Fluorescence diffusion tomography method and system for full-angle line scanning excitation

Abstract

The invention discloses a fluorescence diffusion tomography method and system based on full-angle line scanning excitation, and relates to the technical field of optical and biomedical engineering, an excitation scanning module and a detection module are designed, a near-infrared light beam can be generated, the near-infrared light beam is focused on the surface of a to-be-detected sample to form a diffusible line light source, and the diffusible line light source is focused on the surface of the to-be-detected sample; therefore, line scanning excitation is realized. A forward process modeling method is designed, field intensity distribution of linear light source diffusion is regarded as weighted accumulation of field intensity distribution of discrete point light source diffusion, and a system forward matrix is obtained. A system calibration method is designed, the spatial position of the linear beam under different biaxial galvanometer voltage values is calibrated by means of a steel bar, and determination of space coordinates of starting points at the two ends of the linear beam and determination of the relation between the deflection angle of the linear beam and the biaxial galvanometer voltage are achieved. According to the method, the FDT imaging speed is remarkably increased while the reconstruction precision is guaranteed, and further application and expansion of the FDT technology in the fields such as dynamic imaging and the like with high real-time performance requirements are assisted.

Description

Technical Field

[0001] This application relates to the technical fields of optics and biomedical engineering, and particularly relates to a fluorescence diffuse 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 new type of macroscopic optical imaging technology. Thanks to the great development of fluorescence-labeled molecule imaging technology, FDT was proposed in 2002. FDT uses specific molecular fluorescence probes to label specific regions inside biological tissues, excites biological tissues with exogenous near-infrared light from multiple angles, and uses detectors to detect the fluorescence diffusion light signals on the surface of biological tissues. Based on the FDT detection data, the three-dimensional distribution and quantitative information of the fluorescence probes in the biological tissue in vivo are reconstructed. Due to its advantages such as non-radiation, non-invasive, strong specificity, high sensitivity, and low cost, FDT has broad application prospects in the fields of early diagnosis of tumors, development of anti-cancer drugs, brain function imaging, protein motion tracing, etc.

[0003] In recent years, with the increasing demand of scientific research for the depth and breadth of information, single-modal imaging technology has shown limitations. Developing multi-modal imaging technology to simultaneously obtain the internal structure and function information of 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 obtain the structural and functional information in living small animals, and is widely used in small animal imaging, providing strong technical support and data guarantee for key links such as drug research and development, disease model construction, and early diagnosis of tumors.

[0004] With the continuous progress of technology, FDT systems have gradually been applied to dynamic imaging fields with high requirements for real-time performance, such as surgical navigation, pharmacokinetics research, etc. This poses higher requirements for the imaging speed of FDT to meet the stringent accuracy and timeliness requirements of cutting-edge application scenarios. Most existing FDT systems adopt a point-scanning excitation mode, which requires point-by-point scanning excitation within the three-dimensional surface range of the imaging object. Each complete scan takes at least several minutes to obtain FDT detection data for subsequent image reconstruction. It can be seen that the imaging speed of the traditional point-scanning excitation mode is relatively slow, restricting the further development and application of FDT in the field of dynamic imaging. At the same time, since the individual excitation point light sources of point-by-point scanning are very close to each other, the fluorescence diffusion light signals have strong correlations and a large degree of information redundancy, increasing the difficulty of accurate reconstruction. To sum up, the traditional FDT with point-scanning excitation has certain limitations in the field of dynamic imaging, and it is necessary to explore a new FDT scanning excitation mode to accelerate the imaging speed while maintaining the reconstruction accuracy. Summary of the Invention

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

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

[0007] In the first aspect, this application provides a fluorescence diffuse tomography system with full-angle line-scanning excitation. The fluorescence diffuse tomography system with full-angle line-scanning excitation includes: An excitation scanning module, which is used to generate a near-infrared light beam and use the near-infrared light beam to perform line-scanning excitation on a sample to be measured; there is a fluorescence probe in the sample to be measured; A detection module, which is used to detect the diffuse light beam of the near-infrared light beam on the surface of the sample to be measured and the fluorescence light beam on the surface of the sample to be measured respectively to obtain FDT detection data; the FDT detection data includes excitation light detection data corresponding to the diffuse light beam and fluorescence detection data corresponding to the fluorescence light beam.

[0008] In the second aspect, this application provides a fluorescence diffuse tomography method with full-angle line-scanning excitation, which is applied to the fluorescence diffuse tomography system with full-angle line-scanning excitation described above. The fluorescence diffuse tomography method with full-angle line-scanning excitation includes: Regarding the near-infrared light spot as a line light source and modeling the line light source 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, solve the steady-state diffusion equation with boundary conditions to obtain a linear equation characterizing the linear relationship between the flux density and the light source term; solve the linear equation to obtain the field strength distribution in the excitation light band and the field strength distribution in the fluorescence band corresponding to the point light source; Perform weighted summation on the field strength distributions in the excitation light band corresponding to all point light sources to obtain the field strength distribution in the excitation light band corresponding to the line light source; Perform normalized Born approximation on the field strength distribution in the excitation light band and the field strength distribution in the fluorescence band corresponding to the line light source to obtain the forward matrix of the system; Perform image reconstruction based on the forward matrix of the system and the FDT detection data.

[0009] According to the specific embodiments provided in this application, the following technical effects are disclosed in this application: This application provides a fluorescence diffusion tomography method and system for full-angle line-scanning excitation. The excitation scanning module is used to generate a near-infrared light beam and perform line-scanning excitation on the sample to be measured using the near-infrared light beam. The detection module is used to detect the diffused light beam of the near-infrared light beam on the surface of the sample to be measured and the fluorescence beam on the surface of the sample to be measured respectively, and obtain FDT detection data. The FDT detection data includes the excitation light detection data corresponding to the diffused light beam and the fluorescence detection data corresponding to the fluorescence beam. This 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 large information redundancy caused by the close distance between the individual excitation point light sources in point-by-point scanning is avoided. While maintaining the reconstruction accuracy, the imaging speed is significantly accelerated. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] In order to more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings in the following description are only some embodiments of this application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0011] Figure 1 It is a schematic structural diagram of a fluorescence diffusion tomography system for full-angle line-scanning excitation provided in Embodiment 1 of this application.

