A fluorescence diffusion tomography method and system using full-angle line scanning excitation

Abstract

The present application discloses a fluorescence diffusion tomography method and system with full-angle line scanning excitation, which relates to the fields of optics and biomedical engineering technology. An excitation scanning module and a detection module are designed to generate a near-infrared light beam. The near-infrared light beam is focused on the surface of the sample to be measured to form a diffusible line light source, thereby realizing line scanning excitation. A forward process modeling method is designed to regard the field intensity distribution of the diffusion of the line light source as the weighted accumulation of the field intensity distribution of the diffusion of discrete point light sources to obtain the system forward matrix. A system calibration method is designed to use a steel rod to calibrate the spatial position of the line light beam under different dual-axis galvanometer voltage values, thereby realizing the determination of the spatial coordinates of the starting points at both ends of the line light beam and the determination of the relationship between the deflection angle of the line light beam and the dual-axis galvanometer voltage. The present application aims to ensure the reconstruction accuracy while significantly accelerating the FDT imaging speed, and to help further expand the application of FDT technology in fields with high real-time requirements such as dynamic imaging.

Description

Technical Field

[0001] The present application relates to the field of optics and biomedical engineering technology, and in particular to a fluorescence diffusion tomography method and system with full-angle line scanning excitation. Background Art

[0002] Fluorescence diffusion tomography (FDT), also known as fluorescence molecular tomography (FMT), is a novel macroscopic optical imaging technique. Introduced in 2002, FDT leverages the rapid development of fluorescent labeling molecular imaging technology. FDT uses specific molecular fluorescent probes to label specific regions within biological tissues. Exogenous near-infrared light is used to excite the tissue at multiple angles. A detector detects the fluorescent diffuse light signal on the tissue surface, and the FDT detection data is used to reconstruct the three-dimensional distribution and quantitative information of the fluorescent probes within the tissue. Due to its radiation-free, non-invasive nature, strong specificity, high sensitivity, and low cost, FDT holds broad application prospects in areas such as early tumor diagnosis, anticancer drug development, brain functional imaging, and protein motion tracking.

[0003] In recent years, with the growing demand for both depth and breadth of information in scientific research, single-modality imaging technology has demonstrated its limitations. Developing multimodal imaging technologies to simultaneously acquire structural and functional information within biological tissues has become a research trend. FDT is often combined with imaging modalities such as CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) to simultaneously acquire structural and functional information within living small animals. It is widely used in small animal imaging, providing strong technical support and data assurance for key processes such as drug development, disease model construction, and early tumor diagnosis.

[0004] With the continuous advancement of technology, FDT systems are increasingly being applied in dynamic imaging applications with stringent real-time requirements, such as surgical navigation and pharmacokinetic research. This places higher demands on FDT imaging speed to meet the stringent accuracy and timeliness demands of cutting-edge applications. Existing FDT systems mostly use a point-scanning excitation mode, requiring point-by-point scanning of the three-dimensional surface of the imaging object. Each complete scan takes at least several minutes to generate FDT detection data for subsequent image reconstruction. Consequently, the slow imaging speed of the traditional point-scanning excitation mode has limited the further development and application of FDT in dynamic imaging. Furthermore, the close spacing of the individual excitation light sources during the point-by-point scanning results in strong correlation between the diffuse fluorescence signals and a high degree of information redundancy, making accurate reconstruction more difficult. In summary, traditional point-scanning FDT has certain limitations in dynamic imaging, necessitating the exploration of new FDT scanning excitation modes that can accelerate imaging speed while maintaining reconstruction accuracy. Summary of the Invention

[0005] The purpose of this application is to provide a fluorescence diffusion tomography method and system with full-angle line scanning excitation, which can use a line light source for scanning excitation, while maintaining reconstruction accuracy and significantly accelerating the imaging speed.

[0006] To achieve the above objectives, this application provides the following solutions.

[0007] In a first aspect, the present application provides a fluorescence diffusion tomography system with full-angle line scanning excitation, the fluorescence diffusion tomography system with full-angle line scanning excitation comprising:

[0008] The excitation scanning module is used to generate a near-infrared beam and use the near-infrared beam to perform line scanning excitation on the sample to be tested; the sample to be tested contains a fluorescent probe;

[0009] The detection module is used to detect the diffuse beam of the near-infrared light beam and the fluorescent light beam on the surface of the sample to be tested respectively to obtain FDT detection data; the FDT detection data includes excitation light detection data corresponding to the diffuse beam and fluorescence detection data corresponding to the fluorescent light beam.

[0010] In a second aspect, the present application provides a full-angle line scanning excitation fluorescence diffusion tomography method, which is applied to the above-mentioned full-angle line scanning excitation fluorescence diffusion tomography system, and the full-angle line scanning excitation fluorescence diffusion tomography method includes:

[0011] The near-infrared light spot is regarded as a line light source, and the line light source is modeled as multiple discrete point light sources; the near-infrared light spot is the light spot formed after the near-infrared light beam is focused on the surface of the sample to be measured;

[0012] For each point light source, the steady-state diffusion equation with boundary conditions is solved to obtain a linear equation that characterizes the linear relationship between flux density and light source terms. The linear equation is solved to obtain the field intensity distribution of the excitation light band and the fluorescence band corresponding to the point light source.

[0013] Perform weighted summation on the field intensity distribution of the excitation light band corresponding to all point light sources to obtain the field intensity distribution of the excitation light band corresponding to the line light source;

[0014] Perform normalized Born approximation on the field intensity distribution of the excitation light band and the fluorescence band corresponding to the line light source to obtain the system forward matrix;

[0015] Image reconstruction is performed based on the system forward matrix and FDT detection data.

[0016] According to the specific embodiments provided in this application, this application discloses the following technical effects:

[0017] The present application provides a fluorescence diffusion tomography method and system with full-angle line scanning excitation, wherein the excitation scanning module is used to generate a near-infrared light beam, and use the near-infrared light beam to perform line scanning excitation on the sample to be tested, and the detection module is used to respectively detect the diffuse light beam of the near-infrared light beam on the surface of the sample to be tested and the fluorescent light beam on the surface of the sample to be tested, to obtain FDT detection data, wherein the FDT detection data includes excitation light detection data corresponding to the diffuse light beam and fluorescence detection data corresponding to the fluorescent light beam. The present application can generate a near-infrared light beam, and the near-infrared light beam is focused on the sample surface to form a diffusible line light source, thereby realizing line scanning excitation. Compared with the traditional point scanning excitation mode, the point-by-point scanning process along a certain direction is omitted, the imaging speed is faster, and the problem of high information redundancy caused by the close spacing of each excitation point light source in the point-by-point scanning is avoided, while maintaining the reconstruction accuracy, the imaging speed is significantly accelerated. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0019] Figure 1 This is a structural schematic diagram of a fluorescence diffusion tomography system with full-angle line scanning excitation provided in Example 1 of the present application.

[0020] Figure 2 Schematic diagram of the calibration principle of the line scan excitation FDT system provided in Example 1 of the present application.

[0021] Figure 3 Schematic diagram of X-ray projection of a steel bar at different angles during the system calibration process provided in Example 1 of the present application; wherein, Figure 3 (a) is the X-ray projection of the steel rod when the rotating stage is at 0 degrees. Figure 3 (b) in the figure is the X-ray projection of the steel rod when the rotating stage is 90 degrees.

[0022] Figure 4 This is a schematic diagram of the X-ray projection of the phantom in the phantom experiment provided in Example 1 of the present application.

[0023] Figure 5 This is a schematic diagram of the line light source and point light source provided in the phantom experiment provided in Example 1 of the present application; wherein, Figure 5 (a) in the figure is a line light source. Figure 5 (b) in the figure is a point light source.

