CN108335338A - Experimental animals multimodality fusion imaging system and application method - Google Patents

Experimental animals multimodality fusion imaging system and application method Download PDF

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CN108335338A
CN108335338A CN201810268753.9A CN201810268753A CN108335338A CN 108335338 A CN108335338 A CN 108335338A CN 201810268753 A CN201810268753 A CN 201810268753A CN 108335338 A CN108335338 A CN 108335338A
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experimental animals
fmt
modules
imaging system
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CN108335338B (en
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田捷
王坤
高源�
尹琳
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Institute of Automation of Chinese Academy of Science
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Institute of Automation of Chinese Academy of Science
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    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T11/00—2D [Two Dimensional] image generation
    • G06T11/003—Reconstruction from projections, e.g. tomography
    • G06T11/005—Specific pre-processing for tomographic reconstruction, e.g. calibration, source positioning, rebinning, scatter correction, retrospective gating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/0035—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for acquisition of images from more than one imaging mode, e.g. combining MRI and optical tomography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
    • A61B6/02—Devices for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
    • A61B6/03—Computerised tomographs
    • A61B6/032—Transmission computed tomography [CT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
    • A61B6/44—Constructional features of apparatus for radiation diagnosis
    • A61B6/4417—Constructional features of apparatus for radiation diagnosis related to combined acquisition of different diagnostic modalities
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
    • A61B6/50—Clinical applications
    • A61B6/508—Clinical applications for non-human patients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D3/00—Appliances for supporting or fettering animals for operative purposes
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T5/00—Image enhancement or restoration
    • G06T5/50—Image enhancement or restoration by the use of more than one image, e.g. averaging, subtraction
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T7/00—Image analysis
    • G06T7/30—Determination of transform parameters for the alignment of images, i.e. image registration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40—Animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/42—Evaluating a particular growth phase or type of persons or animals for laboratory research
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D3/00—Appliances for supporting or fettering animals for operative purposes
    • A61D2003/003—Appliances for supporting or fettering animals for operative purposes with head or neck restraining means
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/10—Image acquisition modality
    • G06T2207/10072—Tomographic images
    • G06T2207/10081—Computed x-ray tomography [CT]
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    • G06T2207/10—Image acquisition modality
    • G06T2207/10072—Tomographic images
    • G06T2207/10084—Hybrid tomography; Concurrent acquisition with multiple different tomographic modalities
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    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/10—Image acquisition modality
    • G06T2207/10072—Tomographic images
    • G06T2207/10088—Magnetic resonance imaging [MRI]
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    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/20—Special algorithmic details
    • G06T2207/20212—Image combination
    • G06T2207/20221—Image fusion; Image merging

Abstract

A kind of experimental animals multimodality fusion imaging system of disclosure offer and application method, including：Optical image unit, the optical sectioning imaging information for acquiring experimental animals, including：FMT modules, the FMT information for acquiring experimental animals, the FMT modules reduce pollution of the exciting light reflected light to acquisition signal using minute surface filtering method；MRI units are arranged, the MRI information for acquiring experimental animals with the optical image unit interval；Fixed bed, respectively with the optical image unit and the MRI unit matchings, makes experimental animals carry out rigidity between the two mobile for fixing experimental animals；And data processing unit, carry out Pixel-level fusion for the optical sectioning imaging information and MRI information to experimental animals.The experimental animals multimodality fusion imaging system and application method that the disclosure provides remove the exciting light reflected light in transmitting light by minute surface filtering method, and then alleviate pollution problem of the reflected light of exciting light in FMT gatherer processes to transmitting light.

Description

Experimental animals multimodality fusion imaging system and application method
Technical field
This disclosure relates to medicine molecular image technical field more particularly to a kind of experimental animals multimodality fusion imaging system And application method.
Background technology
Toy medicine tomography technology is a kind of with experimental animals (such as mouse or other imaging organ mass In 5cm*5cm*5cm animals below) be imaging object tomography technology.Pass through the disease to being established in experimental animals Model is shot and is rebuild, and distribution and the shape of lesion three-dimensional are obtained.Corresponding biomedicine experiment is assisted with this, to Contribute to the research of related fields.The technology is all widely used in tumor research, drug metabolism study etc..
Nmr imaging technique (MRI) and Diffuse Optical Tomography imaging technique are common experimental animals medicine The technological means of tomography technology.Nmr imaging technique utilizes the proton in tissue under uniform magnetic field, receives radio frequency After driving pulse excitation, nmr phenomena, this characteristic of generation NMR signal, by NMR signal occurs It obtains, and then high-resolution anatomy image forming is carried out to tissue.In Diffuse Optical Tomography imaging technique, more generally use For biological autofluorescence computer tomography (BLT) and excitation fluorescence computer tomography (FMT).BLT imaging technique profits Chemical reaction occurs with the fluorescein substrate (Luciferin) being injected in vivo with the luciferase in organism and generates fluorescence, and Hot spot is generated in organism surface, is received by a detector, and then obtain the space distribution information of luciferase in vivo. FMT imaging techniques utilize the biological tissue that there is the fluorescence probe of targeting fluorogen to be brought into target.It is glimmering in biological tissue Light blob is irradiated by outer source laser (i.e. exciting light), and electronics moves jump and arrives excitation state.Then, electronics returns to ground state from excitation state In the process, the fluorescence (emitting light) released.After these fluorescence are propagated in vivo, hot spot is generated in organism surface, It is received by a detector, to obtain the space distribution information of fluorescence targeted probes in vivo.
However, present inventor has found during realizing the disclosure, due to fluorescence when across organism by The absorption and scattering of various tissues in organism, the hot spot for traveling to organism surface have been subjected to serious distortion, this makes It is difficult to carry out reestablishment imaging to the morphologic information of biological tissue in organism to obtain Diffuse Optical Tomography imaging.Although also, FMT Imaging technique select exciting light with transmitting light be different spectral bands, and acquire transmitting light use optical filter to exciting light into Row filters out.But exciting light still generates pollution to transmitting light, influences the precision of biological tissue's morphological reconstruction.Further, since core Magnetic imaging technology is needed in imaging at imaging object in uniform magnetic field, which can be imaged Diffuse Optical Tomography and be used The electronic equipments such as camera have an impact, and then cause other mode that can not be acquired.
