CN108335338B

CN108335338B - Experimental animal multi-mode fusion imaging system and using method

Info

Publication number: CN108335338B
Application number: CN201810268753.9A
Authority: CN
Inventors: 田捷; 王坤; 高源�; 尹琳
Original assignee: Institute of Automation of Chinese Academy of Science
Current assignee: Institute of Automation of Chinese Academy of Science
Priority date: 2018-03-28
Filing date: 2018-03-28
Publication date: 2021-01-05
Anticipated expiration: 2038-03-28
Also published as: CN108335338A

Abstract

The utility model provides a multimode fusion imaging system of experimental animal and a using method, comprising: an optical imaging unit for acquiring optical tomography information of an experimental animal body, comprising: the FMT module is used for collecting FMT information of an experimental animal body, and the FMT module reduces pollution of exciting light reflected light to collected signals by using a mirror filtering method; the MRI unit is arranged at a distance from the optical imaging unit and is used for acquiring MRI information of the experimental animal body; the fixed bed is used for fixing a test animal body and is respectively matched with the optical imaging unit and the MRI unit so that the test animal body can move rigidly between the optical imaging unit and the MRI unit; and the data processing unit is used for carrying out pixel-level fusion on the optical tomography information and the MRI information of the experimental animal body. According to the experimental animal multi-mode fusion imaging system and the using method, exciting light reflected light in emitted light is removed through a mirror filtering method, and then the problem of pollution of the reflected light of the exciting light to the emitted light in the FMT collection process is solved.

Description

Experimental animal multi-mode fusion imaging system and using method

Technical Field

The disclosure relates to the technical field of medical molecular imaging, in particular to an experimental animal multi-mode fusion imaging system and a using method thereof.

Background

The medical tomography technology for small animals is a tomography technology which takes experimental animals (such as mice, or other animals with the volume of imaging organs below 5cm by 5 cm) as imaging objects. The three-dimensional distribution and the shape of the focus are obtained by shooting and reconstructing a disease model established on an experimental animal body. The corresponding biomedical experiments are assisted, thereby being beneficial to the research of relevant aspects. The technology has wide application in tumor research, drug metabolism research and other aspects.

Magnetic Resonance Imaging (MRI) and diffuse optical tomography are common techniques for medical tomography of experimental animals. The nuclear magnetic resonance imaging technology utilizes the characteristic that protons in tissues generate nuclear magnetic resonance phenomenon after receiving radio frequency excitation pulse excitation under a uniform magnetic field to generate nuclear magnetic resonance signals, and high-resolution anatomical tomography imaging is further carried out on the tissues by acquiring the nuclear magnetic resonance signals. Among the diffuse optical tomography techniques, bio-autofluorescence computed tomography (BLT) and excitation fluorescence computed tomography (FMT) are more commonly used. The BLT imaging technology utilizes the chemical reaction between luciferase in an organism and a Luciferin substrate (Luciferin) injected into the organism to generate fluorescence, generates light spots on the surface of the organism and is received by a detector, and further obtains the spatial distribution information of the luciferase in the organism. FMT imaging techniques utilize targeted fluorescent probes to bring fluorophores into targeted biological tissue. Fluorophores in biological tissue are irradiated by an exogenous laser (i.e., excitation light) and their electrons transition to an excited state. Then, in the process of returning the electrons from the excited state to the ground state, fluorescence is released (i.e., light is emitted). After the fluorescence propagates in the organism, a light spot is generated on the surface of the organism and is received by the detector, so that the spatial distribution information of the fluorescence targeting probe in the organism is obtained.

However, in the process of implementing the present disclosure, the inventors found that since fluorescence is absorbed and scattered by various tissues in a living body while passing through the living body, a light spot propagating to the surface of the living body has been severely distorted, which makes it difficult to perform reconstruction imaging of morphological information of biological tissues in the living body by diffuse optical tomography. Moreover, although the FMT imaging technology selects the excitation light and the emission light in different spectral bands, the emission light is collected and filtered by using an optical filter. But the excitation light still pollutes the emitted light and affects the accuracy of the biological tissue morphological reconstruction. In addition, in the magnetic resonance imaging technology, an imaging object needs to be in a uniform magnetic field during imaging, and the magnetic field can affect electronic equipment such as a camera used for diffuse optical tomography imaging, so that other modalities cannot be acquired.

BRIEF SUMMARY OF THE PRESENT DISCLOSURE

Technical problem to be solved

Based on the technical problems, the present disclosure provides an experimental animal multimode fusion imaging system and a use method thereof, so as to alleviate the technical problem that excitation light pollutes emitted light and affects the accuracy of biological tissue morphological reconstruction in the FMT imaging technology in the prior art.

(II) technical scheme

According to one aspect of the present disclosure, there is provided a multimode fusion imaging system for laboratory animals, comprising: an optical imaging unit for acquiring optical tomography information of an experimental animal body, comprising: the FMT module is used for collecting FMT information of an experimental animal body, and the FMT module reduces pollution of reflected light of exciting light to collected signals by using a mirror filtering method; the MRI unit is arranged at a distance from the optical imaging unit and is used for acquiring MRI information of the experimental animal body; the fixed bed is used for fixing a test animal body and is respectively matched with the optical imaging unit and the MRI unit so that the test animal body can move rigidly between the optical imaging unit and the MRI unit; and the data processing unit is used for carrying out pixel-level fusion on the optical tomography information and the MRI information of the experimental animal body.

In some embodiments of the present disclosure, the mirror filtering method includes: calculating mirror filter wavelength lambda_f，λ_f＝2λ₁-λ₂(ii) a Respectively collecting the wavelengths of the optical filters as lambda₂And λ_fTime of excitation of fluorescent surface light spot result b₂And b_f(ii) a And calculating the final surface fluorescence spot b_p＝b₂-α*b_f(ii) a Wherein λ is₁Is the wavelength of the excitation light, λ₂To send outThe wavelength of the emitted light is determined,

b_2nto use a wavelength of lambda without using a fluorescent probe₂The light spot result on the surface of the fluorescence excited by the light filter b_fnTo use a wavelength of lambda without using a fluorescent probe_fThe obtained result of exciting the fluorescent surface light spot is collected when the optical filter is used.

