CN105748040A - Three-dimensional structure functional imaging system - Google Patents

Three-dimensional structure functional imaging system Download PDF

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CN105748040A
CN105748040A CN201610081461.5A CN201610081461A CN105748040A CN 105748040 A CN105748040 A CN 105748040A CN 201610081461 A CN201610081461 A CN 201610081461A CN 105748040 A CN105748040 A CN 105748040A
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light
subsystem
light source
imaging
frequency domain
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CN105748040B (en
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廖洪恩
范应威
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Tsinghua University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062Arrangements for scanning
    • A61B5/0066Optical coherence imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073Measuring 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

Abstract

The invention provides a three-dimensional structure functional imaging system which comprises a frequency domain optical coherence tomography subsystem, a fluorescence imaging and spectral analysis subsystem and a front-end scanning structure subsystem. According to the frequency domain optical coherence tomography subsystem, low coherence light is used as a light source, and the light source is input into a coupler after passing through a polarization controller, split to a reference arm and a sample arm and then returned back to the coupler to form a coherent light field. The fluorescence imaging and spectral analysis subsystem can be provided with multiple selectable light sources, a light way is adjusted at the light machine part, and a light source with the preset power is obtained and coupled to a sample light way of the frequency domain optical coherence tomography subsystem. The front-end scanning structure subsystem is used for coupling the light sources of the fluorescence imaging and spectral analysis subsystem and the sample light of the frequency domain optical coherence tomography subsystem into the same light way, a two-dimensional scanning galvanometer is used for scanning emergent light to form a dot matrix image of a two-dimensional structure, and therefore a three-dimensional image comprising surface fluorescence signals and a structure fault is obtained. The three-dimensional structure functional imaging system has the advantages of being high in resolution ratio, low in cost, good in stability and high in reliability and achieving noninvasive imaging.

Description

Stereochemical structure function imaging system
Technical field
The present invention relates to medical imaging technical field, particularly to a kind of stereochemical structure function imaging system.
Background technology
Central nervous system pathological change becomes the big killer threatening human life, enjoys people to pay close attention to because of its high fatality rate caused and disability rate.At present, operation is the prefered method of radical cure central nervous system pathological change, tumor, and high-resolution 26S Proteasome Structure and Function image will provide for operation and guide accurately.Owing to current imaging Analysis checkout and diagnosis means exist, resolution is low, have the shortcoming such as radioactivity, single structure function imaging, therefore develop the equipment of radiationless, high-resolution, integrated morphology functional imaging it is critical that, and the imaging of structure function is the important means solving the problems referred to above.
Identification pathological changes at present conventional art, tumor method be mainly in intraoperative ultrasound, art point analysis method such as x-ray, frozen section analysis, cytology of impression slide, but these methods have respective shortcomings and limitations.Intraoperative ultrasound detection needs contact and also needs to increase couplant, and spatial resolution can only achieve grade simultaneously, is difficult to differentiate accurately tumor and pathological changes;In art, the resolution of x-ray is also relatively low, and has radioactivity, and the relatively low specificity of sensitivity is also relatively low simultaneously;Frozen section length consuming time, cost are high;Printingout cell analysis is only able to detect the tissue on surface, and deep tissues but cannot be detected.Therefore current detection method also needs to continuously improve and improve.Photoacoustic imaging progressively becomes study hotspot in recent years, but the spatial resolution of photoacoustic imaging up to a hundred microns is for being relatively low in cell aspect accurately.
Frequency domain optical-coherence tomography (FrequencyDomain-OpticalCoherenceTomography, FD-OCT) there is provided the stereochemical structure imaging pattern of histoorgan.The ultimate principle of FD-OCT is well-known, use near infrared light source, the diagnostic image that can realize tissue has the spatial resolution of 10-20um, tissue can be realized high-resolution, noinvasive, contactless, radiationless image acquisition, and can reach in real time to biological tissue's identification and analysis.At present, it is widely used in the diagnosis of the pathological changes such as ophthalmology, skin, blood vessel internal medicine based on the imaging system of FD-OCT.
