A method for simultaneously measuring tissue optical parameters and blood flow information

Abstract

The present invention discloses a method for simultaneously measuring tissue optical parameters and blood flow information, the method comprising: obtaining the effective attenuation coefficient of tissue based on speckle images at different light source-detector distances; establishing an objective function for simultaneously solving multiple parameters based on the effective attenuation coefficient and the diffuse speckle contrast at different exposure times and different light source-detector distances. The global minimum value of the objective function is obtained based on an optimization solution algorithm, thereby achieving simultaneous acquisition of tissue optical parameters and blood flow information. The present invention provides a new technical approach for comprehensively describing the hemodynamic and metabolic characteristics of tissues.

Description

Technical Field

[0001] The invention belongs to the technical field of multi-parameter measurement, and in particular to a method for simultaneously measuring tissue optical parameters and blood flow information. Background Art

[0002] Blood vessels with diameters ranging from a few micrometers to more than ten millimeters are distributed throughout the human body. Any problem with a blood vessel can induce the occurrence of disease. Compared with traditional imaging methods, optical imaging technology plays an increasingly important role in tissue blood flow monitoring due to its simplicity and non-invasiveness. The currently commonly used laser speckle contrast imaging (Richards LM, Kazmi SS, Olin KE, Waldron JS, Fox DJ, Dunn A K. Intraoperative multi-exposurespeckle imaging of cerebral blood flow[J]. Journal of Cerebral Blood Flow&Metabolism, 2017, 37(9): 271678X16686987) has the advantages of high temporal and spatial resolution, simple system and full-field imaging. It is widely used in various tissues for blood flow monitoring and disease assessment, but its imaging characteristics limit the penetration depth of light in the tissue and are still limited to imaging the surface of the tissue.

[0003] Diffuse speckle contrast analysis (Bi R, Dong J and Lee K. Deep tissue flowmetry basedon diffuse speckle contrast analysis [J]. Optics Letters, 2013, 38(9): 1401-1403) is a new technology developed in recent years for measuring blood flow in deep tissues. This method has certain similarities with diffusion correlation spectroscopy technology, both of which use near-infrared light as a measurement method. The difference is that diffuse speckle contrast analysis uses a combination of CCD camera and imaging lens to achieve large-area, high-resolution rapid imaging, and calculates the diffusion movement of red blood cells inside the tissue through the diffuse speckle contrast. The applicant previously established a quantitative diffuse speckle contrast model and its linear approximate model (Liu J, Zhang H, Lu J, Ni X, Shen Z. Quantitative model of diffuse speckle contrast analysis for flow measurement[J]. Journal of Biomedical Optics, 2017, 8(10): 076016), describing the functional relationship between diffuse speckle contrast and multiple parameters such as tissue blood flow and optical parameters. The applicant also used the functional relationship between diffuse speckle contrast and the light source-detector distance and exposure time to achieve simultaneous measurement of multiple parameters of tissue (Liu J, Zhang H, Lu J, Ni X, Shen Z. Simultaneously extracting multiple parameters via multi-distance and multi-exposure diffuse speckle contrast analysis[J]. Biomedical Optics Express, 2017, 8(10): 4537-4550). At the same time, the signal-to-noise ratio of the speckle image will decrease with the increase of the light source-detector distance, and the sensitivity of the speckle contrast to each parameter will also decrease accordingly. However, the error disturbance caused by noise may cause changes in the solutions of multiple parameters, making the existing solution method unstable, especially the absorption coefficient, which is easily affected by noise, has poor solution stability, and is limited to a smaller light source-detector distance range (less than 1 cm).

[0004] Therefore, how to further increase the light source-detector and exposure time range and improve the accuracy and stability of multi-parameter measurement results is an urgent problem to be solved. Summary of the invention

[0005] The purpose of the present invention is to provide a method for simultaneously measuring tissue optical parameters and blood flow information in order to solve the problems existing in the above-mentioned prior art.

[0006] The technical solution to achieve the purpose of the present invention is: on the one hand, a method for simultaneously measuring tissue optical parameters and blood flow information is provided, the method comprising:

[0007] Step 1, obtaining diffuse speckle images at different exposure times;

[0008] Step 2, obtaining the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances;

[0009] Step 3: Based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, an optimization solution method is used to simultaneously obtain the optical parameters and blood flow information of the tissue.