In some embodiments of the present disclosure, the optical imaging unit further comprises: the BLT module is used for collecting BLT information of the experimental animal; and the CT module is used for acquiring CT information of the experimental animal.

In some embodiments of the present disclosure, the data processing unit includes: the system matrix construction module is used for constructing a system matrix by utilizing FMT information and BLT information; the reconstruction module is used for constructing a regularization matrix by adopting a Gaussian weight Laplace matrix method, and calculating the light intensity distribution of the fluorescent light source in the experimental animal body by using a conjugate gradient method in combination with a system matrix; the registration module is used for registering the reconstruction result of the FMT information and the BLT information and the MRI information by the reconstruction module by taking the CT information as a reference; and the fusion module is used for performing pixel-level fusion on the reconstruction results of the FMT information and the BLT information and the MRI information by utilizing the mapping relation of the FMT information, the BLT information and the MRI information obtained by the registration module.

In some embodiments of the present disclosure, the system matrix construction module comprises: the correction submodule corrects the FMT system matrix by adopting an excitation light threshold correction method, and the excitation light threshold correction method comprises the following steps: acquisition of phi_x(j) Maximum value of (1)_xmax(j) (ii) a Let all phi_x(j)＜0.4φ_xmax(j) Phi of_x(j) Are all set to 0.4 phi_xmax(j) (ii) a Correcting the FMT system matrix according to the following formula;

wherein phi is_x(j) Is exciting light in the body of the experimental animalIntensity distribution of fluorescent light, [ phi ]_m(i) Eta mu to measure the intensity distribution of the obtained surface fluorescence spot_af(j) Is the distribution of fluorescence light source in the body of the experimental animal.

In some embodiments of the present disclosure, the regularization matrix L is constructed by the reconstruction module by using a laplacian matrix with gaussian weights as follows:

L_G＝(l_i，j)_N×N

wherein l_ijRepresents an attenuating element, d_ijRepresenting the spatial distance between two voxels, ρ S_kFor the radial softening function, R is the gaussian kernel radius, and in the gaussian weighted laplace matrix method, R is 0.4.

In some embodiments of the present disclosure, the calculating the light intensity distribution of the fluorescent light source inside the experimental animal body by using a conjugate gradient method in combination with the system matrix in the reconstruction module includes: step A: establishing a target optimization function;

wherein the content of the first and second substances,

is a least-squares equation of the equation,

the regularization term is a Gihono Voff regularization term, lambda is a regularization parameter, L is the regularization matrix, and A is the system matrix; and B: taking an initial value x⁽⁰⁾C, calculating an initial residual vector r⁽⁰⁾＝b-Ax⁽⁰⁾And let p stand for⁽⁰⁾＝r⁽⁰⁾Wherein p is⁽⁰⁾Is the initial iteration direction;

and C: if r^(k)||₂C is less than or equal to c, let x be x^(k)The calculation terminates, otherwise the following is calculated:

x^(k+1)＝x^(k)+t_k*p^(k)

wherein r is^(k)Is the residual vector for the k-th iteration,

step size, p, for the k-th iteration^(k)Is the k iteration direction;

and correcting the obtained elements in x by the following formula:

wherein the content of the first and second substances,

representing the result of the kth iteration of the ith element of vector x,

is the corrected result vector;

step D: calculating r^(k+1)＝b-Ax^(k+1) And let p stand for^(k+1)＝r^(k+1)+α_kp^(k)

Wherein the content of the first and second substances,

step E: and C, returning the step C to judge if k is k + 1.

In some embodiments of the present disclosure, the fixed bed comprises: the two sides of the bed board are provided with baffles, and the bed board and the baffles are used for placing experimental animals; the optical imaging window is correspondingly arranged in the middle of the bed plate and on the baffle and is used for collecting imaging information of the experimental animal from the bottom and the side surface; the fixing interface is arranged on the bed board and/or the baffle and is used for assisting in fixing the experimental animal; the positioning point is arranged on the bed plate and/or the baffle and is used for positioning the optical imaging unit or the MRI unit; wherein, the bed board with the baffle contains organic glass.

In some embodiments of the present disclosure, the optical imaging unit includes: the BLT module, the FMT module and the CT module are all fixedly arranged on the plane turntable; the translation table reciprocates along the normal vector direction of the plane turntable and is detachably connected with the bed plate and/or the baffle; the translation table moves along the normal vector direction of the plane turntable, so that the optical imaging window on the fixed bed is exposed in the imaging range of the BLT module, the FMT module and the CT module, the BLT module, the FMT module and the CT module are driven to rotate through the plane turntable, and the optical tomography information of the experimental animal is acquired.

In some embodiments of the disclosure, wherein: the BLT module is a fluorescence camera and is used for collecting BLT information of the experimental animal body; the FMT module comprises: excitation light emitting means for emitting excitation light, comprising: the first rotating device is connected with the plane turntable and drives the rocker arm to rotate in a plane parallel to the plane turntable; the second rotating device is connected with the first rotating device through the rocker arm, and the rotating shaft of the second rotating device is vertical to the normal vector of the plane turntable; the optical fiber translation clamp is connected with the second rotating device, stretches along the rotating shaft of the second rotating device and forms a W-degree included angle with the rotating shaft of the second rotating device, wherein W is more than or equal to 0 degree and less than or equal to 15 degrees; the laser emergent port is connected with the optical fiber translation clamp, and is provided with a speed expanding head wheel for emitting a point light source or a surface light source; and a fluorescence camera for collecting FMT information of the experimental animal; the CT module includes: an X-ray bulb for emitting X-rays; the X-ray detection plate and the X-ray bulb tube are respectively arranged on two sides of the translation table and used for receiving X-rays penetrating through the experimental animal body; wherein the BLT module and the FMT module share the same fluorescence camera.