At present, Functional MRI (functionalmagneticresonanceimaging, fMRI) is the mainstream technology of functional imaging, but as it has been described above, its imaging resolution is relatively low, pathological changes identification difficulty accurately is determined.
Summary of the invention
It is contemplated that one of technical problem solved at least to a certain extent in above-mentioned correlation technique.
For this, it is an object of the invention to propose a kind of stereochemical structure function imaging system, this system has resolution height, cost is low, good stability, reliability high and the advantage of noinvasive imaging.
To achieve these goals, embodiments of the invention propose a kind of stereochemical structure function imaging system, including: frequency domain optical-coherence tomography subsystem, described frequency domain light coherence tomography subsystem adopts low-coherent light as light source, and described light source is input to bonder by after Polarization Controller, by returning to described bonder after described bonder light splitting to reference arm and sample arm to form coherent states field, and spectrogrph and CCD is adopted to gather described coherent states field storage and display in external host;Fluorescence imaging and spectrum analysis subsystem, described fluorescence imaging and spectrum analysis subsystem have multiple optional light source, the light path of the plurality of optional light source is regulated by ray machine unit, obtain the light source of predetermined power, and by the light source couples of described predetermined power to the sample arm of described frequency domain optical-coherence tomography subsystem;Front end Scan Architecture subsystem, described front end Scan Architecture subsystem for by the light source of described fluorescence imaging and spectrum analysis subsystem and the sample of described coherence in frequency domain fault imaging subsystem optically coupling in same light path, and use two-dimensional scanning mirrors that emergent light scans the dot matrix image to form two-dimensional structure, and the dot matrix image according to described two-dimensional structure constitutes a structure tomography stereo-picture comprising surface fluorescence spectral signal and have the degree of depth.
Stereochemical structure function imaging system according to embodiments of the present invention, fusion of imaging in conjunction with stereochemical structure imaging and functional imaging and two kinds of images, both can to the stereochemical structure functional imaging of biologic soft tissue especially cerebral tissue and brain stem tissue, frequency domain optical-coherence tomography and fluorescent high spectral image can be gathered again respectively, the realtime imaging in art can also be gathered simultaneously.The analysis of precisely diagnosis is provided and accurately guides by micron-sized stereo structure image, and the tissue optical property such as tumor, pathological changes and spectral characteristic all can change relative to normal structure;Functional image to the change extracting tissue signal before being organized in morbidity, can predict the generation of pathological changes at premorbid, and lesion degree and scope are made assessment, the optical theory foundation that the early screening offer of tumor is feasible.The pathological changes metabolic signals of tissue, neural cortex excitatory transmission etc. can be detected in pathological tissues functional areas by stereochemical structure functional imaging technology, provide important Research approach particularly in location, brain domain and clinical central nervous system mechanism of action aspect;Its and pathology aspect offer optical theory foundation coupled for the function detecting biological tissue simultaneously.The pathological changes identification suitable in neurosurgery of this system and detection, have that volume is little, it is flexible, easy to operate to use, integrated level is high, resolution is high, cost is low, good stability, reliability high and the advantage of noinvasive imaging.
It addition, stereochemical structure function imaging system according to the above embodiment of the present invention can also have following additional technical characteristic:
In some instances, the size of described stereo-picture is determined by microscopical enlargement ratio, the surface image spatial resolution of described stereo-picture is determined by described microscopical enlargement ratio and spot size, and the surface image longitudinal resolution of described stereo-picture is determined by the coherence length of laser of described frequency domain optical-coherence tomography subsystem.
In some instances, described fluorescence imaging and spectrum analysis subsystem include photomultiplier tube detectors and imaging spectrometer, wherein, described imaging spectrometer is for carrying out light splitting by fluorescence signal by grating, and by described photomultiplier tube detectors, the fluorescence signal after light splitting is transferred to external host carries out storing and showing.
In some instances, described fluorescence imaging and spectrum analysis subsystem have first to fourth light source interface, and wherein, described first to fourth light source interface correspondence connects first to fourth fluorescence excitation light source of different wave length.
