A method and system for monitoring deep tissue oxygen tension

Abstract

The application discloses a deep tissue oxygen partial pressure monitoring method and system, and relates to the technical field of oxygen partial pressure monitoring.The method comprises the following steps: adding a coupling probe into deep tissue; exciting the coupling probe in the deep tissue by using an X-ray source to make the coupling probe emit specific spectrum fluorescent light, collecting a fluorescent image of the specific spectrum fluorescent light, irradiating a deep tissue sample by using an external light source, and collecting a white light image of the deep tissue every certain angle; converting each white light image into a binary image; performing three-dimensional reconstruction on the converted binary image, and constructing a three-dimensional surface profile of the deep tissue; uniformly selecting sampling points from the three-dimensional surface profile, mapping the fluorescent image to the three-dimensional surface profile of the deep tissue according to the structural relationship between the fluorescent image and the three-dimensional surface profile, and obtaining three-dimensional light intensity distribution of the coupling probe; and obtaining three-dimensional partial pressure of the deep tissue according to the three-dimensional light intensity distribution and a Stern-Volmer equation, so that rapid and convenient monitoring of the oxygen partial pressure of the deep tissue is realized.

Description

Technical Field

[0001] This invention relates to the field of oxygen partial pressure monitoring technology, specifically to a method and system for monitoring oxygen partial pressure in deep tissues. Background Technology

[0002] The partial pressure of oxygen in deep tissues is an important indicator for assessing whether tissues are hypoxic and thus determining their condition.

[0003] Currently, common methods for monitoring oxygen partial pressure include oxygen electrode method, magnetic resonance imaging (MRI), photoacoustic imaging, and optical imaging. Among these, the oxygen electrode method is invasive, unsuitable for real-time monitoring, and has limited detection depth; MRI is time-consuming and expensive; photoacoustic imaging indirectly assesses tissue hypoxia by evaluating blood oxygen saturation, but cannot accurately and quickly visualize tissue oxygen partial pressure. In invention patent CN101788477B, oxygen partial pressure monitoring is achieved through an oxygen partial pressure monitor, which is invasive and can cause damage to the monitored object; in patent CN 116718574A, this method is applied to oxygen partial pressure in extracorporeal circulation tubing, but can only obtain a single value of oxygen partial pressure in the tubing, making it difficult to obtain three-dimensional distribution data of oxygen partial pressure.

[0004] In summary, current oxygen partial pressure monitoring methods can only obtain a single value of oxygen partial pressure, making it difficult to monitor the three-dimensional oxygen partial pressure in deep tissues. Summary of the Invention

[0005] To address the shortcomings of existing technologies in monitoring three-dimensional oxygen partial pressure within deep tissues, this invention proposes a method and system for monitoring oxygen partial pressure in deep tissues. By using single-view fluorescence molecule reconstruction technology, the three-dimensional fluorescence intensity distribution within the tissue is obtained, thereby enabling rapid and convenient monitoring of oxygen partial pressure in deep tissues, thus solving the problems existing in the prior art.

[0006] A method for monitoring oxygen partial pressure in deep tissues includes the following steps:

[0007] A coupling probe was synthesized using X-ray luminescent materials and oxygen-sensitive materials. The coupling probe was placed inside a deep tissue sample. An X-ray source was used to excite the coupling probe inside the deep tissue sample to emit fluorescence in a specific spectral band. Fluorescence images of the specific spectral band emitted from multiple angles of the deep tissue sample were collected.

[0008] With the X-ray source turned off, the deep tissue sample was irradiated with an external light source, and white light images of the deep tissue sample were acquired from multiple angles to construct a three-dimensional surface contour of the deep tissue. Sampling points were uniformly selected from the three-dimensional surface contour, and the difference between the fluorescence value of the sampling point and the fluorescence value of the fluorescence image was calculated based on the structural relationship between the fluorescence image and the three-dimensional surface contour. Based on this difference, the fluorescence image was mapped onto the three-dimensional surface contour of the deep tissue to obtain the three-dimensional light intensity distribution of the coupled probe.

[0009] The three-dimensional oxygen partial pressure of deep tissues was obtained based on the three-dimensional light intensity distribution of the coupling probe.

[0010] Furthermore, an electron multiplier charge-coupled device (EMCCD) was used to acquire fluorescence images of specific spectral bands.

[0011] Furthermore, the step of illuminating the deep tissue sample with an external light source and acquiring white light images of the deep tissue sample from multiple angles to construct a three-dimensional surface contour of the deep tissue specifically includes the following steps:

[0012] Using an external light source, a white light image of a deep tissue sample is acquired at regular intervals until a 360-degree rotation is completed.

[0013] A threshold segmentation algorithm is used to convert each white light image into a binary image;

[0014] The transformed binary image is input into a filtered back projection algorithm for 3D reconstruction, thereby constructing the 3D surface contour of deep tissues.

