CN110859972A - Reagent, preparation method and application thereof - Google Patents
Reagent, preparation method and application thereof Download PDFInfo
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- CN110859972A CN110859972A CN201911154288.7A CN201911154288A CN110859972A CN 110859972 A CN110859972 A CN 110859972A CN 201911154288 A CN201911154288 A CN 201911154288A CN 110859972 A CN110859972 A CN 110859972A
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- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 129
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000003384 imaging method Methods 0.000 claims abstract description 46
- 239000000126 substance Substances 0.000 claims abstract description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 11
- 201000011510 cancer Diseases 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims description 36
- 239000000499 gel Substances 0.000 claims description 33
- 239000002960 lipid emulsion Substances 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 14
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 11
- 230000000762 glandular Effects 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000004408 titanium dioxide Substances 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 238000002604 ultrasonography Methods 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims 1
- 239000001046 green dye Substances 0.000 claims 1
- 230000001678 irradiating effect Effects 0.000 claims 1
- 230000003287 optical effect Effects 0.000 abstract description 50
- 238000001514 detection method Methods 0.000 abstract description 33
- 238000004458 analytical method Methods 0.000 abstract description 12
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- 238000003825 pressing Methods 0.000 description 16
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- 239000007924 injection Substances 0.000 description 15
- 238000004806 packaging method and process Methods 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 10
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- 230000009286 beneficial effect Effects 0.000 description 9
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- 210000005075 mammary gland Anatomy 0.000 description 7
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- 238000002600 positron emission tomography Methods 0.000 description 3
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- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000001056 green pigment Substances 0.000 description 2
- 239000000976 ink Substances 0.000 description 2
- 229910052750 molybdenum Inorganic materials 0.000 description 2
- 239000011733 molybdenum Substances 0.000 description 2
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- 230000035945 sensitivity Effects 0.000 description 2
- 238000012285 ultrasound imaging Methods 0.000 description 2
- 208000000265 Lobular Carcinoma Diseases 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000011358 absorbing material Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 201000003714 breast lobular carcinoma Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000002596 diffuse optical imaging Methods 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical compound [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
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- 239000010936 titanium Substances 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/226—Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
The invention discloses a reagent, which comprises a substance capable of absorbing light and/or a substance capable of scattering light; the reagent also includes water and/or a gel. The invention also discloses a preparation method and application of the reagent. The reagent prepared by the invention has moderate fluidity, the optical characteristic of the reagent is consistent with or close to that of the organism tissue, the optical characteristic of the organism tissue can be well simulated, the reagent can be applied to near infrared diffuse light imaging detection equipment, and further can be used for detecting the organism tissue cancer, and the subsequent processing and analysis of the detection data are facilitated.
Description
Technical Field
The invention particularly relates to a reagent, a preparation method and application thereof.
Background
Accurate diagnosis of breast cancer at an early stage is the key to the treatment of breast cancer. Conventional breast imaging systems include molybdenum target X-ray examination, breast ultrasound imaging technology, and Magnetic Resonance Imaging (MRI) examination, in which the sensitivity of the molybdenum target has a strong dependence on the density of the breast. Breast ultrasound imaging is problematic in detecting very small tumors, does not distinguish between benign and malignant tumors, and is very dependent on the experience and technique of the operating physician. MRI imaging has long imaging time and is too sensitive, so that the MRI imaging is not suitable for patients with metal objects in the body.
With the rapid development of molecular imaging technology in recent years, the functions of imaging technologies such as Positron Emission Tomography (PET), optical/fluorescence imaging and the like, which can realize functional imaging and molecular specific imaging, in early accurate detection of tumors are becoming more and more important. Several research units developed PET systems (PEM) specifically for breast detection. Published data indicate that PEM has 90% sensitivity and 86% specificity in detecting breast malignancies, and PEM has better spatial resolution and higher detectability than PET/CT for tumors smaller than 1 em. PEM is mainly imaged through 18F-FDG by utilizing the characteristic of tumor metabolism exuberance, but partial acute or chronic inflammation can also cause the metabolism exuberance so as to cause the false negative problem of PEM detection, and some tumors with relatively slow metabolism, such as lobular carcinoma, can cause the missed detection of PEM.
The discovery of the 650-950nm near-infrared window in 1999 and the subsequent development of near-infrared optical imaging technology, the diagnosis of early breast tumors using near-infrared light has become a hot point of research. Research teams of professor Brian Pogue and professor Keith Paulsen of the university of Dalmatian of America have carried out long-term and deep research work in the aspect of optical imaging of mammary glands, and in recent years, the research teams are dedicated to the research of near-infrared mammary gland optical imaging of wide spectral bands, and in 2014, the research teams adopt a detection array combining a photomultiplier tube and a photodiode to realize the combined detection of 6 spectral bands of a frequency domain and 3 spectral bands of continuous waves, so that good imaging results are obtained.
However, there are still some problems to be improved.
