodiments, the heater driver module 1564 implements functionality for setting and monitoring power delivered to the heater 1524. In some embodiments, the default setting of heater power is low enough to prevent overheating of the coil 1524. For example, the default coil power setting can be 0.25 W. In some embodiments, the default power setting can be changed by a user or set by the manufacturer.

[0329] In some embodiments, the heater driver module 1564 implements a safety feature that limits power that can be provided to the heater 1524. In some embodiments, the safety feature provides three user input fields for specifying a maximum heater power, a maximum heater voltage, and a maximum heater current. The heater driver module 1564 calculates three values for electric potential corresponding to the three inputs using the heater resistance.

[0330] In further embodiments, the heater driver module 1564 is configured to calculate power dissipation by the heater from measurements of electric potential and current. This calculation can be used to detect error conditions or other events that could result in overheating of the coil 1524. If the heater is short-circuited, for example, or if the nominal heater resistance is entered incorrectly, the heater driver module 1564 can be configured to automatically reduce the power to a safe level and inform the user. This functionality can be implemented by measuring voltage and current across the heating element 1524 periodically. For example, measurements can be taken during iterations of a data acquisition loop. The voltage and current measurements can be compared to default values or values provided by the user. In some embodiments, the range of acceptable measurements is expanded by a suitable amount, such as, for example, 10%, to avoid unnecessary triggering of power throttling due to noise. In such embodiments, the heater driver module 1564 throttles back or deactivates the heater drive signal when the voltage as measured exceeds a voltage limit by more than 10%, the current as measured exceeds a current limit by more than 10%, or the power as measured exceeds the power limit by more than 10%. Default values for the voltage, current, and power limits can be specified by the manufacturer. The default values can be, for example, 5 V, 0.4 A, and 0.25 W, for example. In some embodiments, the user can change the voltage, current, and power limits. In some embodiments, the user is not allowed to raise the voltage, current, and power limits higher than specified maximum values. In some embodiments, the maximum values are the default limits.

[0331] In some embodiments, the monitoring system 1550 relies on the algorithm module 1566 to estimate blood flow within the radial artery using a probe placed within the artery. In some embodiments, the algorithm module 1566 uses measurements of radial artery flow and pressure to estimate cardiac output (CO). The algorithm module 1566 can implement one or more of several algorithms to create a CO estimate. In some cases, the algorithms can include parameters which are not well fixed (for example, physiological parameters that have not been determined with precision) by the data presently available. As additional data become available, at least some of these parameters may become better fixed. In some instances, the parameters may depend on patient demographics or other factors.

[0332] In some embodiments, the algorithm module 1566 can implement an algorithm to convert blood flow and arterial pressure values measured by the controller 1502 into estimates of cardiac output (for example, continuous cardiac output or "CCO"). The algorithms can be used in conjunction with the radial artery probe system 1550 for real-time production of CCO values.

[0333] Figure 47 shows an embodiment of a method 1600 for estimating blood flow in a patient. The heating element 1524 is used to transfer energy to the blood stream as it flows past. The transfer of energy creates a stimulus pattern (1602) that is governed by a stimulus signal generated by the data acquisition and control module 1560. A temperature sensor 1528 is used to measure the resulting temperature changes (1604). After raw data is acquired, a response signal can be extracted from the acquired data (1608). In some embodiments, the response signal includes gain and phase measurements determined using the acquired data and the stimulus signal. A volumetric blood flow estimate may be calculated from the response signal (1612). In some embodiments, the method 1600 can include noise filtering to overcome issues of signal recovery in the presence of the noisy environment in the body.

[0334] In some embodiments, the gain measurement is the quotient of a temperature rise in the blood stream and the power of the stimulus signal that produces the temperature rise. The following equation shows a relationship between flow rate and gain:

Flow Rate = 1 ÷ ( Gain x P_bi_ood ^x Pbiood ), where Pbiood is the specific heat of blood, pwood is the density of blood, and Gain is defined as ΔTemperature (⁰C) / Power (W).

[0335] In some embodiments, the phase measurement represents the time delay between the generation of the stimulus pattern by the heater 1524 and the measurement of the resulting temperature changes by the sensor 1528. The following equation shows a relationship between flow rate and phase:

Flow Rate = Mixing Volume ÷ { [ Stimulus Period x ( Phase ÷ 2π ) ] - T_sys }, where T_sys is the sum of time constants for the system components (such as, for example, the heater 1524, the vessel, and the sensor 1528).

[0336] The arterial flow rate estimate can be estimated from the gain, the phase, or both the gain and the phase. Arterial flow and pressure measurements in the radial artery can be used to estimate cardiac output.