In some instances, described first to fourth fluorescence excitation light source is connected with described front end Scan Architecture subsystem by optical fiber, wherein, described front end Scan Architecture subsystem includes the first wave filter, the second wave filter, power attenuator and fluorescence excitation light-receiving unit, described first wave filter is connected with described fluorescence excitation light-receiving unit, the optical signal of fluorescence excitation light source described in high pass, the sample reflection light of high anti-described frequency domain optical-coherence tomography subsystem.
In some instances, described fluorescence excitation light-receiving unit is made up of spectrogrph and photomultiplier tube detectors.
In some instances, described sample light directly arrives described front end Scan Architecture subsystem after optical fiber connects, and by arriving sample through overscanning object lens after being connected to galvanometer after the second wave filter and described first wave filter, wherein, the sample light of the high anti-described frequency domain optical-coherence tomography subsystem of described first wave filter, the exciting light of high anti-described fluorescence imaging and spectrum analysis subsystem, the light source of frequency domain optical-coherence tomography subsystem described in described second wave filter high pass, the light source light of high anti-described fluorescence imaging and spectrum analysis subsystem.
In some instances, the light source of described frequency domain light coherence tomography subsystem is bandwidth light source, and the centre wavelength of described bandwidth light source is 1310nm, and the bandwidth of described bandwidth light source is 60nm.
In some instances, the splitting ratio of described bonder is 50:50, and the signal of described light source is divided into reference light and sample light by described bonder.
In some instances, described front end Scan Architecture subsystem is made up of one-dimensional or 2-D vibration mirror system.
The additional aspect of the present invention and advantage will part provide in the following description, and part will become apparent from the description below, or is recognized by the practice of the present invention.
Accompanying drawing explanation
Above-mentioned and/or the additional aspect of the present invention and advantage are from conjunction with will be apparent from easy to understand the accompanying drawings below description to embodiment, wherein:
Fig. 1 is the structural principle schematic diagram of stereochemical structure function imaging system according to an embodiment of the invention;
Fig. 2 is the structural representation of fluorescence imaging and spectrum analysis subsystem according to an embodiment of the invention;
Fig. 3 is the structural representation of frequency domain optical-coherence tomography subsystem according to an embodiment of the invention;
Fig. 4 is the Canis familiaris L. schematic diagram of front end Scan Architecture subsystem according to an embodiment of the invention;And
Fig. 5 is the system block diagram of stereochemical structure function imaging system according to an embodiment of the invention.
Detailed description of the invention
Being described below in detail embodiments of the invention, the example of described embodiment is shown in the drawings, and wherein same or similar label represents same or similar element or has the element of same or like function from start to finish.The embodiment described below with reference to accompanying drawing is illustrative of, and is only used for explaining the present invention, and is not considered as limiting the invention.
Below in conjunction with accompanying drawing, stereochemical structure function imaging system according to embodiments of the present invention is described.
Fig. 1 is the structural principle schematic diagram of stereochemical structure function imaging system according to an embodiment of the invention.As it is shown in figure 1, stereochemical structure function imaging system according to embodiments of the present invention includes: frequency domain optical-coherence tomography subsystem 1 (FD-OTC), fluorescence imaging and spectrum analysis subsystem 2 and front end Scan Architecture subsystem 3.Wherein, the light channel structure of frequency domain optical-coherence tomography subsystem 1, fluorescence imaging and spectrum analysis subsystem 2 and front end Scan Architecture subsystem 3 can be coupled as the light path of a convertible adjustment, the output of respective light path can also be realized by single channel, all can realize the collection of two images.
Specifically, frequency domain optical-coherence tomography subsystem 1 adopts low-coherent light as light source, and light source is input to bonder after Polarization Controller (polarization), by returning to bonder after bonder light splitting to reference arm and sample arm to form coherent states field, and spectrogrph and CCD is adopted to gather coherent states field and carry out storing and showing in external host.More specifically, in some instances, as shown in Figure 3, the light source of frequency domain light coherence tomography subsystem 1 is bandwidth light source, and the centre wavelength of this bandwidth light source is 1310nm, and the bandwidth of bandwidth light source is 60nm, spectrogrph adopts imaging spectrometer (OCTS-1280-1310-1340, BaySpecCo.), this imaging spectrometer contains high-velocity scanning OCT photographic head, the best 91911/sec of line scan rate.Frequency domain optical-coherence tomography subsystem 1 uses frequency domain optical-coherence tomography, decreases sweep time, adopts vibration mirror scanning to complete whole sector scanning process.Wherein, as it is shown on figure 3, frequency domain optical-coherence tomography subsystem 1 through wideband light source through three oar Polarization Controllers, it is connected to bonder, bonder has the splitting ratio of 50:50, and the signal of light source is divided into reference light and sample light, has respectively entered respective passage afterwards.In reference arm one end, reference light irradiates after lens focus and returns according to original optical path on the mirror.