[0024] Figure 6 This is a schematic diagram of the reconstruction results of the phantom experiment in the line scan excitation mode provided in Example 1 of the present application; wherein, Figure 6 (a) is the reconstruction of the three-dimensional distribution of fluorophores. Figure 6 (b) is the reconstructed slice of the middle layer of the fluorophore. Figure 6 (c) in the figure is the reconstructed slice of the last layer of the fluorophore.

[0025] Figure 7 This is a schematic diagram of the reconstruction results of the phantom experiment in the point scanning excitation mode provided in Example 1 of the present application; wherein, Figure 7 (a) is the reconstruction of the three-dimensional distribution of fluorophores. Figure 7 (b) is the reconstructed slice of the middle layer of the fluorophore. Figure 7 (c) in the figure is the reconstructed slice of the last layer of the fluorophore.

[0026] Figure 8 This is a flow chart of a method for fluorescence diffusion tomography with full-angle line scanning excitation provided in Example 2 of the present application.

[0027] Reference numerals:

[0028] 1-Near-infrared laser; 2-First lens; 3-Pinhole; 4-Second lens; 5-Shutter; 6-Aperture; 7-Cylindrical lens; 8-Dual-axis galvanometer; 9-Flat-field scanning lens; 10-Rotating stage; 11-Filter set; 12-Camera lens; 13-Electron multiplying charge-coupled device; 14-X-ray tube; 15-X-ray detector; 16-Computer. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0030] Example 1.

[0031] This embodiment provides a fluorescence diffusion tomography system with full-angle line scanning excitation, such as Figure 1 As shown, the full-angle line scanning excitation fluorescence diffusion tomography system includes the following modules.

[0032] The excitation scanning module is used to generate a near-infrared beam and use the near-infrared beam to perform line scanning excitation on the sample to be tested, where there is a fluorescent probe in the sample to be tested.

[0033] The detection module is used to respectively detect the diffuse beam of the near-infrared light beam and the fluorescent light beam on the surface of the sample to be tested, and obtain FDT detection data. The FDT detection data includes excitation light detection data corresponding to the diffuse beam and fluorescence detection data corresponding to the fluorescent light beam.

[0034] In this embodiment, the excitation scanning module includes: a near-infrared laser 1, and a first lens 2, a pinhole 3, a second lens 4, a shutter 5, an aperture 6, a cylindrical lens 7, a biaxial galvanometer 8, and a flat-field scanning lens 9, which are arranged in sequence along the output optical path of the near-infrared laser 1. The cylindrical lens 7 is used to convert the near-infrared parallel beam emitted by the aperture 6 into a near-infrared light beam.

[0035] The near-infrared laser 1 uses a 750nm multi-mode semiconductor laser. This is because the scattering and absorption of the near-infrared light beam in biological tissue is weaker than that of visible light, which is beneficial to improving the FDT imaging quality. The first lens 2 is used to focus the near-infrared light beam to facilitate the filtering and subsequent collimation of the pinhole 3. The pinhole 3 is used to filter the multi-mode near-infrared light beam. The second lens 4 is used to convert the focused near-infrared light beam into a near-infrared parallel light beam. The shutter 5 is used to control the opening and closing of the light path. When the shutter 5 is open, the near-infrared parallel light beam emitted by the second lens 4 is incident on the aperture 6. The aperture 6 is used to limit the diameter of the near-infrared parallel light beam. The cylindrical lens 7 is used to focus the near-infrared parallel light beam in one direction to form a near-infrared light beam. Figure 1The plane shown is the Xc-Yc plane of the CT coordinate system, and the near-infrared beam is a line beam extending in the Zc-axis direction of the CT coordinate system. The biaxial galvanometer 8 is used to change the direction of the near-infrared beam to achieve two-dimensional scanning. The biaxial galvanometer 8 includes an X-axis reflector lens and a Y-axis reflector lens, which respectively achieve scanning along the X-axis direction and the Y-axis direction of the galvanometer coordinate system. The flat-field scanning lens 9 is used to focus the near-infrared beam on the surface of the sample to be tested. The near-infrared light spot formed on the surface of the sample to be tested is a diffusible line light source. In this case, the near-infrared beam can be called excitation light, and the sample to be tested can be biological tissue.

[0036] In this embodiment, a cylindrical lens 7 is provided to converge the light beam in the horizontal direction, thereby forming a line beam. In conjunction with a dual-axis galvanometer 8 and a flat field scanning lens 9, the line beam can be focused and scanned on the surface of the sample to be measured, thereby realizing line scanning excitation.

[0037] There is a fluorescent probe inside the tissue to be tested. When the near-infrared light beam scans and excites the sample to be tested, the fluorescent probe generates fluorescence. At this time, a fluorescent beam is generated on the surface of the sample to be tested.

[0038] In this embodiment, the excitation scanning module also includes: a rotating stage 10, on which the sample to be tested is located, and the rotating stage 10 is used to drive the sample to be tested to rotate, so that the near-infrared light beam scans and excites the sample to be tested at different angles, thereby achieving 360-degree full-angle scanning excitation of the sample to be tested.

[0039] In the excitation scanning module of the line scanning excitation FDT system, the near-infrared light beam is generated by a near-infrared laser 1, focused by the first lens 2, filtered by the pinhole 3, and formed into a near-infrared parallel light beam by the second lens 4. It then passes through the shutter 5 and the aperture 6 in sequence to form a collimated near-infrared parallel light beam, which is then focused in the horizontal direction by the cylindrical lens 7 to form a near-infrared light beam. The near-infrared light beam is then scanned and excited on the sample to be tested on the rotating stage 10 by a dual-axis galvanometer 8 and a flat field scanning lens 9.

[0040] In this embodiment, the detection module includes a filter set 11 , a camera lens 12 , and an electron multiplying charge-coupled device (EMCCD) 13 .

[0041] The filter set 11 includes an excitation light filter, a fluorescence filter and a turntable, and the excitation light filter and the fluorescence filter are both mounted on the turntable. The excitation light filter is used to filter the diffuse light beam of the near-infrared light beam on the surface of the sample to be tested and the fluorescence light beam on the surface of the sample to be tested to obtain a diffuse light beam. The fluorescence filter is used to filter the diffuse light beam of the near-infrared light beam on the surface of the sample to be tested and the fluorescence light beam on the surface of the sample to be tested to obtain a fluorescence light beam. The excitation light filter and the fluorescence filter are placed at different positions on the turntable. When detecting different wavelength bands, the corresponding filter needs to be adjusted to the front of the camera lens 12 through the turntable. When it is necessary to collect the diffuse light beam, the excitation light filter is adjusted to the front of the camera lens 12. When it is necessary to collect the fluorescence light beam, the fluorescence filter is adjusted to the front of the camera lens 12.

[0042] The camera lens 12 is used to collect light beams, that is, to collect the diffuse light beam obtained by the excitation light filter and the fluorescent light beam obtained by the fluorescent light filter.

[0043] The electron multiplying charge coupled device 13 is used to detect the excitation light signal and the fluorescence signal respectively, that is, to detect the diffuse light beam collected by the camera lens 12 to obtain excitation light detection data, and to detect the fluorescence light beam collected by the camera lens 12 to obtain fluorescence detection data. The excitation light detection data and the fluorescence detection data constitute the FDT detection data.

[0044] In this embodiment, the detection module further includes a computer 16, which is communicatively connected to the electron multiplying charge coupled device 13 and is configured to receive and store FDT detection data and subsequently perform image reconstruction based on the FDT detection data. The computer 16 is also control-connected to the near-infrared laser 1 to control its operation. Furthermore, the computer 16 is also control-connected to the shutter 5 and the dual-axis galvanometer 8 to control the opening and closing of the shutter 5 and the operating voltage of the dual-axis galvanometer 8.