In some embodiments of the present disclosure, the MRI unit includes: a nuclear magnetic cavity for collecting MRI information; and the experimental animal bracket is detachably connected with the bed board and/or the baffle and drives the fixed bed to stretch into the nuclear magnetic cavity for nuclear magnetic imaging.

According to another aspect of the present disclosure, there is also provided a method for using a multimode fusion imaging system for a laboratory animal, the multimode fusion imaging system for a laboratory animal provided by the present disclosure includes: step 100: fixing a test animal to the optical imaging unit through the fixed bed; step 200: respectively collecting BLT information, FMT information and CT information of the experimental animal body, and correcting the FMT information by using a mirror filtering method; step 300: fixing a test animal body to the MRI unit through the fixed bed; step 400: collecting MRI information of the experimental animal; and step 500: performing pixel-level fusion on the BLT information, the FMT information, and the MRI information using the data processing unit.

In some embodiments of the present disclosure, collecting FMT information of the experimental animal body comprises: collecting FMT information by using a transmission model and selecting point laser; and/or collecting FMT information by using a reflection model and selecting planar laser; wherein the mirror filtering method is used when FMT information is collected using a reflection model.

In some embodiments of the present disclosure, selecting a spot laser to acquire FMT information using a transmission model comprises: the experimental animal body is a mouse, and the four limbs of the mouse are fixed by a wire through the fixing interface, so that the chest and abdomen of the mouse are exposed at the optical imaging window; adjusting the first rotating device to enable the laser emergent port and the fluorescence camera to be respectively positioned at two sides of the mouse; and adjusting the telescopic distance and angle of the optical fiber translation clamp, and acquiring the thoracic and abdominal FMT information under different excitation conditions.

In some embodiments of the present disclosure, selecting a facet laser to collect FMT information using a reflection model includes: the experimental animal body is a mouse, and the neck of the experimental animal body is fixed by using an adhesive tape, so that the head of the experimental animal body is exposed at the optical imaging window; selecting a filter with a wave band of 50nm wavelength less than the exciting light; collecting reflected light spot information of the exciting light under the condition of not using a fluorescent probe; using a fluorescent probe to collect FMT information of the head; and correcting the FMT information of the head by utilizing the reflected light spot information of the exciting light in combination with a mirror filtering method.

(III) advantageous effects

According to the technical scheme, the experimental animal multimode fusion imaging system and the using method have one or part of the following beneficial effects:

(1) fitting the reflected light distribution information of the excitation light under the emission light wavelength by a mirror filtering method, namely selecting the reflected light distribution information of the excitation light collected under the spectral band far away from the emission light wavelength, wherein the reflected light of the excitation light does not enter the body of the experimental animal, so that the reflected light of the excitation light under different wavelengths belongs to a linear relation, and fitting the reflected light distribution of the excitation light polluting the emission light by the reflected light distribution information of the excitation light collected under the band far away from the emission light wavelength, so that the reflected light of the excitation light in the emission light is removed, and the pollution problem of the reflected light of the excitation light on the emission light in the FMT collection process;

(2) the ill-posed property of a system matrix under a planar excitation light reflection model is reduced by using an excitation light threshold correction method;

(3) the method is based on the assumption that the correlation between two voxels is reduced along with the increase of the space distance between the two voxels, a Gaussian weight Laplacian matrix is designed as a regular matrix, the problem of the smoothness of diffusion optical reconstruction is successfully solved, the morphological information of a reconstruction object is provided, and the problems that the light spots transmitted to the surface of the organism are seriously distorted due to the absorption and scattering of various tissues in the organism when fluorescence passes through the organism, and the morphological information of the biological tissues in the organism is difficult to reconstruct and image are solved;

(4) the fixed bed is arranged to provide convenience for carrying the experimental animal body between the optical imaging unit and the MRI unit, so that the experimental animal body is guaranteed to be in rigid change under the imaging visual fields of the two units, registration and fusion among multi-mode imaging results are facilitated, and the influence of a uniform strong magnetic field of the MRI unit on electronic equipment in the optical imaging unit can be relieved.

Drawings

Fig. 1 is a schematic structural diagram of a multimode fusion imaging system of an experimental animal body according to an embodiment of the present disclosure.

Fig. 2 is a schematic structural diagram of a fixed bed in the experimental animal multi-mode fusion imaging system shown in fig. 1.

Fig. 3 is a schematic front view of an excitation light emitting device in the experimental animal multi-mode fusion imaging system shown in fig. 1.

Fig. 4 is a left side view of the excitation light emitting device in the experimental animal multi-mode fusion imaging system shown in fig. 1.

Fig. 5 is a schematic top view of an excitation light emitting device in the experimental animal multi-mode fusion imaging system shown in fig. 1.

Fig. 6 is a schematic flow chart of information acquisition in a method for using the experimental animal multi-mode fusion imaging system according to the embodiment of the disclosure.

Fig. 7 is a flowchart of data processing in the experimental animal multimodal fusion imaging system according to the embodiment of the disclosure.

[ description of main reference numerals in the drawings ] of the embodiments of the present disclosure

100-an optical imaging unit;

110-a planar turntable;

120-a translation stage;

130-a fluorescent camera;

140-excitation light emitting means;

141-first rotating means; 142-a rocker arm;

143-second rotating means; 144-translating the fiber clamp;

145-laser exit port; 146-speed expanding head wheel;

150-X-ray tube;

160-X-ray detection plate;

200-an MRI unit;

210-a nuclear magnetic cavity; 220-laboratory animal body holder;

300-fixed bed;

310-bed board; 320-a baffle plate;

330-an optical imaging window; 340-a fixed interface;

350-locating points;

400-data processing unit.

Detailed Description

In the experimental animal multimode fusion imaging system and the using method provided by the embodiment of the disclosure, the reflected light of the excitation light in the emission light is removed by a mirror filtering method, so that the pollution problem of the reflected light of the excitation light to the emission light in the FMT collection process is further alleviated, and the accuracy of biological tissue morphological reconstruction is improved.