In near-infrared diffuse optical imaging systems, the diffusion equation is widely used to model light propagation in tissue. To improve the efficiency of image processing, researchers typically utilize analytical models of diffusion equations and extend them to some conventional shapes, such as semi-infinite media, infinite flat panels, spheres, and infinite cylinders, among others. However, for an object with a complex boundary shape, such as easily deformable biological tissue: mammary tissue, solving the diffusion equation typically requires a significant amount of computational time and resources.
Disclosure of Invention
Aiming at the situation, the invention provides a reagent, a preparation method and application thereof to overcome the defects of the prior art. The reagent has moderate fluidity, and the optical parameters of the reagent are consistent with or close to those of the organism tissue, so that the optical characteristics of the organism tissue can be well simulated.
In order to achieve the purpose, the invention provides the following technical scheme:
a reagent comprising a substance capable of absorbing light and/or a substance capable of scattering light.
Further, the reagent also comprises water and/or gel.
Further, the substance capable of absorbing light is selected from one or more of black pigment, green pigment, and ink; however, the substance capable of absorbing light is not limited to three types of black pigment, green pigment, and ink; other light-absorbing materials may also be used to prepare the reagents of the invention. The substance capable of absorbing light has the functions of promoting optical absorption, increasing the absorption coefficient of the reagent to be consistent with or close to that of the organism tissue, and is used for simulating the absorption of the organism tissue to the light; the substance capable of absorbing light is added in order to make the optical characteristics of the prepared agent close to those of the living tissue.
Further, the light-absorbing substance is selected from one or more of black natural pigment, green natural pigment, and ink.
Further, the substance capable of scattering light is selected from one or more of fat emulsion, titanium dioxide powder, and silicon dioxide powder; however, the substances capable of scattering light are not limited to three types of fat emulsion, titanium dioxide powder, and silicon dioxide powder, and other substances capable of scattering light may be used to prepare the reagent of the present invention; the substance capable of scattering light has a function of promoting optical scattering, increasing the scattering coefficient of the reagent so as to match or approach the scattering coefficient of the living tissue, and is used for simulating scattering of light by the living tissue. The substance capable of scattering light is added in order to make the optical properties of the prepared reagent close to those of the living tissue.
Further, the fat emulsion is selected from fat emulsion injection with the mass fraction of 10%, 20%, 30% or other mass fractions.
Further, the mixture ratio of each component is as follows: and (3) gel: water: substance capable of scattering light: the material capable of absorbing light is 1: 0.6-1.5: 0.05-0.222: 0.00012-0.0012, and the ratio is a mass ratio or a volume ratio.
Further, the water is purified water; the purified water serves to dilute the gel so that the diluted gel has proper fluidity (gel viscosity range: 800Pa.s-1600 Pa.s).
Further, the gel is an ultrasound gel, such as a medical ultrasound gel; the gel component comprises high molecular compound, ethyl p-hydroxybenzoate and deionized water.
In some preferred forms, an agent, comprising the following components, a medical ultrasound gel: purified water: the mass fraction is 20% fat emulsion injection: and (3) diluting the black natural pigment solution by 10 times to obtain a black natural pigment solution, wherein the black natural pigment solution is 1:1:0.083-0.105:0.00048, and the ratio is a mass ratio or a volume ratio. This allows the absorption and scattering coefficients of the formulated agent to be adapted to the optical parameters of the tissue of the living being, such as the glandular tissue of the living being, including mammary tissue, brain tissue. The fat emulsion injection and the black natural pigment are added to simulate the optical characteristics of human tissues.
Further, any black natural pigment on the market is adopted as the black natural pigment, and because the black natural pigment has strong absorption to light, the mass ratio of the black natural pigment: pure water 1: 9, diluting to obtain a black natural pigment solution which is diluted by 10 times.
A method of preparing a reagent for use in preparing a reagent as described above, comprising the steps of:
1) weighing the components according to the proportion;
2) adding gel, water, substance capable of scattering light, and substance capable of absorbing light into a mixing container, and mixing;
3) stirring the mixture until the gel, water, substance capable of scattering light, and substance capable of absorbing light are uniformly distributed;
4) placing the mixed solution obtained in the step 3) at an ambient temperature of not higher than 25 ℃, and standing for more than 1 day to obtain the reagent. The mixture may deteriorate at too high a temperature. The prepared reagents are generally stored in a refrigerator freezer.
Use of an agent for the preparation of a formulation for diffuse light imaging for the detection of cancer of a gland of an organism, said agent being as described above.
Further, the organism is a human or a mammal.
Further, the cancer is breast cancer.
Further, the diffused light image is a diffused light image of light of any wavelength or any section of wavelength from visible light to near-infrared light.
Further, the diffuse light is imaged as: the light with any wavelength or any section of wavelength from visible light to near infrared light irradiates the mammary tissue, and the transmitted light is imaged.
The reagent can be applied to detection of glandular tissues, such as detection of mammary tissues or brain tissues.