Disclosure
(1) technical problems to be solved
Based on above-mentioned technical problem, a kind of experimental animals multimodality fusion imaging system of disclosure offer and application method, Pollution is generated to transmitting light to alleviate exciting light in FMT imaging techniques in the prior art, influences biological tissue's morphological reconstruction Precision the technical issues of.
(2) technical solution
According to one aspect of the disclosure, a kind of experimental animals multimodality fusion imaging system is provided, including：Optical imagery Unit, the optical sectioning imaging information for acquiring experimental animals, including：FMT modules, for acquiring experimental animals FMT information, the FMT modules reduce pollution of the exciting light reflected light to acquisition signal using minute surface filtering method；MRI units, with The optical image unit interval setting, the MRI information for acquiring experimental animals；Fixed bed, for fixing experimental animal Body makes experimental animals carry out rigid shifting between the two respectively with the optical image unit and the MRI unit matchings It is dynamic；And data processing unit, for experimental animals optical sectioning imaging information and MRI information carry out Pixel-level melt It closes.
In some embodiments of the present disclosure, the minute surface filtering method includes：Calculate minute surface filter wavelength λf, λf=2 λ1-λ2；Acquisition optical filter wavelength is λ respectively2With λfWhen excitation fluorescent surface hot spot result b2And bf；And calculate final table Face fluorescence hot spot bp=b2-α*bf；Wherein, λ1For excitation wavelength, λ2For wavelength of transmitted light,b2nIt is glimmering not use It is λ that wavelength is used in the case of light probe2Optical filter when the excitation fluorescent surface hot spot that collects as a result, bfnIt is glimmering not use It is λ that wavelength is used in the case of light probefOptical filter when the excitation fluorescent surface hot spot result that collects.
In some embodiments of the present disclosure, the optical image unit further includes：BLT modules, it is dynamic for acquiring experiment The BLT information of object；And CT modules, the CT information for acquiring experimental animals.
In some embodiments of the present disclosure, the data processing unit includes：Sytem matrix builds module, utilizes FMT Information and BLT information architecture sytem matrixes；Module is rebuild, regularization square is built using Gauss weight Laplacian Matrix method Battle array, and use conjugate gradient method combination sytem matrix, the light distribution of experiment with computing animal body Internal Fluorescent light source；With quasi-mode Block will be rebuild module and be registrated with MRI information to the reconstructed results of FMT information and BLT information on the basis of CT information；With And Fusion Module, the mapping relations of the FMT information, BLT information and MRI information that are obtained using registration module, by FMT information and The reconstructed results of BLT information carry out Pixel-level with MRI information and merge.
In some embodiments of the present disclosure, the sytem matrix structure module includes：Submodule is corrected, excitation is used Photo threshold modification method is modified FMT sytem matrixes, which includes：Obtain φx(j) in most Big value φxmax(j)；Enable all φx(j) 0.4 φ of ＜xmax(j) φx(j) element is all set to 0.4 φxmax(j)；Under It states formula and corrects FMT sytem matrixes；
Wherein, φx(j) it is fluorescent intensity distribution of the exciting light in experimental animals body, φm(i) it is the table for measuring gained Face fluorescence spot intensity distribution, η μaf(j) it is that fluorescent light source is distributed in experimental animals body.
In some embodiments of the present disclosure, built using Gauss weight Laplacian Matrix method in the reconstruction module Regularization matrix L is as follows：
LG=(lI, j)N×N
Wherein, lijRepresent decaying element, dijIndicate the space length between two voxels, ρskFor radial softening function, R For Gauss nuclear radius, R=0.4 is taken in Gauss weight Laplacian Matrix method.
In some embodiments of the present disclosure, conjugate gradient method combination sytem matrix is used in the reconstruction module, is calculated The light distribution of experimental animals Internal Fluorescent light source includes：Step A：Establish objective optimization function；
Wherein,For least squares equation,For lucky big vast promise husband's regular terms, λ is regularization parameter, L For the regularization matrix, A is the sytem matrix；Step B：Take initial value x(0), computational accuracy c, calculate initial residual error to Measure r(0)=b-Ax(0), and enable p(0)=r(0), wherein p(0)For primary iteration direction；
Step C：If | | r(k)||2≤ c, then enable x=x(k), calculate and terminate, otherwise calculate following formula：
x(k+1)=x(k)+tk*p(k)
Wherein, r(k)For the residual vector of kth time iteration,For the step-length of kth time iteration, p(k)It is K iteration direction；
And element is modified by following formula in the x to acquiring：
Wherein,Indicate the kth time iteration result of i-th of element of vector x,It is the result vector after correction；
Step D：Calculate r(k+1)=b-Ax(k+1), and enable p(k+1)=r(k+1)+αkp(k)
Wherein,
Step E：K=k+1, return to step C is enabled to be judged.
In some embodiments of the present disclosure, the fixed bed includes：Bed board, both sides are provided with baffle, the bed board With the baffle for putting experimental animals；Optical imagery window, correspondence are opened in the middle part of the bed board and the gear On plate, the image-forming information for acquiring experimental animals from bottom and side；Fixed interface, be opened in the bed board and/or On the baffle, for experimental animals to be auxiliarily fixed；And anchor point, it is set on the bed board and/or the baffle, uses In with the optical image unit or the MRI cell locations；Wherein, the bed board and the baffle include organic glass.
In some embodiments of the present disclosure, the optical image unit includes：Plane rotary disc is vertically arranged, the BLT Module, the FMT modules and the CT modules are fixed on the plane rotary disc；And translation stage, along described flat The normal vector direction of face turntable moves back and forth, and is detachably connected with the bed board and/or the baffle；Wherein, the translation stage It is moved along the normal vector direction of the plane rotary disc, the optical imagery window in the fixed bed is made to be exposed to the BLT In the areas imaging of module, the FMT modules and the CT modules, the BLT modules, described are driven by the plane rotary disc FMT modules and CT modules rotation, acquire the optical sectioning imaging information of experimental animals.