For the purpose of promoting a better understanding of the objects, aspects and advantages of the present disclosure, reference is made to the following detailed description taken in conjunction with the accompanying drawings.

According to an aspect of the present disclosure, as shown in fig. 1, there is provided a multimode fusion imaging system for laboratory animals, comprising: an optical imaging unit 100 for collecting optical tomographic imaging information of the experimental animal; an MRI (magnetic Resonance imaging) unit 200 spaced apart from the optical imaging unit 100 for collecting MRI information of the experimental animal; a fixed bed 300 for fixing the experimental animal body, which is respectively matched with the optical imaging unit 100 and the MRI unit 200 to make the experimental animal body perform rigid movement between the two; and a data processing unit 400 for performing pixel-level fusion of the optical tomographic imaging information and the MRI information of the experimental animal.

In some embodiments of the present disclosure, as shown in fig. 1, the optical imaging unit 100 includes: the FMT module is used for collecting FMT information of an experimental animal body, and the FMT module reduces pollution of reflected light of exciting light to collected signals by using a mirror filtering method; the BLT module is used for collecting BLT information of the experimental animal; and the CT module is used for acquiring CT information of the experimental animal.

In the present disclosureIn some embodiments, a mirror filtering method includes: calculating mirror filter wavelength lambda_f，λ_f＝2λ₁-λ₂(ii) a Respectively collecting the wavelengths of the optical filters as lambda₂And λ_fTime of excitation of fluorescent surface light spot result b₂And b_f(ii) a And calculating the final surface fluorescence spot b_p＝b₂-α*b_f。

Wherein λ is₁Is the wavelength of the excitation light, λ₂In order to emit the wavelength of the light,

b_2nto use a wavelength of lambda without using a fluorescent probe₂The light spot result on the surface of the fluorescence excited by the light filter b_fnTo use a wavelength of lambda without using a fluorescent probe_fThe filter is used for collecting the obtained result of exciting the fluorescent surface light spot, the reflected light distribution information of the exciting light under the emission wavelength is fitted by selecting the reflected light distribution information of the exciting light collected under the spectral waveband far away from the emission wavelength through a mirror filtering method, the reflected light distribution information of the exciting light under the emission wavelength is fitted, the reflected light of the exciting light polluting the emission light is fitted through the reflected light distribution information of the exciting light collected under the waveband far away from the emission wavelength because the reflected light of the exciting light does not enter the body of the experimental animal, and therefore the problem of pollution of the reflected light of the exciting light in the emission light to the emission light in the FMT collection process is solved.

In some embodiments of the present disclosure, a data processing unit includes: the system matrix construction module is used for constructing a system matrix by utilizing FMT information and BLT information; the reconstruction module is used for constructing a regularization matrix by adopting a Gaussian weight Laplace matrix method, and calculating the light intensity distribution of the fluorescent light source in the experimental animal body by using a conjugate gradient method in combination with a system matrix; the registration module is used for registering the reconstruction result of the FMT information and the BLT information and the MRI information by the reconstruction module by taking the CT information as a reference; and the fusion module is used for performing pixel-level fusion on the reconstruction results of the FMT information and the BLT information and the MRI information by utilizing the mapping relation of the FMT information, the BLT information and the MRI information obtained by the registration module.

The specific registration steps of the registration module are as follows: obtaining a three-dimensional anatomical tomographic structure diagram of organs (brain, lung, liver, skeleton, kidney, heart and the like) by segmentation from the reconstructed CT tomographic image, wherein each segmented image of the organs obtained by segmentation is marked as a subgraph; registering the subgraph with the FMT information and the BLT information to obtain a mapping relation between the FMT information and the BLT information; and then, the CT image and the MRI information are registered, so that the mapping relation between the FMT information and the BLT information and the MRI information is obtained.

The FMT and BLT imaging methods include a process with two cores, a forward problem and a reverse problem. The forward problem is to describe a complex physical process of transmitting fluorescence from a light source to the surface of a living body by a diffusion filter equation, establish a propagation model of the light in a biological tissue, solve the model and finally establish a linear relation between a fluorescence acquisition signal on the surface of the living body and the three-dimensional distribution of the fluorescence in the living body. The linear relationship can be expressed by a linear matrix equation:

Ax＝b

where a is a system matrix describing the forward problem, x represents the light intensity distribution of the fluorescent light source inside the imaged object, and b represents the light intensity distribution of the fluorescent light spot on the surface of the imaged object.

The reconstruction process of BLT and FMT can be summarized as the following steps:

respectively carrying out BLT and FMT data acquisition experiments, and acquiring the light intensity distribution b of the fluorescence light spots on the surface of the imaging object under different conditions;

constructing a system matrix A of a BLT and an FMT forward process, wherein FMT imaging in principle comprises two associated processes, excitation and emission (BLT only comprises emission), can be described by two coupled equations:

two equations are formed by_x(r) coupled together, derived to give the following equation:

wherein phi_m(i) Eta mu to measure the intensity distribution of the obtained surface fluorescence spot_af(j) I.e. the distribution of the fluorescent light source inside the object to be imaged, phi_x(j) Is the intensity distribution of the fluorescence of the excitation light in vivo, and phi_x(j) Decays continuously as the depth of the imaged object increases (in BLT reconstruction, this value is constant). When phi is_x(j) If it is too small, the matrix of the system will be ill-conditioned.

Thus, in some embodiments of the present disclosure, the system matrix construction module comprises: the correction submodule corrects the FMT system matrix by adopting an excitation light threshold correction method, and the excitation light threshold correction method comprises the following steps:

acquisition of phi_x(j) Maximum value of (1)_xmax(j)；

Let all phi_x(j)＜0.4φ_xmax(j) Phi of_x(j) Are all set to 0.4 phi_xmax(j)；

Correcting the FMT system matrix according to the following formula;

by using the excitation light threshold correction method, the ill-posed property of the system matrix under the planar excitation light reflection model is reduced.