Further, the reagent is used in the following manner (taking the detection of human breast tissue as an example for illustration):
1) selecting a stop block with a proper size according to the size of the mammary tissue of the examinee, and placing the stop block on a lower pressing plate of the diffuse light imaging device;
2) placing the mammary tissue on one side of the examined person on the upper surface of the lower pressing plate, so that the mammary tissue is positioned in the notch, and simultaneously, the body is tightly attached to the front end surface of the lower pressing plate;
3) lowering an upper pressing plate of the diffused light imaging device to be tightly pressed on the upper surface of the stop block;
4) reagent is injected into the notch through the catheter, so that the reagent is filled around the mammary tissue, and no gap is left between the mammary tissue and the stop block.
Further, the stopper has a definite, regular shape.
Further, the stop is made of a material having optical properties that are consistent with or approximate to those of human tissue.
Further, the block has a regular shape, for example, the block is integrally rectangular, square, cylindrical or the like, and in some preferred modes, one side surface of the block is recessed inwards to form a notch; the notch can be used for placing the tissue of a living body, for example, when the mammary gland tissue is detected, the stop block is placed on the lower pressing plate of the detection instrument, and the mammary gland tissue is placed at the notch; the notches are designed into different shapes and sizes, and can meet the requirements of organism tissues with different shapes and sizes. In some preferred forms, the notch is an arcuate notch, or the notch is a U-shaped notch; in some preferred modes, the size and shape of the notch can be designed according to A cups, B cups, C cups and the like, so that the requirements of most people can be met, and the gap between human tissues and the stop block can be reduced.
Further, a through hole is formed in the notch, and the through hole is configured to be communicated with the outside through the other side face of the stop block; the catheter can be communicated with the through hole, the through hole can be filled with the reagent through the catheter, the reagent is the reagent, the reagent can flow through the through hole to enter the notch and fill the gap between the organism tissue and the notch, and the reagent is in contact with the mammary tissue; the optical parameters of the reagent are consistent with or close to the optical parameters of the organism tissue, so that the block, the reagent and the organism tissue can be regarded as a whole with the optical parameters close to each other, and the block has a regular shape and a regular boundary condition, so that the whole has the regular boundary condition, the reconstruction of an image is facilitated, the complexity of an imaging algorithm is reduced, and the adverse effect of an air gap and an irregular geometric shape on the image reconstruction can be reduced. In some preferred forms, the stop may have a height of 5-6cm, which is sufficient for most biological tissues.
Furthermore, one or more small stoppers can be added on the stoppers, the small stoppers and the stoppers have the same shape and different heights, and the notches of the small stoppers are not provided with through holes; the small block can increase the height of the block, thereby meeting the requirements of organism tissues with different heights. In some preferred modes, the height of the small block is 0.5-1 cm; when the height of the living tissue is high, one or more small stoppers may be placed on the upper surface of the stopper to increase the height of the stopper.
Further, the stop can be mounted on the coaming; in some preferred modes, the enclosing plate is connected with the stop block in a clamping mode, in some preferred modes, an opening is formed in the enclosing plate, the shape of the opening is consistent with the overall shape of the stop block, and the stop block can be clamped at the opening. In some preferred modes, the coaming is made of a material different from that of the stop block, the coaming is configured to be embedded on a lower pressing plate of the detection instrument, and a stop strip is arranged on the lower pressing plate, so that the position of the stop block is fixed, but the coaming does not change the shape of the stop block and does not influence the detection result of the instrument, and the stop block is always in contact with the lower pressing plate of the detection instrument.
The invention has the beneficial effects that:
(1) according to the invention, the substance capable of absorbing light or the substance capable of scattering light is added in the process of preparing the reagent, so that the prepared reagent is close to or consistent with the optical characteristics of the biological tissue, when the substance capable of absorbing light and the substance capable of scattering light are added, the prepared reagent can effectively simulate the optical characteristics of the biological tissue, the reagent is filled around the biological tissue, and the adverse effect of air filling on imaging can be avoided.
(2) The invention selects the gel as a component in the reagent, because the gel is a gel substance formed by dissolving or swelling by taking water as a solvent and a macromolecular compound as a solute. The product is colorless or light-colored transparent gel, has no insoluble foreign matters and has good optical characteristics. By varying the formulation, a wide range of viscosities (25 ℃) can be achieved. Under normal storage conditions, no layering, mildew or peculiar smell occurs.
(3) The invention also selects water as a component in the reagent, and the mobility of the gel can be effectively improved by changing the proportion of the water in the reagent, thereby avoiding forming obvious gaps or spaces in the filling process; and the amount of gel used can be reduced.
(4) The reagent of the invention has good optical performance, proper viscosity, imitation ability to human gland tissues and compliance with the regulation requirement of biocompatibility, and can be filled around human tissues. The reagent prepared by the invention can be used for detecting organism tissues by near-infrared diffuse light imaging detection equipment, and can isolate air in the imaging process, simulate human gland tissues, reduce the adverse effect of air gaps on image reconstruction and reduce the complexity of an imaging algorithm.