[0012] Figure 2 It is a schematic diagram of the calibration principle of the line-scanning excitation FDT system provided in Embodiment 1 of this application.

[0013] Figure 3 It is a schematic diagram of the X-ray projection of the steel rod at different angles during the system calibration process provided in Embodiment 1 of this application; among them,Figure 3 In (a), it is the X-ray projection of the steel bar when the rotary stage is at 0 degrees. Figure 3 In (b), it is the X-ray projection of the steel bar when the rotary stage is at 90 degrees.

[0014] Figure 4 It is a schematic diagram of the X-ray projection of the phantom in the phantom experiment provided in Embodiment 1 of the present application.

[0015] Figure 5 It is a schematic diagram of the line light source and the point light source set in the phantom experiment provided in Embodiment 1 of the present application; among them, Figure 5 In (a), it is the line light source, Figure 5 In (b), it is the point light source.

[0016] Figure 6 It is a schematic diagram of the reconstruction result of the phantom experiment in the line scan excitation mode provided in Embodiment 1 of the present application; among them, Figure 6 In (a), it is the reconstructed three-dimensional distribution of the fluorophore, Figure 6 In (b), it is the reconstructed slice image of the middle layer of the fluorophore, Figure 6 In (c), it is the reconstructed slice image of the last layer of the fluorophore.

[0017] Figure 7 It is a schematic diagram of the reconstruction result of the phantom experiment in the point scan excitation mode provided in Embodiment 1 of the present application; among them, Figure 7 In (a), it is the reconstructed three-dimensional distribution of the fluorophore, Figure 7 In (b), it is the reconstructed slice image of the middle layer of the fluorophore, Figure 7 In (c), it is the reconstructed slice image of the last layer of the fluorophore.

[0018] Figure 8 It is a method flow chart of a fluorescence diffusion tomography method with full-angle line scan excitation provided in Embodiment 2 of the present application.

[0019] Reference numerals: 1 - near-infrared laser; 2 - first lens; 3 - small hole; 4 - second lens; 5 - shutter; 6 - diaphragm; 7 - cylindrical lens; 8 - biaxial galvanometer; 9 - flat-field scanning lens; 10 - rotary stage; 11 - filter set; 12 - camera lens; 13 - electron multiplying charge coupled device; 14 - X-ray tube; 15 - X-ray detector; 16 - computer. Detailed implementation manners

[0020] Next, the technical solutions in the embodiments of the present application will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present application without creative efforts shall fall within the protection scope of the present application.

[0021] Embodiment 1.

[0022] This embodiment provides a fluorescence diffuse optical tomography (FDT) system with full-angle line-scanning excitation, as Figure 1 shown. The FDT system with full-angle line-scanning excitation includes the following modules.

[0023] An excitation scanning module, configured to generate a near-infrared light beam and use the near-infrared light beam to perform line-scanning excitation on a sample to be measured, where there is a fluorescence probe in the sample to be measured.

[0024] A detection module, configured to detect the diffuse light beam of the near-infrared light beam on the surface of the sample to be measured and the fluorescence light beam on the surface of the sample to be measured respectively, to obtain FDT detection data, where the FDT detection data includes excitation light detection data corresponding to the diffuse light beam and fluorescence detection data corresponding to the fluorescence light beam.

[0025] In this embodiment, the excitation scanning module includes: a near-infrared laser 1, and a first lens 2, a small hole 3, a second lens 4, a shutter 5, a diaphragm 6, a cylindrical lens 7, a two-axis galvanometer 8, and a flat-field scanning lens 9 arranged in sequence along the outgoing light path of the near-infrared laser 1. Among them, the cylindrical lens 7 is used to convert the near-infrared parallel light beam emitted from the diaphragm 6 into a near-infrared light beam.

[0026] The near-infrared laser 1 uses a multimode semiconductor laser with a wavelength of 750 nm because the scattering and absorption of the near-infrared light beam in biological tissues are relatively weak compared to 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 filtering by the small hole 3 and subsequent collimation. The small hole 3 is used to filter the multimode 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 from the second lens 4 is incident on the diaphragm 6. The diaphragm 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 light beam is a line light beam extending in the Zc-axis direction of the CT coordinate system. The two-axis galvanometer 8 is used to change the direction of the near-infrared light beam to achieve two-dimensional scanning. The two-axis galvanometer 8 includes an X-axis reflecting lens and a Y-axis reflecting lens, which respectively achieve scanning along the X-axis direction of the galvanometer coordinate system and scanning along the Y-axis direction of the galvanometer coordinate system. The flat-field scanning lens 9 is used to focus the near-infrared light beam on the surface of the sample to be measured, and the near-infrared light spot formed on the surface of the sample to be measured is a diffusible line light source. At this time, the near-infrared light beam can be called the excitation light, and the sample to be measured can be biological tissue.

[0027] In this embodiment, by setting the cylindrical lens 7, the cylindrical lens 7 converges the light beam in the horizontal direction to form a line light beam. Cooperating with the two-axis galvanometer 8 and the flat-field scanning lens 9, the focusing and scanning of the line light beam on the surface of the sample to be measured can be realized, so as to realize line-scanning excitation.

[0028] There are fluorescent probes inside the tissue to be measured. When the near-infrared light beam scans and excites the sample to be measured, the fluorescent probes generate fluorescence. At this time, a fluorescence light beam is generated on the surface of the sample to be measured.

[0029] In this embodiment, the excitation scanning module further includes: a rotary stage 10, and the sample to be measured is located on the rotary stage 10. The rotary stage 10 is used to drive the sample to be measured to rotate, so that the near-infrared light beam scans and excites different angles of the sample to be measured, and 360-degree full-angle scanning excitation of the sample to be measured can be realized.

[0030] In the excitation scanning module of the line-scanning excitation FDT system, the near-infrared light beam is generated by the near-infrared laser 1, is focused by the first lens 2, is filtered by the small hole 3, forms a near-infrared parallel light beam after passing through the second lens 4, and then passes through the shutter 5 and the aperture 6 in sequence to form a collimated near-infrared parallel light beam, is focused in the horizontal direction by the cylindrical lens 7 to form a near-infrared light beam, and scans and excites the sample to be measured on the rotary stage 10 through the two-axis galvanometer 8 and the flat-field scanning lens 9.