[0010] Furthermore, the diffuse speckle image in step 1 is expressed as , is the exposure time of the i-th camera, , N is the total number of exposure times, Exposure time The jth image obtained under , M is the number of images collected at each exposure time, Represents different light source-detector distances, , is the minimum source-detector distance, is the maximum source-detector distance.

[0011] Furthermore, the step 2 of obtaining the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances specifically includes:

[0012] Step 2-1: Change the exposure time M diffuse speckle images under Sum and normalize to get the image ;

[0013] Step 2-2, based on the diffusion approximation theory, using different light source-detector distances Image , the effective attenuation coefficient of tissue is obtained by linear fitting method , the calculation formula is:

[0014] ;

[0015] In the formula, is the intercept, which is the distance between the source and the detector No matter, Exposure time The effective attenuation coefficient of tissue measured under

[0016] Step 2-3, repeat steps 2-1 to 2-2 to obtain N exposure times. The measured values ​​are averaged to obtain the effective attenuation coefficient of tissue .

[0017] Furthermore, in step 3, based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, an optimization solution method is used to simultaneously obtain the optical parameters and blood flow information of the tissue, which specifically includes:

[0018] Step 3-1: Change the exposure time M diffuse speckle images under Calculate the time contrast value to obtain the time contrast image , the calculation formula is:

[0019] ;

[0020] In the formula, is M speckle images The average image is calculated as:

[0021] ;

[0022] Step 3-2, repeat step 3-1 to obtain time contrast images at N exposure times , ;

[0023] Step 3-3, based on the time contrast image and tissue effective attenuation coefficient obtained in the above process, establish an objective function for simultaneously acquiring tissue optical parameters and blood flow information :

[0024] ;

[0025] In the formula, is the theoretical calculated value of diffuse speckle contrast, including blood flow information. is a constant factor, , represents the weight ratio of the effective attenuation coefficient in the objective function; and are tissue optical parameters, which are the reduced scattering coefficient and absorption coefficient respectively;

[0026] Step 3-4, for the objective function An optimization solution is performed to obtain the global minimum, thereby simultaneously obtaining the optical parameters and blood flow information of the tissue.

[0027] Furthermore, the theoretical calculated value of the diffuse speckle contrast ratio is It is expressed as:

[0028] ;

[0029] in,

[0030] ;

[0031] In the formula, , is a constant factor, is a constant factor, , is the light wave number, For blood flow information.

[0032] On the other hand, a device for simultaneously measuring tissue optical parameters and blood flow information is provided, the device comprising:

[0033] The first module is used to obtain diffuse speckle images at different exposure times;

[0034] The second module is used to obtain the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances;

[0035] The third module is used to simultaneously obtain the optical parameters and blood flow information of the tissue by using an optimization solution method based on the effective attenuation coefficient and the diffuse speckle images at different exposure times.

[0036] On the other hand, a computer device is provided, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor implements the method for simultaneously measuring tissue optical parameters and blood flow information when executing the computer program.

[0037] On the other hand, a computer-readable storage medium is provided, on which a computer program is stored. When the computer program is executed by a processor, the method for simultaneously measuring tissue optical parameters and blood flow information is implemented.

[0038] Compared with the prior art, the present invention has the following significant advantages:

[0039] (1) The present invention provides a new technical approach for comprehensively describing the hemodynamic and metabolic characteristics of tissues.

[0040] (2) The present invention uses the functional relationship between diffuse speckle contrast and the light source-detector distance and exposure time, combined with the diffusion approximation theory, to establish a cost function for multi-parameter measurement, which can reduce the space where multi-parameter solutions exist during the multi-parameter inversion process and realize the simultaneous measurement of tissue multi-parameters. Compared with the existing methods, the present invention can achieve large-area, high-resolution rapid imaging. The combination of "multi-distance" and "multi-exposure" can obtain a wider range of diffuse speckle contrast measurement values. At the same time, combined with the effective attenuation coefficient of the tissue, it can further reduce the space where multi-parameter solutions exist during the multi-parameter inversion calculation process, and improve the accuracy and stability of the multi-parameter measurement results.

[0041] (3) The present invention proposes a quantitative tissue multi-parameter simultaneous measurement method with wide applicability and high stability. The wide applicability is reflected in that it is not limited to a small light source-detector range and has a wide range of applicable media; the high stability is reflected in that the coupling relationship between parameters can be quickly removed during the inversion calculation process, thereby realizing the simultaneous measurement of tissue multi-parameters.