(5) The reagent prepared by the invention can better simulate the optical characteristics of the organism tissue, the reagent is added into the block with a regular shape, the reagent is filled in the gap between the organism tissue and the block, and the material adopted by the block can also better simulate the optical characteristics of the organism tissue, so in the optical imaging system, the optical characteristics of the block and the optical characteristics of the substances in the block (the substances in the block comprise the organism tissue and the reagent) are consistent with the optical characteristics of the organism tissue. In the optical imaging system, the stopper and the substance in the stopper can be considered as a whole, so that the living tissue having an irregular shape can be unified into a shape having a regular boundary condition. Because the human glandular tissues are irregular in shape and different human glandular tissues are different in shape, the human glandular tissues do not have fixed shapes, good data cannot be obtained when the detection equipment is used for detecting the glandular tissues, and the detection equipment is complex and large in calculation amount during later-stage calculation and analysis.
Compared with an irregular boundary, the regularized boundary condition has higher dimensional accuracy, and the accuracy of a calculation result can be improved; irregular boundaries, the dimensions of which are difficult to measure accurately, especially in biological tissue that is prone to deformation; moreover, the regularized boundary conditions can reduce the calculation amount in the subsequent algorithm analysis process and shorten the calculation time. For irregular boundary conditions, no analytic solution exists, hundreds of iteration calculations are carried out by using simulation methods such as finite elements or finite differences to obtain accurate parameters, and the calculation amount is very large. The finite element means that a calculation domain is divided into a finite number of units which are not overlapped with each other, in each unit, a plurality of proper nodes are selected as interpolation points of a solving function, variables in a differential equation are rewritten into a linear expression which is composed of the node values of the variables or derivatives thereof and the selected interpolation function, and the differential equation is discretely solved by means of a variational principle or a weighted residue method; the finite difference refers to dividing a solution domain into differential grids, and replacing a continuous solution domain with a finite number of network nodes; the finite difference method uses Taylor series expansion and other methods to replace the derivative in the control equation with the difference quotient of function values on the network nodes for discretization, thereby establishing an algebraic equation system taking the values on the network nodes as unknowns.
For the regularized boundary conditions, parameters required by image reconstruction are calculated in advance; for different batches of examinations, the image can be reconstructed using this set of parameters, as long as the same stops are used, and the total imaging time is about 1 minute. For irregular boundaries, the parameters must be recalculated for each detection, typically taking 7-8 hours.
(6) When the mammary tissue is detected, the analytical model of the diffusion equation is adopted, and the mammary tissue is easy to deform; the invention adopts the stop block to surround the mammary tissue and fills the reagent in the gap between the mammary tissue and the stop block, the stop block has a regular shape, and the reagent and the stop block can better simulate the optical characteristics of the normal mammary tissue, so that the stop block, the reagent and the organism tissue can be considered as a whole, the natural boundary of the mammary tissue is expanded into a regular boundary shape, the solving process of a diffusion equation is greatly simplified, and the calculation precision is favorably improved.
Drawings
Fig. 1 is a schematic view of a structure in which a stopper is placed on a lower pressure plate.
Figure 2 is a top view of the placement of breast tissue at the notch of the block (showing the configuration of the through-holes in the block).
Fig. 3 is a diagram of a single data acquisition of breast tissue using a scientific grade CMOS embedded imaging system without a gap between the notch and the breast tissue filled with reagent.
Fig. 4 is a distribution diagram of gray scale values of the area covered by the white line b1 in fig. 3.
FIG. 5 is a diagram of data acquisition of breast tissue using a scientific grade CMOS embedded imaging system after the gap between the notch and the breast tissue is filled with reagent.
Fig. 6 is a distribution diagram of gray scale values of the area covered by the white line b2 in fig. 5.
FIG. 7 is a gray scale value distribution graph of reagents prepared after adding different masses of black natural pigment solution.
Figure 8 is a grey value profile of reagents prepared after addition of different volumes of 20% by mass fat emulsion injection.
Fig. 9 is a schematic view of a structure in which a small stopper is placed on the stopper.
Detailed Description
The technical solutions of the present invention are further described in detail below with reference to the accompanying drawings, and it should be noted that the detailed description is only for describing the present invention, and should not be construed as limiting the present invention.
