Multifunctional polarization imaging system and accurate tumor identification method thereof

Abstract

The invention discloses a multifunctional polarization imaging system and an accurate tumor recognition method thereof, and relates to the technical field of optical imaging, the system performs imaging by using the optical characteristics of tissues, and exogenous fluorescent dyes are not needed, so that the problems of sensitivity and specificity caused by dye labeling are avoided. According to the technical scheme, the OCT imaging system comprises a Stokes-Muller imaging module, a rotatable sample table module, a non-coaxial reflection type and transmission type illumination module and a multifunctional OCT module. According to the multifunctional polarization imaging system, transmission type, coaxial reflection type and non-coaxial reflection type Stokes-Mueller imaging, OCT imaging, PS-OCT imaging and OCTA imaging can be achieved while a sample is not moved. The multifunctional OCT module can simultaneously obtain an intensity attenuation curve, a polarization information image and an angiography image of light passing through a sample.

Description

Technical Field

[0001] The present invention relates to the field of optical imaging technology, and in particular to a multifunctional polarization imaging system and a method for accurately identifying tumors thereof. Background Art

[0002] Cancer is one of the leading causes of death worldwide. Accurate identification and detection of cancer tissues and rapid and accurate intraoperative resection are crucial to improving patients' survival rates and quality of life. Early detection and accurate identification of tumors are key factors in successful treatment. Although traditional imaging techniques, such as CT and MRI, play an important role in cancer detection, their equipment is complex and the detection time is long, which cannot achieve real-time rapid imaging, affecting their application in intraoperative detection. Fluorescence imaging technology is a technology widely used in tumor detection and surgical guidance. This technology uses fluorescent dyes to mark tumor cells, making them glow during imaging, thereby helping doctors locate and remove tumors. However, the current fluorescence imaging technology still has the following major defects in its application: some patients have immune rejection reactions to fluorescent dyes; the sensitivity and specificity of fluorescent dyes are insufficient: the ability of fluorescent dyes to selectively mark tumor cells is limited, and they are easily interfered by nonspecific dye aggregation and background fluorescence, resulting in false detection and missed detection. Fluorescence attenuation and photobleaching: fluorescent dyes will undergo photobleaching under long-term excitation light irradiation, resulting in weakened fluorescence signals, affecting imaging quality and accuracy. Difficulty in quantitative analysis: Fluorescence intensity is affected by many factors, such as dye concentration, tissue absorption and scattering, making it difficult to achieve accurate quantitative analysis.

[0003] Problems with current technology: Although traditional imaging technologies, such as CT and MRI, play an important role in cancer detection, their equipment is complex, the detection time is long and they cannot achieve real-time rapid imaging, which affects their application in intraoperative detection.

[0004] Fluorescence imaging is a widely used technology for tumor detection and surgical guidance. This technology helps doctors locate and remove tumors by labeling tumor cells with fluorescent dyes, causing them to glow during imaging. However, the ability of fluorescent dyes to selectively label tumor cells is limited and is easily interfered by nonspecific dye aggregation and background fluorescence, leading to false detection and missed detection. Fluorescence attenuation and photobleaching: Fluorescent dyes will undergo photobleaching under long-term excitation light, resulting in weakened fluorescence signals and affecting imaging quality and accuracy.

[0005] Current fluorescence imaging technology has problems with insufficient sensitivity and specificity due to the need for exogenous labeling in its application. Summary of the invention

[0006] In view of this, the present invention provides a multifunctional polarization imaging system and a method for accurately identifying tumors thereof. The system uses the optical properties of the tissue itself for imaging without the need for exogenous fluorescent dyes, thereby avoiding the sensitivity and specificity problems caused by dye labeling.

[0007] To achieve the above-mentioned purpose, the technical solution of the present invention includes a Stokes-Muller imaging module, a rotatable sample stage module, a non-coaxial reflective and transmissive illumination module, and a multifunctional OCT module;

[0008] The Stokes-Muller imaging module, the rotatable sample stage module and the multifunctional OCT module are installed together on a base; the non-coaxial reflection and transmission illumination modules are installed on the rotatable sample stage module;

[0009] The Stokes-Muller imaging module includes: an objective lens, a beam splitter, a polarization state analyzer module, a data processing module, a polarization generator module, and a light source module, which are installed in a cage system;

[0010] The non-coaxial reflective and transmissive illumination module includes: a light source module, a polarization state generator module and a condenser, which are sequentially connected and assembled on a rotating base that rotates 360 degrees around the sample stage module;

[0011] The multifunctional OCT module includes: a swept-frequency light source, a 90 / 10 coupler, a polarization delay module, a reference light modulation module, a sample scanning module, a polarization detection module and a data processing module; the swept-frequency light source is connected to the 90 / 10 coupler, and the two outputs of the 90 / 10 coupler, one of which is sent to the sample scanning module via the polarization delay module, and the other is sent to the data processing module via the reference light modulation module and the polarization detection module;

[0012] The reference light modulation module comprises a vertical polarization controller, a polarization beam splitter, a quarter wave plate, a reflector and a horizontal polarization controller; wherein the polarization beam splitter is arranged between the vertical polarization controller and the horizontal polarization controller.