[0042] The present invention is further described in detail below in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 This is a flow chart of the method for simultaneously measuring tissue optical parameters and blood flow information of the present invention.

[0044] Figure 2 It is a schematic diagram of a diffuse speckle contrast imaging device for simultaneously acquiring tissue optical parameters and blood flow information in one embodiment.

[0045] Figure 3 is a contour plot of a relevant objective function in one embodiment, wherein Figure 3 (a) is the contour map of the objective function when the reduced scattering coefficient remains unchanged. Figure 3 (b) in the figure is the contour plot of the objective function when the absorption coefficient remains unchanged.

[0046] Figure 4 A process diagram for solving the global extreme value of the objective function in one embodiment. DETAILED DESCRIPTION

[0047] In order to make the purpose, technical solution and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0048] It should be noted that if there are descriptions involving "first", "second", etc. in the embodiments of the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In addition, the technical solutions between the various embodiments can be combined with each other, but they must be based on the ability of ordinary technicians in the field to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0049] In one embodiment, in combination Figure 1 , provides a method for simultaneously measuring tissue optical parameters and blood flow information, the method comprising:

[0050] Step 1: Obtain diffuse speckle images at different exposure times , For the i The camera exposure time, , N is the total exposure time, Exposure time Get the following j images, , M is the number of images collected at each exposure time, Represents different light source-detector distances, , is the minimum source-detector distance, is the maximum source-detector distance;

[0051] In some embodiments, the number of different exposure times is set to N, where For the i The camera exposure time, i Less than or equal to N. Taking N=15 as an example, 15 different exposure times can be selected within the range of 0.1ms-10ms (taking this range as an example, the exposure time range can be expanded or reduced). They can be selected evenly or according to the non-uniformity of the blood flow parameter information of the sample to be tested (for example, 10 between 0.1ms-1ms and 5 within the range of 2ms-10ms).

[0052] The number of speckle images recorded at each exposure time is M (taking M=30 as an example), each speckle image has the same imaging field of view, and each pixel in each speckle image has a different distance from the light source. ρ .

[0053] Step 2, obtaining the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances;

[0054] Step 3: Based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, an optimization solution method is used to simultaneously obtain the optical parameters and blood flow information of the tissue.

[0055] In some embodiments, in combination Figure 2 , which is a schematic diagram of a diffuse speckle contrast imaging device for simultaneously acquiring tissue optical parameters and blood flow information, the device comprises a laser 01, a lens 02, a fiber coupler 03, a multimode optical fiber 04 and a tissue sample to be measured 05. The laser 01 is used to emit a laser beam, which enters the fiber coupler 03 after being focused and coupled by the lens 02, and irradiates the surface of the tissue sample 05 to be measured after passing through the multimode optical fiber 04.

[0056] Taking the phantom tissue as an example, the tissue sample to be tested is a mixed solution of fat emulsion and ink, which is used to simulate biological tissue fluid. The Brownian motion of the particles in the fat emulsion is used to simulate blood flow, the reduced scattering coefficient of the fat emulsion itself is the reduced scattering coefficient of the simulated biological tissue, and the absorption coefficient of the ink itself is the absorption coefficient of the simulated biological tissue. The backscattered photons from the simulated biological tissue are collected by the camera, and the imaging lens of the camera itself can control the imaging field of view of the camera and the size of the recorded speckle particles. The exposure time of the camera can be changed to obtain speckle images under different exposure times.

[0057] Further, in one embodiment, the step 2 of obtaining the tissue effective attenuation coefficient based on the diffuse speckle images at different light source-detector distances specifically includes:

[0058] Step 2-1: Change the exposure time Next M Diffuse Speckle Image Sum and normalize to get the image ;

[0059] Step 2-2, based on the diffusion approximation theory, using different light source-detector distances Image , the effective attenuation coefficient of tissue is obtained by linear fitting method , the calculation formula is:

[0060] ;

[0061] In the formula, is the intercept, which is the distance between the source and the detector No matter, Exposure time The effective attenuation coefficient of tissue measured under

[0062] Step 2-3, repeat steps 2-1 to 2-2 to obtain N exposure time Measured values ​​and N The effective attenuation coefficient of tissue is obtained by averaging the measured values. .