In some embodiments of the present disclosure, wherein：The BLT modules are fluorescence camera, dynamic for acquiring the experiment The BLT information of object；The FMT modules include：Excitation light emission device, for emitting exciting light, including：First rotating dress It sets, is connect with the plane rotary disc, drive rocking arm in the rotation in surface parallel with the plane rotary disc；Second rotating device, It is connect with first rotating device by the rocking arm, the normal direction of the rotary shaft of second rotating device and the plane rotary disc Amount is vertical；Optical fiber translation folder, connect with second rotating device, and the rotary shaft along second rotating device is flexible, and with The rotary shaft of second rotating device is in W ° of angle, wherein 0 °≤W≤15 °；And laser emitting mouth, it is flat with the optical fiber Folder connection is moved, expansion speed great wheel is provided with, for projecting point light source or area source；And fluorescence camera, it is described for acquiring The FMT information of experimental animals；The CT modules include：X-ray bulb, for emitting X-ray；And X-ray detection plate, with The X-ray bulb is separately positioned on the both sides of the translation stage, for receiving the X-ray for being perforated through experimental animals；Wherein, The BLT modules and the FMT modules share the same fluorescence camera.
In some embodiments of the present disclosure, the MRI units include：Nuclear-magnetism cavity, for acquiring MRI information；And Experimental animals bracket is detachably connected with the bed board and/or the baffle, and the fixed bed is driven to stretch into the nuclear-magnetism In cavity, NMR imaging is carried out.
According to another aspect of the disclosure, a kind of user of experimental animals multimodality fusion imaging system is also provided Method, the experimental animals multimodality fusion imaging system provided using the disclosure, including：Step 100：It will be real by the fixed bed It tests animal body and is fixed to the optical image unit；Step 200：Respectively the acquisition BLT information of experimental animals, FMT information with And CT information, and FMT information is modified using minute surface filtering method；Step 300：By the fixed bed by experimental animal Body is fixed to the MRI units；Step 400：Acquire the MRI information of experimental animals；And step 500：Utilize the data Processing unit carries out Pixel-level fusion to the BLT information, the FMT information and the MRI information.
In some embodiments of the present disclosure, the FMT information for acquiring experimental animals includes：Point is selected using transmission model Shape laser acquires FMT information；And/or planar laser is selected to acquire FMT information using reflection model；Wherein, using reflection model When acquiring FMT information, the minute surface filtering method is used.
In some embodiments of the present disclosure, include using transmission model selection point-like laser acquisition FMT information：Experiment is dynamic Object is mouse, passes through fixed interface to fix the four limbs of mouse using wire rod, its thorax abdomen is made to be exposed at optical imagery window； The first rotating device is adjusted, laser emitting mouth is made to be located at the both sides of mouse with fluorescence camera；It is flexible to adjust optical fiber translation folder Distance and angle acquire thorax abdomen FMT information in the case of different excitations.
In some embodiments of the present disclosure, include using reflection model selection planar laser acquisition FMT information：Experiment is dynamic Object is mouse, and the neck of experimental animals is fixed using adhesive tape, makes its head exposure at optical imagery window；Selection is less than The optical filter of the wave band of exciting light 50nm wavelength；In the case that without using fluorescence probe, exciting light reflected light facula information is acquired； Using fluorescence probe, head FMT information is acquired；Head is corrected using exciting light reflected light facula information combination minute surface filtering method FMT letters are thought.
(3) advantageous effect
It can be seen from the above technical proposal that experimental animals multimodality fusion imaging system and the user of disclosure offer Method has the advantages that one of them or in which a part：
(1) by minute surface filtering method, i.e., by selecting the exciting light acquired under the spectral band far from wavelength of transmitted light Reflected light distribution information, be fitted wavelength of transmitted light under exciting light reflected light distribution information, due to exciting light transmitting light not Have into experimental animals body, therefore belong to linear relationship between exciting light reflected light under different wave length, by far from transmitting The exciting light reflected light distribution information acquired under the wave band of optical wavelength, the exciting light reflected light distribution of fitting pollution transmitting light, from And the exciting light reflected light in transmitting light is removed, and then alleviate dirt of the reflected light of exciting light in FMT gatherer processes to transmitting light Dye problem；
(2) using excitation photo threshold modification method, the pathosis of sytem matrix under planar excitation light reflectance model is reduced；
(3) correlation is with to each other between utilizing Gauss weight Laplce's method for reconstructing, this method to be based on two voxels The increase of space length and reduce it is assumed that design Gauss weight Laplacian Matrix as regular matrix, successfully alleviate expansion Astigmatism rebuild smoothing problasm, provided the morphologic information of reconstructed object, alleviate due to fluorescence when across organism by The absorption and scattering of various tissues in organism, cause it to travel to the hot spot of organism surface by serious distortion, in turn The problem of being difficult to carry out reestablishment imaging to the morphologic information of biological tissue in organism；
(4) it is carried between optical image unit and MRI units for experimental animals by setting fixed bed and facility is provided, Ensure that experimental animals belong to variation in rigidity under the visual field of two units with this, and then is conducive to multi-modality imaging result Between registration and fusion, and influence of the uniform magnetic field of MRI units to the electronic equipment in optical image unit can be alleviated.
Description of the drawings
Fig. 1 is the structural schematic diagram of embodiment of the present disclosure experimental animals multimodality fusion imaging system.
Fig. 2 is the structural schematic diagram of fixed bed in experimental animals multimodality fusion imaging system shown in Fig. 1.
Fig. 3 is the schematic front view of excitation light emission device in experimental animals multimodality fusion imaging system shown in Fig. 1.
Fig. 4 is the left view schematic diagram of excitation light emission device in experimental animals multimodality fusion imaging system shown in Fig. 1.
Fig. 5 is the schematic top plan view of excitation light emission device in experimental animals multimodality fusion imaging system shown in Fig. 1.
Fig. 6 shows for acquisition information flow in the application method of embodiment of the present disclosure experimental animals multimodality fusion imaging system It is intended to.
Fig. 7 is flow chart of data processing figure in embodiment of the present disclosure experimental animals multimodality fusion imaging system.
【Embodiment of the present disclosure main element symbol description in attached drawing】
100- optical image units；
110- plane rotary discs；
120- translation stages；
130- fluorescence cameras；
140- excitation light emission devices；
The first rotating devices of 141-；142- rocking arms；
The second rotating devices of 143-；144- translates fibre clip；
145- laser emitting mouths；146- expansion speed great wheels；
150-X ray tubes；
160-X X-ray detection X plates；
200-MRI units；
210- nuclear-magnetism cavitys；220- experimental animals brackets；
300- fixed beds；
310- bed boards；320- baffles；
330- optical imagery windows；340- fixed interfaces；
350- anchor points；
400- data processing units.
Specific implementation mode
In experimental animals multimodality fusion imaging system and application method that the embodiment of the present disclosure provides, filtered by minute surface Method, removal emit the exciting light reflected light in light, and then alleviate the reflected light of exciting light in FMT gatherer processes to transmitting light Pollution problem improves the precision of biological tissue's morphological reconstruction.