[0045] In the detection module of the online scanning excitation FDT system, a near-infrared light beam is used as the excitation light to excite the fluorophores in the sample to be tested to produce fluorescence. The fluorescence on the sample surface and the diffuse light of the excitation light are detected by the electron multiplying charge coupled device 13 after passing through the filter group 11 and the camera lens 12 to obtain FDT detection data, which is then transmitted to the computer 16.

[0046] FDT systems are often used in conjunction with other imaging modalities such as XCT (X-ray Computed Tomography) systems. XCT systems can provide prior structural information of the sample to be tested for image reconstruction and play an important role in system calibration. Figure 1Figure 1 shows a line-scanning excitation FDT system coupled to an XCT system. The XCT system includes an X-ray tube 14, a rotating stage 10 shared with the line-scanning excitation FDT system, an X-ray detector 15, and a computer 16 shared with the line-scanning excitation FDT system. Rotating stage 10 and computer 16 are common to both systems. Rotating stage 10 is used to carry and rotate the sample to be tested, while computer 16 controls the operation of both systems and stores detection data from both systems.

[0047] The line-scanning fluorescence diffusion tomography system in this embodiment also includes an X-ray tube 14 and an X-ray detector 15. The X-ray tube 14 is used to emit X-rays toward the sample to be tested, and the X-ray detector 15 is used to detect the X-rays after they have passed through the sample to be tested. A computer 16 is communicatively connected to the X-ray detector 15 and is used to receive and store XCT detection data from the X-ray detector 15 and subsequently determine prior structural information about the sample to be tested based on the XCT detection data. The computer 16 is also in control communication with the X-ray tube 14 to control its operation.

[0048] Based on the above structure, the imaging steps of a line-scanning excitation FDT system proposed in this embodiment are as follows: a sample to be tested containing a fluorescent probe (also called a fluorescent target) is placed on a rotating stage 10. A near-infrared laser 1 and shutter 5 are turned on. The near-infrared beam is focused by a first lens 2, filtered by a pinhole 3, and formed into a near-infrared parallel beam by a second lens 4. The near-infrared beam then passes through shutter 5 and aperture 6 to become a collimated near-infrared parallel beam. After passing through a cylindrical lens 7, the near-infrared parallel beam is horizontally focused to form a near-infrared beam. The scanning direction of the near-infrared beam is controlled by a dual-axis galvanometer 8. After passing through a flat-field scanning lens 9, the beam is focused onto the surface of the sample to form a near-infrared spot (i.e., a line light source). By controlling the rotation of the rotating stage 10, line-scanning excitation of the sample at different angles is achieved. Upon impacting the surface of the sample, the near-infrared beam diffuses within it. Upon reaching the fluorescent probe, it excites the fluorophore to produce fluorescence. The fluorescence then diffuses within the sample before reaching the surface and being detected by the EMCCD. When using an EMCCD to detect fluorescence, a fluorescence filter is first placed in front of the camera lens 12 to filter out the excitation light. The fluorescence beam is then focused onto the EMCCD through the camera lens 12. Similar operations are performed when using the EMCCD to detect excitation light. An excitation filter is first placed in front of the camera lens 12 to filter out the fluorescence. The excitation light beam (i.e., a diffuse light beam) is then focused onto the EMCCD through the camera lens 12. After these operations are completed, an XCT system is used to image the sample to be tested. Computer 16 controls the rotating stage 10 to rotate 400 times at 0.9° intervals. The X-ray detector 15 detects at each angle once, generating XCT detection data. This XCT detection data is then reconstructed using a filtered back-projection algorithm to obtain information about the external boundaries and internal structure of the sample to be tested. Based on the external boundary and internal structure information of the sample to be tested, the steady-state diffusion equations of the excitation light and fluorescence are constructed. The system forward matrix is ​​obtained using the finite element numerical solution method. The system forward matrix and the FDT detection data of the excitation light and fluorescence detected by the FDT system are used to reconstruct the image, thereby realizing line scanning fluorescence diffusion tomography.

[0049] This embodiment provides a fluorescence diffusion tomography system with full-angle line scanning excitation. It is based on the traditional point scanning excitation FDT system, improves the scanning excitation mode, and adopts a line beam for scanning excitation, which significantly accelerates the FDT imaging speed without sacrificing reconstruction accuracy.

[0050] The current image reconstruction process is based on a point light source. Therefore, this embodiment further explores the corresponding system forward process modeling method and system calibration method, so as to significantly accelerate the FDT imaging speed without sacrificing reconstruction accuracy.

[0051] The system forward process modeling method aims to accurately model the diffusion motion of a line light source within a sample under line scanning excitation mode, thereby ensuring reconstruction quality. A finite element numerical solution is used to discretize the solution domain and construct the corresponding linear discrete equations for the steady-state diffusion equation of a conventional point scanning excitation FDT system. This linear equation is then applied to the flux density and light source terms. The field intensity distributions in the fluorescence and excitation bands are then solved, and the normalized Born approximation is applied to obtain the system forward matrix for the point scanning excitation FDT system. To ensure accurate modeling of the FDT system under line scanning excitation mode, the line light source is modeled as a single entity composed of multiple discrete point light sources. The field intensity distribution of the line light source can be viewed as a weighted superposition of the field intensity distributions of the multiple point light sources. Similar to the forward modeling steps for point scanning excitation FDT, the field intensity distributions in the excitation and fluorescence bands are subjected to the normalized Born approximation to obtain the system forward matrix for the line scanning excitation FDT system. This method effectively describes the diffusion of the line light source within the sample under test, ensuring reconstruction accuracy. That is, for a line light source, it can be modeled as a collection of multiple point light sources. The number of segmented point light sources is determined by the shape of the sample surface and the size of the CT voxel. Then, the field intensity distribution formed by the diffusion of the line light source as a whole can be approximated to the accumulation of the field intensity distributions diffused by the segmented point light sources. Considering that the line light source presents an intensity distribution that is strong in the middle and weak at both ends, different summation weights can be assigned to the field intensity distributions of discrete point light sources at different positions on the line light source. Finally, the field intensity distributions of the processed fluorescence band and excitation light band are used for normalized Born approximation processing to obtain the system forward matrix of the line scanning excitation FDT system.

[0052] The most commonly used forward model for FDT is the diffusion equation (DE), which is a first-order spherical harmonic approximation of the radiative transfer function (RTE). The steady-state diffusion equation for FDT is:

[0053] (1)

[0054] (2)

[0055] (3)

[0056] In the above formula, the subscript x Indicates the excitation light band, subscript m represents the fluorescence band; is the absorption coefficient, is the absorption coefficient of the excitation light band, is the absorption coefficient of the fluorescence band; is the flux density, is the spatial coordinate of the area to be reconstructed in the sample to be tested, is the flux density of the excitation light band, which represents the field intensity distribution of the excitation light. is the flux density of the fluorescence band; is the gradient operator; is the diffusion coefficient, is the reduced scattering coefficient, is the diffusion coefficient of the excitation light band, is the diffusion coefficient of the fluorescence band; is the light source term, is the light source term of the excitation light band, is the light source term in the fluorescence band; is the fluorescence yield, which is the quantity to be reconstructed and is a known quantity in the forward process modeling of the system. is the fluorescence quantum efficiency, is the fluorescence absorption coefficient.

[0057] The boundary conditions for the steady-state diffusion equation are as follows:

[0058] (4)

[0059] (5)

[0060] In the above formula, is the reflection coefficient at the tissue boundary; is the unit normal vector pointing to the interior of the sample at the tissue boundary.