[0013] Furthermore, the system has four imaging modes, namely, coaxial reflection Stokes-Muller imaging, non-coaxial reflection Stokes-Muller imaging, transmission Stokes-Muller imaging, and multifunctional OCT system imaging;

[0014] When the imaging mode is coaxial reflection Stokes-Muller imaging, the light emitted by the light source of the light source module enters the polarization generator module to generate light with a specific polarization state. After being reflected by the beam splitter, it is focused by the objective lens and irradiated onto the sample on the sample stage. The coaxial-backscattered light of the sample is collected by the objective lens, then passes through the beam splitter, is demodulated and detected by the polarization state analyzer module, and finally enters the data processing module.

[0015] When the imaging mode is non-coaxial reflective Stokes-Muller imaging, first, the non-coaxial reflective and transmissive illumination modules rotate around the sample driven by the rotating base, and are at a specified angle with the Stokes-Mueller imaging module as required; when the angle adjustment is completed, the light emitted by the light source module enters the polarization state generator module, generates light with a specific polarization state, is converged by the condenser, and irradiates the sample on the sample stage; the non-coaxial backscattered light of the sample is collected by the objective lens, then passes through the spectroscope, is demodulated and detected by the polarization state analyzer module, and finally enters the data processing module.

[0016] When the imaging mode is transmission Stokes-Muller imaging, first the non-coaxial reflective and transmission illumination modules rotate around the sample driven by the rotating base and become collinear with the Stokes-Mueller imaging module; when the angle adjustment is completed, the light emitted by the light source module enters the polarization state generator module, generates light of a specific polarization state, is converged by the condenser, and irradiates the sample on the sample stage; the transmitted light of the sample is collected by the objective lens, then passes through the beam splitter, is demodulated and detected by the polarization state analyzer module, and finally enters the data processing module.

[0017] When the imaging mode is multifunctional OCT system imaging, the sample stage module rotates the sample to the focal plane of the sample scanning module; after the rotation is completed, the coherent light emitted by the swept light source is divided into sample light and reference light by a 90 / 10 coupler; the reference light enters the reference light modulation module and is modulated into linearly polarized light; at the same time, the sample light enters the polarization delay module to achieve spatial separation of different polarization states, and then enters the sample scanning module to perform a three-dimensional scan of the sample on the sample stage; after the scan is completed, the sample light carrying the sample structure information enters the polarization detection module to interfere with the reference light, and the interference signal is detected and enters the data processing module.

[0018] Furthermore, when the system modulates the reference light, the reference light first enters the vertical polarization controller in the reference-controlled light modulation module through the coupler, and then passes through the polarization beam splitter, quarter-wave plate and reflector. After the reference light is reflected, it passes through the quarter-wave plate and polarization beam splitter again and enters the horizontal polarization controller. In order to achieve high-quality measurement, it is usually necessary to manually adjust the vertical polarization controller and the horizontal polarization controller before measurement so that the difference in signal intensity detected by the polarization detection module in the two channels is within the set range.

[0019] Furthermore, the reference light modulation module also includes a piezoelectric system 1 and a piezoelectric system 2, which will adaptively adjust the pressure of the two polarization controllers according to the potential difference transmitted by the module so that the difference in the signal strength of the two channels is within a set range.

[0020] Furthermore, the polarization detection module includes a horizontal balanced detector and a vertical detector; the data processing module performs the following calculation according to the output of the polarization detection module:

[0021] The original interference fringe signal detected by the horizontally balanced detector is

[0022] I h (Δz)=J 11 e ikΔz +J 12 e ik(Δz+ξ) +cc

[0023] Where k is the wave number of the swept light source, Δz is the optical path difference between the sample light and the reference light at different depths, ξ is the optical path difference between different polarization states introduced by the polarization delay module, and cc represents J 11 and J 12 The Jones component J of the sample at different depths can be obtained by removing the DC term and performing discrete Fourier transform. 11 With J 12 ,

[0024]

[0025] Where z represents the detection depth, Δz is the optical path difference between the sample light and the reference light at different depths, ξ is the optical path difference between different polarization states introduced by the polarization delay module; δ(*) is the unit impact function.