To make the purpose, technical scheme and advantage of the disclosure be more clearly understood, below in conjunction with specific embodiment, and reference The disclosure is further described in attached drawing.
Fig. 1 is the structural schematic diagram of embodiment of the present disclosure experimental animals multimodality fusion imaging system.
According to one aspect of the disclosure, as shown in Figure 1, providing a kind of experimental animals multimodality fusion imaging system, packet It includes：Optical image unit 100, the optical sectioning imaging information for acquiring experimental animals；MRI(Magnetic Resonance Imaging) unit 200, it is spaced and is arranged with optical image unit 100, the MRI for acquiring experimental animals believes Breath；Fixed bed 300 coordinates with optical image unit 100 and MRI units 200 for fixing experimental animals, makes experiment respectively It is mobile that animal body carries out rigidity between the two；And data processing unit 400, for the optical fault to experimental animals Image-forming information and MRI information carry out Pixel-level fusion.
In some embodiments of the present disclosure, as shown in Figure 1, optical image unit 100 includes：FMT modules, for acquiring The FMT information of experimental animals, the FMT modules reduce dirt of the exciting light reflected light to acquisition signal using minute surface filtering method Dye；BLT modules, the BLT information for acquiring experimental animals；And CT modules, the CT information for acquiring experimental animals.
In some embodiments of the present disclosure, minute surface filtering method includes：Calculate minute surface filter wavelength λf, λf=2 λ1-λ2； Acquisition optical filter wavelength is λ respectively2With λfWhen excitation fluorescent surface hot spot result b2And bf；And to calculate final surface glimmering Light hot spot bp=b2-α*bf。
Wherein, λ1For excitation wavelength, λ2For wavelength of transmitted light,b2nMake in the case of fluorescence probe not use It is λ with wavelength2Optical filter when the excitation fluorescent surface hot spot that collects as a result, bfnMake in the case of fluorescence probe not use It is λ with wavelengthfOptical filter when the excitation fluorescent surface hot spot that collects as a result, by minute surface filtering method, that is, pass through choosing With the reflected light distribution information of the exciting light acquired under the spectral band far from wavelength of transmitted light, it is fitted under wavelength of transmitted light and excites Light reflection light distribution information swashs since the transmitting light of exciting light is not introduced into experimental animals body under different wave length Belong to linear relationship between the reflected light that shines, is believed by the exciting light reflected light distribution acquired under the wave band far from wavelength of transmitted light Breath, the exciting light reflected light distribution of fitting pollution transmitting light, to remove the exciting light reflected light in transmitting light, and then alleviates Pollution problem of the reflected light of exciting light to transmitting light in FMT gatherer processes.
In some embodiments of the present disclosure, data processing unit includes：Sytem matrix builds module, utilizes FMT information With BLT information architecture sytem matrixes；Module is rebuild, regularization matrix is built using Gauss weight Laplacian Matrix method, and Use conjugate gradient method combination sytem matrix, the light distribution of experiment with computing animal body Internal Fluorescent light source；Registration module, with CT On the basis of information, module will be rebuild, the reconstructed results of FMT information and BLT information are registrated with MRI information；And fusion mould Block, the mapping relations of the FMT information, BLT information and MRI information that are obtained using registration module, by FMT information and BLT information Reconstructed results carry out Pixel-level with MRI information and merge.
Wherein, the specific step of registration of registration module is：Segmentation obtains organ from the CT faultage images that reconstruction obtains The 3 D anatomical fault structure figure of (brain, lung, liver, bone, kidney, heart etc.), each organ segmentation's seal divided are subgraph；It will Subgraph is registrated with FMT information and BLT information, obtains the mapping relations of FMT information and BLT information；Again by CT images and MRI Information is registrated, and then obtains the mapping relations of FMT information and BLT information and MRI information.
FMT and BLT imaging methods include the process of two cores of forward problem and Reverse Problem.Wherein, forward problem is The complicated physical process of organism surface is transferred to portray fluorescence by light source by diffusing filter equation, establishes light at biological group Propagation model in knitting, then solves the model, finally establishes organism surface fluorescent collecting signal with organism Internal Fluorescent The linear relationship of distributed in three dimensions.The linear relationship can be indicated with linear matrix equation：
Ax=b
Wherein, A is the sytem matrix for describing forward problem, and x indicates the light distribution of the fluorescent light source of imaging interior of articles, B indicates the light distribution of the fluorescence hot spot of imaging body surface.
The reconstruction process of BLT and FMT can be summarized as following steps：
BLT and FMT data acquisition systems are carried out respectively, acquire the imaging object surface fluorescence hot spot light intensity under different situations It is distributed b；
The sytem matrix A of BLT and FMT forward process is built, wherein FMT imagings include excitation process and transmitting in principle The two associated processes (BLT only includes emission process) of process, can be described with following two equations being coupled：
By two equations by φx(r) it is coupled together, following formula can be obtained by derivation：
Wherein φm(i) it is the surface fluorescence spot intensity distribution for measuring gained, η μaf(j) it is the required imaging object solved The fluorescent light source distribution of internal portion, φx(j) it is the fluorescent intensity distribution of exciting light in vivo, and φx(j) with imaging object depth Increase and constantly decays (in BLT reconstructions, which is constant).Work as φx(j) when too small, the pathosis of sytem matrix can be increased.
Therefore, in some embodiments of the present disclosure, sytem matrix structure module includes：Submodule is corrected, is used sharp Lasing threshold modification method is modified FMT sytem matrixes, which includes：
Obtain φx(j) the maximum value φ inxmax(j)；
Enable all φx(j) 0.4 φ of ＜xmax(j) φx(j) element is all set to 0.4 φxmax(j)；
FMT sytem matrixes are corrected according to following formula；
Using excitation photo threshold modification method, the pathosis of sytem matrix under planar excitation light reflectance model is reduced.
In some embodiments of the present disclosure, rebuilds in module and canonical is built using Gauss weight Laplacian Matrix method It is as follows to change matrix L：
LG=(lI, j)N×N
Wherein, lI, jRepresent decaying element, dI, jIndicate the space length between two voxels, ρskFor radial softening function, R For Gauss nuclear radius, R=0.4 is taken in Gauss weight Laplacian Matrix method.