In some embodiments of the present disclosure, the regularization matrix L is constructed in the reconstruction module by using a laplacian matrix with gaussian weights as follows:

L_G＝(l_i，j)_N×N

wherein l_i，jRepresents an attenuating element, d_i，jRepresenting the spatial distance between two voxels, ρ s_kFor the radial softening function, R is the gaussian kernel radius, and in the gaussian weighted laplace matrix method, R is 0.4.

In some embodiments of the present disclosure, calculating the light intensity distribution of the fluorescent light source inside the experimental animal (i.e. solving the inverse problem in the FMT and BLT imaging methods using the conjugate gradient method) using the conjugate gradient method in combination with the system matrix in the reconstruction module comprises:

step A: establishing a target optimization function;

wherein the content of the first and second substances,

is a least-squares equation of the equation,

the regularization term is a Gihono Voff regularization term, lambda is a regularization parameter, L is the regularization matrix, and A is the system matrix;

and B: taking an initial value x⁽⁰⁾C, calculating an initial residual vector r⁽⁰⁾＝b-Ax⁽⁰⁾And let p stand for⁽⁰⁾＝r⁽⁰⁾Wherein p is⁽⁰⁾Is the initial iteration direction

And C: if r^(k)||₂C is less than or equal to c, let x be x^(k)The calculation is terminated, otherwise the calculation is

x^(k+1)＝x^(k)+t_k*p^(k)

Wherein r is^(k)Is the residual vector for the k-th iteration,

step size, p, for the k-th iteration^(k)Is the k iteration direction;

according to the characteristic that the fluorescence light source value has nonnegativity, correcting the obtained x elements by the following formula:

wherein the content of the first and second substances,

representing the result of the kth iteration of the ith element of vector x,

is the corrected result vector;

step D: calculating r^(k+1)＝b-Ax^(k+1)And let p stand for^(k+1)＝r^(k+1)+α_kp^(k)

Wherein the content of the first and second substances,

step E: c, enabling k to be k +1, and returning to the step C for judgment; the Gaussian weight Laplace reconstruction method is used, based on the assumption that the correlation between two voxels is reduced along with the increase of the space distance between the two voxels, a Gaussian weight Laplace matrix is designed to serve as a regular matrix, the problem of over-smooth diffusion optical reconstruction is successfully solved, morphological information of a reconstruction object is provided, and the problem that due to the fact that fluorescence is absorbed and scattered by various tissues in a living body when passing through the living body, light spots transmitted to the surface of the living body are seriously distorted, and then the morphological information of the biological tissues in the living body is difficult to reconstruct and image is solved.

In some embodiments of the present disclosure, as shown in fig. 2, the fixed bed 300 comprises: the two sides of the bed plate 310 are provided with baffle plates 320, and the bed plate 310 and the baffle plates 320 are used for placing experimental animals; the optical imaging window 330 is correspondingly arranged in the middle of the bed plate 310 and on the baffle 320 and is used for collecting imaging information of the experimental animal from the bottom and the side; the fixing interface 340 is arranged on the bed plate 310 and/or the baffle 320 and is used for assisting in fixing the experimental animal; the positioning point 350 is arranged on the bed plate 310 and/or the baffle 320 and is used for positioning the optical imaging unit 100 or the MRI unit 200; the bed plate 310 and the baffle plate 320 contain organic glass, the connection mode of the fixed bed 300 and the optical imaging unit 100 or the MRI unit 200 is clamping connection, bolt connection or buckle connection and the like, the connection mode of collecting optical tomography information or MRI information is not affected at will, convenience is brought to carrying of the experimental animal body between the optical imaging unit 100 and the MRI unit 200 through the fixed bed 300, accordingly, the experimental animal body is guaranteed to be in rigid change under the imaging visual fields of the two units, registration and fusion between multi-mode imaging results are facilitated, and the influence of a uniform magnetic field of the MRI unit 200 on electronic equipment in the optical imaging unit 100 can be relieved.

In some embodiments of the present disclosure, as shown in fig. 1, the optical imaging unit 100 includes: the flat rotary table 110 is vertically arranged, and the BLT module, the FMT module and the CT module are all fixedly arranged on the flat rotary table 110; and a translation stage 120 which reciprocates in the normal vector direction of the plane turntable 110 and is detachably connected to the bed plate 310 and/or the baffle 320.

The translation table 120 moves along the normal vector direction of the plane turntable 110, so that the optical imaging window 330 on the fixed bed 300 is exposed in the imaging range of the BLT module, the FMT module and the CT module, the BLT module, the FMT module and the CT module are driven to rotate by the plane turntable 110, and the optical tomography information of the experimental animal is acquired.

In some embodiments of the present disclosure, as shown in fig. 1, wherein: the BLT module is a fluorescent camera 130 and is used for collecting BLT information of experimental animals; the FMT module comprises: an excitation light emitting device 140 for emitting excitation light; and a fluorescence camera 130 for collecting FMT information of the experimental animal; the CT module includes: an X-ray tube 150 for emitting X-rays; and X-ray detecting plates 160 respectively disposed at both sides of the fixed bed 300 together with the X-ray bulb 150 for receiving X-rays penetrating through the test animal; wherein the BLT module and the FMT module share the same fluorescence camera 130.

Fig. 3 is a schematic front view of an excitation light emitting device in the experimental animal multi-mode fusion imaging system shown in fig. 1. Fig. 4 is a left side view of the excitation light emitting device in the experimental animal multi-mode fusion imaging system shown in fig. 1. Fig. 5 is a schematic top view of an excitation light emitting device in the experimental animal multi-mode fusion imaging system shown in fig. 1.

In some embodiments of the present disclosure, as shown in fig. 3 to 5, the excitation light emission device 140 includes: the first rotating device 141 is connected with the plane turntable 110 and drives the rocker arm 142 to rotate in a plane parallel to the plane turntable 110; a second rotating device 143 connected to the first rotating device 141 through a swing arm 142, wherein a rotation axis of the second rotating device 143 is perpendicular to a normal vector of the plane turntable 110; the optical fiber translation clamp 144 is connected with the second rotating device 143, extends and retracts along the rotating shaft of the second rotating device 143, and forms a W-degree included angle with the rotating shaft of the second rotating device 143, wherein W is more than or equal to 0 degree and less than or equal to 15 degrees; and a laser exit 145 connected to the fiber translation clamp 144, on which a speed expanding head wheel 146 is provided for emitting a point light source or a surface light source.