In the following examples, the type of the medical ultrasonic gel used was TM-100, the specification was 2500 ml/barrel, and the manufacturer was made by Siyuan temple in Tianjin. The fat emulsion injection with the mass fraction of 20% has the model of C14-24 and the specification of 250mL, and is manufactured by Sichuan Konlun pharmaceutical industry Co. The specification of the black natural pigment is 30 g, and the manufacturer is NanoQuel food Limited liability company in Guangzhou city. The specification of the green natural pigment is 30 g, and the manufacturer is NanoQuel food Limited liability company in Guangzhou city. The ink brand is Baoke, the specification is 120 g, and the manufacturer is Guangdong Baoke stationery Co. The titanium dioxide powder is high-purity anatase type nano titanium dioxide powder with the model of VK-TA200 and the particle size of 200nm, and is produced by Hangzhou Zhi titanium purification technology Co. The diffuse light imaging system adopts near infrared light with wavelength of 808nm as a light source, the data acquisition equipment is a scientific grade CMOS embedded imaging system which is produced by Fuzhou Xin picture photoelectricity limited company and has the model of Dhyana 201DS, and the exposure time is set to be 20 ms. Other materials or instruments used may be commercially available.
Example 1
500g of medical ultrasonic gel is put into a mixing container; then 500g of purified water is taken and put into a mixing container; putting 41.67mL of 20% fat emulsion injection into a mixing container, and stirring with a stirrer to obtain a gel-fat emulsion mixture with the fat emulsion mass fraction of 0.8%; adding 0.3g of black natural pigment solution (the black natural pigment solution is obtained by diluting black natural pigment by 10 times according to the mass ratio by using purified water) into a mixing container, and fully stirring the mixture by using a stirrer until a milky uniform colloid is formed. The mixture was allowed to stand at an ambient temperature of not higher than 25 ℃ for 1 day to obtain a reagent. And packaging the prepared reagent in a packaging bottle for later use.
Example 2
500g of medical ultrasonic gel is put into a mixing container; 500g of purified water is then taken and placed in a mixing container. 52.63mL of fat emulsion injection with the mass fraction of 20% is placed in a mixing container and is fully stirred by a stirrer, and a gel-fat emulsion mixture with the mass fraction of 1% of fat emulsion is obtained. 0.3g of a black natural pigment solution (the black natural pigment solution is obtained by diluting black natural pigment by 10 times according to a mass ratio with purified water) is added into a mixing container. The mixture was stirred well with a stirrer until a milky homogeneous gel was formed. The mixture was allowed to stand at an ambient temperature of not higher than 25 ℃ for 1 day to obtain a reagent. And packaging the prepared reagent in a packaging bottle for later use.
Example 3
The reagent was used as follows: as shown in fig. 1-2, (described by taking the examination of breast tissue as an example),
1) selecting a block 1 with a proper size according to the size of the mammary tissue of the examinee, and placing the block 1 on a lower pressing plate 3 of the diffuse light imaging device;
2) placing the mammary tissue on one side of the examined person on the upper surface of the lower pressing plate 3, so that the mammary tissue is positioned in the notch 2, and simultaneously, the body is tightly attached to the front end surface of the lower pressing plate 3;
3) lowering an upper pressing plate 9 of the diffused light imaging device to be pressed on the upper surface of the stop block 1;
4) the reagent is injected into the recess 2 through the catheter 8, so that the reagent fills around the breast tissue a, so that there is no gap between the breast tissue a and the stopper 1.
The optical parameters of the material used for the block 1 are consistent with or close to the optical parameters of the glandular tissues of the organism.
As shown in fig. 1-2, the block 1 of the present invention has a regular shape, and the block 1 is configured to be able to regularize the shape of irregular living tissue, for example, the block 1 has a rectangular or square shape as a whole, and in some preferred modes, one side of the block 1 is recessed inward to form a notch 2; the notch 2 can be used for placing the tissue of a living body, for example, when the mammary gland tissue is detected, the block 1 is placed on the lower pressing plate 3 of the detection instrument, and the mammary gland tissue A is placed at the notch 2; the notch 2 is designed into different shapes and sizes, so that the requirements of organism tissues with different shapes and sizes can be met. In some preferred forms, the notch 2 is an arc-shaped notch 2, or the notch 2 is a U-shaped notch 2; in some preferred forms, the size and shape of the recess 2 can be designed according to a cup or B cup or C cup, etc., which can satisfy most people's needs and reduce the gap between the human tissue and the block 1.
In some preferred modes, as shown in fig. 1-2 and 9, the notch 2 is provided with a through hole 4, and the through hole 4 is configured to be communicated with the outside through the other side surface of the block 1; the conduit 8 can be communicated with the through hole 4, reagent can be injected into the through hole 4 through the conduit 8, the reagent can flow into the notch 2 through the through hole 4 and fill a gap 10 between the organism tissue A and the notch 2, and the reagent is contacted with the mammary tissue; in some preferred modes, the used reagent has good optical performance, proper viscosity and meets the regulation requirement of biocompatibility, and the reagent is a reagent which is consistent with or close to the scattering coefficient and the absorption coefficient of normal organism tissues, so that the reagent does not influence the detection of the organism tissues, the block 1, the reagent and the organism tissues can be considered as a whole, and the block 1 has a regular shape and a regular boundary condition, so that the whole has the regular boundary condition, the reconstruction of an image is facilitated, the complexity of an imaging algorithm is reduced, and the adverse effect of air gaps and irregular geometric shapes on the reconstruction of the image can be reduced. In some preferred modes, the height of the block 1 can be 5-6cm, which can satisfy most organism tissues.