[0061] The finite element numerical solution method is used to solve the steady-state diffusion equation with boundary conditions (i.e., Equations (1) to (5) above). Specifically, according to the principle of functional variation or the weighted residual method, the solution domain is discretized and the corresponding discrete equation group is constructed to establish the linear relationship between the flux density and the light source term, as follows:

[0062] (6)

[0063] (7)

[0064] In the above formula, is the stiffness matrix of the excitation light band; is the stiffness matrix of the fluorescence band.

[0065] For the point scanning excitation FDT system, the field intensity distribution of the excitation light band and the fluorescence band can be obtained by equations (6) and (7), and the normalized Born approximation is further performed to obtain the system forward matrix as follows:

[0066] (8)

[0067] In formula (8), is the system forward matrix, is the spatial coordinate of the detector, and the detector is the detection point on the sample to be tested selected by the user. is the spatial coordinate of the point light source, is the spatial coordinate of the area to be reconstructed in the sample to be tested; is the field intensity distribution of the fluorescence band; and All are the field intensity distribution of the excitation light band.

[0068] For a line light source, the line light source can be modeled as a whole composed of multiple point light sources. The field intensity distribution of the line light source diffusion can be regarded as the accumulation of the field intensity distribution of the point light sources diffusion, as follows:

[0069] (9)

[0070] (10)

[0071] In the above formula, the superscript Indicates a line light source, with a superscript p Represents a point light source; and The field intensity distribution of the excitation light band of the linear light source is shown; For the p Normalized weight coefficient of each point light source; and All are p The field intensity distribution of the excitation light band of a point light source.

[0072] superscript p The number of accumulated values ​​is determined by the surface shape of the sample to be tested and the size of the CT voxel. Since the energy of the line light source presents a Gaussian function distribution with strong center and weak ends, a normalized weight coefficient is introduced. , assign different summation weights to the field intensity distribution of the excitation light band of discrete point light sources at different positions on the line light source, According to the following formula (11) and formula (12), according to the length and energy distribution of the line light source, the standard deviation in formula (11) is Set to around 0.74, sorting of point light sources The value range is [1, p], the step size is 1, p is the number of point light sources segmented, and the weight coefficient is calculated according to formula (11) , and then according to formula (12) the weight coefficient Perform maximum value normalization to obtain the normalized weight coefficient .

[0073] (11)

[0074] (12)

[0075] In the above formula, For the sorting of point light sources, all point light sources are sorted in order from the first end (i.e., the upper end) to the second end (i.e., the lower end) of the line light source.

[0076] Substitute equations (9)-(12) into equation (8), replace the field intensity distribution of the excitation light band, and update the system forward matrix of the line scanning excitation FDT system to obtain: , we further obtain the forward model of the line scan excitation FDT system as follows:

[0077] (13)

[0078] In formula (13), It represents the ratio of fluorescence detection data to excitation light detection data; is the three-dimensional distribution of the fluorescent target inside the sample to be tested. Using formula (13), the image reconstruction of the line scanning excitation FDT system can be performed by combining the detected excitation light detection data and fluorescence detection data.

[0079] Of course, this embodiment can also be used without normalizing the weight coefficients. In this case, a weighted summation of the field intensity distributions of the excitation light band corresponding to all point light sources is performed to obtain the field intensity distribution of the excitation light band corresponding to the line light source. Specifically, the method includes: for each point light source, calculating the product of the weight coefficient corresponding to the point light source and the field intensity distribution of the excitation light band corresponding to the point light source; and summing all the products to obtain the field intensity distribution of the excitation light band corresponding to the line light source. The calculation formula for the weight coefficient corresponding to the point light source is formula (11).

[0080] Because the distance between the centers of the two reflective lenses in the dual-axis galvanometer 8 is much smaller than the working distance of the fθ lens, the excitation light can be roughly assumed to be emitted from the center of the Y-axis reflective lens. Its propagation direction depends on the deflection angle of the dual-axis galvanometer 8 (determined by the input voltage). Calibration of the dual-axis galvanometer 8 can determine the parameters related to the starting point and direction of the excitation light. The system calibration method aims to accurately extract the spatial coordinates of the line light spot (i.e., the near-infrared light spot, also known as the line light source) on the surface of the sample to be measured by determining the spatial coordinates of the starting points of the line beam (i.e., the near-infrared light beam) at both ends and the relationship between the line beam deflection angle and the dual-axis galvanometer voltage. The spatial coordinates of the line light spot are the light source term in the steady-state diffusion equation, providing accurate light source information for subsequent reconstruction. Based on the geometric principle that two points determine a straight line, through the coordinated control of the dual-axis galvanometer and background plate, a cylindrical thin steel rod of the same length and width as the line spot is used to calibrate the spatial position of the line spot. With the help of the spatial positioning capability of the XCT system, the spatial coordinates of the starting points at both ends of the line beam and the relationship between the line beam deflection angle and the dual-axis galvanometer voltage are determined. Subsequently, accurate spatial coordinate information of the line light source on the sample surface can be obtained, ensuring the quality of line scanning excitation FDT reconstruction.

[0081] The system calibration method proposed in this embodiment needs to be implemented with the help of an XCT system. It also requires a background plate made of foam or glass that absorbs less X-rays, and a cylindrical thin steel rod with the same length and width as the line spot. Figure 2 As shown, to determine the spatial coordinates of the starting points at both ends of a line beam, a background plate is first fixed vertically on the rotating stage 10 at a position within the focusing range of the line spot to intercept the line beam and visualize the line spot. A thin cylindrical steel rod, covered with double-sided tape, is then placed on the background plate to calibrate the position of the line spot. Several sets of significantly varying voltage values ​​are then selected (to drive the dual-axis galvanometer 8). At each set of voltage values, the steel rod is moved until it coincides with the position of the line spot on the background plate. Using the XCT system, the spatial coordinates of the two ends of the steel rod are determined, i.e., the spatial coordinates of the two ends of the line spot on the background plate. Next, the background plate is moved within a small range to a second position within the focusing range of the line spot and fixed. Similarly, the above process of moving the steel rod to calibrate the spatial position of the line spot is repeated at the same set of voltage values ​​selected previously. In this way, following the geometric principle that two points determine a straight line, several non-parallel light rays can be determined for each end of the line beam. By finding the intersection of these light rays, the spatial coordinates of the starting points of the two ends of the line beam can be determined.

[0082] Specifically, the calibration process is as follows: controlling the background plate to be at the first position of the rotating stage (i.e., position one), for each calibration voltage value, controlling the biaxial galvanometer to operate at the calibration voltage value, determining the position where the near-infrared beam hits the background plate, and based on the position where the near-infrared beam hits the background plate, placing a steel rod on the background plate, and using an X-ray tube and an X-ray detector to determine the first spatial coordinates of the first end of the steel rod and the first spatial coordinates of the second end of the steel rod; controlling the background plate to be at the second position of the rotating stage (i.e., position two), for each calibration voltage value, controlling the biaxial galvanometer to operate at the calibration voltage value, determining the position where the near-infrared beam hits the background plate, and based on the position where the near-infrared beam hits the background plate, placing a steel rod on the background plate, and using an X-ray tube and an X-ray detector to determine the second spatial coordinates of the first end of the steel rod and the second spatial coordinates of the second end of the steel rod; determining the starting spatial coordinates of the first end of the line beam and the starting spatial coordinates of the second end of the line beam based on the first spatial coordinates and the second spatial coordinates of the second end of the steel rod corresponding to all calibration voltage values.

[0083] The expression for finding the intersection point of non-parallel rays is as follows:

[0084] (14)

[0085] In formula (14), is the first objective function; For the k The first spatial coordinate corresponding to the calibration voltage value represents the spatial coordinate vector of the position of the line light spot on the background plate before the background plate is moved at the first end (second end) of the line light beam under the same set of voltage values; For the k The second spatial coordinate corresponding to the calibration voltage value represents the spatial coordinate vector of the position of the line light spot on the background plate after the background plate is moved at the first end (second end) of the line beam under the same set of voltage values; is the starting point space coordinate of the first end (second end) of the line light source, indicating the starting position vector of the first end (second end) of the line light beam; the normr function is used to find the unit vector.