In some embodiments of the present disclosure, as shown in fig. 1, the MRI unit 200 includes: a nuclear magnetic cavity 210 for collecting MRI information; and the experimental animal bracket 220 is detachably connected with the bed plate 310 and/or the baffle 320 and drives the fixed bed to extend into the nuclear magnetic cavity 210 for nuclear magnetic imaging.

According to another aspect of the present disclosure, there is also provided a method for using a multimode fusion imaging system for a laboratory animal, where the multimode fusion imaging system for a laboratory animal provided by an embodiment of the present disclosure includes: step 100: fixing the experimental animal body to the optical imaging unit 100 through the fixed bed 300; step 200: respectively collecting BLT information, FMT information and CT information of the experimental animal body, and correcting the FMT information by using a mirror filtering method; step 300: fixing the experimental animal body to the MRI unit 200 through the fixed bed 300; step 400: collecting MRI information of the experimental animal; and step 500: the BLT information, FMT information, and MRI information are pixel-level fused using the data processing unit 400.

In some embodiments of the present disclosure, collecting FMT information of the experimental animal body comprises: collecting FMT information by using a transmission model and selecting point laser; and/or collecting FMT information by using a reflection model and selecting planar laser; wherein, when the FMT information is collected by using the reflection model, a mirror filtering method is used.

In some embodiments of the present disclosure, selecting a spot laser to acquire FMT information using a transmission model comprises: the experimental animal body is a mouse, and the four limbs of the experimental animal body are fixed by a wire through the fixing interfaces 340, so that the chest and abdomen of the experimental animal body are exposed at the optical imaging window 330; adjusting the first rotating device 141 to enable the laser emitting port 145 and the fluorescence camera 130 to be respectively located at two sides of the experimental animal body; the telescopic distance (plus or minus 1 cm) and the angle (plus or minus 10 degrees) of the optical fiber translation clamp 144 are adjusted, and the chest and abdomen FMT information under different excitation conditions is collected.

In some embodiments of the present disclosure, selecting a facet laser to collect head FMT information using a reflectance model comprises: the experimental animal body is a mouse, and the neck of the experimental animal body is fixed by using an adhesive tape, so that the head of the experimental animal body is exposed at the optical imaging window 330; selecting a filter (selecting a wave band with the wavelength less than 50nm of the exciting light) far away from the wavelength of the exciting light and the wavelength of the emitted light; collecting reflected light spot information of the exciting light under the condition of not using a fluorescent probe; using a fluorescent probe to collect FMT information of the head; and correcting the FMT information of the head by utilizing the reflected light spot information of the exciting light in combination with a mirror filtering method.

Fig. 6 is a schematic view of an acquisition process in a using method of the experimental animal multi-mode fusion imaging system according to the embodiment of the disclosure.

As shown in FIG. 6, the information acquisition process of the multimode fusion imaging system of the experimental animal body according to the embodiment of the disclosure is as follows

Step 1, starting the optical imaging unit 100 and starting the MRI unit 200;

step 2, fixing the experimental animal on the fixed bed 300, and using different fixing modes according to different shooting positions, which can be specifically divided into:

step 21: if the chest and the abdomen are shot, the limbs of the subject are bound by using a medical suture, and the thread passes through the fixing interface 340 to be bound and fixed;

step 23: if the head is shot, fixing the neck of the shot object by using a medical adhesive tape;

and step 3: after the experimental animal body is fixed, the fixed bed 300 is placed on the translation table 120 and moved to the position below the fluorescence camera 130, the camera shoots a two-dimensional picture of the experimental animal body under natural light, the proper placing position is determined, and whether all positioning points 350 on the fixed bed 300 are clear or not is determined;

and 4, step 4: closing natural light, and shooting an autofluorescence spot of the experimental animal;

and 5: securing the laser fiber in the translating fiber clamp 144 of the excitation light emitting apparatus 140;

step 6: if the chest and abdomen part is shot, entering the step 7; if the head is shot, the first rotating device 141 is adjusted to adjust the optical fiber to the same side as the fluorescence camera 130, and the reflection model shooting is performed. Entering a step 8;

and 7: if the chest and abdomen part is shot, the speed expanding head wheel 146 is adjusted, a proper speed expanding head is selected, laser irradiates a shooting target in a point laser mode, and the first rotating device 141 is adjusted to adjust the optical fiber to the opposite side of the fluorescence camera 130;

and 8: translating the optical fiber translation clamp 144 (plus or minus 1 cm) and the second rotating device 143 (plus or minus 10 degrees), and shooting the result of the fluorescent surface light spot excited by the experimental animal under different excitation conditions;

and step 9: if the head is photographed, that is, photographed using a reflection model, information on a reflection spot of excitation light necessary for mirror filtering is photographed. The method comprises the following specific steps:

step 91: selecting an optical filter (namely, a wave band with the wavelength less than 50nm of the excitation light) far away from the wavelength of the excitation light and the emission light, fixing the optical filter at the front end of the fluorescence camera 130, and filtering the emission light;

and step 92: shooting reflected light spot information of the exciting light, wherein the reflected light spot information of the exciting light is used for filtering the reflected light spot information of the exciting light mixed in the emitting light in the reflection model, and the reflected light spot information is specifically seen in a mirror filtering method;

step 10: after the fluorescent imaging acquisition is finished, the plane turntable 110 starts to rotate, and simultaneously the CT module starts to continuously acquire (1 degree and 1 piece) X-ray images of the experimental animal body, and the acquired X-ray image data is stored until the acquisition of 360 degrees is finished;

step 11: processing the acquired result, and reconstructing a three-dimensional tomographic anatomical structure (namely CT) of the shooting object by using a 360-degree X-ray image;

step 12: moving the fixed bed 300, transferring the fixed bed 300 into the experimental animal holder 220 in the MRI unit 200, and after fixing the fixed bed 300 in the experimental animal holder 220, sleeving a radio frequency coil;

step 13: the test object holder 220 is moved into the nuclear magnetic cavity 210 and MRI information of the test object is captured.