Specifically, frequency domain optical-coherence tomography is also progressively becoming study hotspot in the utilization of cerebral tissue, because of the imaging mode that the resolution of its imaging is significantly high, noinvasive is radiationless, embodies greater advantage in the imaging particularly in tumor identification.Structure image is that the mode adopting spot scan is rebuild, and each point is exactly a pixel, and each point also has certain depth information simultaneously, namely illustrates stereo structure image.
In image reconstruction process, it is necessary first to function i (h) is determined, wherein transform such as following formula:
| i ( h ) | = TRA 2 R r | g ( h ) | + TRA 2 Σ i R i | g ( h ) | + TRA 2 Σ i ≠ j R i R j | g ( h - ( h i - h j ) ) | + TRA 2 Σ i ≠ j R i R j | g ( h + ( h i - h j ) ) | + TRA 2 Σ i R i R r | g ( h - h i ) | + TRA 2 Σ i R i R r | g ( h + h i ) | , - - - ( 1 )
In formula, the power reflectance of beam splitter and power transmittance respectively R and T, if beam splitter is desirable, then T+R=1;RiBeing the power scattered power dorsad of i point, peak swing when A is h=0, g represents Gaussian function.TRA in above formula2Rr| g (h) | represents the image of reference light source, TRA2iRiThe image of | g (h) | expression sample light source, namely DC terms,WithRepresent the image (" auto-correlation " item) and its mirror image that cause " light source " interfered between evanescent light wve dorsad on any two sides in all chromatography faces of sample depth respectively,WithRepresent image (" cross-correlation " item) and its mirror image of " light source " interfered mutually between evanescent light wve and reference light wave dorsad that cause sample depth to have all chromatography faces respectively.
Real data (the interference light power spectrum that CCD collects) is carried out Fourier transformation and defines the mirror image of " auto-correlation " item and the mirror image of " cross-correlation " item.The Section 5 of above formula (1)(" cross-correlation " item) is only the useful image information required for sample, g (h-hi) determine the picture position of sample axial depth i point and the information of axial resolution.The image of sample depth i point is not a desirable point, but with h=hiLength centered by (in optical path difference spatial domain) place is lcShort-term, and the gray scale on this short-term is Gauss distribution, its coefficientDetermining the gray scale of image, the gray scale determiner of image is the power reflectance of the scattered power of power dorsad in sample chromatography face, light source output power and reference arm.Because | g | function determines the axial true picture of all scattering points of sample and the position of spurious image and image resolution ratio, its coefficient determines the gray scale of image, so | i (h) | is called SDOCT image function.
That is, the structural information that frequency domain optical-coherence tomography subsystem 1 realizes the degree of depth by Fourier transformation is extracted, and this information contains information on the morphosis of tissue, and this information contains the structural information of biological tissue surface, provide depth information simultaneously, obtain 3-D solid structure image.Tumor for brain and brain stem, atypia according to its structure, the i.e. specificity of cellular morphology and organizational structure, adopt the frequency domain optical-coherence tomography subsystem 1 that the degree of depth is relevant to its imaging, adopt optics decay characteristics in the tissue simultaneously, precisely differentiate the structure of tumor epithelial cell, mesenchyma stroma of tumors and normal structure.
Fluorescence imaging and spectrum analysis subsystem 2 have multiple optional light source, the light path of multiple optional light sources is adjusted, obtain the light source of predetermined power, namely reduce light source power, and by the light source couples of predetermined power to the sample arm of frequency domain optical-coherence tomography subsystem 1.