[0337] An algorithm to estimate total cardiac output from measurements of the arterial flow and pressure in the radial artery can be derived from an appropriate model of the cardiovascular system. The behavior of the cardiovascular system can be represented as an electrical (or fluidic) circuit. Models of this type are sometimes known as "Windkessel" models. A Windkessel model of pulsatile flow is given by the circuit shown in Figure 48. In this model, the pumping action of the heart is modeled as a pulsatile current source, the compliance of the major vessels is given by the capacitance C, and the resistance of the arterioles and capillaries is given, in aggregate, by the resistance R. This model is suitable for modeling an AC (pulsatile) waveform of blood pressure, and elaborations on this circuit account for finer effects such as inertia of blood.

[0338] For the purposes of modeling time-averaged flow from the heart (for example, CCO) the model in Figure 48 can be simplified to a DC model. In this case, the capacitance becomes an open circuit, effectively disappearing, and the heart is modeled as a DC current source. A circuit representing a time-averaged flow from the heart is shown in Figure 49. The mean arterial pressure (MAP, represented as the "voltage" in the circuit) is given by the product of the CO and the vascular resistance R.

[0339] The total vascular resistance is split into four parts in the circuit shown in Figure 50 to indicate the role of the radial artery in the model. The heart is represented by a DC current source. The vascular resistances are: R_COre, representing the total resistance of the vasculature of the body core; R_peπph, representing the resistance of the peripheral vasculature except for the radial artery; Rradiai, representing the resistance of the radial artery tree (the radial artery and the smaller vessels fed by the radial artery); and R_anom, representing the "anomalous" resistance upstream of the peripheral tree.

[0340] The resistance of the radial artery being monitored together with its downstream arteries, arterioles, and capillaries is represented by R_radiai- R_Peπ_Ph represents that portion of the vasculature the resistance of which changes proportionally to Rradiai • This relationship can be written as:

^periph ^{~ a '} ^radial J where "a" is a constant of proportionality.

[0341] The portion of vascular resistance that is not proportional to R_radiai is represented by R_COre- This definition suggests that Rcore is the resistance of the core organs.

[0342] Ranom is a term that causes the pressure at the radial artery to be different from the mean arterial pressure (MAP, e.g. at the heart). In some embodiments, it is assumed that Ranom is zero and, therefore, that the pressure at the radial artery is equal to MAP. In alternative embodiments, a nonzero value for R_anom is used to generate an algorithm.

[0343] When R_anom is assumed to be zero, and given the circuit of Figure 50, an equation for the total flow from the heart (CO) can be written: MAP MAP

R R penph + R. "adial [0344] This equation states that the total cardiac output is given by the flow through the core plus the flow through the periphery. The assumption that the peripheral resistance is proportional to the radial artery resistance can be used to substitute terms and create the following equation:

MAP MAP MAP MAP

= a = a ^■ b r ,„adial

^Rpenph ^{+ R} _raώal ^aRraώal + ^{' R} radial (^{a + l})^Rraώal ^Rraώal

[0345] In the above equation, a new constant of proportionality, a ≡ a + 1 expresses the result that the peripheral flow is proportional to the radial artery flow.

[0346] In some embodiments, Rc_Ore is assumed to be a constant. In alternative embodiments, a non-constant expression can be used to provide an estimate of Rc_Ore or to define a relationship between Rc_Ore and other values. When Rc_Ore is assumed to be a constant,

a second new constant can be written as: β ≡ . After substituting terms, the flow

^Rcore equation becomes:

C0 = a - F_radιal + β -MAP

[0347] As mentioned above, the values a and β are assumed to be constant, at least for a given patient. Animal tests and human trials can be used to develop meaningful estimates of these constants or to develop a model to calculate these constants from more easily measured characteristics.

[0348] In some embodiments, the values of a and β depend on measurable characteristics of the patient such as height, weight, age, or sex. Using those patient characteristics, an absolute estimate of CCO may be produced. In alternative embodiments, normalized values of the constants are used to determine a relative estimate of CCO. Changes in the relative estimate of CCO can also provide value in patient care.

[0349] Radial artery flow estimates can be corrupted for short periods by disturbances such as draping or undraping the site of the probe, wetting the site, or moving the limb. Thus, trimmed-mean filters can be used to smooth the CCO estimates. Trimmed- mean filters can also be used to mimic the temporal response characteristics of a PA CCO system. [0350] Although the inventions have been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the inventions extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses and obvious modifications and equivalents thereof. In particular, while the present cardiac output monitoring devices and methods have been described in the context of particularly preferred embodiments, the skilled artisan will appreciate, in view of the present disclosure, that certain advantages, features and aspects of certain systems disclosed herein may be realized in a variety of other applications, many of which have been noted above.