[0063] Further, in one embodiment, step 3, based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, using an optimization solution method to simultaneously obtain the optical parameters and blood flow information of the tissue specifically includes:

[0064] Step 3-1: Change the exposure time Next M Diffuse Speckle Image Calculate the time contrast value to obtain the time contrast image , the calculation formula is:

[0065] ;

[0066] In the formula, for M Speckle image The average image is calculated as:

[0067] ;

[0068] Step 3-2, repeat step 3-1 to obtain N Time contrast image at exposure time, ;

[0069] Step 3-3, based on the time contrast image and tissue effective attenuation coefficient obtained in the above process, establish an objective function for simultaneously acquiring tissue optical parameters and blood flow information :

[0070] ;

[0071] In the formula, is the theoretical calculated value of diffuse speckle contrast, including blood flow information. is a constant factor, , represents the weight ratio of the effective attenuation coefficient in the objective function; and are tissue optical parameters, which are the reduced scattering coefficient and absorption coefficient respectively;

[0072] Step 3-4, for the objective function An optimization solution is performed to obtain the global minimum, thereby simultaneously obtaining the optical parameters and blood flow information of the tissue.

[0073] Here, in some embodiments, the theoretical calculated value of the diffuse speckle contrast is It is expressed as:

[0074] ;

[0075] in,

[0076] ;

[0077] In the formula, , is a constant factor, is a constant factor, , is the light wave number, For blood flow information.

[0078] Here, the problem of simultaneous measurement of multiple parameters is essentially to solve the global extreme value problem of the objective function. The entire solution calculation process is as follows: Figure 4 As shown. Currently, the commonly used nonlinear optimization algorithms are mainly divided into two categories, one is the need to use the derivative of the cost function, and the other is the direct method. The derivative optimization method has the advantage of fast convergence speed. How to choose the search direction is the core of the optimization method using derivatives. Among them, the most commonly used are the steepest descent method, Newton method and quasi-Newton method, conjugate gradient method, etc. The disadvantage is that the calculation results are strongly dependent on the initial value. The direct method only uses the function value and only examines the relative advantages and disadvantages between the function values. Its convergence speed is slow. However, the direct method can solve problems that other algorithms cannot solve, and its unique search characteristics can avoid the defects of other algorithms.

[0079] The present invention utilizes the objective function expression to analyze the sensitivity of each parameter in the objective function and selects the variation interval of these parameters in the optimization inversion, thereby reducing the optimization search range and improving the calculation efficiency, thereby achieving accurate and stable measurement of tissue optical parameters and blood flow information.

[0080] In one embodiment, a device for simultaneously measuring tissue optical parameters and blood flow information is provided, the device comprising:

[0081] The first module is used to obtain diffuse speckle images at different exposure times;

[0082] The second module is used to obtain the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances;

[0083] The third module is used to simultaneously obtain the optical parameters and blood flow information of the tissue by using an optimization solution method based on the effective attenuation coefficient and the diffuse speckle images at different exposure times.

[0084] For the specific definition of the device for simultaneous measurement of tissue optical parameters and blood flow information, please refer to the definition of the method for simultaneous measurement of tissue optical parameters and blood flow information in the above text, which will not be repeated here. Each module in the above-mentioned device for simultaneous measurement of tissue optical parameters and blood flow information can be implemented in whole or in part by software, hardware and a combination thereof. The above-mentioned modules can be embedded in or independent of the processor in the computer device in the form of hardware, or can be stored in the memory of the computer device in the form of software, so that the processor can call and execute the operations corresponding to the above modules.

[0085] In one embodiment, a computer device is provided, including a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein when the processor executes the computer program, the following is achieved:

[0086] Step 1, obtaining diffuse speckle images at different exposure times;

[0087] Step 2, obtaining the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances;

[0088] Step 3: Based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, an optimization solution method is used to simultaneously obtain the optical parameters and blood flow information of the tissue.

[0089] For the specific limitations of each step, please refer to the limitations of the method for simultaneous measurement of tissue optical parameters and blood flow information in the above text, which will not be repeated here.

[0090] In one embodiment, a computer-readable storage medium is provided, on which a computer program is stored, and when the computer program is executed by a processor, the computer program implements:

[0091] Step 1, obtaining diffuse speckle images at different exposure times;

[0092] Step 2, obtaining the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances;

[0093] Step 3: Based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, an optimization solution method is used to simultaneously obtain the optical parameters and blood flow information of the tissue.