[0026] Similarly, the vertical detector obtains another set of Jones components J of the sample 21 With J 22

[0027]

[0028] The OCT depth tomography image of the sample can be obtained by averaging the squares of the four components of the Jones matrix of the sample.

[0029]

[0030] After obtaining the depth tomography image, the intensity attenuation curve of the sample can be obtained according to the light intensity attenuation formula;

[0031]

[0032] Where z is the sample depth, z0 is the sample surface, A is the system constant, μbs is the backscattering constant, μext is the intensity attenuation coefficient of the sample at different depths, and h(z) is the point spread function of the system.

[0033] At the same time, the Jones matrix of the sample is converted to the Stokes vector

[0034]

[0035] Where I represents the light intensity, Q and U represent the polarization degree of linear polarized light, and V represents the polarization degree of circular polarized light.

[0036] That is, the polarization uniformity DOPU of the sample at different depths is obtained

[0037]

[0038] in Represents the mean polarization degree within the window, and i represents the i-th pixel in the kernel window.

[0039] After obtaining multi-scale information in the depth direction of the sample, the scanning galvanometer of the sample scanning module will scan the sample in the x and y directions to obtain the two-dimensional B-scan and three-dimensional C-scan information of the sample. Based on this information, the angiography algorithm is used to obtain the vascular image of the sample.

[0040]

[0041] Where M and N represent the grid sizes selected at the lateral position x and depth position z, I A (x+p,z+q) represents the intensity value at the horizontal position p and the depth position q in the grid, I B (x+p,z+q) represents the intensity value of adjacent images at the same position. represents the average intensity value within the grid, Represents the average intensity value of adjacent images in the same grid.

[0042] Another embodiment of the present invention further provides a method for accurately identifying a tumor, which uses the above-mentioned multifunctional polarization imaging system to accurately identify a tumor, and includes the following steps:

[0043] Step 1: Determine whether to use the transmission Stokes-Muller imaging mode or the reflection Stokes-Muller imaging mode according to the form of the sample; if the sample is translucent, use the transmission Stokes-Muller imaging mode, otherwise choose the reflection Stokes-Muller imaging mode.

[0044] Step 2: Obtain the polarization information of the sample according to the selected transmission Stokes-Muller imaging mode or reflection Stokes-Muller imaging mode.

[0045] Step 3: When the difference in polarization information between different areas of the sample exceeds the threshold, the detection area is determined, the sample stage is rotated ninety degrees, and the detection area of ​​the sample is detected using the multifunctional OCT system imaging mode.

[0046] The multifunctional OCT system simultaneously obtains the intensity attenuation curve of light passing through the sample, polarization information image and angiography image, based on which it determines whether the detection area is tumor tissue.

[0047] Further, step 2: according to the selected transmission Stokes-Muller imaging mode or reflection Stokes-Muller imaging mode, polarization information of the sample is obtained, specifically:

[0048] The data processing module obtains two-dimensional image information with the polarization information of the sample, and first uses a low-magnification objective lens to perform large-field imaging according to needs. When the difference in polarization information of different areas of the sample in the detected two-dimensional polarization image information exceeds the set threshold, the high-magnification objective lens is switched for detection to obtain the polarization information of the sample.

[0049] The low-magnification objective lens is an objective lens with a magnification of 4X or 10X; the high-magnification objective lens is an objective lens with a magnification of 20X, 40X or 60X.

[0050] Beneficial effects:

[0051] 1: The present invention provides a multifunctional polarization imaging system, which integrates optical coherence tomography (OCT), polarization optical coherence tomography (PS-OCT), optical coherence tomography angiography (OCTA) and Stokes-Mueller imaging technology, and can provide rich tissue information for co-localization detection of the same part, thereby improving the accuracy and reliability of tumor detection. The system has the following significant advantages: No exogenous labeling is required: The system uses the optical properties of the tissue itself for imaging, without the need for exogenous fluorescent dyes, thereby avoiding the sensitivity and specificity problems caused by dye labeling. Avoid photobleaching and fluorescence attenuation caused by the use of fluorescent dyes.

[0052] 2: The present invention provides a multifunctional polarization imaging system, which is portable and non-contact measurement: the system is designed to be portable and can perform non-contact real-time measurement during surgery, thereby improving the accuracy and safety of surgical operations.

[0053] 3: The present invention provides a multifunctional polarization imaging system, in terms of automatic adjustment of polarization devices: In order to obtain the best measurement effect, the traditional PS-OCT system usually requires manual adjustment of the polarization device in the system. This system introduces a piezoelectric system to realize the automation of this process.