In one embodiment of the invention, as shown in Figure 2, fluorescence imaging and spectrum analysis subsystem 2 include photomultiplier tube PMT detector and imaging spectrometer, wherein, imaging spectrometer is such as Monochromator-SpectrograohMS2004i (SOLinstruments) imaging spectrometer, for fluorescence signal is carried out light splitting by grating therein, and the fluorescence signal after light splitting is transferred to external host by PMT detector carries out storing and showing.Wherein, imaging spectrometer is connected by optical fiber-spectrogrph adapter.
Further, as in figure 2 it is shown, fluorescence imaging and spectrum analysis subsystem 2 have four light source interface, i.e. first to fourth light source interface, wherein, first to fourth light source interface connects first to fourth fluorescence excitation light source of different wave length by correspondence.
Specifically, in fluorescence imaging and spectrum analysis subsystem 2, what high light spectrum image-forming adopted is photomultiplier tube (PMT) and spectrogrph, adds real-time storage and the analysis of image simultaneously.In light source part, design adds multiple access port (first to fourth light source interface described above), the light source of different wave length and different capacity can be connected, for fluorometric reagent conventional at present, consist predominantly of 5-ALA (5-aminolevulinicacid, 5-ALA), yellow fluorescence, indocyanine green (Indocyaninegreen, ICG), their optical source wavelength is not quite similar, wherein in the imaging device of invention, mainly use according to patient, the actual clinical situation of pathology.
Owing to fluorescence is had different effects by pathological tissues, particularly under different light sources, exciting light also differs.Therefore obtaining spectral components according to spectrum frequency analysis, comprise harmonic wave remainder, amplitude, phase place, the hop count t of spectral space represents, the cycle represents with L, launches to be transformed to:
Wherein M h = 2 L Σ t = 1 L s ( t ) c o s ( 2 h π t L ) , N h = 2 L Σ t = 1 L s ( t ) s i n ( 2 h π t L )
In formula, t represents wave band count, and L represents wave band sum, and spectrum vector is (S1,S2...,SL)T, M0Representing harmonic wave remainder, h represents frequency analysis number of times, AhRepresent amplitude,Represent the initial phase of h subharmonic.
That is, fluorescence imaging and spectrum analysis subsystem 2 mainly provide structure and the function information thereof on the surface of tissue, the functional strong structures such as the arteries fine especially for shallow-layer and nerve, it is provided that abundant identification function of organization information, thus differentiating this mechanics of biological tissue accurately.For tumor tissues, especially cerebral tumor medium vessels distribution concentration, tumor epithelial cell and the more sufficient part of interstitial, structural information and comprehensive function information will judge for tumor and excise the guarantee providing stronger accurately.
It addition, the collection that fluorescence imaging and spectrum analysis subsystem 2 are also provided that high spectrum image while providing spectrum analysis is implemented.Frequency domain optical-coherence tomography subsystem 1 and fluorescence imaging and spectrum analysis subsystem 2 common optical pathways part.Common optical pathways is frequency domain optical-coherence tomography subsystem 1 and the basic light path of fluorescence imaging and spectrum analysis subsystem 2, frequency domain optical-coherence tomography subsystem 1 belongs to sample arm part, is the light channel structure of front-end collection in fluorescence imaging and spectrum analysis subsystem 2.Wherein containing scan control part, its mode uses spot scan, and adopts snake scan to complete two-dimensional array scanning.Integrated optical circuit primary concern is that fluorescence light source, fluorescent exciting, frequency domain optical-coherence tomography light source and sample reflection light light path part in light subsystems, adopt different wave filter according to wavelength, power, use power governor (attenuator etc.) to be regulated in light path safety range.
Further, fluorescence imaging and spectrum analysis subsystem 2 are to light path and the design driving scanning, for the speed of frequency domain optical-coherence tomography subsystem 1 and the image/signals collecting of photoelectric detector (PMT), Scan Architecture must assure that and can keep consistent with it, namely can gather storage image when scanning diverse location, it is ensured that the real-time of image also reduces redundancy simultaneously.Therefore, the collection of image needs the probe that design is suitable, and provides certain moving sweep function that overall region is done comprehensive collection.