[0031] In this embodiment, the detection module includes a filter set 11, a camera lens 12, and an electron multiplying charge-coupled device 13 (Electronic Multiplying Charge-Coupled Devices, EMCCD).

[0032] The filter set 11 includes an excitation light filter, a fluorescence filter and a turntable. The excitation light filter and the fluorescence filter are both mounted on the turntable. The excitation light filter is used to filter the diffused beam of the near-infrared light beam on the surface of the sample to be measured and the fluorescence beam on the surface of the sample to be measured, so as to obtain a diffused beam. The fluorescence filter is used to filter the diffused beam of the near-infrared light beam on the surface of the sample to be measured and the fluorescence beam on the surface of the sample to be measured, so as to obtain a fluorescence 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 diffused beam, the excitation light filter is adjusted to the front of the camera lens 12. When it is necessary to collect the fluorescence beam, the fluorescence filter is adjusted to the front of the camera lens 12.

[0033] The camera lens 12 is used to collect light beams, that is, to collect the diffused beam obtained by the excitation light filter and the fluorescence beam obtained by the fluorescence filter.

[0034] 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 diffused beam collected by the camera lens 12 to obtain excitation light detection data, and to detect the fluorescence 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.

[0035] 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 used to receive and store the FDT detection data, and subsequently complete image reconstruction based on the FDT detection data. The computer 16 is also controllably connected to the near-infrared laser 1, and is used to control the operation of the near-infrared laser 1. Of course, the computer 16 can also be controllably connected to the shutter 5 and the two-axis galvanometer 8, and is used to control the opening or closing of the shutter 5 and the operating voltage of the two-axis galvanometer 8.

[0036] In the detection module of the online scanning excitation FDT system, the near-infrared light beam is used as the excitation light to excite the fluorophore in the sample to be measured to generate fluorescence. The fluorescence on the surface of the sample and the diffused light of the excitation light are detected by the electron multiplying charge coupled device 13 after passing through the filter set 11 and the camera lens 12, and the FDT detection data is obtained and transmitted to the computer 16.

[0037] The FDT system is often used in combination with other imaging modalities such as XCT (X-ray Computed Tomography) system. The XCT system can provide prior structural information of the sample to be measured for image reconstruction and play an important role in system calibration. Such as Figure 1As shown, it 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. The rotating stage 10 and the computer 16 are the parts shared by the two systems. The rotating stage 10 is used to carry the sample to be measured and realize the rotation function, and the computer 16 is used to control the operation of the two systems and store the detection data of the two systems.

[0038] The fluorescence diffusion tomography imaging system with line-scanning excitation in this embodiment further includes: an X-ray tube 14 and an X-ray detector 15. The X-ray tube 14 is used to emit X-rays to the sample to be measured, and the X-ray detector 15 is used to detect the X-rays passing through the sample to be measured. The computer 16 is communicatively connected to the X-ray detector 15, and is used to receive and store the XCT detection data of the X-ray detector 15, and subsequently determine the prior structural information of the sample to be measured based on the XCT detection data. The computer 16 is also control-connected to the X-ray tube 14 and is used to control the operation of the X-ray tube 14.

[0039] Based on the above structure, the specific imaging steps of an FDT system with line-scanning excitation proposed in this embodiment are as follows: Place the sample to be measured containing fluorescent probes (which can also be called fluorescent targets) on the rotating stage 10. Turn on the near-infrared laser 1 and the shutter 5. The near-infrared beam is focused by the first lens 2, filtered by the small hole 3, and forms a near-infrared parallel beam through the second lens 4. It successively passes through the shutter 5 and the aperture 6 to become a collimated near-infrared parallel beam. After passing through the cylindrical lens 7, the near-infrared parallel beam is focused in the horizontal direction to form a near-infrared light beam. After the scanning direction of the near-infrared light beam is adjusted by the biaxial galvanometer 8, it passes through the flat-field scanning lens 9 and is focused on the surface of the sample to be measured, forming a near-infrared light spot (i.e., a line light source). By controlling the rotation of the rotating stage 10, line-scanning excitation of the sample to be measured at different angles is achieved. After the near-infrared light beam hits the surface of the sample to be measured, it will diffuse inside the sample. When it reaches the fluorescent probe, it will excite the fluorophore to generate fluorescence. Then, the fluorescence will also diffuse inside the sample to be measured and reach the surface of the sample to be measured and be detected by the EMCCD. When using the EMCCD to detect fluorescence, first place the fluorescence filter in front of the camera lens 12 to filter out the excitation light. The fluorescence beam is converged onto the EMCCD through the camera lens 12. The operation when using the EMCCD to detect the excitation light is similar. First place the excitation light filter in front of the camera lens 12 to filter out the fluorescence. The excitation light beam (i.e., the diffuse beam) is converged onto the EMCCD through the camera lens 12. After the above operations are completed, use the XCT system to image the sample to be measured. The computer 16 controls the rotating stage 10 to rotate at intervals of 0.9° for 400 angles. The X-ray detector 15 will detect once at each angle to obtain XCT detection data. After the XCT detection data is reconstructed by the filtered back-projection algorithm, the external boundary and internal structure information of the sample to be measured are obtained. Based on the obtained external boundary and internal structure information of the sample to be measured, the steady-state diffusion equations of the excitation light and fluorescence are constructed, and the forward matrix of the system is obtained by using the finite element numerical solution method. Image reconstruction is performed using the forward matrix of the system and the FDT detection data of the excitation light and fluorescence detected by the FDT system, thereby realizing line-scanning fluorescence diffusion tomography.

[0040] This embodiment provides a fluorescence diffusion tomography system with full-angle line-scanning excitation. Based on the traditional point-scanning excitation FDT system, the scanning excitation mode is improved, and a line beam is used for scanning excitation. Without loss of reconstruction accuracy, the FDT imaging speed is significantly accelerated.

[0041] The current image reconstruction process is based on a point light source. Therefore, this embodiment further explores the corresponding forward process modeling method and system calibration method of the system, so as to significantly accelerate the FDT imaging speed without loss of reconstruction accuracy.