[0054] 3: The present invention provides a method for accurate tumor identification using a multifunctional polarization imaging system. The detection of cancer tissue by the multifunctional polarization imaging system using multiple imaging technologies can achieve low-resolution to high-resolution measurements, and measurements from two-dimensional polarization information to three-dimensional polarization information, and can obtain measurement results quickly and in real time. The information carried in the measurement results can help distinguish cancer tissue from healthy tissue, so no exogenous labeling is required. The method can provide real-time automatic detection and data processing: It has advanced automatic detection and data processing functions, and can provide accurate tumor identification and positioning information in real time during surgery, assisting doctors in accurate resection. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] Figure 1 Schematic diagram of a multifunctional polarization imaging system; wherein 101 is a Stokes-Muller imaging module, 102 is a sample stage module, 103 is a non-coaxial reflection and transmission illumination module, and 104 is a multifunctional OCT module;

[0056] Figure 2 Schematic diagram of Stokes-Mueller imaging module; wherein 201-objective lens, 202-beam splitter, 203-polarization state analyzer module, 204-data processing module, 205-polarization generator module, 206-light source module;

[0057] Figure 3 It is a schematic diagram of a non-coaxial reflective and transmissive illumination module; 301-light source module, 302-polarization state generator module, 303-condenser, 304-rotating base;

[0058] Figure 4 Schematic diagram of the imaging module of the multifunctional OCT system; 401-sweep frequency light source, 402-90 / 10 coupler, 403-polarization delay module, 404-reference light modulation module, 405-sample scanning module, 406-polarization detection module, 407-data processing module;

[0059] Figure 5It is a reference light modulation module; 501-vertical polarization controller, 502-polarization beam splitter, 503-quarter wave plate, 504-reflector, 505-horizontal polarization controller, 506-piezoelectric system 1, 507-piezoelectric system 2;

[0060] Figure 6 This is a specific working principle diagram of the piezoelectric system in the multifunctional OCT system; 601-piezoresistor, 602-conductor ground wire, 603-spring tensioner. DETAILED DESCRIPTION

[0061] The present invention is described in detail below with reference to the accompanying drawings and embodiments.

[0062] The present invention provides a multifunctional polarization imaging system, such as Figure 1 As shown, it includes a Stokes-Muller imaging module 101, a rotatable sample stage module 102, a non-coaxial reflection and transmission illumination module 103, and a multifunctional OCT module 104; 101, 102 and 104 are installed together on a base. 103 is installed on the rotatable sample stage module 102.

[0063] Stokes-Muller imaging modules, such as Figure 2 As shown, it includes an objective lens 201, a spectroscope 202, a polarization state analyzer module 203PSA, a data processing module 204, a polarization generator module 205PSG, and a light source module 206. 201-206 are installed and connected by a cage system.

[0064] Non-coaxial reflective and transmissive illumination modules, such as Figure 3 As shown, it includes a light source module 301, a polarization state generator module 302, and a condenser lens 303. These components are installed on a rotating base 304 that can rotate 360 ​​degrees around the sample stage module.

[0065] The multifunctional OCT module 104, such as Figure 4 As shown, it includes a swept frequency light source 401 , a 90 / 10 coupler 402 , a polarization delay module 403 , a reference light modulation module 404 , a sample scanning module 405 , a polarization detection module 406 , and a data processing module 407 .

[0066] Reference optical modulation module, such as Figure 5 As shown, it includes a vertical polarization controller 501, a polarization beam splitter 502, a quarter wave plate 503, a reflector 504, a horizontal polarization controller 505, and piezoelectric systems 506 and 507.

[0067] During coaxial reflection Stokes-Muller imaging, the light emitted by the light source 206 enters the polarization generator module 205, generates light of a specific polarization state, is reflected by the beam splitter 202, is focused by the objective lens 201, and irradiates the sample on the sample stage 102. The coaxial backscattered light of the sample is collected by the objective lens 201, then passes through the beam splitter 202, is demodulated and detected by the polarization state analyzer module 203, and finally enters the data processing module 204.

[0068] During non-coaxial reflective Stokes-Muller imaging, first, the non-coaxial reflective and transmissive illumination module 103 rotates around the sample driven by the rotating base 304, and is at a specified angle with the Stokes-Mueller imaging module 101 as required. When the angle adjustment is completed, the light emitted by the light source module 301 enters the polarization generator module 302, generates light of a specific polarization state, is converged by the condenser 303, and irradiates the sample located on the sample stage 102. The non-coaxial backscattered light of the sample is collected by the objective lens 201, then passes through the spectroscope 202, is demodulated and detected by the polarization state analyzer module 203, and finally enters the data processing module 204.