Further, as shown in fig. 9, one or more small stoppers 5 may be added to the stopper 1, the small stoppers 5 have the same shape as the stopper 1, and may have different heights, and the notches 2 of the small stoppers 5 are not provided with through holes 4; the small block 5 can increase the height of the block 1, thereby satisfying different heights of organism tissues. In some preferred modes, the height of the small block 5 is 0.5-1 cm; when the height of the living tissue is high, one or more small stoppers may be placed on the upper surface of the stopper 1 to increase the height of the stopper.
In some preferred forms, as shown in fig. 1, the block 1 can be mounted on a shroud 7; in some preferred modes, the enclosing plate 7 is connected with the stop block 1 in a clamping mode, in some preferred modes, an opening is formed in the enclosing plate 7, the shape of the opening is consistent with the overall shape of the stop block 1, and the stop block 1 can be clamped at the opening. In some preferred modes, the material of the enclosing plate 7 is different from that of the first stopper, the enclosing plate 7 is configured to be capable of being embedded on the lower pressing plate 3 of the detection instrument, the blocking strip 6 is arranged on the lower pressing plate 3, the blocking strip 6 can enable the enclosing plate 7 to be in a fixed position, so that the position of the stop 1 is fixed, but the enclosing plate 7 does not change the shape of the stop 1 and does not influence the detection result of the instrument, and the stop 1 is always in contact with the lower pressing plate 3 of the detection instrument.
The reagent prepared by the invention can also be used for detecting tissues of other organisms, and is not limited to the detection of mammary gland tissues.
The reagent prepared by the present invention can be used for stoppers of any structure, and is not limited to the structure of the stopper in the present embodiment.
An image without the gap 10 between the recess and the breast tissue filled with reagent is taken with an imaging system in a diffuse light imaging device for light intensity comparison, as shown in fig. 3.
The diffuse light imaging system adopts near infrared light with wavelength of 808nm as a light source, the data acquisition equipment is a scientific grade CMOS embedded imaging system which is produced by Fuzhou Xin picture photoelectricity limited company and has the model of Dhyana 201DS, and the exposure time is set to be 20 ms.
Injecting the prepared reagent (the reagent prepared in the embodiment 2 is adopted in the embodiment) into the gap 10 between the block 1 and the mammary tissue A through the catheter 8 until the gap 10 is completely filled with the reagent; an imaging system in the diffuse light imaging device is used for shooting an image when a gap between the notch and the breast tissue is filled with a reagent for light intensity comparison, as shown in fig. 5, after the gap 10 is filled with the reagent, a near infrared light (808nm) light source scans a stop block, the reagent and the breast tissue line by line according to a scanning interval of 5mm, and images acquired by a scientific grade CMOS embedded imaging system are superposed in the vertical direction and then averaged to obtain the image.
Measuring the light intensity distribution states of the same position in the same detection area when the reagent is not filled and after the reagent is filled by using ImageJ software, wherein the light intensity distribution states are respectively shown in figures 4 and 6; fig. 4 is a distribution diagram of gray scale values of the covered area of the white line b1 in fig. 3, the white line b1 covers the block 1, the gap 10 and the breast tissue a, and in fig. 4, the gray scale values in the dashed circle correspond to the gray scale values in the covered area of the white line b1 in the dashed circle in fig. 3, respectively; according to the gray value distribution result of the image in fig. 4, when the gap 10 is not filled with the reagent, the gray values at the left and right gaps of the breast tissue a have a large jump, and the gray values at the two gaps are far greater than the gray values at the breast tissue. Because the light intensity value at the gap is far greater than that of the breast gland tissue, the optical signal of the breast gland tissue is submerged in noise and cannot be used for algorithm analysis and calculation.
Fig. 6 is a distribution diagram of gray scale values at white line b2 in fig. 5, white line b2 covers the silica gel enclosure, gap 10, gland tissue a, in fig. 6, the gray scale values in the dotted circle are optical signals of the gland tissue and the reagent; as can be seen from fig. 6, after the gap is sufficiently filled with the reagent, the signal of the glandular tissue region is significantly larger than the background noise signal, and the gap has no larger abrupt change due to the filling of the reagent, so that the optical signal of the glandular tissue region at this time can be regarded as the effective signal and used for the algorithmic analysis processing.
Example 4:
when the reagent is prepared, pigments with different masses are added, so that the prepared corresponding reagents have different optical parameters (different gray values), and the specific experimental process is as follows:
500g of medical ultrasonic gel is put into a mixing container; then 500g of purified water is taken and put into a mixing container; 52.63mL of 20% fat emulsion injection is put into a mixing container, and the mixture is fully stirred by a stirrer until a milky homogeneous colloid is formed. The optical signal at this time is detected in the diffused-light imaging system, and data is recorded. The diffuse light imaging system adopts near infrared light with wavelength of 808nm as a light source, the data acquisition equipment is a scientific grade CMOS embedded imaging system which is produced by Fuzhou Xin picture photoelectricity limited company and has the model of Dhyana 201DS, and the exposure time is set to be 20 ms.