In some embodiments of the present disclosure, rebuilds and use conjugate gradient method combination sytem matrix, experiment with computing in module The light distribution of animal body Internal Fluorescent light source (solves inversely asking in FMT and BLT imaging methods using conjugate gradient method Topic) include：
Step A：Establish objective optimization function；
Wherein,For least squares equation,For lucky big vast promise husband's regular terms, λ is regularization parameter, L For the regularization matrix, A is the sytem matrix；
Step B：Take initial value x(0), computational accuracy c calculates initial residual vector r(0)=b-Ax(0), and enable p(0)=r(0), wherein p(0)For primary iteration direction
Step C：If | | r(k)||2≤ c, then enable x=x(k), calculate and terminate, otherwise calculate
x(k+1)=x(k)+tk*p(k)
Wherein, r(k)For the residual vector of kth time iteration,For the step-length of kth time iteration, p(k)It is K iteration direction；
The characteristic according to fluorescent light source value with nonnegativity is modified element in the x that acquires by following formula：
Wherein,Indicate the kth time iteration result of i-th of element of vector x,It is the result vector after correction；
Step D：Calculate r(k+1)=b-Ax(k+1), and enable p(k+1)=r(k+1)+αkp(k)
Wherein,
Step E：K=k+1, return to step C is enabled to be judged；Utilize Gauss weight Laplce's method for reconstructing, this method Based on correlation between two voxels reduce with the increase of space length to each other it is assumed that design Gauss weight Laplce Matrix successfully alleviates diffusion optics and rebuild smoothing problasm, provide the morphologic information of reconstructed object, delay as regular matrix It has solved due to fluorescence when across organism by the absorption and scattering of various tissues in organism, it is caused to travel to organism The hot spot on surface is difficult to carry out asking for reestablishment imaging to the morphologic information of biological tissue in organism by serious distortion Topic.
Fig. 2 is the structural schematic diagram of fixed bed in experimental animals multimodality fusion imaging system shown in Fig. 1.
In some embodiments of the present disclosure, as shown in Fig. 2, fixed bed 300 includes：Bed board 310, both sides are provided with gear Plate 320, bed board 310 and baffle 320 are for putting experimental animals；Optical imagery window 330, correspondence are opened in bed board 310 On middle part and baffle 320, the image-forming information for acquiring experimental animals from bottom and side；Fixed interface 340, opens up In on bed board 310 and/or baffle 320, for experimental animals to be auxiliarily fixed；And anchor point 350, be set to bed board 310 and/ Or on baffle 320, for being positioned with optical image unit 100 or MRI units 200；Wherein, bed board 310 and baffle 320 include Machine glass, fixed bed 300 and the connection type of optical image unit 100 or MRI units 200 are clamping, are bolted or buckle The arbitrary connection type for not influencing to acquire optical sectioning imaging information or MRI information such as connection, by the way that fixed bed 300 is arranged It is carried between optical image unit 100 and MRI units 200 for experimental animals and facility is provided, experimental animals are ensured with this Belong to variation in rigidity under the visual field of two units, and then is conducive to the registration between multi-modality imaging result and fusion, and And influence of the uniform magnetic field of MRI units 200 to the electronic equipment in optical image unit 100 can be alleviated.
In some embodiments of the present disclosure, as shown in Figure 1, optical image unit 100 includes：Plane rotary disc 110, vertically Setting, BLT modules, FMT modules and CT modules are fixed on plane rotary disc 110；And translation stage 120, along plane The normal vector direction of turntable 110 moves back and forth, and is detachably connected with bed board 310 and/or baffle 320.
Wherein, translation stage 120 is moved along the normal vector direction of plane rotary disc 110, makes the optical imagery window in fixed bed 300 Mouth 330 is exposed in the areas imaging of BLT modules, FMT modules and CT modules, is passed through plane rotary disc 110 and is driven BLT modules, FMT Module and the rotation of CT modules, acquire the optical sectioning imaging information of experimental animals.
In some embodiments of the present disclosure, as shown in Figure 1, wherein：BLT modules are fluorescence camera 130, for acquiring reality Test the BLT information of animal body；FMT modules include：Excitation light emission device 140, for emitting exciting light；And fluorescence camera 130, the FMT information for acquiring experimental animals；CT modules include：X-ray bulb 150, for emitting X-ray；And X is penetrated Line detecting plate 160 is separately positioned on the both sides of fixed bed 300 with X-ray bulb 150, and experimental animals are perforated through for receiving X-ray；Wherein, BLT modules and FMT modules share same fluorescence camera 130.
Fig. 3 is the schematic front view of excitation light emission device in experimental animals multimodality fusion imaging system shown in Fig. 1.Figure 4 be the left view schematic diagram of excitation light emission device in experimental animals multimodality fusion imaging system shown in Fig. 1.Fig. 5 is shown in Fig. 1 The schematic top plan view of excitation light emission device in experimental animals multimodality fusion imaging system.
In some embodiments of the present disclosure, as shown in Figures 3 to 5, excitation light emission device 140 includes：First rotation Device 141 is connect with plane rotary disc 110, drives rocking arm 142 in the rotation in surface parallel with plane rotary disc 110；Second rotation Device 143 is connect by rocking arm 142 with the first rotating device 141, the rotary shaft and plane rotary disc of second rotating device 143 110 normal vector is vertical；Optical fiber translation folder 144, connect with the second rotating device 143, along the rotary shaft of the second rotating device 143 It is flexible, and be in W ° of angle with the rotary shaft of the second rotating device 143, wherein 0 °≤W≤15 °；And laser emitting mouth 145, It is connect with optical fiber translation folder 144, expansion speed great wheel 146 is provided with, for projecting point light source or area source.
In some embodiments of the present disclosure, as shown in Figure 1, MRI units 200 include：Nuclear-magnetism cavity 210, for acquiring MRI information；And experimental animals bracket 220, it is detachably connected with bed board 310 and/or baffle 320, and fixed bed is driven to stretch Enter in nuclear-magnetism cavity 210, carries out NMR imaging.
According to another aspect of the disclosure, a kind of user of experimental animals multimodality fusion imaging system is also provided Method, the experimental animals multimodality fusion imaging system provided using the embodiment of the present disclosure, including：Step 100：Pass through fixed bed Experimental animals are fixed to optical image unit 100 by 300；Step 200：The BLT information of acquisition experimental animals, FMT respectively Information and CT information, and FMT information is modified using minute surface filtering method；Step 300：It will be real by fixed bed 300 It tests animal body and is fixed to MRI units 200；Step 400：Acquire the MRI information of experimental animals；And step 500：Utilize data Processing unit 400 carries out Pixel-level fusion to BLT information, FMT information and MRI information.