[0094] For the specific limitations of each step, please refer to the limitations of the method for simultaneous measurement of tissue optical parameters and blood flow information in the above text, which will not be repeated here.

[0095] As a specific example, in one of the embodiments, the present invention is further verified and explained in detail.

[0096] by , and For example, , the maximum and minimum light source-detector distance range is 1cm-2cm, and the exposure time is 0.1ms-10ms. The relevant objective function The contour map of Figure 3 As shown by Figure 3 It can be seen that the functional relationship between diffuse speckle contrast and light source-detector distance and exposure time can reduce the space where the target function solution exists. The effective attenuation coefficient can further reduce the space where the multi-parameter solution exists, and the target parameter value of the tissue can be accurately obtained.

[0097] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for simultaneously measuring tissue optical parameters and blood flow information, characterized in that: The method comprises: Step 1, obtaining diffuse speckle images at different exposure times; Step 2, based on the diffuse speckle images at different light source-detector distances, obtain the effective attenuation coefficient of the tissue; specifically including: Step 2-1: Change the exposure time M diffuse speckle images under Sum and normalize to get the image ; Step 2-2, based on the diffusion approximation theory, using different light source-detector distances Image , the effective attenuation coefficient of tissue is obtained by linear fitting method , the calculation formula is: ； In the formula, is the intercept, which is the distance between the source and the detector No matter, Exposure time The effective attenuation coefficient of tissue measured under Step 2-3, repeat steps 2-1 to 2-2 to obtain N exposure times. The measured values ​​are averaged to obtain the effective attenuation coefficient of tissue ; Step 3: Based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, an optimization solution method is used to simultaneously obtain the optical parameters and blood flow information of the tissue.

2. The method for simultaneously measuring tissue optical parameters and blood flow information according to claim 1, characterized in that: The diffuse speckle image in step 1 is expressed as , is the exposure time of the i-th camera, , N is the total number of exposure times, Exposure time The jth image obtained under , M is the number of images collected at each exposure time, Represents different light source-detector distances, , is the minimum source-detector distance, is the maximum source-detector distance.

3. The method for simultaneously measuring tissue optical parameters and blood flow information according to claim 1, characterized in that: The step 3, based on the effective attenuation coefficient and the diffuse speckle images at different exposure times, uses an optimization solution method to simultaneously obtain the optical parameters and blood flow information of the tissue, specifically including: Step 3-1: Change the exposure time M diffuse speckle images under Calculate the time contrast value to obtain the time contrast image , the calculation formula is: ； In the formula, is M speckle images The average image is calculated as: ； Step 3-2, repeat step 3-1 to obtain time contrast images at N exposure times , ; Step 3-3, based on the time contrast image and tissue effective attenuation coefficient obtained in the above process, establish an objective function for simultaneously acquiring tissue optical parameters and blood flow information : ； In the formula, is the theoretical calculated value of diffuse speckle contrast, including blood flow information. is a constant factor, , represents the weight ratio of the effective attenuation coefficient in the objective function; and are tissue optical parameters, which are the reduced scattering coefficient and absorption coefficient respectively; Step 3-4, for the objective function An optimization solution is performed to obtain the global minimum, thereby simultaneously obtaining the optical parameters and blood flow information of the tissue.

4. The method for simultaneously measuring tissue optical parameters and blood flow information according to claim 3, characterized in that: The theoretical calculation value of the diffuse speckle contrast It is expressed as: ； in, ； In the formula, , is a constant factor, is a constant factor, , is the light wave number, For blood flow information.

5. A device for simultaneously measuring tissue optical parameters and blood flow information based on the method according to any one of claims 1 to 4, characterized in that: The device comprises: The first module is used to obtain diffuse speckle images at different exposure times; The second module is used to obtain the effective attenuation coefficient of the tissue based on the diffuse speckle images at different light source-detector distances; The third module is used to simultaneously obtain the optical parameters and blood flow information of the tissue by using an optimization solution method based on the effective attenuation coefficient and the diffuse speckle images at different exposure times.

6. A computer device comprising a memory, a processor and a computer program stored in the memory and executable on the processor, characterized in that: When the processor executes the computer program, the method according to any one of claims 1 to 4 is implemented.

7. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the method according to any one of claims 1 to 4 is implemented.

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