As shown in fig. 7, the data processing flow in the multimode fusion imaging system of the experimental animal in the embodiment of the disclosure is as follows:

step 1: selecting different acquisition modes according to the diffuse optical imaging modality to be acquired: if the FMT is the FMT, entering the step 2; otherwise, entering step 3;

step 2: in the FMT data acquisition process, if the FMT data acquisition process is head acquisition, a mirror filtering method is used, and pollution of reflected light of exciting light to light spot results on the surface of emitted light is reduced. Then entering step 4;

and step 3: in the BLT data acquisition process, an optical filter with the wavelength of 620nm is adopted to carry out a data acquisition experiment to obtain the autofluorescence intensity distribution of the surface of the organism under the wavelength;

and 4, step 4: acquiring a CT image, segmenting the acquired CT image according to organs (heart, lung, brain, bone, liver and kidney respectively), and registering the CT image with an FMT or BLT image;

and 5: after CT collection is completed, moving the shot object to an MRI module, and shooting an MRI image of the experimental animal;

step 6: after all the images are acquired, synchronously performing FMT reconstruction and BLT reconstruction, wherein if the FMT reconstruction is performed, the step 7 is performed, and otherwise, the step 9 is performed;

and 7: solving diffusion equations of an excitation process and an emission process of the FMT, and solving a forward problem to obtain a system matrix of the FMT;

and 8: correcting the fluorescence intensity distribution of the exciting light in the organism by adopting an exciting light threshold correction method so as to correct the system matrix of the FMT;

and step 9: solving a diffusion equation in the BLT transmitting process, and solving a forward problem to obtain a system matrix of the BLT;

step 10: after the system matrix construction is completed, entering a reconstruction module, namely solving the BLT and FMT reconstruction problems by adopting a Gaussian weight Laplace matrix method;

step 11: registering CT and MRI by using a mutual information registration method, and obtaining the mapping relation of BLT, FMT and MRI by registration;

step 12: and according to the mapping relation obtained by the registration of the CT and the MRI, carrying out pixel-level fusion on the BLT reconstruction result, the FMT reconstruction result and the MRI result to form the multi-modal imaging result of the experimental animal.

So far, the embodiments of the present disclosure have been described in detail with reference to the accompanying drawings. It is to be noted that, in the attached drawings or in the description, the implementation modes not shown or described are all the modes known by the ordinary skilled person in the field of technology, and are not described in detail. Further, the above definitions of the various elements and methods are not limited to the various specific structures, shapes or arrangements of parts mentioned in the examples, which may be easily modified or substituted by those of ordinary skill in the art.

From the above description, those skilled in the art should clearly recognize that the experimental animal multimodal fusion imaging system and the method of use provided by the present disclosure.

In summary, the experimental animal multimode fusion imaging system and the using method provided by the disclosure remove the excitation light reflected light in the emission light through a mirror filtering method, correct the fluorescence intensity distribution of the excitation light in the living body by adopting an excitation light threshold correction method, and solve the BLT and FMT reconstruction problems by adopting a gaussian weight laplacian matrix method, thereby alleviating the problem of pollution of the reflected light of the excitation light to the emission light in the FMT acquisition process and improving the accuracy of biological tissue morphology reconstruction.

It should also be noted that directional terms, such as "upper", "lower", "front", "rear", "left", "right", and the like, used in the embodiments are only directions referring to the drawings, and are not intended to limit the scope of the present disclosure. Throughout the drawings, like elements are represented by like or similar reference numerals. Conventional structures or constructions will be omitted when they may obscure the understanding of the present disclosure.

And the shapes and sizes of the respective components in the drawings do not reflect actual sizes and proportions, but merely illustrate the contents of the embodiments of the present disclosure. Furthermore, in the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

Similarly, it should be appreciated that in the foregoing description of exemplary embodiments of the disclosure, various features of the disclosure are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various disclosed aspects. However, the disclosed method should not be interpreted as reflecting an intention that: that is, the claimed disclosure requires more features than are expressly recited in each claim. Rather, as the following claims reflect, disclosed aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this disclosure.

The above-mentioned embodiments are intended to illustrate the objects, aspects and advantages of the present disclosure in further detail, and it should be understood that the above-mentioned embodiments are only illustrative of the present disclosure and are not intended to limit the present disclosure, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present disclosure should be included in the scope of the present disclosure.

Claims

1. A laboratory animal multimodal fusion imaging system comprising:

an optical imaging unit for acquiring optical tomography information of an experimental animal body, comprising:

an FMT module for collecting FMT information of an experimental animal, the FMT module reducing contamination of collected signals by reflected light of excitation light by using a mirror filtering method, wherein the mirror filtering method comprises:

calculating mirror filter wavelength lambda_f，λ_f＝2λ₁-λ₂；

Respectively collecting the wavelengths of the optical filters as lambda₂And λ_fTime of excitation of fluorescent surface light spot result b₂And b_f(ii) a And

calculating the final surface fluorescence spot b_p＝b₂-α*b_f；

b_2nto use a wavelength of lambda without using a fluorescent probe₂The light spot result on the surface of the fluorescence excited by the light filter b_fnTo use a wavelength of lambda without using a fluorescent probe_fThe obtained result of exciting the fluorescent surface light spot is collected when the optical filter is used;

the MRI unit is arranged at a distance from the optical imaging unit and is used for acquiring MRI information of the experimental animal body;

the fixed bed is used for fixing a test animal body and is respectively matched with the optical imaging unit and the MRI unit so that the test animal body can move rigidly between the optical imaging unit and the MRI unit; and

and the data processing unit is used for carrying out pixel-level fusion on the optical tomography information and the MRI information of the experimental animal body.

