Multi-mode co-location measurement system for biological tissue birefringence and blood flow detection

Abstract

The invention discloses a multi-mode co-location measuring system and a multi-mode co-location measuring method for birefringence and blood flow detection of biological tissues, and the multi-mode co-location measuring system for birefringence and blood flow detection of the biological tissues comprises a multi-mode co-location measuring system and a multi-mode co-location measuring method, two technologies of measuring tissue birefringence characteristics through speckle interferometry and measuring micro blood flow distribution through speckle contrast imaging are fused on a single optical platform, and by controlling opening and closing of a reference light path, the system can realize high-sensitivity phase / birefringence interferometry and closing of the reference light when the reference light is opened, so that high-sensitivity phase / birefringence interferometry is realized. And the dynamic speckle statistics is used for measuring blood flow distribution for switching. According to the two modes, a homologous illumination light path and a shared core detection light path are used, it is ensured that after the modes are switched, the same area of a biological sample is imaged, image registration errors which are difficult to overcome in traditional subsystem imaging are eliminated, fine structure information and microcirculation hemodynamic information of tissue are synchronously obtained, and the imaging accuracy is improved. And a co-location and real-time imaging means is provided for researching space-time correlation between tissue microstructure change and local hemodynamic change.

Description

Technical Field

[0001] This application relates to biomedical monitoring systems, and more particularly to a multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues. Background Technology

[0002] Biological tissues (such as collagen-rich tendons, cornea, nerve fiber layers, and cartilage) possess inherent birefringence properties, stemming from the regular arrangement of their internal microstructures. Measuring birefringence provides crucial structural and functional information: quantitative analysis of collagen arrangement, density, and pathological changes, such as corneal scarring, tendon degeneration, osteoarthritis-related cartilage degeneration, and matrix destruction caused by tumor invasion. Furthermore, birefringence is related to tissue stiffness and can be used to assess biomechanical properties; for example, thinning of the retinal nerve fiber layer in glaucoma leads to altered birefringence patterns, making birefringence measurement an important parameter for assessing ophthalmic diseases. Monitoring tissue microcirculation is crucial for physiological and pathological research, such as in neuroscience for studying brain function (neurovascular coupling), ischemic stroke, and brain injury; in cardiovascular medicine for assessing myocardial perfusion and peripheral vascular disease; in tumors for monitoring tumor angiogenesis and treatment response; and in wound healing for assessing tissue survival and regenerative potential.

[0003] Developing an optical system capable of co-positioning and real-time measurement of tissue birefringence and blood flow allows for direct observation of how changes in microstructure (collagen arrangement / density alterations) instantly affect local microcirculation (blood flow velocity / perfusion), and vice versa. This is crucial for understanding fundamental biological processes such as neurovascular coupling, tissue damage / repair mechanisms (e.g., collagen deposition and angiogenesis during wound healing), and tumor matrix-vascular interactions. In improving the accuracy of disease diagnosis and monitoring, combining these two parameters provides a more comprehensive "panoramic view" of tissue status. For example, in cerebral ischemia, simultaneously observing the integrity of nerve fiber structure (birefringence) and blood flow occlusion / recovery allows for a more accurate assessment of the extent of damage and prognosis. In ophthalmology (e.g., glaucoma), combining retinal nerve fiber layer structure (birefringence) and optic disc blood flow information can significantly improve early diagnosis and progression monitoring capabilities. In osteoarthritis, simultaneously assessing cartilage matrix destruction (decreased birefringence) and subchondral bone blood flow abnormalities provides a deeper understanding of disease progression. Summary of the Invention

[0004] The purpose of this application is to provide a multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues, thereby solving the problem that current optical instruments can only measure a single parameter.

[0005] The embodiments of this application are implemented as follows:

[0006] In a first aspect, this application provides a multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues, including a laser for generating initial linearly polarized light;

[0007] A polarization angle scanner is used to change the polarization angle of the initially linearly polarized light;

[0008] A beam splitter is used to split the beam adjusted by the polarization angle scanner into an object beam that is emitted toward the target and a reference beam that is emitted in another direction.