Front end Scan Architecture subsystem 3 for by the light source of fluorescence imaging and spectrum analysis subsystem 2 and the sample of coherence in frequency domain fault imaging subsystem 1 optically coupling in same light path, and use two-dimensional scanning mirrors to be scanned emergent light processing the dot matrix image to form two-dimensional structure, constitute a stereo-picture comprising surface fluorescence signal and structure faultage image according to the dot matrix image of two-dimensional structure.Wherein, the size of this stereo-picture is determined by microscopical enlargement ratio, the surface image spatial resolution of this stereo-picture is determined by microscopical enlargement ratio and spot size, and the surface image longitudinal resolution of this stereo-picture is determined by the coherence length of laser of frequency domain optical-coherence tomography subsystem 1.Wherein, front end Scan Architecture subsystem 3 is such as made up of one-dimensional or 2-D vibration mirror system.In this example, it is preferable that 2-D vibration mirror scanning system, the time greatly and is saved in the region of single sweep operation.
In one embodiment of the invention, shown in Fig. 4, first to fourth above-mentioned fluorescence excitation light source is connected with front end Scan Architecture subsystem 3 (i.e. ray machine unit) by optical fiber, wherein, front end Scan Architecture subsystem 3 includes the first wave filter, the second wave filter, power attenuator and fluorescence excitation light-receiving unit, wherein, the first wave filter is connected with fluorescence excitation light-receiving unit, and uses the first wave filter before fluorescence excitation light-receiving unit.First wave filter for the optical signal of high pass fluorescence excitation light source, the sample reflection light of high anti-frequency domain optical-coherence tomography subsystem, the reflection light of reflected sample light, thus to imaging in biological tissues.Wherein, fluorescence excitation light-receiving unit is such as made up of spectrogrph and photomultiplier tube PMT detector.
Wherein, fluorescence light source light needs to arrive sample after front end galvanometer scanning system and scanning objective (microscope) focus on, and meanwhile, fluorescence photosensitizer excites generation exciting light thus according in backtracking to acquisition component through light source.Wherein, scanning objective is the structure in microscope, and scanning objective amplification is 10 times.Connection microscopic system composition is optionally just being put or is being inverted mirror and forming various selection imaging system.
Fluoroscopic image and fluorescent high spectrum use hardware-accelerated, realize the raising of the image taking speed of EO-1 hyperion on GPU.
Wherein, sample light directly arrives front end Scan Architecture subsystem 3 (ray machine unit) after optical fiber connects, and by arriving sample through overscanning object lens (microscope) after being connected to galvanometer after the second wave filter and the first wave filter, wherein, the sample light of the high anti-frequency domain optical-coherence tomography subsystem 1 of the first wave filter, the exciting light of high anti-fluorescence imaging and spectrum analysis subsystem 2, the light source of the second wave filter high pass frequency domain optical-coherence tomography subsystem 1, the light source light of high anti-fluorescence imaging and spectrum analysis subsystem 2.
Further, sample light is backtracking after sample reflects, frequency domain optical-coherence tomography subsystem 1 is entered by the first wave filter and the second wave filter (i.e. wave filter 1 and 2 in figure), thus formed with reference light and interfere thus obtaining the depth information of sample and then obtaining its depth structure imaging, excite fluorescence to pass through the first wave filter and enter fluorescence imaging and spectrum analysis subsystem 2 and realize the analysis of fluorescence spectrum.
Further, in specific implementation process, the stereochemical structure function imaging system of the embodiment of the present invention provides multiple different types of micro-subsystem, the multiplying power scalable of scanning objective in micro-subsystem, therefore also can change the horizontal and vertical spatial resolution of biological tissue, namely add the controllability of visual field.Can integrated common optical pathways part in micro-subsystem, the light path of spectrofluorimetry light path and frequency domain optical-coherence tomography system can be coupled to a light path, it is scanned through after object lens imaging in biological tissues, therefore the sector scanning of Centimeter Level is reached, binding probe design reaches bigger sector scanning and obtains the imaging of whole operative region, thus giving doctor's image-guided surgery accurately.