[0351] Additionally, it is contemplated that various aspects and features of the inventions described can be practiced separately, combined together, or substituted for one another, and that a variety of combinations and subcombinations of the features and aspects can be made and still fall within the scope of the inventions.

[0352] As used in this application, the terms "comprising," "including," "having," and the like are synonymous and are used inclusively, in an open-ended fashion, and do not exclude additional elements, features, acts, operations, and so forth. Also, the term "or" is used in its inclusive sense (and not in its exclusive sense) so that when used, for example, to connect a list of elements, the term "or" means one, some, or all of the elements in the list.

[0353] Similarly, it should be appreciated that in the above description of embodiments, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that any claim require more features than are expressly recited in that claim. Rather, it is believed that inventive aspects exist in a combination of fewer than all features of any single foregoing disclosed embodiment.

[0354] Embodiments of the disclosed systems and methods may be used and/or implemented with local and/or remote devices, components, and/or modules. The term "remote" may include devices, components, and/or modules not stored locally, for example, not accessible via a local bus. Thus, a remote device may include a device which is physically located in the same room and connected via a device such as a switch or a local area network. In other situations, a remote device may also be located in a separate geographic area, such as, for example, in a different location, building, city, country, and so forth.

[0355] Methods and processes described herein may be embodied in, and partially or fully automated via, software code modules executed by one or more general and/or special purpose computers. The word "module" refers to logic embodied in hardware and/or firmware, or to a collection of software instructions, possibly having entry and exit points, written in a programming language, such as, for example, C or C++. A software module may be compiled and linked into an executable program, installed in a dynamically linked library, or may be written in an interpreted programming language such as, for example, BASIC, Perl, or Python. It will be appreciated that software modules may be callable from other modules or from themselves, and/or may be invoked in response to detected events or interrupts. Software instructions may be embedded in firmware, such as an erasable programmable read-only memory (EPROM). It will be further appreciated that hardware modules may be comprised of connected logic units, such as gates and flip-flops, and/or may be comprised of programmable units, such as programmable gate arrays, application specific integrated circuits, and/or processors. The modules described herein are preferably implemented as software modules, but may be represented in hardware and/or firmware. Moreover, although in some embodiments a module may be separately compiled, in other embodiments a module may represent a subset of instructions of a separately compiled program, and may not have an interface available to other logical program units.

[0356] In certain embodiments, code modules may be implemented and/or stored in any type of computer-readable medium or other computer storage device. In some systems, data (and/or metadata) input to the system, data generated by the system, and/or data used by the system can be stored in any type of computer data repository, such as a relational database and/or flat file system. Any of the systems, methods, and processes described herein may include an interface configured to permit interaction with patients, health care practitioners, administrators, other systems, components, programs, and so forth.

[0357] Further, no component, feature, or method described herein is deemed to be essential or indispensable to the disclosed inventions. Thus, it is intended that the scope of the inventions herein disclosed should not be limited by the particular embodiments described above.

Claims

WHAT IS CLAIMED IS:

1. An apparatus for measuring a physiological parameter in a radial artery of a patient, the apparatus comprising: an elongate body configured to be inserted at least partially into a radial artery upstream from an insertion point in the radial artery and to remain temporarily at least partially inserted into the radial artery; a delivery element positioned in proximity to a distal end of the body, the delivery element configured to deliver a quantity of matter or energy to blood within the radial artery in proximity to the delivery element; a sensing element fixed to the body and spaced from the delivery element at a position proximal to the delivery element, the sensing element configured to sense a characteristic of the blood that is changed by the delivery of the quantity of matter or energy; and at least one support coupled with the body and configured to inhibit contact between the delivery element and a wall of the radial artery while permitting blood to flow through the radial artery.

2. The apparatus of Claim 1, wherein the at least one support is configured to inhibit motion of the elongate body relative to the radial artery.

3. The apparatus of Claim 1, further comprising at least one additional support.

4. The apparatus of Claim 3, wherein the at least one additional support is configured to inhibit motion of the elongate body relative to the radial artery.

5. The apparatus of Claim 3, wherein the at least one support and the at least one additional support have the same configuration.

6. The apparatus of Claim 1, wherein the at least one support comprises a plurality of members.

7. The apparatus of Claim 6, wherein the members are selected from a group consisting of fins, extensions, protrusions, casings, arms, arcs, arches, lobes, spacers, projections, extensions, filaments, threads, and wires.

8. The apparatus of Claim 7, wherein the members are netted, woven, or braided.

9. The apparatus of Claim 1, wherein the at least one support is integrally formed with the elongate body.

10. The apparatus of Claim 1, wherein the at least one support is movable between a compacted configuration to facilitate insertion of the elongate body at least partially into the radial artery and an expanded configuration to inhibit contact between the delivery element and a wall of a radial artery.