[0086] Figure 3 The X-ray projections of the thin steel rod at different angles are shown. By using 400 projections for CT reconstruction, the CT coordinate data of the two ends of the line spot hitting the background plate at different voltage values ​​can be obtained in Table 1. Using the data in Table 1 and combining it with formula (14), the more accurate spatial coordinates of the starting points of the two ends of the line beam can be obtained by fitting. and (Unit: mm) and the corresponding error and , , , , .

[0087] Table 1 CT coordinates of the two end points of the line spot on the background plate at different voltage values ​​(mm)

[0088]

[0089] To determine the relationship between the line beam deflection angle and the dual-axis galvanometer voltage, it is also necessary to first vertically fix the background plate on the rotating stage 10 within the focusing range of the line spot. Then, it is necessary to select several different sets of dual-axis galvanometer voltage values, that is, select several sets of dual-axis galvanometer voltage values ​​with significant changes in the X-axis and Y-axis directions (including X-axis voltage and Y-axis voltage). At each set of voltage values, move the steel rod so that it coincides with the line spot on the background plate. Use the XCT system to determine the spatial coordinates of the steel rod's midpoint (i.e., center point) at different voltage values. This is also the spatial coordinate of the line spot midpoint. Finally, based on the determined spatial coordinates of the starting point of the line beam midpoint, the spatial coordinates of the line spot midpoint and the corresponding voltage value data are fitted. Based on the fitting of the spatial coordinates and voltage values ​​of the line spot midpoint, the relationship between the line beam deflection angle and the dual-axis galvanometer voltage is determined.

[0090] Specifically, the calibration process is as follows: controlling the background plate to be at the third position of the rotating stage, for each set of calibration X-axis voltage values ​​and calibration Y-axis voltage values, controlling the dual-axis galvanometer to operate with the calibration X-axis voltage value and the calibration Y-axis voltage value, determining the position where the near-infrared beam hits the background plate, and based on the position where the near-infrared beam hits the background plate, placing a steel rod on the background plate, and using an X-ray tube and an X-ray detector to determine the third spatial coordinate of the midpoint of the steel rod; based on all the calibration X-axis voltage values, calibration Y-axis voltage values ​​and the third spatial coordinate of the midpoint of the steel rod, determining the relationship between the line beam deflection angle and the dual-axis galvanometer voltage.

[0091] The relationship between the line beam deflection angle and the dual-axis galvanometer voltage is as follows:

[0092] (15)

[0093] (16)

[0094] In the above formula, and They represent the angles between the propagation direction of the line beam and the positive directions of the Xc axis and Zc axis in the CT coordinate system respectively; and They represent the angles between the propagation direction of the line beam and the positive directions of the Xc axis and Zc axis in the CT coordinate system when the input voltage is (0 V, 0 V); and are the deflection angles of the X-axis reflective lens and the Y-axis reflective lens in the dual-axis galvanometer caused by unit input voltage respectively; and Respectively k The X-axis voltage (i.e. the X-axis voltage value for calibration) and the Y-axis voltage (i.e. the Y-axis voltage value for calibration) are set by the group.

[0095] The unit direction vector of a line beam can be expressed as:

[0096] (17)

[0097] In formula (17), is the unit direction vector of the near-infrared beam.

[0098] It can be obtained by minimizing the following formula (18): 、 、 and Other key parameters:

[0099] (18)

[0100] In formula (18), is the second objective function; is the unit direction vector of the near-infrared beam; is the starting point spatial coordinate of the midpoint of the line beam, which can be obtained by a fitting method similar to the starting point spatial coordinates of the first end and the second end of the line beam; For the k The third space coordinate corresponding to the X-axis voltage value and the Y-axis voltage value for calibration is represented by the k The spatial coordinates of the midpoint of the line spot of the linear beam hitting the background plate under the group voltage value.

[0101] Table 2 CT coordinates of the midpoint of the line spot on the background plate at different voltage values ​​(mm)

[0102]

[0103] Using the different voltage values ​​in Table 2 and the corresponding CT coordinates of the midpoint of the line spot on the background plate, combined with formula (18), the function minimization fitting is obtained 、 、 and Key parameters and corresponding errors g , , , , , g=0.1985.

[0104] This example aims to overcome the imaging speed limitations of existing FDT technology by proposing a fluorescence diffusion tomography system with full-angle line scanning excitation. This system shortens data acquisition time and accelerates FDT imaging while ensuring reconstruction quality. Based on the traditional point-scanning excitation FDT system, this example improves the scanning excitation mode, employing a line beam for scanning excitation. Furthermore, corresponding forward process modeling and system calibration methods are explored to accelerate FDT imaging without sacrificing reconstruction accuracy.

[0105] In order to verify the improvement in imaging speed and the maintenance of reconstruction quality of the line scanning excitation FDT system proposed in this embodiment, a phantom experiment was designed. In the phantom experiment, a beaker with a diameter of approximately 40 mm and filled with 1% fat emulsion was used as a phantom. A small amount of 2 μmol / L DIR (cell membrane near-infrared fluorescent probe) solution was placed in a glass tube with a diameter of approximately 2 mm, sealed at both ends, and inserted into the beaker. The upper end of the glass tube was fixed with a glass container with double-sided tape fixed to the upper edge of the beaker. The DIR solution could be suspended in the fat emulsion, simulating the fluorescent group inside the phantom. The X-ray projection of the phantom is shown below. Figure 4 shown.

[0106] The phantom experiment was conducted on the phantom by line scanning excitation imaging and point scanning excitation imaging. The line light source and point light source were as follows. Figure 5 As shown. Both scanning excitation modes excite at evenly spaced intervals at 48 angles. The line light source is approximately 13 mm long. The point light source scans five times along the Z axis at each angle, and the scanning range is consistent with the length of the line light source. In the line scanning excitation mode, the system forward matrix is ​​constructed according to equations (1) to (13), and each line light source is discretized into 30 point light sources. The reconstruction regularization term for the two scanning excitation modes selects L1 regularization, and the optimization algorithm selects the Fast Iterative Shrinkage Thresholding Algorithm (FISTA). The experimental parameter settings are shown in Table 3.

[0107] Table 3 Experimental parameter settings and imaging time comparison

[0108]

[0109] Figure 6 and Figure 7(a), (b), and (c) show the reconstructed three-dimensional distribution of fluorophores, the reconstructed slice image of the middle layer of fluorophores, and the reconstructed slice image of the last layer of fluorophores, respectively. The area enclosed by the white circle represents the actual distribution of fluorophores. The reconstruction results show that the line scanning excitation mode and the point scanning excitation mode achieve comparable reconstruction quality in the middle layer of fluorophores. However, in the last layer of fluorophores, only the line scanning excitation mode reconstructs a good signal, while the point scanning excitation mode fails to reconstruct a signal. This may be due to insufficient Z-axis acquisition density of the point scanning excitation mode and excessive redundant information in the system's forward matrix, which affects the reconstruction quality. The imaging data acquisition time for the two scanning excitation modes is shown in Table 3. It is important to note that after capturing a fluorescence image or excitation light image at each angle, the system must capture a dark-field image of the corresponding fluorescence band or excitation light band. Therefore, the imaging time ratio between the two modes is approximately 1:3. In summary, the phantom experiment verifies that the line scanning excitation FDT system not only significantly reduces imaging time but also effectively improves reconstruction quality.