Feature by stereo structure image and the fusion of functional image about the embodiment of the present invention is described below.Depth structure image based on frequency domain optical-coherence tomography and the planar structure four-dimension image based on fluorescent high spectrum and the fusion of spectral information image are the bases of high-precision diagnosis, the basic feature information of structure image and functional image is extracted, the convergence analysis of image will be realized after accurate for the dot information of planar functional-structural information and three dimensional structure registration;And by the information retrieval of pathological changes, it is achieved the identification of structure function pathological changes.The at present conventional amalgamation mode based on Pixel-level, image adopt two-dimensional structure show after by different conversion process, after realize comprehensive through certain rule of combination, then employing inverse transformation is to the image after operation recovery fusion.Secondly, the image co-registration of feature based level uses the information such as characteristics of image, the sufficient statistic of pixel or expression amount, object edge information, direction, merges after its sort merge is processed.Image co-registration in native system is obtained by the amalgamation mode of Pixel-level and feature level, owing to the dimension of two-dimensional fluoroscopic image and three-dimensional light coherence tomography images differs, adopting the light coherence tomography images of two dimension to merge after converting with fluoroscopic image is the preferred embodiments of the present invention.
Simple fusion estimation to image is to adopt weighting pattern, it may be assumed that
F (x, y)=Wa*A (x, y)+Wb*B (x, y) (3)
Wherein, F represents the image after fusion, and A represents the surface texture image of OCT, and B represents that fluoroscopic image, Wa represent the weight of A image, and Wb represents the weight of B image.
Further, the time-frequency combination of image can also be analyzed result according to wavelet transformation and propose deeper analysis by image co-registration: OCT surface image A and fluoroscopic image B is used wavelet analysis, making it obtain multiple dimensioned and multiresolution high and low frequency component respectively, corresponding high fdrequency component and low frequency component obtain syncretizing effect image according to different fusion rules.
Image co-registration carries out wavelet decomposition firstly the need of to source images, it is assumed that the conversion coefficient of source images can be represented by formula (4), (5):
f A ( x , y ) → ( C 1 , 1 A ( x , y ) , C 1 , 2 A ( x , y ) , ... , C i , j A ( x , y ) , C i 0 A ( x , y ) ) - - - ( 4 )
f B ( x , y ) → ( C 1 , 1 B ( x , y ) , C 1 , 2 B ( x , y ) , ... , C i , j B ( x , y ) , C i 0 B ( x , y ) ) - - - ( 5 )
Wherein, F represents the image after fusion, and A represents the surface texture image of OCT, and B represents fluoroscopic image,WithIt is low frequency sub-band coefficient, Ci,j(x, the conversion coefficient of y) to be i-th layer decompose jth directional subband, i.e. high-frequency sub-band coefficient, take different fusion rule to calculate the coefficient after merging the low frequency after conversion and high-frequency sub-band coefficient respectively.
Because low frequency sub-band coefficient illustrates the profile information of image, adopt average rule that it is processed for multiple focussing image:
C i 0 F ( x , y ) = C i 0 A ( x , y ) + C i 0 B ( x , y ) 2 - - - ( 6 )
WhereinWithRepresent the low frequency sub-band coefficient of correspondence position in source images respectively.
Owing to the detailed information in image such as edge, texture etc. are represented by high frequency coefficient, it is necessary to select source images partly obtains fusion coefficients clearly as far as possible, therefore in this example, select weights method that high frequency coefficient is merged:
C i , j F ( x , y ) = α * C i . j A ( x , y ) + ( 1 - α ) * C i , j B ( x , y ) - - - ( 7 )
Wherein α is weight coefficient, and in an embodiment of the present invention, α weight computing is determined by Total Variation formula (8), then carries out multi-scale wavelet inverse transformation and carrys out restored image.
m i n { E [ c ( x , y ) ] = β ∫ ∫ | ▿ c | 2 d x d y - ∫ ∫ [ ( c F - αc A ) + ( c - ( 1 - α ) c B ) ] 2 d x d y } = min { β ∫ ∫ | ▿ c | 2 d x d y - ∫ ∫ [ ( 1 - α ) c B + αc A ] 2 d x d y } - - - ( 8 )
Wherein, β represents the smooth item factor, ▿ c = ( ( c x ) 2 + ( c y ) 2 ) 1 2 , cx、cyProvided by formula (7).