[0009] An optical shutter, which includes an optical shutter and control circuitry, is used to control the on / off state of the reference light.

[0010] A beam expander is used to expand an object beam into a spherical wave beam.

[0011] An imaging lens group is used to collect photons scattered by the object under test and to image the object under test.

[0012] An aperture stop includes two light-passing holes: a central hole for adjusting the spatial frequency of the object light imaging, and a side hole for adjusting the carrier frequency of the reference light based on its relative position to the central hole. The camera is used to receive the image of the target being measured and the reference light.

[0013] This application provides a multimodal co-position measurement system for detecting birefringence and blood flow in biological tissues. When the optical shield is open, the reference beam can illuminate the CCD camera, forming a speckle interferometry system with the object beam, and the system operates in birefringence measurement mode. When the reference beam is blocked, the system has no reference beam, and the object beam illuminates the surface of the object being measured, and the system operates in speckle imaging blood flow monitoring mode. The system integrates two technologies—speckle interferometry for measuring tissue birefringence and speckle contrast imaging for measuring micro-blood flow distribution—into a single optical platform. By precisely controlling the opening and closing of the reference optical path, the system can quickly, stably, and without mechanical movement switch between "birefringence measurement mode" (reference beam on, achieving high-sensitivity phase / polarization state interferometry) and "blood flow measurement mode" (reference beam off, utilizing dynamic speckle statistical characteristics). This solves the problems of complex and time-consuming switching or the need for beam splitting to reduce the signal-to-noise ratio in traditional multimodal systems.

[0014] It is understood that this application discloses a multimodal co-location measurement method for birefringence and blood flow detection in biological tissues, which can perform co-location imaging of birefringence and blood flow distribution in biological tissues. The birefringence measurement system determines the azimuth angle of the birefringence optical axis by interferometric light intensity, and, combined with a space carrier method or a four-step phase-shifting method, can obtain the full-field birefringence distribution of the birefringence target. When the optical shutter blocks the reference light, the system uses the existing illumination and imaging system to perform speckle imaging on the tissue, and through the time-varying characteristics of the dynamic speckle pattern, calculates the local speckle contrast, mapping the spatial distribution of the contrast value to a spatial distribution map of the relative blood flow velocity. In the scattering polarization analysis system for infrastructure detection and monitoring described in any of the first aspects above, this method includes steps S1 to S3. Here, S1, S2, etc., are merely step identifiers, and the execution order of the method does not necessarily follow an ascending numerical order; for example, step S3 can be executed first, followed by step S2. This application does not impose any restrictions.

[0015] S1, Select the working mode of the synthesis system. When the optical shutter passes through the reference light, it is laser speckle interference biological tissue birefringence measurement mode A. When the optical shutter blocks the reference light, it is blood flow monitoring mode B.

[0016] S2, Select working mode A, adjust the linear polarization direction of the laser beam within a preset range by unit angle using the polarization controller, and obtain the phase difference of the birefringence orthogonal direction based on the polarization interference image;

[0017] S3, select working mode B, continuously acquire speckle images of the tissue being tested, and calculate blood flow through speckle contrast.

[0018] Beneficial effects

[0019] This application provides a multimodal co-location measurement system for birefringence and blood flow detection in biological tissues, capable of operating in both birefringence and blood flow distribution detection modes. Both modes utilize a common illumination optical path and a shared core probe optical path, ensuring imaging of the same region of the biological sample after mode switching. This eliminates image registration errors that are difficult to overcome in traditional subsystem imaging, and simultaneously acquires fine structural information of the tissue (such as collagen fiber orientation, density changes, and tissue hardening caused by lesions) and microcirculatory hemodynamic information (such as blood flow velocity, perfusion volume, and vascular density). This provides an unprecedented co-location, real-time imaging method for studying the spatiotemporal correlation between changes in tissue microstructure and local hemodynamic changes. The combination of dual-modal information can potentially be used in surgery to distinguish tumor boundaries (tissue stiffness changes) and identify key vascular structures (blood flow information) in real time, improving surgical accuracy and safety, representing an important innovative direction in the development of biomedical optical imaging instruments. Attached Figure Description

[0020] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of a multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues, provided in this application.