In some embodiments of the present disclosure, the FMT information for acquiring experimental animals includes：Point is selected using transmission model Shape laser acquires FMT information；And/or planar laser is selected to acquire FMT information using reflection model；Wherein, using reflection model When acquiring FMT information, minute surface filtering method is used.
In some embodiments of the present disclosure, include using transmission model selection point-like laser acquisition FMT information：Experiment is dynamic Object is mouse, using wire rod pass through fixed interface 340 fix experimental animals four limbs, make its thorax abdomen be exposed to optics at As at window 330；The first rotating device 141 is adjusted, laser emitting mouth 145 is made to be located at experimental animal with fluorescence camera 130 The both sides of body；Optical fiber translation 144 distance of stretch out and draw back of folder (positive and negative 1 centimetre) and angle (positive and negative 10 degree) are adjusted, different excitation feelings are acquired Thorax abdomen FMT information under condition.
In some embodiments of the present disclosure, include using reflection model selection planar laser acquisition head FMT information：It is real It is mouse to test animal body, and the neck of experimental animals is fixed using adhesive tape, makes its head exposure at optical imagery window 330； Select the optical filter (selecting the wave band less than exciting light 50nm wavelength) far from excitation wavelength and wavelength of transmitted light；Without using In the case of fluorescence probe, exciting light reflected light facula information is acquired；Using fluorescence probe, head FMT information is acquired；Utilize excitation Light reflection light facula information combination minute surface filtering method corrects head FMT information.
Fig. 6 illustrates for collecting flowchart in the application method of embodiment of the present disclosure experimental animals multimodality fusion imaging system Figure.
As shown in fig. 6, the flow of the acquisition information of embodiment of the present disclosure experimental animals multimodality fusion imaging system is
Step 1, optical image unit 100 is opened, MRI units 200 are opened；
Step 2, experimental animals are fixed in fixed bed 300, according to different shooting positions, use different fixations Mode particularly may be divided into：
Step 21：If shooting thorax abdomen, object four limbs are bundled using suture, line is passed through into fixed interface 340, bundle It pricks and fixes；
Step 23：If head shot, medical adhesive tape establishing shot object neck is used；
Step 3：After completing experimental animals fixation, fixed bed 300 is placed on translation stage 120, fluorescence camera is moved to 130 lower sections, camera shoot experimental animals two-dimension picture under natural light, determine that placement position is suitable, determine institute in fixed bed 300 There is anchor point 350 whether clear；
Step 4：Natural light is closed, experimental animals autofluorescence hot spot is shot；
Step 5：Laser fiber is fixed in the translation fibre clip 144 of excitation light emission device 140；
Step 6：It is shot if thorax abdomen, enters step 7；It is shot if head, the first rotating device 141 is adjusted, by light Fibre is adjusted to 130 homonymy of fluorescence camera, carries out reflection model shooting.Enter step 8；
Step 7：It is shot if thorax abdomen, adjusts expansion speed great wheel 146, select suitable expansion speed head, make laser with dot laser shape Formula irradiates photographic subjects, and adjusts the first rotating device 141, and optical fiber is adjusted to 130 offside of fluorescence camera；
Step 8：Optical fiber translation 144 (positive and negative 1 centimetres) of folder and the second rotating device 143 (positive and negative 10 degree) are translated, shooting is not Fluorescent surface hot spot result is excited with experimental animals in the case of excitation；
Step 9：If head shot is shot using reflection model, then the exciting light reflected light needed for minute surface filtering is shot Spot information.It is as follows：
Step 91：The optical filter far from exciting light and wavelength of transmitted light is selected (to be less than the wave of exciting light 50nm wavelength Section), it is fixed on 130 front end of fluorescence camera, filters out transmitting light；
Step 92：Exciting light reflected light facula information is shot, which will be used to filter out reflection The exciting light reflected light facula information being mingled in model in transmitting light, is specifically shown in minute surface filtering method；
Step 10：After fluorescence imaging acquires, plane rotary disc 110 starts to rotate, while CT modules start continuous acquisition The X ray picture of (1 degree 1) experimental animals, and obtained X-ray diagram data is preserved, after completing 360 degree of acquisitions Stop；
Step 11：Institute's collection result is handled, the three-dimension disclocation solution of reference object is rebuild using 360 degree of X ray pictures Cut open structure (i.e. CT)；
Step 12：Mobile fixed bed 300, the experimental animals bracket 220 fixed bed 300 being transferred in MRI units 200 In, after fixed bed 300 is fixed in experimental animals bracket 220, put on radio-frequency coil；
Step 13：Experimental animals bracket 220 is moved in nuclear-magnetism cavity 210, shooting experimental animals MRI letters are thought.
Fig. 7 is flow chart of data processing figure in embodiment of the present disclosure experimental animals multimodality fusion imaging system.
As shown in fig. 7, flow chart of data processing is in embodiment of the present disclosure experimental animals multimodality fusion imaging system：
Step 1：Different acquisition modes is selected for the diffusion Optical imaging modalities to be acquired：If FMT, into step Rapid 2；Otherwise, 3 are entered step；
Step 2：In FMT data acquisitions, is acquired if head, using minute surface filtering method, reduce the anti-of exciting light Penetrate pollution of the light to transmitting optical surface hot spot result.Subsequently into step 4；
Step 3：BLT data acquisitions use wavelength to carry out data acquisition system for the optical filter of 620nm, are somebody's turn to do Organism surface autofluorescence light distribution under wavelength；
Step 4：Carry out CT Image Acquisition, and the CT images of acquisition are split by organ (be respectively heart, lung, brain, Bone, liver, kidney), then, CT images are registrated with FMT or BLT images；
Step 5：After completing CT acquisitions, reference object is moved into MRI modules, the MRI imagings of shooting experimental animals；
Step 6：After completing all Image Acquisition, the synchronous FMT that carries out is rebuild and BLT reconstructions, wherein it is rebuild if FMT, into Enter step 7, otherwise, enters step 9；
Step 7：The diffusion equation for solving the excitation process and emission process of FMT, obtains FMT's to the solution of forward problem Sytem matrix；
Step 8：The fluorescent intensity distribution of exciting light in vivo is corrected using excitation photo threshold modification method, in turn The sytem matrix of FMT is modified；
Step 9：The diffusion equation for solving BLT emission process, the sytem matrix of BLT is obtained to the solution of forward problem；
Step 10：After completing sytem matrix structure, into module is rebuild, that is, Gauss weight Laplacian Matrix method is used To solve BLT and FMT Problems of Reconstruction；
Step 11：Using mutual information registration method, CT and MRI are registrated, registration obtains reflecting for BLT, FMT and MRI Penetrate relationship；
Step 12：According to the mapping relations of CT and MRI being registrated, by BLT reconstructed results and FMT reconstructed results with MRI results carry out Pixel-level fusion, form experimental animals multi-modality imaging result.