[0015] Furthermore, the three-dimensional light intensity distribution of the coupled probe is obtained by using a fusion group sparse prior and depth compensation method, specifically including the following steps:

[0016]

[0017] Where Φ is the fluorescence value mapped onto the surface, Y is the three-dimensional light intensity distribution, and W is the system matrix. d and W m Both are depth compensation matrices, λ1 and λ2 are regularization parameters, and R is constructed as follows:

[0018]

[0019] Where i and j represent the row number and column number of the voxel, respectively;

[0020] Depth compensation matrix W d and W m They are represented as follows:

[0021]

[0022] in The matrix represents an initial distribution of the probes, and q represents the weights.

[0023]

[0024] Among them, W j β represents the j-th column of the W matrix. j Let represent the weight of the j-th voxel, and n be the column number of W.

[0025] Furthermore, the three-dimensional oxygen partial pressure of the deep tissue is obtained based on the three-dimensional light intensity distribution of the coupling probe; specifically, the three-dimensional oxygen intensity distribution of the coupling probe is input into the parameter-calibrated Stern-Volmer equation to obtain the three-dimensional oxygen partial pressure of the deep tissue; the Stern-Volmer equation is expressed as:

[0026] Y0 / Y=1+k q pO2

[0027] Where Y0 represents the three-dimensional light intensity distribution when the nitrogen-to-oxygen ratio is 1:0; pO2 represents the oxygen partial pressure; and k q Let be a constant, and Y be the three-dimensional light intensity distribution.

[0028] Furthermore, the parameter calibration process for the Stern-Volmer equation includes the following steps:

[0029] Oxygen and nitrogen are introduced separately into a solution containing a coupling probe, and an oxygen electrode is inserted into the solution to measure the partial pressure of oxygen in the current solution.

[0030] Turn on the X-ray source, set the current and voltage parameters, and activate the electron multiplier charge coupler (EMCCD) to capture a fluorescence image; the sum of the fluorescence values ​​of all pixels in this image is the three-dimensional light intensity distribution Y corresponding to the current oxygen partial pressure;

[0031] After repeatedly changing the nitrogen and oxygen ratios, the three-dimensional light intensity distribution after each change was obtained. The Stern-Volmer equation was then fitted, and the constant k was calculated. q Numerical values ​​are used to complete the parameter calibration of the equation.

[0032] The present invention also includes a deep tissue oxygen partial pressure monitoring system, comprising:

[0033] A coupling probe is placed inside a deep tissue sample; the coupling probe is a coupling body of an X-ray luminescent material and an oxygen-sensitive probe.

[0034] An X-ray source is used to excite coupled probes within deep tissue samples to emit fluorescence in a specific spectral band.

[0035] Electron-multiplying charge-coupled device (EMCCD) is used to acquire fluorescence images of specific spectral bands emitted from multiple angles in deep tissue samples;

[0036] The 3D reconstruction module is used to shut down the X-ray source, irradiate deep tissue samples with an external light source, acquire white light images of the deep tissue samples from multiple angles, and construct the 3D surface contour of the deep tissue. Sampling points are uniformly selected from the 3D surface contour, and the difference between the fluorescence value of the sampling points and the fluorescence value of the fluorescence image is calculated based on the structural relationship between the fluorescence image and the 3D surface contour. Based on this difference, the fluorescence image is mapped onto the 3D surface contour of the deep tissue to obtain the 3D light intensity distribution of the coupled probe.

[0037] The oxygen partial pressure acquisition module is used to obtain the three-dimensional oxygen partial pressure of deep tissues based on the three-dimensional light intensity distribution of the coupled probe.

[0038] Furthermore, it also includes a rotating platform for placing the bottom of the deep tissue; the rotating platform is used to drive the deep tissue to rotate at an angle.

[0039] Furthermore, it also includes a filter placed at the EMCCD receiver; the filter is used to filter out fluorescence of a specific wavelength.

[0040] This invention provides a method and system for monitoring oxygen partial pressure in deep tissues, which has the following beneficial effects:

[0041] This invention synthesizes a coupling probe by selecting X-ray luminescent materials and oxygen-sensitive materials. The coupling probe is then added to a deep tissue sample, converting the X-rays reaching the deep tissue into fluorescence. This fluorescence then reacts with the oxygen-sensitive material coupled to the tissue, producing a fluorescence quenching effect, facilitating the generation of fluorescence images. Furthermore, by acquiring white light images of the deep tissue sample from each angle using an external light source, a three-dimensional surface contour of the deep tissue is constructed. Based on the structural relationship between the fluorescence image and the three-dimensional surface contour, the fluorescence image is mapped onto the three-dimensional surface contour of the deep tissue, thereby more conveniently obtaining the three-dimensional fluorescence intensity distribution within the tissue and achieving rapid monitoring of the oxygen partial pressure of deep tissue samples. Attached Figure Description

[0042] Figure 1 This is a framework diagram of the deep tissue oxygen partial pressure monitoring system in an embodiment of the present invention.