[0022] Figure 2 This is a schematic diagram of the multimodal co-location measurement method for biological tissue birefringence and blood flow monitoring provided in this application. Detailed Implementation

[0023] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0024] Firstly, such as Figure 1 As shown, this application provides a multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues, comprising: a laser 1, a beam splitter 2, a polarization angle scanner 3, a beam expander 4, a test object 5, an optical shutter 6, an optical fiber 7, an imaging lens 8, an aperture 9, an area array detector 10, and a data processor 11. A multimodal co-location measurement method for detecting birefringence and blood flow in biological tissues provided in this application will be described in parallel during the system introduction. Those skilled in the art can understand the execution method by understanding the system configuration.

[0025] First, the optical shutter 6 controls the object to be blocked by an electrical signal. When it is in the light-passing mode, the system operates under the birefringence measurement mechanism.

[0026] Measurement steps:

[0027] Polarization modulation is first performed by driving the polarization controller to rotate 1° in a single step to adjust the polarization angle of the object light by 2°. The polarization angle ranges from 0 to 180°, and 181 speckle images are collected.

[0028] Determine the azimuth angle of the optical axis. Define the polarization angle corresponding to the maximum interference light intensity as the principal axis direction of birefringence, i.e., the o-ray direction, and define its orthogonal direction as the e-ray direction.

[0029] Calculate the phase difference in orthogonal polarization directions. Using space carrier phase extraction technology, firstly, the interferogram along the principal axis is transformed in the frequency domain to extract high-frequency terms and calculate the phase; secondly, the phase in the orthogonal polarization directions is calculated; finally, phase subtraction is performed to obtain the phase difference map.

[0030] Image processing. Phase filtering is applied to the phase difference map, phase unwrapping is performed on the filtered image, and the birefringence phase delay is calculated.

[0031] The following is a theoretical explanation of the above measurement steps:

[0032] First, in the collected speckle pattern, select the speckle pattern at the maximum interference intensity, i.e., the o-light direction. Assume the object light wavefront is n1 and the reference light wavefront is n2. ox and f oy Let represent the spatial carrier frequencies introduced along the x-axis and y-axis, respectively. The intensity of the speckle interferogram along the fast axis can be expressed as:

[0033]

[0034] Taking a Fourier transform of the above equation, we get:

[0035]

[0036] The above formula contains three basic pieces of information, among which the first term F(|n1|) 2 +|n2| 2 The low-frequency components characterizing the background light intensity are the last two terms |n2|n1(f x -f ox f y -f oy )and This constitutes high-frequency components containing phase modulation information. Through the carrier frequency f... o The introduction of this method enables frequency domain separation of the low-frequency basis and high-frequency phase components in the spectral space. The high-frequency terms are selected for inverse Fourier transform, ultimately yielding the phase distribution:

[0037]

[0038] Similarly, by selecting the intensity diagram of the minimum interference intensity, i.e., the e-ray direction, we can obtain the phase information φ′ along the slow axis. Then, by subtracting the phases along the fast and slow axes, we obtain the phase difference diagram. The phase delay introduced by full-field birefringence can then be calculated.

[0039]

[0040] This is used to obtain birefringence information of biological tissues.

[0041] The optical shutter 6 controls the object to be shaded via electrical signals. When it operates in shading mode, when laser light irradiates the surface of biological tissue, it induces varying degrees of backscattered light, which randomly interferes in the air, forming speckle patterns. The movement of the scattering particles causes changes in speckle intensity, thus reducing the contrast of the speckle image. This effect is described using speckle contrast. By analyzing and calculating the speckle contrast, the velocity changes of red blood cells in the blood can be obtained, thereby determining the perfusion level of blood flow in the vessels.

[0042] Contrast ratio is defined as the ratio of the standard deviation to the mean of the speckle intensity:

[0043]

[0044] Where K represents the contrast, σ represents the standard deviation of the speckle intensity, and I is the mean of the speckle intensity.