2. The experimental animal multimode fusion imaging system of claim 1, said optical imaging unit further comprising:

the BLT module is used for collecting BLT information of the experimental animal; and

and the CT module is used for acquiring CT information of the experimental animal.

3. The experimental animal multimodal fusion imaging system according to claim 2, the data processing unit comprising:

the system matrix construction module is used for constructing a system matrix by utilizing FMT information and BLT information;

the reconstruction module is used for constructing a regularization matrix by adopting a Gaussian weight Laplace matrix method, and calculating the light intensity distribution of the fluorescent light source in the experimental animal body by using a conjugate gradient method in combination with a system matrix;

the registration module is used for registering the reconstruction result of the FMT information and the BLT information and the MRI information by the reconstruction module by taking the CT information as a reference; and

and the fusion module is used for performing pixel-level fusion on the reconstruction results of the FMT information and the BLT information and the MRI information by utilizing the mapping relation of the FMT information, the BLT information and the MRI information obtained by the registration module.

4. The experimental animal multimode fusion imaging system according to claim 3, wherein the regularization matrix L constructed by the reconstruction module by using the Laplace matrix method with Gaussian weight is as follows:

L_G＝(l_i，j)_N×N

wherein l_ijRepresents an attenuating element, d_ijRepresenting the spatial distance between two voxels, ρ s_kFor radial softening functions, R is the radius of the Gaussian kernel, in the Gaussian-weighted Laplace matrix methodAnd taking R as 0.4.

5. The multimode fusion imaging system of experimental animal body as claimed in claim 4, wherein the calculating the light intensity distribution of the fluorescent light source inside the experimental animal body by using the conjugate gradient method in combination with the system matrix in the reconstruction module comprises:

step A: establishing a target optimization function;

wherein the content of the first and second substances,

is a least-squares equation of the equation,

and B: taking an initial value x⁽⁰⁾C, calculating an initial residual vector r⁽⁰⁾＝b-Ax⁽⁰⁾And let p stand for⁽⁰⁾＝r⁽⁰⁾Wherein p is⁽⁰⁾Is the initial iteration direction;

x^(k+1)＝x^(k)+t_k*p^(k)

wherein r is^(k)Is the residual vector for the k-th iteration,

step size, p, for the k-th iteration^(k)Is the k iteration direction;

and correcting the obtained elements in x by the following formula:

wherein the content of the first and second substances,

representing the result of the kth iteration of the ith element of vector x,

is the corrected result vector;

Wherein the content of the first and second substances,

step E: and C, returning the step C to judge if k is k + 1.

6. The experimental animal multimode fusion imaging system of claim 2, said fixed bed comprising:

the two sides of the bed board are provided with baffles, and the bed board and the baffles are used for placing experimental animals;

the optical imaging window is correspondingly arranged in the middle of the bed plate and on the baffle and is used for collecting imaging information of the experimental animal from the bottom and the side surface;

the fixing interface is arranged on the bed board and/or the baffle and is used for assisting in fixing the experimental animal; and

the positioning point is arranged on the bed plate and/or the baffle and is used for positioning the optical imaging unit or the MRI unit;

wherein, the bed board with the baffle contains organic glass.

7. The experimental animal multimode fusion imaging system of claim 6, said optical imaging unit comprising:

the BLT module, the FMT module and the CT module are all fixedly arranged on the plane turntable; and

the translation table reciprocates along the normal vector direction of the plane turntable and is detachably connected with the bed plate and/or the baffle;

the translation table moves along the normal vector direction of the plane turntable, so that the optical imaging window on the fixed bed is exposed in the imaging range of the BLT module, the FMT module and the CT module, the BLT module, the FMT module and the CT module are driven to rotate through the plane turntable, and the optical tomography information of the experimental animal is acquired.

8. The experimental animal multimodal fusion imaging system of claim 7 wherein:

the BLT module is a fluorescence camera and is used for collecting BLT information of the experimental animal body;

the FMT module comprises:

excitation light emitting means for emitting excitation light, comprising:

the first rotating device is connected with the plane turntable and drives the rocker arm to rotate in a plane parallel to the plane turntable;

the second rotating device is connected with the first rotating device through the rocker arm, and the rotating shaft of the second rotating device is vertical to the normal vector of the plane turntable;

the optical fiber translation clamp is connected with the second rotating device, stretches along the rotating shaft of the second rotating device and forms a W-degree included angle with the rotating shaft of the second rotating device, wherein W is more than or equal to 0 degree and less than or equal to 15 degrees; and

the laser emergent port is connected with the optical fiber translation clamp, and is provided with a speed expanding head wheel for emitting a point light source or a surface light source; and

the fluorescence camera is used for collecting FMT information of the experimental animal body;

the CT module includes:

an X-ray bulb for emitting X-rays; and

the X-ray detection plates and the X-ray bulb tubes are respectively arranged on two sides of the translation table and used for receiving X-rays penetrating through the experimental animal body;

wherein the BLT module and the FMT module share the same fluorescence camera.

9. The experimental animal multimodal fusion imaging system according to any one of claims 6 to 8, the MRI unit comprising:

a nuclear magnetic cavity for collecting MRI information; and

the experimental animal bracket is detachably connected with the bed plate and/or the baffle plate and drives the fixed bed to stretch into the nuclear magnetic cavity for nuclear magnetic imaging.

10. A method for using a multimodal fusion imaging system of a laboratory animal, using the multimodal fusion imaging system of a laboratory animal according to any one of claims 1 to 9, comprising:

step 100: fixing a test animal to the optical imaging unit through the fixed bed;

step 200: respectively collecting BLT information, FMT information and CT information of the experimental animal body, and correcting the FMT information by using a mirror filtering method;

step 300: fixing a test animal body to the MRI unit through the fixed bed;

step 400: collecting MRI information of the experimental animal; and

step 500: performing pixel-level fusion on the BLT information, the FMT information, and the MRI information using the data processing unit.