[0110] This embodiment belongs to the field of optics and biomedical engineering technology and provides a full-angle line scanning excitation fluorescence diffusion tomography imaging system, including a line scanning excitation FDT system and corresponding system forward process modeling methods and system calibration methods. The line scanning excitation FDT system includes: a near-infrared laser 1, a first lens 2, a pinhole 3, a second lens 4, a shutter 5, an aperture 6, a cylindrical lens 7, a biaxial galvanometer 8, a flat field scanning lens 9, a rotating stage 10, a filter set 11, a camera lens 12, an EMCCD, and a computer 16. To accurately model the diffusion motion of a line light source within a sample under the line scanning excitation mode and obtain an accurate line scanning FDT forward model, the line light source is modeled as multiple discrete point light sources. The field intensity distribution of the line light source diffusion can be viewed as a weighted superposition of the field intensity distributions of the multiple point light sources diffusion. A normalized Born approximation is then performed on the processed field intensity distributions in the excitation and fluorescence bands to obtain the system forward matrix of the line scanning excitation FDT system. To obtain accurate spatial coordinate information of the line light source on the sample surface and ensure reconstruction quality, a system calibration method was developed. Based on the geometric principle of two points determining a straight line, a cylindrical thin steel rod of the same length and width as the line spot was used to calibrate the spatial position of the line spot through coordinated control of a dual-axis galvanometer and background plate. Leveraging the spatial positioning capabilities of the XCT system, the spatial coordinates of the starting points at both ends of the line beam and the relationship between the line beam deflection angle and the dual-axis galvanometer voltage were determined. This embodiment aims to significantly accelerate FDT imaging while ensuring reconstruction accuracy, thereby further expanding the application of FDT technology in areas with high real-time requirements, such as dynamic imaging.

[0111] To address the limitations of slow imaging speed in existing point scanning excitation FDT systems, this embodiment improves the scanning excitation mode and innovatively proposes a line scanning excitation FDT system, which can significantly improve imaging speed while ensuring reconstruction accuracy. This embodiment has the following advantages.

[0112] (1) The full-angle line scanning excitation FDT system proposed in this embodiment uses only one line light source for single scanning excitation at each angle, avoiding the time-consuming operation of traditional point scanning excitation that requires multiple scanning excitations at intervals in the Z-axis direction. Combined with the forward process modeling method and system calibration method proposed in this embodiment, it can significantly speed up the imaging speed without losing the reconstruction accuracy, and help further expand the application of FDT technology in fields with high real-time requirements such as dynamic imaging.

[0113] (2) The forward process modeling method proposed in this embodiment can accurately model the diffusion movement of the line light source inside the sample by discretizing the line light source into multiple point light sources and considering the field intensity distribution of the diffusion of the line light source as the weighted accumulation of the field intensity distribution of the diffusion of the point light sources, thereby ensuring the accuracy of forward modeling and reverse reconstruction.

[0114] (3) The system calibration method proposed in this embodiment is based on the geometric principle of determining a straight line by two points. Through the coordinated control of the dual-axis galvanometer and the background plate, a cylindrical thin steel rod with the same length and width as the line spot is used to calibrate the spatial position of the line spot. With the help of the spatial positioning capability of the XCT system, the spatial coordinates of the starting points of the two ends of the line beam and the relationship between the line beam deflection angle and the dual-axis galvanometer voltage can be determined more accurately, providing accurate light source position information for subsequent reconstruction.

[0115] Example 2.

[0116] This embodiment provides a fluorescence diffusion tomography method with full-angle line scanning excitation, which is applied to the fluorescence diffusion tomography system with full-angle line scanning excitation described in Example 1. Figure 8 As shown, the fluorescence diffusion tomography method with full-angle line scanning excitation includes the following steps.

[0117] S1: The near-infrared light spot is regarded as a line light source, and the line light source is modeled as multiple discrete point light sources; the near-infrared light spot is the light spot formed after the near-infrared light beam is focused on the surface of the sample to be measured.

[0118] S2: For each point light source, the steady-state diffusion equation with boundary conditions is solved to obtain a linear equation used to characterize the linear relationship between flux density and light source terms; the linear equation is solved to obtain the field intensity distribution of the excitation light band and the fluorescence band corresponding to the point light source.

[0119] S3: performing weighted summation on the field intensity distributions of the excitation light bands corresponding to all point light sources to obtain the field intensity distributions of the excitation light bands corresponding to the line light source.

[0120] S4: Perform normalized Born approximation on the field intensity distribution of the excitation light band and the fluorescence band corresponding to the line light source to obtain the system forward matrix.

[0121] S5: Image reconstruction based on the system forward matrix and FDT detection data.

[0122] In S4, a weighted summation is performed on the field intensity distributions of the excitation light band corresponding to all point light sources to obtain the field intensity distribution of the excitation light band corresponding to the line light source, specifically including: for each point light source, calculating the product of the weight coefficient corresponding to the point light source and the field intensity distribution of the excitation light band corresponding to the point light source; and summing all products to obtain the field intensity distribution of the excitation light band corresponding to the line light source.

[0123] The calculation formula for the weight coefficient corresponding to the point light source is:

[0124] (19)

[0125] In formula (19), is the weight coefficient; is the standard deviation; For the sorting of point light sources, all point light sources are sorted in order from the first end to the second end of the line light source.

[0126] The method for determining the spatial coordinates of the point light source in the system forward matrix is ​​as follows: using the actual dual-axis galvanometer voltage as input, and based on the pre-calibrated spatial coordinates of the starting point of the first end of the line light beam, the spatial coordinates of the starting point of the second end of the line light beam, and the relationship between the line light beam deflection angle and the dual-axis galvanometer voltage, determine the spatial plane corresponding to the line light source; calculate the spatial coordinates of the intersection of the spatial plane corresponding to the line light beam and the surface of the sample to be measured to obtain the spatial coordinates of the line light source; determine the spatial coordinates of the point light source based on the spatial coordinates of the line light source, and specifically discretize the spatial coordinates of the line light source to obtain the spatial coordinates of the point light source of each point light source.

[0127] The calibration method of the relationship between the spatial coordinates of the starting point of the first end of the line beam, the spatial coordinates of the starting point of the second end of the line beam, and the line beam deflection angle and the dual-axis galvanometer voltage includes the following steps.

[0128] (1) The background plate is controlled to be at the first position of the rotating stage. For each calibration voltage value, the dual-axis galvanometer is controlled to operate at the calibration voltage value to determine the position where the near-infrared light beam hits the background plate. Based on the position where the near-infrared light beam hits the background plate, a steel rod is placed on the background plate. The first spatial coordinates of the first end of the steel rod and the first spatial coordinates of the second end of the steel rod are determined using an X-ray tube and an X-ray detector. The shape, size and position of the steel rod are the same as those of the near-infrared light spot.

[0129] (2) The background plate is controlled to be at the second position of the rotating stage. For each calibration voltage value, the dual-axis galvanometer is controlled to operate at the calibration voltage value to determine the position where the near-infrared light beam hits the background plate. Based on the position where the near-infrared light beam hits the background plate, a steel rod is placed on the background plate, and the second spatial coordinates of the first end of the steel rod and the second spatial coordinates of the second end of the steel rod are determined using an X-ray tube and an X-ray detector.

[0130] (3) Based on the first spatial coordinates and the second spatial coordinates of the first end of the steel rod and the first spatial coordinates and the second spatial coordinates of the second end of the steel rod corresponding to all calibration voltage values, determine the starting spatial coordinates of the first end of the line beam and the starting spatial coordinates of the second end of the line beam.

[0131] (4) The background plate is controlled to be at the third position of the rotating stage. For each set of calibration X-axis voltage values ​​and calibration Y-axis voltage values, the dual-axis galvanometer is controlled to operate with the calibration X-axis voltage values ​​and calibration Y-axis voltage values ​​to determine the position where the near-infrared beam hits the background plate. Based on the position where the near-infrared beam hits the background plate, a steel rod is placed on the background plate, and the third spatial coordinate of the midpoint of the steel rod is determined using an X-ray tube and an X-ray detector.