[0045] Ideally, the contrast value changes dynamically within the range of 0 to 1. When the speckle image is free of blurring and fully developed (without dynamic scatterers), the contrast value will approach 1. If dynamic scattering exists in the image, the increased speed of the scattering particles will lead to a greater blurring of the speckle pattern, resulting in a more uniform light intensity distribution. When the average light intensity remains stable, the contrast value will approach 0.

[0046] Taking the Lorentz velocity distribution model as an example, the contrast K is expressed using the camera exposure time T and the time-dependent τ. c To indicate:

[0047]

[0048] Here, β is a system factor, which is related to the polarization of the light source and the speckle size. To quantify blood flow velocity, the concept of the Blood Flow Index (BFI) is introduced. It is generally considered that the flow velocity υ and the decorrelation time τ... c There is an inverse proportional relationship between them, and x = T / τ c As the object of the comparison degree calculation, the approximate solution is:

[0049] x = 1 / K 2

[0050] That is, blood flow velocity and K 2 Inversely proportional, that is:

[0051] BFI = 1 / K 2

[0052] The Absorbed Blood Flow Index (ABFI) is used to characterize changes in the blood flow index. A contrast image refers to a BFI value image obtained by contrast analysis of a speckle image. The distribution of blood flow can be visually observed through the BFI image.

[0053] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element. Furthermore, components, features, and elements with the same names in different embodiments of this application may have the same meaning or different meanings, the specific meaning of which must be determined by its interpretation in that specific embodiment or further in conjunction with the context of that specific embodiment.

[0054] The above description is merely an optional embodiment of this application and an explanation of the technical principles employed. Those skilled in the art should understand that the scope of the invention involved in this application is not limited to technical solutions formed by specific combinations of the above-described technical features, but should also cover other technical solutions formed by arbitrary combinations of the above-described technical features or their equivalents without departing from the above-described inventive concept. For example, technical solutions formed by substituting the above-described features with (but not limited to) technical features with similar functions disclosed in this application.

[0055] The above description is merely an optional embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues, characterized in that, include A laser used to generate initially linearly polarized light; A polarization angle scanner is used to change the polarization angle of the initially linearly polarized light; A beam splitter is used to split the beam adjusted by the polarization angle scanner into an object beam that is emitted toward the target and a reference beam that is emitted in another direction. Optical masker, used to control the on / off state of the reference light; A beam expander is used to expand an object beam into a spherical wave beam. An imaging lens group is used to collect photons scattered by the object under test and to image the object under test. An aperture stop includes two light-passing holes: a central hole for adjusting the imaging spatial frequency of the object light, and a side hole for adjusting the carrier frequency of the reference light, with the relative position of the side hole to the central hole. The camera is used to receive the image of the target being measured and the reference light.

2. The multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues according to claim 1, characterized in that, The polarization angle scanner includes a half-wave plate and a mechanism for driving the half-wave plate to rotate.

3. The multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues according to claim 1, characterized in that, The light shutter includes the light shutter and control circuitry.

4. A multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues according to claims 1 to 3, characterized in that, When the light shield is on, the system operates in birefringence measurement mode; when the reference light is blocked, the system operates in speckle imaging blood flow monitoring mode.

5. A multimodal co-location measurement method for detecting birefringence and blood flow in biological tissues, applied to the multimodal co-location measurement system for detecting birefringence and blood flow in biological tissues as described in any one of claims 1 to 4, characterized in that, Includes the following steps: S1, Select the working mode of the synthesis system. When the optical shutter passes through the reference light, it is laser speckle interference biological tissue birefringence measurement mode A. When the optical shutter blocks the reference light, it is blood flow monitoring mode B. S2, Select working mode A, adjust the linear polarization direction of the laser beam by unit angle within the preset range through the polarization controller, and obtain the phase difference of the birefringence orthogonal direction based on the polarization interference image; S3, select working mode B, continuously acquire the image to be measured, and calculate blood flow through speckle ratio.

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