[0069] During transmission Stokes-Muller imaging, the non-coaxial reflection and transmission illumination module 103 first rotates around the sample driven by the rotating base 304, and is in line with the Stokes-Mueller imaging module 101. After the angle adjustment is completed, the light emitted by the light source module 301 enters the polarization generator module 302, generates light with a specific polarization state, is converged by the condenser 303, and irradiates the sample located on the sample stage 102. The transmitted light of the sample is collected by the objective lens 201, then passes through the beam splitter 202, is demodulated and detected by the polarization state analyzer module 203, and finally enters the data processing module 204.

[0070] When the multifunctional OCT system is imaging, the sample stage module 102 rotates the sample to the focal plane of the sample scanning module 405. After the rotation is completed, the low coherence light (coherence length is less than 10 microns) emitted by the swept light source 401 is divided into sample light and reference light by the 90 / 10 coupler 402. The reference light enters the reference light modulation module 404 and is modulated into linearly polarized light. At the same time, the sample light enters the polarization delay module 403 to achieve spatial separation of different polarization states, and then enters the sample scanning module 405 to perform a three-dimensional scan of the sample located on the sample stage 102. After the scan is completed, the sample light carrying the sample structure information enters the polarization detection module 406 and interferes with the reference light. The interference signal is detected by 406 and enters the data processing module 407.

[0071] When modulating the reference light, the reference light first enters the vertical polarization controller 501 in the reference-controlled light modulation module 404 through the coupler 402, and then passes through the polarization beam splitter 502, the quarter-wave plate 503 and the reflector 504. The reference light reaching 504 is reflected and passes through 503 and 502 again and enters the horizontal polarization controller 505. In order to achieve high-quality measurement, it is usually necessary to manually adjust the two polarization controllers 501 and 505 before measurement so that the signal strength detected by the 406 module in the two channels is close, specifically, the signal strength difference is less than 0.01V. Two piezoelectric systems 506 and 507 are introduced in this design, which will adaptively adjust the pressure of the two polarization controllers 501 and 505 according to the potential difference transmitted by the 406 module, so that the signals of the two channels are close, thereby realizing fully automated measurement. In the embodiment of the present invention, it is set that when the difference in signal strength between the two is less than 0.01V, it is determined that the signals of the two channels are close.

[0072] In the present invention, the piezoelectric system in the multifunctional OCT system can adaptively modulate the reference light in real time according to the intensity difference of the two balanced detector signals at the detection end of the system. The specific working principle is as follows: Figure 6 As shown. The potential difference between the two detectors of the polarization detection module 406 is transmitted to the varistor 601 through the wire, and the varistor is then connected to the ground wire 602 through the wire to form a closed loop. When there is a potential difference, the inverse piezoelectric effect will cause the resistor to apply pressure in the corresponding direction to the spring tensioner 603, thereby driving the polarization controller 501 to deviate in the correct direction, realizing real-time modulation of the polarization degree of the reference light.

[0073] The polarization detection module 406 is composed of a horizontal balanced detector and a vertical balanced detector. The original interference fringe signal detected by the horizontal balanced detector is

[0074] I h (Δz) = J 11 e ikΔz +J 12 e jk(Δz+ξ) +cc

[0075] Where k is the wave number of the frequency sweeping light source, Δz is the optical path difference between the sample light and the reference light at different depths, ξ is the optical path difference between different polarization states introduced by the polarization delay module 403, and cc represents J 11 and J 12 The Jones component J of the sample at different depths can be obtained by removing the DC term and performing discrete Fourier transform. 11 With J 12 ,

[0076]

[0077] Where z represents the detection depth, Δz is the optical path difference between the sample light and the reference light at different depths, and ξ is the optical path difference between different polarization states introduced by the polarization delay module 403. δ(*) Unit impulse function

[0078] Similarly, the vertical detector obtains another set of Jones components J of the sample 21 With J 22

[0079]

[0080] The OCT depth tomography image of the sample can be obtained by averaging the squares of the four components of the Jones matrix of the sample.

[0081]

[0082] After obtaining the depth tomography image, the intensity attenuation curve of the sample can be obtained according to the light intensity attenuation formula.

[0083]

[0084] Where z is the sample depth, z0 is the sample surface, A is the system constant, μ bs is the backscattering constant, μ ext is the intensity attenuation coefficient of the sample at different depths, and h(z) is the point spread function of the system.

[0085] At the same time, the Jones matrix of the sample is converted to the Stokes vector

[0086]

[0087] Where I represents the light intensity, Q and U represent the polarization degree of linear polarized light, and V represents the polarization degree of circular polarized light.

[0088] The polarization uniformity DOPU of the sample at different depths can be obtained

[0089]

[0090]

[0091] in Represents the mean polarization degree within the window, and i represents the i-th pixel in the kernel window.