So far, attached drawing is had been combined the embodiment of the present disclosure is described in detail.It should be noted that in attached drawing or saying In bright book text, the realization method for not being painted or describing is form known to a person of ordinary skill in the art in technical field, and It is not described in detail.In addition, the above-mentioned definition to each element and method be not limited in mentioning in embodiment it is various specific Structure, shape or mode, those of ordinary skill in the art simply can be changed or replaced to it.
According to above description, those skilled in the art should be imaged system to the experimental animals multimodality fusion that the disclosure provides System and application method have clear understanding.
In conclusion experimental animals multimodality fusion imaging system and application method that the disclosure provides are filtered by minute surface Method, removal emit the exciting light reflected light in light, and exciting light is corrected in vivo using excitation photo threshold modification method Fluorescent intensity distribution, BLT and FMT Problems of Reconstruction is solved using Gauss weight Laplacian Matrix method, and then alleviate FMT Pollution problem of the reflected light of exciting light to transmitting light, improves the precision of biological tissue's morphological reconstruction in gatherer process.
It should also be noted that, the direction term mentioned in embodiment, for example, "upper", "lower", "front", "rear", " left side ", " right side " etc. is only the direction of refer to the attached drawing, not is used for limiting the protection domain of the disclosure.Through attached drawing, identical element by Same or similar reference numeral indicates.When that understanding of this disclosure may be caused to cause to obscure, conventional structure will be omitted Or construction.
And the shape and size of each component do not reflect actual size and ratio in figure, and only illustrate the embodiment of the present disclosure Content.In addition, in the claims, any reference mark between bracket should not be configured to the limit to claim System.
Similarly, it should be understood that in order to simplify the disclosure and help to understand one or more of each open aspect, Above in the description of the exemplary embodiment of the disclosure, each feature of the disclosure is grouped together into single implementation sometimes In example, figure or descriptions thereof.However, the method for the disclosure should be construed to reflect following intention：It is i.e. required to protect The disclosure of shield requires features more more than the feature being expressly recited in each claim.More precisely, such as front Claims reflect as, open aspect is all features less than single embodiment disclosed above.Therefore, Thus the claims for following specific implementation mode are expressly incorporated in the specific implementation mode, wherein each claim itself All as the separate embodiments of the disclosure.
Particular embodiments described above has carried out further in detail the purpose, technical solution and advantageous effect of the disclosure It describes in detail bright, it should be understood that the foregoing is merely the specific embodiment of the disclosure, is not limited to the disclosure, it is all Within the spirit and principle of the disclosure, any modification, equivalent substitution, improvement and etc. done should be included in the guarantor of the disclosure Within the scope of shield.

Claims (15)

1. a kind of experimental animals multimodality fusion imaging system, including：
Optical image unit, the optical sectioning imaging information for acquiring experimental animals, including：
FMT modules, the FMT information for acquiring experimental animals, the FMT modules are anti-using minute surface filtering method reduction exciting light Penetrate pollution of the light to acquisition signal；
MRI units are arranged, the MRI information for acquiring experimental animals with the optical image unit interval；
Fixed bed, respectively with the optical image unit and the MRI unit matchings, makes experiment for fixing experimental animals It is mobile that animal body carries out rigidity between the two；And
Data processing unit carries out Pixel-level fusion for the optical sectioning imaging information and MRI information to experimental animals.
2. experimental animals multimodality fusion imaging system according to claim 1, the minute surface filtering method include：
Calculate minute surface filter wavelength λf, λf=2 λ1-λ2；
Acquisition optical filter wavelength is λ respectively2With λfWhen excitation fluorescent surface hot spot result b2And bf；And
Calculate final surface fluorescence hot spot bp=b2-α*bf；
Wherein, λ1For excitation wavelength, λ2For wavelength of transmitted light,b2nWave is used in the case of fluorescence probe not use A length of λ2Optical filter when the excitation fluorescent surface hot spot that collects as a result, bfnWave is used in the case of fluorescence probe not use A length of λfOptical filter when the excitation fluorescent surface hot spot result that collects.
3. experimental animals multimodality fusion imaging system according to claim 1, the optical image unit further include：
BLT modules, the BLT information for acquiring experimental animals；And
CT modules, the CT information for acquiring experimental animals.
4. experimental animals multimodality fusion imaging system according to claim 3, the data processing unit include：
Sytem matrix builds module, utilizes FMT information and BLT information architecture sytem matrixes；
Module is rebuild, regularization matrix is built using Gauss weight Laplacian Matrix method, and combine using conjugate gradient method Sytem matrix, the light distribution of experiment with computing animal body Internal Fluorescent light source；
Registration module, on the basis of CT information, will rebuild module to the reconstructed results of FMT information and BLT information and MRI information into Row registration；And
Fusion Module, the mapping relations of the FMT information, BLT information and MRI information that are obtained using registration module, by FMT information and The reconstructed results of BLT information carry out Pixel-level with MRI information and merge.
5. experimental animals multimodality fusion imaging system according to claim 4, the sytem matrix structure module include： Submodule is corrected, uses excitation photo threshold modification method to be modified FMT sytem matrixes, the excitation photo threshold modification method Including：
Obtain φx(j) the maximum value φ inxmax(j)；
Enable all φx(j) 0.4 φ of ＜xmax(j) φx(j) element is all set to 0.4 φxmax(j)；
FMT sytem matrixes are corrected according to following formula；
Wherein, φx(j) it is fluorescent intensity distribution of the exciting light in experimental animals body, φm(i) glimmering to measure the surface of gained Light spot intensity is distributed, η μaf(j) it is that fluorescent light source is distributed in experimental animals body.