[0132] (5) Based on all the calibration X-axis voltage values, calibration Y-axis voltage values ​​and the third spatial coordinate of the midpoint of the steel rod, determine the relationship between the line beam deflection angle and the dual-axis galvanometer voltage.

[0133] Among them, based on the first spatial coordinates and the second spatial coordinates of the first end of the steel rod corresponding to all calibration voltage values ​​and the first spatial coordinates and the second spatial coordinates of the second end of the steel rod, the starting spatial coordinates of the first end of the line beam and the starting spatial coordinates of the second end of the line beam are determined, specifically including: taking the first spatial coordinates and the second spatial coordinates of the first end of the steel rod corresponding to all calibration voltage values ​​as input, and using the first calibration formula to determine the starting spatial coordinates of the first end of the line beam; taking the first spatial coordinates and the second spatial coordinates of the second end of the steel rod corresponding to all calibration voltage values ​​as input, and using the first calibration formula to determine the starting spatial coordinates of the second end of the line beam.

[0134] The first calibration formula is:

[0135] (20)

[0136] In formula (20), is the first objective function; For the k A first space coordinate corresponding to a calibration voltage value; For the k A second space coordinate corresponding to a calibration voltage value; The starting point space coordinates of the first or second end of the line light source.

[0137] Among them, based on all the calibration X-axis voltage values, the calibration Y-axis voltage values ​​and the third space coordinate of the midpoint of the steel rod, the relationship between the line beam deflection angle and the dual-axis galvanometer voltage is determined, specifically including: taking all the calibration X-axis voltage values, the calibration Y-axis voltage values ​​and the third space coordinate of the midpoint of the steel rod as input, and using the second calibration formula to determine the relationship between the line beam deflection angle and the dual-axis galvanometer voltage.

[0138] The second calibration formula is:

[0139] (twenty one)

[0140] In formula (21), is the second objective function; is the unit direction vector of the near-infrared beam; is the starting point space coordinate of the midpoint of the line beam; For the k The third space coordinate corresponding to the calibration X-axis voltage value and the calibration Y-axis voltage value is set.

[0141] (twenty two)

[0142] In formula (22), is the angle between the propagation direction of the near-infrared beam and the positive direction of the Zc axis in the CT coordinate system; It is the angle between the propagation direction of the near-infrared beam and the positive direction of the Xc axis in the CT coordinate system.

[0143] (twenty three)

[0144] In formula (23), The angle between the propagation direction of the near-infrared beam and the positive direction of the Xc axis in the CT coordinate system when the calibration X-axis voltage value and the calibration Y-axis voltage value are both 0; is the deflection angle of the X-axis reflective lens in the dual-axis galvanometer caused by unit input voltage; For the k The X-axis voltage value is used for calibration.

[0145] (twenty four)

[0146] In formula (24), The angle between the propagation direction of the near-infrared beam and the positive direction of the Zc axis in the CT coordinate system when the calibration X-axis voltage value and the calibration Y-axis voltage value are both 0; is the deflection angle of the Z-axis reflective lens in the dual-axis galvanometer caused by unit input voltage; For the k The Y-axis voltage value is used for calibration.

[0147] The technical features of the above embodiments can be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0148] This document uses specific examples to illustrate the principles and implementation methods of this application. The description of the above examples is only intended to help understand the method and core concept of this application. At the same time, for those skilled in the art, based on the concept of this application, there may be changes in the specific implementation methods and application scope. In summary, the content of this specification should not be understood as limiting this application.

Claims

1. A fluorescence diffusion tomography system with full-angle line scanning excitation, characterized in that: The full-angle line scanning excited fluorescence diffusion tomography system comprises: The excitation scanning module is used to generate a near-infrared beam and use the near-infrared beam to perform line scanning excitation on the sample to be tested; the sample to be tested contains a fluorescent probe; The detection module is used to detect the diffuse beam of the near-infrared light beam and the fluorescent light beam on the surface of the sample to be tested, respectively, to obtain FDT detection data; the FDT detection data includes excitation light detection data corresponding to the diffuse beam and fluorescence detection data corresponding to the fluorescent light beam; The detection module includes a computer, which is used to receive and store FDT detection data and complete image reconstruction based on the FDT detection data; The full-angle line scanning excited fluorescence diffusion tomography system further comprises: an X-ray tube and an X-ray detector; the X-ray tube is used to emit X-rays toward the sample to be tested; the X-ray detector is used to detect the X-rays passing through the sample to be tested; The computer is used for receiving and storing XCT detection data of the X-ray detector; After the XCT detection data is reconstructed through the filtered back-projection algorithm, the external boundary and internal structure information of the sample to be tested are obtained. Based on the obtained external boundary and internal structure information of the sample to be tested, the steady-state diffusion equation of the excitation light and fluorescence is constructed; The fluorescence diffusion tomography imaging method of the full-angle line scanning excited fluorescence diffusion tomography imaging system includes: regarding a near-infrared light spot as a line light source, and modeling the line light source as multiple discrete point light sources, wherein the near-infrared light spot is a light spot formed after the near-infrared light beam is focused on the surface of the sample to be measured; for each point light source, solving a steady-state diffusion equation with boundary conditions to obtain a linear equation for characterizing the linear relationship between flux density and light source terms; solving the linear equation to obtain an excitation light band field intensity distribution and a fluorescence band field intensity distribution corresponding to the point light source; performing a weighted summation on the excitation light band field intensity distributions corresponding to all point light sources to obtain an excitation light band field intensity distribution corresponding to the line light source; performing a normalized Born approximation on the excitation light band field intensity distribution and the fluorescence band field intensity distribution corresponding to the line light source to obtain a system forward matrix; and performing image reconstruction based on the system forward matrix and FDT detection data.

2. The fluorescence diffusion tomography system with full-angle line scanning excitation according to claim 1, characterized in that: The excitation scanning module includes: a near-infrared laser and a first lens, a pinhole, a second lens, a shutter, an aperture, a cylindrical lens, a biaxial galvanometer and a flat field scanning lens arranged in sequence along the output light path of the near-infrared laser; The cylindrical lens is used to convert the near-infrared parallel light beam emitted by the aperture into a near-infrared light beam.

3. The fluorescence diffusion tomography system with full-angle line scanning excitation according to claim 2, characterized in that: The excitation scanning module further includes: a rotating stage; the sample to be tested is located on the rotating stage, and the rotating stage is used to drive the sample to be tested to rotate.

4. The fluorescence diffusion tomography system with full-angle line scanning excitation according to claim 1, characterized in that: The detection module includes a filter set, a camera lens, and an electron multiplying charge-coupled device; The filter set includes an excitation light filter, a fluorescence filter, and a turntable, wherein the excitation light filter and the fluorescence filter are both mounted on the turntable; the excitation light filter is used to filter the diffuse beam of the near-infrared light beam on the surface of the sample to be tested and the fluorescence beam on the surface of the sample to be tested to obtain a diffuse beam; the fluorescence filter is used to filter the diffuse beam of the near-infrared light beam on the surface of the sample to be tested and the fluorescence beam on the surface of the sample to be tested to obtain a fluorescence beam; The camera lens is used to collect the diffuse light beam obtained by the excitation light filter and the fluorescent light beam obtained by the fluorescence filter; The electron multiplying charge coupled device is used to detect the diffuse light beam collected by the camera lens to obtain excitation light detection data, and to detect the fluorescent light beam collected by the camera lens to obtain fluorescence detection data.