[0042] The system forward process modeling method aims to accurately model the diffusion movement of the line light source in the sample to be measured under the line scan excitation mode, so as to ensure the reconstruction quality. For the steady-state diffusion equation of the traditional point scan excitation FDT system, the finite element numerical solution method is used to discretize the solution domain and construct the corresponding linear discrete equations, establish the linear equation between the flux density and the light source term, obtain the field strength distributions in the fluorescence band and the excitation light band by solving the linear equation, and finally perform the normalized Born approximation processing to obtain the system forward matrix of the point scan excitation FDT system. To ensure the accurate modeling of the FDT system under the line light source scan excitation mode, the line light source is modeled as an overall composed of multiple discrete point light sources. Then, the field strength distribution diffused by the line light source can be regarded as the weighted superposition of the field strength distributions diffused by multiple point light sources. Similar to the forward modeling steps of the point scan excitation FDT, the normalized Born approximation processing is performed on the processed field strength distributions in the excitation light band and the fluorescence band to obtain the system forward matrix of the line scan excitation FDT system. This method can well describe the diffusion of the line light source inside the sample to be measured and ensure the reconstruction accuracy. That is, for the line light source, it can be modeled as a set of multiple point light sources. The number of divided point light sources is determined by the shape of the sample surface and the CT voxel size. Then, as a whole, the field strength distribution formed by the diffusion of the line light source can be approximated as the accumulation of the field strength distributions diffused by the divided point light sources. Considering that the line light source shows an intensity distribution with strong in the middle and weak at both ends, different summation weights can be assigned to the field strength distributions of the discrete point light sources at different positions on the line light source. Finally, the normalized Born approximation processing is performed using the processed field strength distributions in the fluorescence band and the excitation light band to obtain the system forward matrix of the line scan excitation FDT system.

[0043] The most commonly used forward model of FDT is the diffusion equation (DE) obtained by performing the first-order spherical harmonic approximation on the radiative transfer equation (RTE). The steady-state diffusion equation for FDT is: (1) (2) (3) In the above formula, the subscript x represents the excitation light band, and the subscript m represents the fluorescence band; is the absorption coefficient, is the absorption coefficient in the excitation light band, is the absorption coefficient in the fluorescence band; is the flux density, is the spatial coordinate of the region to be reconstructed in the sample to be measured, is the flux density in the excitation light band, representing the excitation light field strength distribution, is the flux density in the fluorescence band; is the gradient operator; is the diffusion coefficient, is the reduced scattering coefficient, is the diffusion coefficient in the excitation light band, is the diffusion coefficient in the fluorescence band; is the source term, is the source term in the excitation light band, is the 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.

[0044] The boundary conditions of the steady-state diffusion equation are as follows: (4) (5) In the above formula, is the reflection coefficient at the tissue boundary; is the unit normal vector pointing into the sample at the tissue boundary.

[0045] The finite element numerical solution method is used to solve the steady-state diffusion equation with boundary conditions (i.e., the above formulas (1)-(5)). Specifically, the solution domain is discretized according to the principle of functional variation or the weighted residual method, and the corresponding discrete equations are constructed to establish the linear relationship between the flux density and the source term, as follows: (6) (7) In the above formula, is the stiffness matrix in the excitation light band; is the stiffness matrix in the fluorescence band.

[0046] For the point-scanning excitation FDT system, the field strength distributions in the excitation light band and the fluorescence band can be obtained through formulas (6) and (7), and further normalized Born approximation can be performed to obtain the forward matrix of the system, as follows: (8) In formula (8), is the forward matrix of the system, is the spatial coordinate of the detector. The detector is the detection point on the sample to be measured selected by the user, is the spatial coordinate of the point light source, is the spatial coordinate of the region to be reconstructed in the sample to be measured; is the field strength distribution in the fluorescence band; and are both the field strength distributions in the excitation light band.

[0047] For a line light source, the line light source can be modeled as an integral composed of multiple point light sources. Then, the field strength distribution diffused by the line light source can be regarded as the accumulation of the field strength distributions diffused by the point light sources, as follows: (9) (10) In the above formula, the superscript represents the line light source, and the superscript p represents the point light source; and are both the field strength distributions in the excitation light band of the line light source; is the p th normalized weight coefficient of the point light source; and are both the field strength distributions in the excitation light band of the p th point light source.

[0048] The number of accumulations of the superscript p is determined by the surface shape of the sample to be measured and the size of the CT voxel. Since the energy of the line light source presents a Gaussian function distribution with strong in the middle and weak at both ends, the normalized weight coefficient is introduced to assign different summation weights to the field strength distributions in the excitation light band of the discrete point light sources at different positions on the line light source. is set according to the following formulas (11) and (12). According to the length and energy distribution of the line light source, the standard deviation in formula (11) is set to about 0.74. The sorting of the point light sources has a value range of [1, p], with a step size of 1 when taking values, where p is the number of point light sources segmented. The weight coefficient is calculated according to formula (11), and then the weight coefficient is normalized to the maximum value according to formula (12) to obtain the normalized weight coefficient .

[0049] (11) (12) In the above formula, is the sorting of the point light sources, and all the point light sources are sorted in the order from the first end (i.e., the upper end) to the second end (i.e., the lower end) of the line light source.

[0050] Substitute formulas (9)-(12) into formula (8), replace the field strength distribution in the excitation light band, and update to obtain the forward matrix , and further obtain the forward model of the line-scanning excitation FDT system as follows: (13) In Equation (13), represents the ratio of the fluorescence detection data to the excitation light detection data; is the three-dimensional distribution of the fluorescence target inside the sample to be measured. Using Equation (13) and combining the detected excitation light detection data and fluorescence detection data, the image reconstruction of the line-scanning excitation FDT system can be performed.

[0051] Of course, in this embodiment, the weight coefficient may not be normalized. At this time, the intensity distributions of the excitation light bands corresponding to all point light sources are weighted and summed to obtain the intensity distribution of the excitation light band corresponding to the line light source. Specifically, for each point light source, calculate the product of the weight coefficient corresponding to the point light source and the intensity distribution of the excitation light band corresponding to the point light source; sum all the products to obtain the intensity distribution of the excitation light band corresponding to the line light source. Among them, the calculation formula for the weight coefficient corresponding to the point light source is Equation (11).