11. The apparatus of Claim 10, further comprising an actuator to selectively move the at least one support between the compacted configuration and the expanded configuration.

12. The apparatus of Claim 1, wherein the delivery element comprises an emitter.

13. The apparatus of Claim 12, wherein the emitter comprises a heating element.

14. The apparatus of Claim 13, where the heating element comprises a heating coil.

15. The apparatus of Claim 1, further comprising at least one mixer.

16. The apparatus of Claim 15, wherein the at least one mixer comprises a plurality of flow directors.

17. The apparatus of Claim 16, wherein the flow directors are selected from a group consisting of fins, bumps, protrusions ridges, bodies, helical sections, and coiled sections.

18. The apparatus of Claim 1, further comprising a pressure sensor.

19. An apparatus for monitoring a patient's cardiac output in a radial artery of a patient, the apparatus comprising: a body comprising a biocompatible material and being sized for at least partial insertion into a radial artery of a patient; an emitting element coupled proximate to a distal end of the body that is to be inserted into the radial artery, the emitting element being configured to emit energy into blood surrounding the emitting element in the radial artery; a detecting element connected to the body at a location that is spaced from the emitting element and is farther from the distal end of the body than the emitting element, the detecting element being configured to detect a change to the blood caused by the energy emitted by the emitting element; at least one positioner configured to position the body within the radial artery such that the emitting element is spaced from a wall of the radial artery; and a controller in communication with at least one of the emitting element to drive the emitting element, and the detecting element to acquire data from the detecting element.

20. The apparatus of Claim 19, wherein the controller is configured to compute a value related to cardiac output.

21. The apparatus of Claim 19, further comprising at least one connector for placing at least one of the delivery element and the sensing element in signal communication with a controller.

22. The apparatus of Claim 19, wherein the controller comprises a display.

23. The apparatus of Claim 19, wherein the at least one positioner is configured to resist motion of the body within the radial artery.

24. The apparatus of Claim 19, wherein the at least one positioner comprises a plurality of members.

25. The apparatus of Claim 24, wherein the members are selected from a group consisting of fins, extensions, protrusions, casings, arms, arcs, arches, lobes, spacers, projections, extensions, filaments, threads, and wires.

26. The apparatus of Claim 19, wherein the at least one positioner is integrally formed with the body.

27. The apparatus of Claim 19, wherein the at least one positioner has a contracted configuration to facilitate insertion of at least a portion the body into the radial artery and an extended configuration to position the body within the radial artery such that the emitting element is spaced from a wall of the radial artery.

28. The apparatus of Claim 27, wherein the positioner is configured to allow a user to selectively change the at least one positioner between the compacted configuration and the expanded configuration.

29. The apparatus of Claim 19, wherein the emitting element comprises a heating element.

30. The apparatus of Claim 29, where the heating element comprises a heating coil.

31. The apparatus of Claim 19, further comprising at least one mixing feature.

32. The apparatus of Claim 31, wherein the at least one mixing feature comprises a plurality of flow directors.

33. The apparatus of Claim 19, further comprising a pressure sensor.

34. A method of estimating cardiac output in a patient, the method comprising the steps of: inserting at least a portion of an elongate body into a radial artery of a patient such that a distal end of the elongate body is upstream of a location where the elongate body is inserted into the radial artery, the elongate body having an emitter attached in proximity to the distal end and a sensing element attached to the elongate body and spaced proximally from the emitter; supporting the elongate body from within the radial artery such that movement of the elongate body within the radial artery is inhibited and a substantial portion of the elongate body is spaced from an interior wall of the radial artery; delivering a quantity of energy from the emitter to blood at a first location within radial artery; detecting an energy level at a second location within the radial artery using the sensing element, the second location being downstream from the first location; calculating a value related to cardiac output based on the quantity of energy delivered to the blood at the first location and the energy level detected at the second location.

35. The method of Claim 34, wherein the elongate body is supported near a center of the radial artery.

36. The method of Claim 34, wherein the elongate body is supported at a plurality of positions along a length of the elongate body.

37. The method of Claim 34, wherein the elongate body is supported such that the emitter is spaced from the interior wall of the radial artery.

38. The method of Claim 34, wherein the energy delivered to the blood is thermal energy.

39. The method of Claim 34, further comprising the steps of generating a stimulus signal and controlling the delivery of energy to the blood according to the stimulus signal.

40. The method of Claim 34, wherein the sensing element is responsive to temperature of the blood.

41. The method of Claim 34, wherein the value related to cardiac output is volumetric blood flow.