[0043] Figure 2 This is a flowchart of the deep tissue oxygen partial pressure monitoring method in an embodiment of the present invention.

[0044] In the diagram, 1-X-ray source; 2-monitoring object; 3-rotating stage; 4-coupled probe; 5-EMCCD; 6-filter; 7-computer. Detailed Implementation

[0045] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0046] This invention proposes a deep tissue oxygen partial pressure monitoring system, such as... Figure 1 As shown, it specifically includes: X-ray source 1, monitoring object 2, rotating stage 3, coupling probe 4, EMCCD 5 (electron multiplier charge-coupled device), filter 6, and computer 7.

[0047] X-ray source 1 is used to excite the coupling probe inside the monitored object; monitored object 2 is an excised deep tissue sample; rotating stage 3 is used to support the monitored object and achieve angular rotation; coupling probe 4 is a coupler between X-ray luminescent material and oxygen-sensitive probe, used to emit fluorescence under X-ray excitation, and the fluorescence undergoes a fluorescence quenching reaction under the action of oxygen-sensitive probe; EMCCD 5 is used to acquire the fluorescence emitted by the coupling probe and for optical three-dimensional reconstruction; filter 6 is used to filter out light of a specific wavelength; computer 7 is used to control other equipment, complete fluorescence three-dimensional reconstruction, and finally calculate and display tissue oxygen partial pressure.

[0048] Based on the above monitoring system, this invention also proposes a method for monitoring oxygen partial pressure in deep tissues, such as... Figure 2 As shown, the specific steps include:

[0049] S1. Coupling Probe Synthesis: Select suitable X-ray luminescent materials and oxygen-sensitive materials, and synthesize the coupling probe via co-precipitation. The synthesis of the coupling probe converts X-rays reaching deep tissues into fluorescence, which then reacts with the oxygen-sensitive material coupled to it, producing a fluorescence quenching effect.

[0050] S2. Preparation of the monitoring object: Place the monitoring object on the rotating stage and add a coupling probe to it; receive the fluorescence emitted by the probe for fluorescence image acquisition.

[0051] S3. Fluorescence Data Acquisition: Turn on the X-ray source, set parameters such as current and voltage, and use the excitation source to excite the coupled probe within the monitored object to emit fluorescence in a specific spectral band (e.g., 460nm). The oxygen-sensitive probe interacts with the fluorescence in the specific spectral band (e.g., 460nm), producing a quenching effect. A filter that allows light of the aforementioned specific wavelength (e.g., 460nm) to pass through is loaded in front of the lens. The EMCCD is turned on, relevant parameters are set, and a fluorescence image is acquired and saved. The fluorescence after X-ray emission and quenching is acquired for subsequent 3D reconstruction, parameter calibration, and oxygen partial pressure calculation.

[0052] S4. Construction of the 3D Contour of the Monitored Object: Turn off the X-ray source, turn on the external light source, remove the filter, and acquire and save a white light image of the monitored object at regular intervals until a 360-degree rotation is completed. For each white light image, convert it into a binary image using algorithms such as threshold segmentation. Reconstruct the 3D contour of the monitored object using a filtered back-projection algorithm. Perform 3D mapping on the acquired fluorescence images, that is, convert the 2D fluorescence values ​​onto the corresponding points on the 3D surface, preparing for subsequent fluorescence 3D reconstruction.

[0053] S5. Fluorescence 3D Reconstruction: The reconstructed 3D fluorescence intensity distribution within the tissue is the basis for calculating the oxygen partial pressure distribution. Sampling points are uniformly selected from the 3D contour, and the 3D light intensity distribution of the coupled probe is obtained using a fusion group sparse prior and depth compensation method. Specifically, this is achieved through the following optimization process:

[0054]

[0055] Where W is the system matrix, establishing the relationship between the three-dimensional light intensity distribution and the photon distribution on the surface, Φ is the fluorescence value mapped onto the surface, Y is the three-dimensional light intensity distribution, and W... d and W m Both are depth compensation matrices, with λ1 and λ2 being regularization parameters. The R structure is as follows:

[0056]

[0057] Where i and j represent the row and column numbers of the voxel, respectively; the depth compensation matrix W d and W m The construction method is as follows:

[0058]

[0059] in The matrix represents an initial distribution of the probes, and q represents the weights. W d It is used to weight the data, providing constraints for the optimization problem described above.