[0052] Since the distance between the centers of the two reflecting lenses in the two-axis galvanometer 8 is much smaller than the working distance of the fθ lens, it can be approximately considered that the excitation light is emitted from the center of the Y-axis reflecting lens, and its propagation direction depends on the deflection angle of the two-axis galvanometer 8 (determined by the input voltage). By calibrating the two-axis galvanometer 8, the relevant parameters of the starting point and direction of the excitation light can be determined. The system calibration method aims to accurately extract the spatial coordinates of the line light spot (i.e., the near-infrared light spot, also the line light source) on the surface of the sample to be measured by determining the starting point spatial coordinates at both ends of the line beam (i.e., the near-infrared beam) and the relationship between the line beam deflection angle and the two-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 two-axis galvanometer and the background plate, a cylindrical thin steel bar with the same length and width as the line light spot is used to calibrate the spatial position of the line light spot, and with the help of the spatial positioning ability of the XCT system, the starting point spatial coordinates at both ends of the line beam and the relationship between the line beam deflection angle and the two-axis galvanometer voltage are determined. Subsequently, accurate spatial coordinate information of the line light source on the sample surface can be obtained, ensuring the reconstruction quality of the line-scanning excitation FDT.

[0053] The system calibration method proposed in this embodiment needs to be implemented with the help of the XCT system, and a background plate made of foam or glass material with less X-ray absorption and a cylindrical thin steel bar with the same length and width as the line light spot also need to be prepared. As Figure 2As shown in the figure, for the determination of the spatial coordinates of the starting points at both ends of the line beam, first, a background plate is vertically fixed at a position within the focusing range of the line spot on the rotary stage 10 to truncate the line beam and reveal the line spot, and a cylindrical thin steel rod is placed on the background plate with double-sided tape attached to calibrate the position of the line spot. Then, several sets of voltage values with obvious changes (used to drive the two-axis galvanometer 8) are selected. At each set of voltage values, the steel rod is moved to coincide with the position of the line spot on the background plate, and the spatial coordinates of both ends of the steel rod are determined with the help of the XCT system, that is, the spatial coordinates of both ends of the line spot on the background plate. Next, the background plate is moved a small distance within the focusing range of the line spot to position two and fixed. Similarly, at the several sets of voltage values selected before, the above operation of moving the steel rod to calibrate the spatial position of the line spot is repeated. In this way, following the geometric principle that two points determine a straight line, several non-parallel light rays can be determined for both ends of the line beam respectively, and the spatial coordinates of the starting points at both ends of the line beam can be determined by finding the intersection points of these several light rays.

[0054] Specifically, the calibration process is as follows: Control the background plate to be in the first position of the rotary stage (i.e., position one). For each calibration voltage value, control the two-axis galvanometer to work with the calibration voltage value, determine the position where the near-infrared light beam hits the background plate, and based on the position where the near-infrared light beam hits the background plate, place the steel rod on the background plate, and use the X-ray tube and the X-ray detector to determine the first spatial coordinate of the first end of the steel rod and the first spatial coordinate of the second end of the steel rod; Control the background plate to be in the second position of the rotary stage (i.e., position two). For each calibration voltage value, control the two-axis galvanometer to work with the calibration voltage value, determine the position where the near-infrared light beam hits the background plate, and based on the position where the near-infrared light beam hits the background plate, place the steel rod on the background plate, and use the X-ray tube and the X-ray detector to determine the second spatial coordinate of the first end of the steel rod and the second spatial coordinate of the second end of the steel rod; Based on the first spatial coordinate and the second spatial coordinate of the first end of the steel rod corresponding to all calibration voltage values and the first spatial coordinate and the second spatial coordinate of the second end of the steel rod, determine the starting point spatial coordinate of the first end of the line beam and the starting point spatial coordinate of the second end of the line beam.

[0055] The expression for finding the intersection point of non-parallel light rays is as follows: (14) In formula (14), is the first objective function; is the k first spatial coordinate corresponding to the th calibration voltage value, representing the spatial coordinate vector of the position where the line spot hits the background plate before moving the background plate at the same set of voltage values for the first end (second end) of the line beam; kThe second spatial coordinates corresponding to a calibration voltage value, representing the spatial coordinate vector at the position of the line light spot hitting the background board after moving the background board under the same set of voltage values at the first end (second end) of the line light beam; It is the starting spatial coordinate of the first end (second end) of the line light source, representing the starting position vector of the first end (second end) of the line light beam; the normr function is a function for finding the unit vector.

[0056] Figure 3 The X-ray projection diagrams of the thin steel rod at different angles are shown. By using 400 projection diagrams for CT reconstruction, the CT coordinate data of both ends of the line light spot hitting the background board at different voltage values in Table 1 can be obtained. Using the data in Table 1 and combining with Equation (14), the starting spatial coordinates of both ends of the line light beam can be obtained more accurately through fitting. and (unit: mm) and the corresponding errors and , , , , .

[0057] Table 1 CT coordinates of both ends of the line light spot hitting the background board at different voltage values (mm)

[0058] For determining the relationship between the deflection angle of the line light beam and the voltage of the two-axis galvanometer, it is also necessary to first vertically fix the background board within the focusing range of the line light spot on the rotary stage 10, and then several different voltage values of the two-axis galvanometer need to be selected, that is, several voltage values of the two-axis galvanometer with obvious changes in the X-axis and Y-axis directions (including the X-axis voltage and the Y-axis voltage) are selected. And under each set of voltage values, the steel rod is moved to coincide with the line light spot on the background board, and the spatial coordinates of the midpoint of the steel rod (i.e., the center point), which is also the spatial coordinates of the midpoint of the line light spot, are determined by means of the XCT system. Finally, combining with the determined starting spatial coordinates of the midpoint of the line light beam, the spatial coordinates of the midpoint of the line light spot and the corresponding voltage value data are fitted, and according to the fitting situation of the spatial coordinates of the midpoint of the line light spot and the voltage value, the relationship between the deflection angle of the line light beam and the voltage of the two-axis galvanometer is determined.