[0092] After obtaining multi-scale information in the depth direction of the sample, the scanning galvanometer of the sample scanning module will scan the sample in the x and y directions to obtain the two-dimensional B-scan and three-dimensional C-scan information of the sample. Based on this information, the angiography algorithm can be used to obtain the vascular image of the sample.

[0093]

[0094] Where M and N represent the grid sizes selected at the lateral position x and depth position z, I A (x+p,z+q) represents the intensity value at the horizontal position p and the depth position q in the grid, I B (x+p,z+q) represents the intensity value of adjacent images at the same position. represents the average intensity value within the grid, Represents the average intensity value of adjacent images in the same grid.

[0095] The above calculation processes are all performed in parallel using CUDA C / C++ programs after the interference data is transmitted to the graphics processing unit GPU of the data processing module 407. The data processing process is carried out simultaneously with the scanning of the sample by the sample scanning module 405, thereby realizing three-dimensional real-time imaging of the multi-scale information of the sample.

[0096] When the multifunctional polarization imaging system is used to accurately identify tumor tissue, the following steps are specifically included:

[0097] Step 1: Determine whether to use the transmission Stokes-Muller imaging mode or the reflection Stokes-Muller imaging mode according to the form of the sample; if the sample is translucent, use the transmission Stokes-Muller imaging mode, otherwise choose the reflection Stokes-Muller imaging mode.

[0098] Step 2: Obtaining polarization information of the sample according to the selected transmission Stokes-Muller imaging mode or reflection Stokes-Muller imaging mode;

[0099] Specifically, Stokes-Muller imaging can obtain two-dimensional image information with sample polarization information (data processing module 204), and can first use a low-magnification objective lens (low-magnification range 4X, 10X objective lens) according to demand to perform large-field imaging. When the detected two-dimensional polarization image information finds that the polarization information difference of different areas of the sample exceeds the set threshold (for example, using transmission Stokes-Mueller imaging to detect melanoma, the depolarization mean of normal skin is about 0.08, and the phase delay mean is about 0.11rad; the depolarization mean of melanoma is about 0.05, and the phase delay mean is about 0.07rad), that is, switch to a high-magnification objective lens for detection (high-magnification range 20X 40X 60X objective lens). When the sample is subjected to reflective Stokes-Muller imaging, in addition to the detection of different magnifications, the base 304 can also be rotated around the sample to realize imaging of polarization information of different scattering angles of the sample, and obtain richer polarization information of the sample.

[0100] Step 3: When the difference in polarization information between different areas of the sample exceeds a threshold, the detection area is determined, the sample stage is rotated 90 degrees, and the detection area of ​​the sample is detected using the imaging mode of the multifunctional OCT system;

[0101] The multifunctional OCT module can simultaneously obtain the intensity attenuation curve of light passing through the sample, polarization information images, and angiography images. The cell arrangement of cancerous tissue usually shows strong disorder, which makes it show obvious differences from normal tissue in optical properties, such as higher intensity attenuation and lower polarization uniformity. Based on these characteristics, the multifunctional OCT system can quickly distinguish whether the detection area has cancer.

[0102] Fluorescence imaging uses excitation light to excite fluorescent dyes modified with biological functions, thereby achieving the detection of specific cancers. The optical coherence tomography (OCT), polarization optical coherence tomography (PS-OCT), optical coherence tomography angiography (OCTA) and Stokes-Mueller imaging technologies of this system do not use exogenous marker fluorescent dyes.

[0103] Among them, optical coherence tomography (OCT), polarization optical coherence tomography (PS-OCT), and optical coherence tomography angiography (OCTA) use low-coherence light to perform interference measurements on samples to obtain the internal reflectivity characteristics of tissues, thereby achieving high-resolution measurements. The information carried in the measurement results can help distinguish cancer tissue from healthy tissue, so no exogenous labeling is required.

[0104] In Stokes-Mueller imaging technology, PSG generates incident polarized light to illuminate the sample, and PSA demodulates the light scattered by the sample to solve the Mueller matrix of the sample. The Muller matrix of the sample is closely related to the microstructure of the sample itself, thereby distinguishing cancer tissue from healthy tissue.