5. A fluorescence diffusion tomography method with full-angle line scanning excitation, applied to the fluorescence diffusion tomography system with full-angle line scanning excitation according to any one of claims 1 to 4, characterized in that: The fluorescence diffusion tomography method using full-angle line scanning excitation includes: The near-infrared light spot is regarded as a line light source, and the line light source is modeled as multiple discrete point light sources; the near-infrared light spot is the light spot formed after the near-infrared light beam is focused on the surface of the sample to be measured; For each point light source, the steady-state diffusion equation with boundary conditions is solved to obtain a linear equation that characterizes the linear relationship between flux density and light source terms. The linear equation is solved to obtain the field intensity distribution of the excitation light band and the fluorescence band corresponding to the point light source. Perform weighted summation on the field intensity distribution of the excitation light band corresponding to all point light sources to obtain the field intensity distribution of the excitation light band corresponding to the line light source; Perform normalized Born approximation on the field intensity distribution of the excitation light band and the fluorescence band corresponding to the line light source to obtain the system forward matrix; Image reconstruction is performed based on the system forward matrix and FDT detection data.

6. The fluorescence diffusion tomography method using full-angle line scanning excitation according to claim 5, characterized in that: Performing a weighted summation of the field intensity distributions of the excitation light band corresponding to all point light sources to obtain the field intensity distribution of the excitation light band corresponding to the line light source, specifically comprising: for each point light source, calculating the product of the weight coefficient corresponding to the point light source and the field intensity distribution of the excitation light band corresponding to the point light source; summing all the products to obtain the field intensity distribution of the excitation light band corresponding to the line light source; The calculation formula for the weight coefficient corresponding to the point light source is: ； in, is the weight coefficient; is the standard deviation; For the sorting of point light sources, all point light sources are sorted in order from the first end to the second end of the line light source.

7. The fluorescence diffusion tomography method using full-angle line scanning excitation according to claim 5, characterized in that: The method for determining the spatial coordinates of the point light source in the system forward matrix is: The excitation scanning module includes: a near-infrared laser and a first lens, a pinhole, a second lens, a shutter, an aperture, a cylindrical lens, a biaxial galvanometer and a flat field scanning lens arranged in sequence along the output light path of the near-infrared laser. The excitation scanning module also includes: a rotating stage, on which the sample to be tested is located, and the rotating stage is used to drive the sample to be tested to rotate. The actual biaxial galvanometer voltage is used as input, and based on the pre-calibrated starting point spatial coordinates of the first end of the line light beam, the starting point spatial coordinates of the second end of the line light beam and the relationship between the line light beam deflection angle and the biaxial galvanometer voltage, the spatial plane corresponding to the line light beam is determined; the spatial coordinates of the intersection line between the spatial plane corresponding to the line light beam and the surface of the sample to be tested are calculated to obtain the spatial coordinates of the line light source; and the spatial coordinates of the point light source are determined based on the spatial coordinates of the line light source. The calibration method of the relationship between the spatial coordinates of the starting point of the first end of the line beam, the spatial coordinates of the starting point of the second end of the line beam, the line beam deflection angle and the dual-axis galvanometer voltage is: A foam or glass background plate and a steel rod are prepared, the background plate is controlled to be in the first position of the rotating stage, and for each calibration voltage value, a dual-axis galvanometer is controlled to operate at the calibration voltage value to determine the position where the near-infrared beam hits the background plate. Based on the position where the near-infrared beam hits the background plate, the steel rod is placed on the background plate, and the first spatial coordinates of the first end of the steel rod and the first spatial coordinates of the second end of the steel rod are determined using an X-ray tube and an X-ray detector; the steel rod and the near-infrared spot have the same shape, size, and position; controlling the background plate to be at a second position of the rotating stage, controlling the biaxial galvanometer to operate at the calibration voltage value for each calibration voltage value, determining a position where the near-infrared beam strikes the background plate, placing a steel rod on the background plate based on the position where the near-infrared beam strikes the background plate, and determining a second spatial coordinate of a first end of the steel rod and a second spatial coordinate of a second end of the steel rod using an X-ray tube and an X-ray detector; Determine the starting point spatial coordinates of the first end of the linear beam and the starting point spatial coordinates of the second end of the linear beam based on the first spatial coordinates and the second spatial coordinates of the first end of the steel rod and the first spatial coordinates and the second spatial coordinates of the second end of the steel rod corresponding to all calibration voltage values; controlling the background plate to be at the third position of the rotating stage, controlling the dual-axis galvanometer to operate with the calibration X-axis voltage value and the calibration Y-axis voltage value for each set of calibration X-axis voltage values ​​and calibration Y-axis voltage values, determining the position where the near-infrared beam strikes the background plate, placing a steel rod on the background plate based on the position where the near-infrared beam strikes the background plate, and determining the third spatial coordinate of the midpoint of the steel rod using the X-ray tube and the X-ray detector; Based on all calibration X-axis voltage values, calibration Y-axis voltage values ​​and the third space coordinate of the midpoint of the steel rod, a relationship between the line beam deflection angle and the dual-axis galvanometer voltage is determined.

8. The fluorescence diffusion tomography method using full-angle line scanning excitation according to claim 7, characterized in that: Determining the starting point spatial coordinates of the first end of the line beam and the starting point spatial coordinates of the second end of the line beam based on the first spatial coordinates and the second spatial coordinates of the first end of the steel rod and the first spatial coordinates and the second spatial coordinates of the second end of the steel rod corresponding to all calibration voltage values ​​specifically includes: Using the first spatial coordinates and the second spatial coordinates of the first end of the steel rod corresponding to all calibration voltage values ​​as input, determine the starting spatial coordinates of the first end of the line beam using a first calibration formula; Using the first spatial coordinates and the second spatial coordinates of the second end of the steel rod corresponding to all calibration voltage values ​​as input, the first calibration formula is used to determine the starting spatial coordinates of the second end of the line beam; The first calibration formula is: ； in, is the first objective function; For the k A first space coordinate corresponding to a calibration voltage value; For the k A second space coordinate corresponding to a calibration voltage value; is the spatial coordinate of the starting point of the first or second end of the line beam.

9. The fluorescence diffusion tomography method using full-angle line scanning excitation according to claim 7, characterized in that: Based on all calibration X-axis voltage values, calibration Y-axis voltage values, and the third spatial coordinate of the midpoint of the steel rod, the relationship between the line beam deflection angle and the dual-axis galvanometer voltage is determined, specifically including: Using all calibration X-axis voltage values, calibration Y-axis voltage values, and the third spatial coordinate of the midpoint of the steel rod as input, the relationship between the line beam deflection angle and the dual-axis galvanometer voltage is determined using the second calibration formula; The second calibration formula is: ； in, is the second objective function; is the unit direction vector of the near-infrared beam; is the starting point space coordinate of the midpoint of the line beam; For the k A third space coordinate corresponding to the calibration X-axis voltage value and the calibration Y-axis voltage value; ； in, is the angle between the propagation direction of the near-infrared beam and the positive direction of the Zc axis in the CT coordinate system; is the angle between the propagation direction of the near-infrared beam and the positive direction of the Xc axis in the CT coordinate system; ； in, The angle between the propagation direction of the near-infrared beam and the positive direction of the Xc axis in the CT coordinate system when the calibration X-axis voltage value and the calibration Y-axis voltage value are both 0; is the deflection angle of the X-axis reflective lens in the dual-axis galvanometer caused by unit input voltage; For the k The X-axis voltage value for calibration; ； in, The angle between the propagation direction of the near-infrared beam and the positive direction of the Zc axis in the CT coordinate system when the calibration X-axis voltage value and the calibration Y-axis voltage value are both 0; is the deflection angle of the Z-axis reflective lens in the dual-axis galvanometer caused by unit input voltage; For the k The Y-axis voltage value is used for calibration.

Images