[0059] Specifically, the calibration process is as follows: control the background plate to be in the third position of the rotary stage. For each set of X-axis voltage values and Y-axis voltage values for calibration, control the dual-axis galvanometer to work with the X-axis voltage value and Y-axis voltage value for calibration, determine the position where the near-infrared light beam hits the background plate, and based on the position where the near-infrared light beam hits the background plate, place a steel bar on the background plate, and use the X-ray tube and X-ray detector to determine the third spatial coordinates of the midpoint of the steel bar; based on all the X-axis voltage values for calibration, Y-axis voltage values for calibration, and the third spatial coordinates of the midpoint of the steel bar, determine the relationship between the line beam deflection angle and the dual-axis galvanometer voltage.

[0060] The relationship between the line beam deflection angle and the dual-axis galvanometer voltage is as follows: (15) (16) In the above formula, and respectively 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; and respectively 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 (0V, 0V); and are respectively the deflection angles of the X-axis reflecting mirror and Y-axis reflecting mirror in the dual-axis galvanometer caused by a unit input voltage; and are respectively the k group-set X-axis voltage (i.e., the X-axis voltage value for calibration) and Y-axis voltage (i.e., the Y-axis voltage value for calibration).

[0061] The unit direction vector of the line beam can be expressed as: (17) In formula (17), is the unit direction vector of the near-infrared light beam.

[0062] The key parameters such as , , and can be obtained by minimizing the following formula (18): (18) In formula (18), is the second objective function; is the unit direction vector of the near-infrared light beam; is the starting point spatial coordinate of the midpoint of the line beam, which can be obtained by a fitting method similar to that of the starting point spatial coordinates of the first end and the second end of the line beam; is the third spatial coordinate corresponding to the X-axis voltage value and the Y-axis voltage value for calibration of the k group, representing the spatial coordinate of the midpoint of the line light spot where the lower-line light beam of the k group of voltage values hits the background board.

[0063] Table 2 CT coordinates (mm) at the midpoint of the line light spot hitting the background board under different voltage values

[0064] Using the different voltage values in Table 2 and the corresponding CT coordinates at the midpoint of the line light spot hitting the background board, and combining with Equation (18), through function minimization fitting, , , and and other key parameters and the corresponding errors g , , , , , g = 0.1985.

[0065] The purpose of this embodiment is to overcome the deficiency of the existing FDT technology in imaging speed, and a fluorescence diffusion tomography imaging system with full-angle line-scanning excitation is proposed, so as to shorten the data acquisition time and accelerate the FDT imaging speed while ensuring the reconstruction quality. Based on the traditional point-scanning excitation FDT system, this embodiment improves the scanning excitation mode, uses a line light beam for scanning excitation, and explores the corresponding forward process modeling method and system calibration method, so as to accelerate the FDT imaging speed without loss of reconstruction accuracy.

[0066] In order to verify the improvement in imaging speed and the preservation effect 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 about 40 mm containing 1% intralipid was used as the phantom, and a small amount of DIR (near-infrared fluorescence probe for cell membrane) solution with a concentration of 2 μmol / L was filled into both ends of a glass capillary with a diameter of about 2 mm and sealed, and then the glass capillary was inserted into the inside of the beaker. The upper end of the glass capillary was fixed with a glassware with double-sided tape on the side fixed to the upper edge of the beaker, so that the DIR solution could be suspended in the intralipid to mimic the fluorophores inside the phantom. The X-ray projection image of the phantom is as Figure 4 shown.

[0067] In the phantom experiment, line-scanning excitation imaging and point-scanning excitation imaging were respectively performed on the phantom. The line light source and the point light source are as Figure 5As shown. Both scanning excitation modes are evenly spaced for excitation at 48 angles. The line light source is about 13 mm long, and the point light source scans 5 times along the Z-axis at each angle, and the scanning range is the same as the length of the line light source. In the line scanning excitation mode, the system forward matrix is constructed according to Equations (1)-(13), and each line light source is discretized into 30 point light sources. The L1 regularization is selected for the reconstruction regularization term of both scanning excitation modes, and the fast iterative shrinkage thresholding algorithm (FISTA) is selected as the optimization algorithm. The experimental parameters are set as shown in Table 3.

[0068] Table 3 Comparison of experimental parameter settings and imaging times

[0069] Figure 6 and Figure 7 In (a), (b), and (c) in [reference], they are the reconstructed three-dimensional distribution of fluorophores, the reconstructed slice map of the middle layer of fluorophores, and the reconstructed slice map of the last layer of fluorophores respectively. Among them, the area enclosed by the white ring represents the true distribution of fluorophores. It can be seen from the reconstruction results that the reconstruction quality of the line scanning excitation mode and the point scanning excitation mode is comparable in the middle layer of fluorophores. However, in the last layer of fluorophores, only the line scanning excitation mode can reconstruct a better signal, while the point scanning excitation mode does not reconstruct a signal. This may be because the acquisition in the Z-axis direction of the point scanning excitation is not dense enough, and too much redundant information in the system forward matrix affects the reconstruction quality. The imaging data acquisition times of the two scanning excitation modes are shown in Table 3. It should be noted that after the system takes a fluorescence image or an excitation light image at each angle, a corresponding dark field image in the fluorescence band or the excitation light band needs to be taken. Therefore, the ratio of the imaging times of the two is about 1:3. In summary, the phantom experiment verifies that the line scanning excitation FDT system not only greatly reduces the imaging time but also effectively improves the reconstruction quality.

[0070] This embodiment belongs to the fields of optics and biomedical engineering, and provides a fluorescence diffuse tomography system with full-angle line-scanning excitation, including a line-scanning excitation FDT system and corresponding system forward process modeling methods and system calibration methods. Among them, the line-scanning excitation FDT system includes: a near-infrared laser 1, a first lens 2, a small hole 3, a second lens 4, a shutter 5, a diaphragm 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. In order to accurately model the diffusion motion of the line light source in the sample in the line-scanning excitation mode and obtain an accurate forward model of line-scanning FDT, the line light source is modeled as multiple discrete point light sources. Then, the field strength distribution of the line light source diffusion can be regarded as the weighted superposition of the field strength distributions of multiple point light sources diffusion. Then, the normalized Born approximation is performed on the processed field strength distributions in the excitation band and the fluorescence band to obtain the system forward matrix of the line-scanning excitation FDT system. In order to obtain accurate spatial coordinate information of the line light source on the sample surface and ensure the reconstruction quality, a system calibration method is formulated. Based on the geometric principle that two points determine a straight line, through the coordinated control of the biaxial 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, and with the help of the spatial positioning ability of the XCT system, the determination of the spatial coordinates of the starting points at both ends of the line beam and the relationship between the deflection angle of the line beam and the voltage of the biaxial galvanometer are realized. The purpose of this embodiment is to significantly accelerate the FDT imaging speed while ensuring the reconstruction accuracy, and help the further application expansion of FDT technology in fields with high real-time requirements such as dynamic imaging.