[0105] In summary, the above are only preferred embodiments of the present invention and are not intended to limit the protection scope of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A multifunctional polarization imaging system, characterized in that: It includes a Stokes-Muller imaging module (101), a rotatable sample stage module (102), a non-coaxial reflection and transmission illumination module (103), and a multifunctional OCT module (104); The Stokes-Muller imaging module (101), the rotatable sample stage module (102) and the multifunctional OCT module (104) are installed together on a base; the non-coaxial reflective and transmissive illumination module (103) is installed on the rotatable sample stage module (102); The Stokes-Muller imaging module (101) comprises: an objective lens (201), a beam splitter (202), a polarization state analyzer module (203), a data processing module (204), a polarization generator module (205) and a light source module (206); wherein (201) to (206) are installed in a cage system manner; The non-coaxial reflective and transmissive illumination module (103) comprises: a light source module (301), a polarization state generator module (302) and a condenser (303), which are sequentially connected and assembled on a rotating base (304) that can rotate 360 ​​degrees around the sample stage module; The multifunctional OCT module (104) comprises: a frequency sweeping light source (401), a 90 / 10 coupler (402), a polarization delay module (403), a reference light modulation module (404), a sample scanning module (405), a polarization detection module (406) and a data processing module (407); wherein the frequency sweeping light source (401) is connected to the 90 / 10 coupler (402), and the two outputs of the 90 / 10 coupler (402), one of which is transmitted through the polarization delay module (403) to the sample scanning module (405), and the other is transmitted through the reference light modulation module (404) and the polarization detection module (406) to the data processing module (407); The reference light modulation module (404) comprises a vertical polarization controller (501), a polarization beam splitter (502), a quarter wave plate (503), a reflector (504) and a horizontal polarization controller (505); wherein the polarization beam splitter (502) is arranged between the vertical polarization controller (501) and the horizontal polarization controller (505).

2. A multifunctional polarization imaging system as claimed in claim 1, characterized in that: The system has four imaging modes, namely coaxial reflection Stokes-Muller imaging, non-coaxial reflection Stokes-Muller imaging, transmission Stokes-Muller imaging, and multifunctional OCT system imaging; When the imaging mode is coaxial reflection Stokes-Muller imaging, the light emitted by the light source of the light source module (206) enters the polarization generator module (205) to generate light with a specific polarization state, which is reflected by the beam splitter (202), focused by the objective lens (201), and irradiated onto the sample located on the sample stage (102); the coaxial backscattered light of the sample is collected by the objective lens (201), then passes through the beam splitter (202), is demodulated and detected by the polarization state analyzer module (203), and finally enters the data processing module (204); When the imaging mode is non-coaxial reflective Stokes-Muller imaging, first, the non-coaxial reflective and transmissive illumination module (103) rotates around the sample driven by the rotating base (304), and is at a specified angle with the Stokes-Mueller imaging module (101) as required; when the angle adjustment is completed, the light emitted by the light source module (301) enters the polarization state generator module (302) to generate light with a specific polarization state, which is converged by the condenser (303) and irradiated on the sample located on the sample stage (102); the non-coaxial backscattered light of the sample is collected by the objective lens (201), then passes through the spectroscope (202), is demodulated and detected by the polarization state analyzer module (203), and finally enters the data processing module (204); When the imaging mode is transmission Stokes-Muller imaging, first, the non-coaxial reflection and transmission illumination module (103) is driven by the rotating base (304) to rotate around the sample and be colinear with the Stokes-Mueller imaging module (101); when the angle adjustment is completed, the light emitted by the light source module (301) enters the polarization state generator module (302), generates light with a specific polarization state, is converged by the condenser (303), and irradiates the sample located on the sample stage (102); the transmitted light of the sample is collected by the objective lens (201), then passes through the beam splitter (202), is demodulated and detected by the polarization state analyzer module (203), and finally enters the data processing module (204); When the imaging mode is multifunctional OCT system imaging, the sample stage module (102) rotates the sample to the focal plane of the sample scanning module (405); after the rotation is completed, the coherent light emitted by the frequency-sweeping light source (401) is divided into sample light and reference light by the 90 / 10 coupler (402); the reference light enters the reference light modulation module (404) and is modulated into linearly polarized light; at the same time, the sample light enters the polarization delay module (403) to achieve spatial separation of different polarization states, and then enters the sample scanning module (405) to perform a three-dimensional scan on the sample located on the sample stage (102); after the scanning is completed, the sample light carrying the sample structure information enters the polarization detection module (406) and interferes with the reference light, and the interference signal is detected by (406) and enters the data processing module (407).

3. A multifunctional polarization imaging system as claimed in claim 2, characterized in that: When the system modulates the reference light, the reference light first enters the vertical polarization controller (501) in the reference-controlled light modulation module (404) through the coupler (402), and then passes through the polarization beam splitter (502), the quarter-wave plate (503) and the reflector (504). After the reference light reaches (504), it is reflected and then passes through the quarter-wave plate (503) and the polarization beam splitter (502) again and enters the horizontal polarization controller (505). In order to achieve high-quality measurement, it is usually necessary to manually adjust the vertical polarization controller (501) and the horizontal polarization controller (505) before measurement so that the difference in signal intensity detected by the polarization detection module (406) in the two channels is within a set range.