6. experimental animals multimodality fusion imaging system according to claim 4, weighed using Gauss in the reconstruction module Weight Laplacian Matrix method structure regularization matrix L is as follows：
LG=(lI, j)N×N
Wherein, lijRepresent decaying element, dijIndicate the space length between two voxels, ρskFor radial softening function, R is height This nuclear radius takes R=0.4 in Gauss weight Laplacian Matrix method.
7. experimental animals multimodality fusion imaging system according to claim 6, conjugation ladder is used in the reconstruction module The light distribution of degree method combination sytem matrix, experiment with computing animal body Internal Fluorescent light source includes：
Step A：Establish objective optimization function；
Wherein,For least squares equation,For lucky big vast promise husband's regular terms, λ is regularization parameter, and L is institute Regularization matrix is stated, A is the sytem matrix；
Step B：Take initial value x(0), computational accuracy c calculates initial residual vector r(0)=b-Ax(0), and enable p(0)=r(0), In, p(0)For primary iteration direction；
Step C：If | | r(k)||2≤ c, then enable x=x(k), calculate and terminate, otherwise calculate following formula：
x(k+1)=x(k)+tk*p(k)
Wherein, r(k)For the residual vector of kth time iteration,For the step-length of kth time iteration, p(k)For kth time Iteration direction；
And element is modified by following formula in the x to acquiring：
Wherein,Indicate the kth time iteration result of i-th of element of vector x,It is the result vector after correction；
Step D：Calculate r(k+1)=b-Ax(k+1), and enable p(k+1)=r(k+1)+αkp(k)
Wherein,
Step E：K=k+1, return to step C is enabled to be judged.
8. experimental animals multimodality fusion imaging system according to claim 3, the fixed bed include：
Bed board, both sides are provided with baffle, the bed board and the baffle for putting experimental animals；
Optical imagery window, correspondence is opened on the middle part and the baffle of the bed board, for being adopted from bottom and side Collect the image-forming information of experimental animals；
Fixed interface is opened on the bed board and/or the baffle, for experimental animals to be auxiliarily fixed；And
Anchor point is set on the bed board and/or the baffle, is used for and the optical image unit or the MRI units Positioning；
Wherein, the bed board and the baffle include organic glass.
9. experimental animals multimodality fusion imaging system according to claim 8, the optical image unit include：
Plane rotary disc is vertically arranged, and the BLT modules, the FMT modules and the CT modules are fixed at the plane On turntable；And
Translation stage is moved back and forth along the normal vector direction of the plane rotary disc, detachable with the bed board and/or the baffle Connection；
Wherein, the translation stage is moved along the normal vector direction of the plane rotary disc, make the optics in the fixed bed at It is exposed to as window in the areas imaging of the BLT modules, the FMT modules and the CT modules, passes through the plane rotary disc The BLT modules, the FMT modules and CT modules rotation are driven, the optical sectioning imaging information of experimental animals is acquired.
10. experimental animals multimodality fusion imaging system according to claim 9, wherein：
The BLT modules are fluorescence camera, the BLT information for acquiring the experimental animals；
The FMT modules include：
Excitation light emission device, for emitting exciting light, including：
First rotating device is connect with the plane rotary disc, drives rocking arm in the rotation in surface parallel with the plane rotary disc；
Second rotating device is connect by the rocking arm with first rotating device, the rotary shaft of second rotating device with The normal vector of the plane rotary disc is vertical；
Optical fiber translation folder, connect with second rotating device, along second rotating device rotary shaft stretch, and with it is described The rotary shaft of second rotating device is in W ° of angle, wherein 0 °≤W≤15 °；And
Laser emitting mouth translates folder connection with the optical fiber, expansion speed great wheel is provided with, for projecting point light source or face light Source；And
Fluorescence camera, the FMT information for acquiring the experimental animals；
The CT modules include：
X-ray bulb, for emitting X-ray；And
X-ray detection plate is separately positioned on the both sides of the translation stage with the X-ray bulb, and experiment is perforated through for receiving The X-ray of animal body；
Wherein, the BLT modules and the FMT modules share the same fluorescence camera.
11. experimental animals multimodality fusion imaging system according to any one of claim 1 to 10, the MRI units Including：
Nuclear-magnetism cavity, for acquiring MRI information；And
Experimental animals bracket is detachably connected with the bed board and/or the baffle, and it is described to drive the fixed bed to stretch into In nuclear-magnetism cavity, NMR imaging is carried out.
12. a kind of application method of experimental animals multimodality fusion imaging system, using any in such as the claims 1 to 11 Experimental animals multimodality fusion imaging system described in, including：
Step 100：Experimental animals are fixed to the optical image unit by the fixed bed；
Step 200：BLT information, FMT information and the CT information of experimental animals are acquired respectively, and utilize minute surface filtering method FMT information is modified；
Step 300：Experimental animals are fixed to the MRI units by the fixed bed；
Step 400：Acquire the MRI information of experimental animals；And
Step 500：Picture is carried out to the BLT information, the FMT information and the MRI information using the data processing unit Plain grade fusion.
13. the application method of experimental animals multimodality fusion imaging system according to claim 12 acquires experimental animal The FMT information of body includes：
Point-like laser is selected to acquire FMT information using transmission model；And/or
Planar laser is selected to acquire FMT information using reflection model；
Wherein, when acquiring FMT information using reflection model, the minute surface filtering method is used.
14. the application method of experimental animals multimodality fusion imaging system according to claim 13, uses transmission model Selection point-like laser acquires FMT information：
Experimental animals are mouse, pass through fixed interface to fix the four limbs of mouse using wire rod, its thorax abdomen is made to be exposed to optics At imaging window；
The first rotating device is adjusted, laser emitting mouth is made to be located at the both sides of mouse with fluorescence camera；
Optical fiber translation folder distance of stretch out and draw back and angle are adjusted, thorax abdomen FMT information in the case of different excitations is acquired.
15. the application method of experimental animals multimodality fusion imaging system according to claim 13, uses reflection model Selection planar laser acquires FMT information：
Experimental animals are mouse, and the neck of experimental animals is fixed using adhesive tape, makes its head exposure in optical imagery window Place；
Select the optical filter of the wave band less than exciting light 50nm wavelength；
In the case that without using fluorescence probe, exciting light reflected light facula information is acquired；
Using fluorescence probe, head FMT information is acquired；
Head FMT information is corrected using exciting light reflected light facula information combination minute surface filtering method.
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