[0071] Aiming at the limitation of the slow imaging speed of the existing point-scanning excitation FDT system, this embodiment improves the scanning excitation mode and innovatively proposes a line-scanning excitation FDT system, which can greatly improve the imaging speed while ensuring the reconstruction accuracy. This embodiment has the following advantages.

[0072] (1) The full-angle line-scanning excitation FDT system proposed in this embodiment performs single-scan excitation with only one line light source at each angle, avoiding the time-consuming operation of the traditional point-scanning excitation that requires multiple scans 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 accelerate the imaging speed without sacrificing the reconstruction accuracy, and help the further application expansion of FDT technology in fields with high real-time requirements such as dynamic imaging.

[0073] (2) The forward process modeling method proposed in this embodiment can accurately model the diffusion motion of the line light source in the sample by discretizing the line light source into multiple point light sources and regarding the field strength distribution of the line light source diffusion as the weighted accumulation of the field strength distributions of point light sources diffusion, ensuring the accuracy of forward modeling and inverse reconstruction.

[0074] (3)The system calibration method proposed in this embodiment is based on the geometric principle that two points determine a straight line. Through the coordinated control of the biaxial 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 ability of the XCT system, the starting spatial coordinates of both ends of the line beam and the relationship between the line beam deflection angle and the biaxial galvanometer voltage can be determined more accurately, providing accurate light source position information for subsequent reconstruction.

[0075] Embodiment 2.

[0076] This embodiment provides a fluorescence diffuse tomography method for full-angle line scanning excitation, which is applied to the fluorescence diffuse tomography system for full-angle line scanning excitation described in Embodiment 1. As Figure 8 shown, the fluorescence diffuse tomography method for full-angle line scanning excitation includes the following steps.

[0077] S1: Regard the near-infrared light spot as a line light source and model the line light source as a plurality of 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.

[0078] S2: For each point light source, solve the steady-state diffusion equation with boundary conditions to obtain a linear equation characterizing the linear relationship between the flux density and the light source term; solve the linear equation to obtain the excitation light band field strength distribution and the fluorescence band field strength distribution corresponding to the point light source.

[0079] S3: Perform weighted summation on the excitation light band field strength distributions corresponding to all point light sources to obtain the excitation light band field strength distribution corresponding to the line light source.

[0080] S4: Perform normalized Born approximation on the excitation light band field strength distribution and the fluorescence band field strength distribution corresponding to the line light source to obtain the system forward matrix.

[0081] S5: Perform image reconstruction based on the system forward matrix and the FDT detection data.

[0082] In S4, performing weighted summation on the excitation light band field strength distributions corresponding to all point light sources to obtain the excitation light band field strength distribution corresponding to the line light source specifically includes: for each point light source, calculate the product of the weight coefficient corresponding to the point light source and the excitation light band field strength distribution corresponding to the point light source; perform summation on all products to obtain the excitation light band field strength distribution corresponding to the line light source.

[0083] The calculation formula for the weight coefficient corresponding to the point light source is: (19) 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 the order from the first end to the second end of the line light source.

[0084] The method for determining the spatial coordinates of the point light source in the system forward matrix is as follows: taking the actual biaxial galvanometer voltage as the input, based on the pre-calibrated starting spatial coordinates of the first end of the line beam, the starting spatial coordinates of the second end of the line beam, and the relationship between the line beam deflection angle and the biaxial galvanometer voltage, determine the spatial plane corresponding to the line light source; calculate the spatial coordinates of the intersection line between the spatial plane corresponding to the line beam and the surface of the sample to be measured to obtain the spatial coordinates of the line light source; based on the spatial coordinates of the line light source, determine the spatial coordinates of the point light source, specifically discretize the spatial coordinates of the line light source to obtain the spatial coordinates of each point light source.

[0085] Among them, the calibration method for the starting spatial coordinates of the first end of the line beam, the starting spatial coordinates of the second end of the line beam, and the relationship between the line beam deflection angle and the biaxial galvanometer voltage includes the following steps.

[0086] (1) Control the background plate to be in the first position of the rotary stage. For each calibration voltage value, control the biaxial galvanometer to work with the calibration voltage value, determine the position where the near-infrared light beam hits the background plate, and based on the position where the near-infrared light beam hits the background plate, place a steel rod on the background plate, and use 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; the shape, size, and position of the steel rod are the same as those of the near-infrared light spot.

[0087] (2) Control the background plate to be in the second position of the rotary stage. For each calibration voltage value, control the biaxial galvanometer to work with the calibration voltage value, determine the position where the near-infrared light beam hits the background plate, and based on the position where the near-infrared light beam hits the background plate, place a steel rod on the background plate, and use 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.

[0088] (3) 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, 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.

[0089] (4) Control the background plate to be in the third position of the rotary stage. For each set of calibrated X-axis voltage values and calibrated Y-axis voltage values, control the two-axis galvanometer to work with the calibrated X-axis voltage values and calibrated Y-axis voltage values, determine the position where the near-infrared light beam hits the background plate, and based on the position where the near-infrared light beam hits the background plate, place a steel rod on the background plate, and use the X-ray tube and X-ray detector to determine the third spatial coordinates of the midpoint of the steel rod.

[0090] (5) Based on all the calibrated X-axis voltage values, calibrated Y-axis voltage values, and the third spatial coordinates of the midpoint of the steel rod, determine the relationship between the line beam deflection angle and the two-axis galvanometer voltage.