Then, 0.06g of a black natural pigment solution (the black natural pigment solution is a solution obtained by diluting a black natural pigment 10 times by mass with purified water) was put into a mixing vessel, the mixture was sufficiently stirred with a stirrer, and the optical signal of the reagent at that time was detected again in a diffused light imaging system, and data was recorded.
Repeating the steps, sequentially adding 0.06g of black natural pigment solution (the black natural pigment solution is obtained by diluting black natural pigment by 10 times according to the mass ratio by using purified water) into a mixing container, fully stirring the mixture by using a stirrer, detecting corresponding reagent optical signals in a diffused light imaging system, and recording data.
The measured experimental data were analyzed using ImageJ software, and the experimental results are shown in fig. 7. When no pigment is added or the addition amount of the pigment is insufficient, the prepared reagent has insufficient absorption of light, the transmitted light intensity is too strong and is higher than the optical parameters of human tissues, and the prepared reagent is not suitable at the moment, is not beneficial to acquisition of detection data and is not beneficial to subsequent analysis and processing. When the mass of the melanin solution is continuously increased to 0.3g, the transmission light intensity of the reagent reaches the range of the optical characteristic gray value corresponding to the human tissue, the optical characteristic (including absorption and scattering) of the reagent is close to the optical characteristic of the human tissue, and the prepared reagent is also suitable, so that the subsequent analysis and processing of the detection data are facilitated; when the amount of the pigment is increased continuously, the light transmission is weakened due to the fact that the absorption of the reagent is too strong, and the light transmission is lower than the optical parameters of human tissues, and the prepared reagent is not suitable at this moment and is not beneficial to subsequent analysis and processing of data.
Example 5
When the reagent is prepared, the fat emulsion injection with different mass or volume mass fraction of 20% is added, so that the prepared corresponding reagent has different optical parameters (different gray values), and the specific experimental process is as follows:
500g of medical ultrasonic gel is put into a mixing container; 500g of purified water is then taken and placed in a mixing container. 0.3g of a black natural pigment solution (the black natural pigment solution is obtained by diluting black natural pigment by 10 times according to a mass ratio with purified water) is added into a mixing container. The mixture was stirred well with a stirrer until a homogeneous gel was formed. This procedure was repeated to prepare 5 parts of the same homogeneous colloidal reagent for use.
Respectively adding 0mL, 25.64mL, 52.63mL, 81.08mL and 111.11mL of 20% fat emulsion injection into 5 prepared uniform colloidal reagents, and fully stirring by using a stirrer to obtain reagents with the fat emulsion mass fractions of 0%, 0.5%, 1.0%, 1.5% and 2.0%.
And sequentially detecting optical signals corresponding to the prepared different reagents in a diffused light imaging system, and recording data. The diffused light imaging system adopts near infrared light with the wavelength of 808nm, the data acquisition equipment is a scientific grade CMOS embedded imaging system which is produced by Fuzhou Xin picture photoelectricity limited company and has the model of Dhyana 201DS, and the exposure time is set to be 20 ms.
The experimental data obtained by analyzing the measured data by using ImageJ software, the experimental result is shown in figure 8, the mass of the added black natural pigment solution is 0.3g, when no fat emulsion injection with the mass fraction of 20% is added, or the volume of the added fat emulsion injection with the mass fraction of 20% is small (namely the added fat emulsion has small mass), the near-infrared light has strong transmission, so that the optical signal of the measured reagent is higher than that of human tissues, and the prepared reagent is not suitable at the moment, is not beneficial to the acquisition of detection data, and is not beneficial to the subsequent analysis and processing of the data; when the volume of the fat emulsion injection with the mass fraction of 20% is 52.63mL (namely the mass fraction of the fat emulsion in the finally obtained reagent is 1.0%), the transmitted light intensity of the reagent reaches the range of the optical characteristic gray value corresponding to the human tissue, the optical characteristic (including absorption and scattering) of the reagent at the moment is close to the optical characteristic (including absorption and scattering) of the human tissue, and the prepared reagent is suitable and is beneficial to the subsequent analysis and processing of detection data; when the volume or the mass of the added fat emulsion is continuously increased, the light intensity of the near infrared light which penetrates through the reagent is gradually weakened and is finally lower than the optical characteristics of human tissues, and at the moment, the prepared reagent is not suitable and is not beneficial to the subsequent analysis and processing of detection data.
Example 6
500g of medical ultrasonic gel is put into a mixing container; then 500g of purified water is taken and put into a mixing container; 52.63mL of fat emulsion injection with the mass fraction of 20 percent is put into a mixing container, stirred by a stirrer, and 0.3g of green natural pigment is added into the mixing container. The mixture was stirred well with a stirrer until a homogeneous gel was formed. The mixture was allowed to stand at an ambient temperature of not higher than 25 ℃ for 1 day to obtain a reagent. And packaging the prepared reagent in a packaging bottle for later use.