4. A multifunctional polarization imaging system as claimed in claim 3, characterized in that: The reference light modulation module also includes a piezoelectric system 1 (506) and a piezoelectric system 2 (507), which will adaptively adjust the pressure of the two polarization controllers (501) and (505) according to the potential difference transmitted by the (406) module so that the difference in the signal strength of the two channels is within a set range.

5. The multifunctional polarization imaging system according to claim 1, characterized in that: The polarization detection module (406) comprises a horizontal balance detector and a vertical detector; the data processing module (407) performs the following calculation according to the output of the polarization detection module (406): The original interference fringe signal detected by the horizontally balanced detector is I h (Δz)=J 11 e ikΔz +J 12 e ik(Δz+ξ) +c.c. Where k is the wave number of the frequency sweeping light source, Δz is the optical path difference between the sample light and the reference light at different depths, ξ is the optical path difference between different polarization states introduced by the polarization delay module (403), and cc represents J 11 and J 12 The Jones component J of the sample at different depths can be obtained by removing the DC term and performing discrete Fourier transform. 11 With J 12 , Wherein z represents the detection depth, Δz is the optical path difference between the sample light and the reference light at different depths, ξ is the optical path difference between different polarization states introduced by the polarization delay module (403); δ(*) is the unit impulse function; Similarly, the vertical detector obtains another set of Jones components J of the sample 21 With J 22 The OCT depth tomography image of the sample can be obtained by averaging the squares of the four components of the Jones matrix of the sample; After obtaining the depth tomography image, the intensity attenuation curve of the sample can be obtained according to the light intensity attenuation formula; Where z is the sample depth, z0 is the sample surface, A is the system constant, μbs is the backscattering constant, μext is the intensity attenuation coefficient of the sample at different depths, and h(z) is the point spread function of the system; At the same time, the Jones matrix of the sample is converted to the Stokes vector Where I represents the light intensity, Q and U represent the polarization degree of linear polarized light, and V represents the polarization degree of circular polarized light; That is, the polarization uniformity DOPU of the sample at different depths is obtained in Represents the mean value of the degree of polarization within the window, i represents the i-th pixel of the kernel window; After obtaining multi-scale information in the depth direction of the sample, the scanning galvanometer of the sample scanning module will scan the sample in the x and y directions, thereby obtaining the two-dimensional B-scan and three-dimensional C-scan information of the sample. Based on this information, the angiography algorithm is used to obtain the vascular image of the sample; Where M and N represent the grid sizes selected at the lateral position x and depth position z, I A (x+p,z+q) represents the intensity value at the horizontal position p and the depth position q in the grid, I B (x+p,z+q) represents the intensity value of adjacent images at the same position. represents the average intensity value within the grid, Represents the average intensity value of adjacent images in the same grid.

6. A method for accurately identifying tumors, characterized in that: Using a multifunctional polarization imaging system as claimed in any one of claims 1 to 5 to accurately identify a tumor comprises the following steps: Step 1: Determine whether to use the transmission Stokes-Muller imaging mode or the reflection Stokes-Muller imaging mode according to the form of the sample; if the sample is transparent, use the transmission Stokes-Muller imaging mode, otherwise use the reflection Stokes-Muller imaging mode; Step 2: Obtaining polarization information of the sample according to the selected transmission Stokes-Muller imaging mode or reflection Stokes-Muller imaging mode; Step 3: When the difference in polarization information between different areas of the sample exceeds a threshold, a detection area is determined, the sample stage (102) is rotated ninety degrees, and the detection area of ​​the sample is detected using a multifunctional OCT system imaging mode; The multifunctional OCT system simultaneously obtains the intensity attenuation curve of light passing through the sample, polarization information image and angiography image, based on which it determines whether the detection area is tumor tissue.

7. A method for accurate tumor identification according to claim 6, characterized in that: The second step is to obtain polarization information of the sample according to the selected transmission Stokes-Muller imaging mode or reflection Stokes-Muller imaging mode, specifically: The data processing module (204) acquires two-dimensional image information with polarization information of the sample, and first uses a low-magnification objective lens to perform large-field imaging according to demand, and when the difference in polarization information of different regions of the sample is found to exceed a set threshold in the detected two-dimensional polarization image information, a high-magnification objective lens is switched to perform detection to acquire the polarization information of the sample; The low-magnification objective lens is an objective lens with a magnification of 4X or 10X; the high-magnification objective lens is an objective lens with a magnification of 20X, 40X or 60X.

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