[0091] Among them, based on the first spatial coordinates and second spatial coordinates of the first end of the steel rod corresponding to all the calibrated voltage values and the first spatial coordinates and second spatial coordinates of the second end of the steel rod, 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, specifically including: using the first spatial coordinates and second spatial coordinates of the first end of the steel rod corresponding to all the calibrated voltage values as inputs, and using the first calibration formula to determine the starting spatial coordinates of the first end of the line beam; using the first spatial coordinates and second spatial coordinates of the second end of the steel rod corresponding to all the calibrated voltage values as inputs, and using the first calibration formula to determine the starting spatial coordinates of the second end of the line beam.

[0092] The first calibration formula is: (20) In formula (20), is the first objective function; is the k first spatial coordinate corresponding to the th calibrated voltage value; k is the second spatial coordinate corresponding to the th calibrated voltage value;

[0093] is the starting spatial coordinate of the first end or the second end of the line light source.

[0093] Among them, based on all the calibrated X-axis voltage values, calibrated Y-axis voltage values, and the third spatial coordinates of the midpoint of the steel rod, determine the relationship between the line beam deflection angle and the two-axis galvanometer voltage, specifically including: using all the calibrated X-axis voltage values, calibrated Y-axis voltage values, and the third spatial coordinates of the midpoint of the steel rod as inputs, and using the second calibration formula to determine the relationship between the line beam deflection angle and the two-axis galvanometer voltage.

[0094] The second calibration formula is: (21) In formula (21), is the second objective function; is the unit direction vector of the near-infrared light beam; is the starting spatial coordinate of the midpoint of the line beam; is the k third spatial coordinate corresponding to the calibration X-axis voltage value and the calibration Y-axis voltage value of the

[0095] (22) In formula (22), is the angle between the propagation direction of the near-infrared light 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 light beam and the positive direction of the Xc axis in the CT coordinate system.

[0096] (23) In formula (23), is the angle between the propagation direction of the near-infrared light beam and the positive direction of the Xc axis in the CT coordinate system when both the calibration X-axis voltage value and the calibration Y-axis voltage value are 0; is the deflection angle of the X-axis reflecting mirror in the biaxial galvanometer caused by a unit input voltage; is the k th calibration X-axis voltage value.

[0097] (24) In formula (24), is the angle between the propagation direction of the near-infrared light beam and the positive direction of the Zc axis in the CT coordinate system when both the calibration X-axis voltage value and the calibration Y-axis voltage value are 0; is the deflection angle of the Z-axis reflecting mirror in the biaxial galvanometer caused by a unit input voltage; is the k th calibration Y-axis voltage value.

[0098] The technical features of the above embodiments can be combined arbitrarily. For the sake of brevity of description, 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, it should be considered as the scope recorded in this specification.

[0099] In this article, specific examples are used to elaborate on the principle and implementation manner of the present application. The description of the above embodiments is only used to help understand the method and its core idea of the present application; at the same time, for those of ordinary skill in the art, according to the idea of the present application, there will be changes in the specific implementation manner and application scope. To sum up, the content of this specification should not be construed as a limitation to the present 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 light 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 light beam and fluorescent detection data corresponding to the fluorescent light beam.

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 from 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 also 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, 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 camera lens is used to collect the diffuse light beam obtained by the excitation light filter and the fluorescent light beam obtained by the fluorescent 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 fluorescent detection data.

5. The fluorescence diffusion tomography system with full-angle line scanning excitation according to claim 1, characterized in that: The full-angle line scanning excited fluorescence diffusion tomography system also includes: an X-ray tube and an X-ray detector; the X-ray tube is used to emit X-rays to the sample to be tested; and the X-ray detector is used to detect the X-rays passing through the sample to be tested.

6. A fluorescence diffusion tomography method with full-angle line scanning excitation, applied to the fluorescence diffusion tomography system with full-angle line scanning excitation as claimed in any one of claims 1 to 5, characterized in that: The full-angle line scanning excited fluorescence diffusion tomography method comprises: 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 tested; 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 field intensity distribution of 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; The normalized Born approximation is performed 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.

7. The fluorescence diffusion tomography method of full-angle line scanning excitation according to claim 6, characterized in that: The field intensity distribution of the excitation light band corresponding to all point light sources is weighted and summed 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; summing all the products to obtain the field intensity distribution of the excitation light band corresponding to the line light source; The calculation formula of 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.

8. The fluorescence diffusion tomography method of full-angle line scanning excitation according to claim 6, characterized in that: The method for determining the spatial coordinates of the point light source in the system forward matrix is: Taking the actual dual-axis galvanometer voltage as input, 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, the spatial plane corresponding to the line light beam is determined; 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 are calculated to obtain the spatial coordinates of the line light source; based on the spatial coordinates of the line light source, the spatial coordinates of the point light source are determined; 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: The background plate is controlled to be at the first position of the rotating stage, and for each calibration voltage value, the dual-axis galvanometer is controlled to work at the calibration voltage value to determine the position where the near-infrared light beam hits the background plate, and 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 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 by using an X-ray tube and an X-ray detector; the steel rod and the near-infrared light spot have the same shape, size and position; Control the background plate to be at the second position of the rotating stage, control the dual-axis galvanometer to work at the calibration voltage value for each calibration voltage value, determine the position where the near-infrared beam hits the background plate, and place a steel rod on the background plate based on the position where the near-infrared beam hits the background plate, and 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 by using an X-ray tube and an X-ray detector; Determine 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; Control the background plate to be at the third position of the rotating stage, control the dual-axis galvanometer to work with the calibration X-axis voltage value and the calibration Y-axis voltage value for each set of calibration X-axis voltage value and calibration Y-axis voltage value, determine the position where the near-infrared beam hits the background plate, and place a steel rod on the background plate based on the position where the near-infrared beam hits the background plate, and determine 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, the relationship between the line beam deflection angle and the dual-axis galvanometer voltage is determined.

9. The fluorescence diffusion tomography method of full-angle line scanning excitation according to claim 8, characterized in that: 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, 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 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, the spatial coordinates of the starting point of the first end of the line beam are determined using the 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 spatial coordinates of the starting point of the second end of the line beam are determined using the first calibration formula; 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 end or the second end of the line beam.

10. The fluorescence diffusion tomography method of full-angle line scanning excitation according to claim 8, 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, including: Taking 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, When the calibration X-axis voltage value and the calibration Y-axis voltage value are both 0, the angle between the propagation direction of the near-infrared beam and the positive direction of the Xc axis in the CT coordinate system; It 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; It 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.

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