Example 7
500g of medical ultrasonic gel is put into a mixing container; then 500g of purified water is taken and put into a mixing container; 10g of titanium dioxide powder is put into a mixing container; adding 0.3g of black natural pigment solution (the black natural pigment solution is obtained by diluting black natural pigment with purified water by 10 times according to the mass ratio) into a mixing container, and fully stirring the mixture by using a stirrer until a uniform colloid is formed. The mixture was allowed to stand at an ambient temperature of not higher than 25 ℃ for 1 day to obtain a reagent. And packaging the prepared reagent in a packaging bottle for later use.
Example 8
500g of medical ultrasonic gel is put into a mixing container; then 500g of purified water is taken and put into a mixing container; 10g of silicon dioxide powder is put into a mixing container; adding 0.3g of black natural pigment solution (the black natural pigment solution is obtained by diluting black natural pigment with purified water by 10 times according to the mass ratio) into a mixing container, and fully stirring the mixture by using a stirrer until a uniform colloid is formed. The mixture was allowed to stand at an ambient temperature of not higher than 25 ℃ for 1 day to obtain a reagent. And packaging the prepared reagent in a packaging bottle for later use.
Example 9
500g of medical ultrasonic gel is put into a mixing container; then 500g of purified water is taken and put into a mixing container; 52.63mL of 20% fat emulsion injection is placed in a mixing container, and 0.3g of ink solution (the ink solution is obtained by diluting ink by 10 times according to the mass ratio with purified water) is added into the mixing container. The mixture was stirred well with a stirrer until a homogeneous gel was formed. The mixture was allowed to stand at an ambient temperature of not higher than 25 ℃ for 1 day to obtain a reagent. And packaging the prepared reagent in a packaging bottle for later use.
The reagent prepared in examples 1-2, 6-9 was filled in the gap 10 between the notch and the breast tissue, images were taken using an imaging system in a diffuse light imaging apparatus, and the measured experimental data were analyzed using ImageJ software to obtain: the optical characteristics of the reagents prepared in examples 1-2, 6-9 are within the range of the gray values of the optical characteristics of human tissues, which indicates that the reagents prepared in examples 1-2, 6-9 can better simulate the optical characteristics of human tissues, and are beneficial to the subsequent analysis and processing of detection data.
It is to be understood that the described embodiments are merely a few embodiments of the invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Claims (14)
1. A reagent characterized by comprising a substance capable of absorbing light and/or a substance capable of scattering light.
2. A reagent according to claim 1, further comprising water and/or a gel.
3. A reagent according to claim 1, wherein the light-absorbing substance is one or more selected from the group consisting of a black dye, a green dye and an ink.
4. A reagent according to claim 1, wherein the substance capable of scattering light is one or more selected from the group consisting of fat emulsion, titanium dioxide powder, and silicon dioxide powder.
5. A reagent according to claim 1, wherein the light-absorbing substance: 0.001 to 0.01: 1, the ratio is a mass ratio or a volume ratio.
6. The reagent as claimed in claim 2, wherein the ratio of each component is as follows: and (3) gel: water: substance capable of scattering light: the material capable of absorbing light is 1: 0.6-1.5: 0.05-0.222: 0.00012-0.0012, and the ratio is a mass ratio or a volume ratio.
7. A reagent according to claim 2, wherein the gel is a medical ultrasound gel.
8. A process for the preparation of a reagent according to any one of claims 1 to 7, comprising the steps of:
1) weighing the components according to the proportion;
2) adding gel, water, substance capable of scattering light, and substance capable of absorbing light into a mixing container, and mixing;
3) stirring the mixture until the gel, water, substance capable of scattering light, and substance capable of absorbing light are uniformly distributed;
4) placing the mixed solution obtained in the step 3) at an ambient temperature of not higher than 25 ℃, and standing for more than 1 day to obtain the reagent.
9. Use of an agent for the preparation of a formulation for diffuse light imaging of cancer in an organism, wherein the agent is according to any one of claims 1 to 7.
10. Use according to claim 9, wherein the organism is a human or other mammal.
11. The use according to claim 9, wherein the cancer is a breast cancer.
12. Use according to claim 9, wherein the diffuse light imaging is of light of any wavelength or any range of wavelengths from visible to near infrared.
13. The use according to claim 9, wherein the diffuse light is imaged by irradiating the mammary tissue with light of any wavelength or range of wavelengths from visible to near-infrared light, and imaging the transmitted light.
14. The use according to claim 13, wherein the biological tissue is glandular tissue of a living body.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112890812A (en) * | 2021-02-20 | 2021-06-04 | 丹阳慧创医疗设备有限公司 | Method, device and system for checking effectiveness of near infrared spectrum imaging equipment |
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