[0060]

[0061] Among them, W j β represents the j-th column of the W matrix. j Let represent the weight of the j-th voxel, and n be the column number of W. m It is used to balance the differences in the contribution of each voxel point of the imaged object to the surface photon intensity.

[0062] S6. Parameter Calibration: The physical properties of this coupling probe are measured experimentally to determine the constant parameters in the formula, providing the formulaic basis for the final oxygen partial pressure calculation. Oxygen and nitrogen are introduced separately into the solution containing the coupling probe, and the oxygen electrode is inserted into the solution to measure the current oxygen partial pressure. The X-ray source is turned on, the current and voltage parameters are set, and an EMCCD image is captured. The sum of the fluorescence values ​​of all pixels in this image is the fluorescence intensity corresponding to the current oxygen partial pressure (i.e., according to the Stern-Volmer equation Y0 / Y=1+k). qThe Y value in pO2. By changing the nitrogen-to-oxygen ratio (e.g., 1:0, 1:0.25, 1:0.75, 1:2, 0:1), a series of fluorescence intensities are obtained (the fluorescence intensity at a nitrogen-to-oxygen ratio of 1:0 is Y0). The Stern-Volmer equation is fitted, and the constant k is calculated. q Numerical values ​​are used to complete the equation calibration.

[0063] S7. Calculation of three-dimensional oxygen partial pressure: Calculate the three-dimensional oxygen partial pressure based on the three-dimensional light intensity distribution of the coupling probe obtained in step 5 and the equation calibrated in step S4.

[0064] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method of deep tissue oxygen tension monitoring, characterized by, The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: wherein is the fluorescence value mapped to the surface, Y is the three-dimensional light intensity distribution, W is the system matrix, and are depth compensation matrices, and are regularization parameters, R is constructed as wherein, The method comprises the following steps: respectively represent the row number, column number of the voxel; Depth compensation matrix and are respectively expressed as: wherein the matrix is an initial distribution of probes, q is a weight; Among them, W j The first W matrix represents the... j List, Indicates the first j The weights of individual elements, where n is W The number of columns; The method comprises the following steps:

2. The method of claim 1, wherein, The method comprises the following steps:

3. The method of claim 1, wherein the method is a method of monitoring deep tissue oxygen tension. The method comprises the following steps: The method comprises the following steps: The method comprises the following steps: The method comprises the following steps:

4. The method of claim 1, wherein, The method comprises the following steps: wherein represents the three-dimensional light intensity distribution for a nitrogen / oxygen ratio of 1:0; represents the oxygen partial pressure, is a constant, Y is the three-dimensional light intensity distribution.

5. The method of claim 4, wherein the method further comprises: The method comprises the following steps: The method comprises the following steps: Turning on the X-ray source, setting the current, voltage parameters, starting the electron multiplication charge-coupled device (EMCCD) to take a fluorescent image; the sum of the fluorescent values of all pixel points of the image is taken as the three-dimensional light intensity distribution corresponding to the current oxygen partial pressure Y ; After several changes of the ratio of nitrogen and oxygen, the three-dimensional light intensity distribution of each change was obtained, the Stern-Volmer equation was fitted, and the parameters of the equation were calibrated. , the equation was completed.

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light images of the deep tissue sample at multiple angles, and constructing a three-dimensional surface profile of the deep tissue; sampling points are uniformly selected from the three-dimensional surface profile, a difference between the sampling points and a fluorescence value of the fluorescence image is calculated according to a structural relationship between the fluorescence image and the three-dimensional surface profile; the fluorescence image is mapped to the three-dimensional surface profile of the deep tissue according to the difference, and a three-dimensional light intensity distribution of the coupling probe is obtained; wherein the three-dimensional light intensity distribution of the coupling probe is obtained by using a method of fusing a group sparse prior and depth compensation, and specifically includes the following steps: wherein is the fluorescence value mapped to the surface, Y is the three-dimensional light intensity distribution, W is the system matrix, and are depth compensation matrices, and are regularization parameters, R the construction mode of is expressed as: wherein, i、j respectively represent the row number, column number of the voxel; depth compensation matrix and are respectively expressed as: wherein the matrix is an initial distribution of probes, q is a weight; Among them, W j The first W matrix represents the... j List, Indicates the first j The weights of individual elements, where n is W The number of columns; The oxygen partial pressure acquisition module is used for obtaining the three-dimensional oxygen partial pressure of the deep tissue according to the three-dimensional light intensity distribution of the coupling probe.

7. The deep tissue oxygen tension monitoring system of claim 6, wherein, The rotating table is further included and is used for placing the bottom of the deep tissue; the rotating table is used for driving the deep tissue to rotate at an angle.

8. The deep tissue oxygen tension monitoring system of claim 6, wherein, The optical filter is further included and is placed at the receiving end of the EMCCD; the optical filter is used for filtering fluorescence of a specific wavelength.

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