As above analyzing, embodiments of the invention have employed the convergence analysis mode of structure function image, adopts volume drawing mode precisely to be analyzed by three-dimensional structure data the functional image of stereochemical structure.
Further, shown in Fig. 5 it is stereochemical structure function imaging system block diagram.This stereochemical structure function imaging system, by the analysis to 26S Proteasome Structure and Function image, is provided that optical characteristics and the spectral characteristic of biological tissue, and optical characteristics includes the spectral characteristic with attenuation characteristic and fluorescence metabolism.
In a particular embodiment, the stereochemical structure function imaging system of the present invention can apply to Wicresoft's imaging and the operation of ophthalmology, skin, breast tumor, liver and gall pancreas tumor, dentistry, Vasculocardiology Deparment, the intestines and stomach, urology department etc..This imaging system includes high-resolution 26S Proteasome Structure and Function image system, and it is provided that anatomic form structure and brain function clearly.OCT and fluoroscopic image and hyperspectral analysis can be respectively used to the depth information structure image of the radiationless biological tissue of noinvasive and functional image thus forming 3 dimension stereochemical structure functional images of resolution biology.Native system imaging includes the information such as the depth information of tissue, anatomic form structure, light-decay characteristic, blood oxygen concentration, blood flow spectrum and biological tissue's spectral signature thereof, the front-end driven Scan Architecture of system integration vibration mirror scanning and optical fiber scan type and light channel structure and forms spot scan mode.This imaging system contains various level image co-registration and image understanding algorithm.By biological tissue being included the imaging analysis tumor epithelial cell of brain and brain stem tissue, junctional area, normal structure, brain tumor and pathological changes precisely being identified simultaneously, providing image accurately to guide for operation.
In a particular embodiment, this imaging system also includes the imaging of the structure function image to biological tissue, and this structure image is hierarchy and the border structure of tissue, and functional image is the detection of the vascularity state in biological tissue, shape, content of hemoglobin.
Further, this imaging system such as also includes the fusion of structure function image, blending algorithm analysis etc., and signal analysis mode is the analysis in conjunction with spectrum analysis and light coherent signal, the structure function identification to tissue.
Further, this imaging system such as also includes the scanheads to front end, and for the imaging function of the pathological changes in surgical procedures, the scanheads of imaging has big FOV and the characteristic such as horizontal linearity degree, vertical linearity degree;Moving process tentatively identifies the approximate location scanned, behind location, precisely scans operative region.
Further, this imaging system such as also includes the snake-shaped robot multiterminal Scan Architecture adopting inner peeping type, adopts flexible robot that the tissue in art does comprehensively scanning and imaging.Wherein, front-end probe uses flexible snake-shaped robot to conduct to optical fiber, and optical fiber moves with it in flexible robot, and forms self-driving type scanning at probe distal end.
Further, this imaging system such as also includes the front end scanning system of inner peeping type, endoscope system is by Fiber optic delivery systems entrance endoscope system the structure function image detecting biological tissue through coupling optical path, wherein adopt single fiber to import the sample light of the light source of spectrofluorimetry system and frequency domain optical-coherence tomography system, formed can front driving type scanning and side type rotation sweep thus imaging while forming structure function image.
Further, this imaging system such as also includes the therapeutic modality structure that adapts with imaging system, for instance photodynamic therapy (PDT), sound motivation therapy (SDT) etc. combine and form novel diagnosis and treatment integral system.The power of the light source of photodynamic therapy and the sound source of sound motivation therapy controls to be combined into differentiating in real time of picture and correspondence provides and reaches therapeutic effect.
Additionally, this imaging system is capable of operation Wicresoft or even noninvasive imaging, biological tissue is had optical attenuator characteristic, fluoroscopic image, Fluorescence Characteristic, stereochemical structure functional image and high light spectrum image-forming analysis, can be combined with three-dimensional stereo display technique in the real-time navigation performed the operation simultaneously.
To sum up, stereochemical structure function imaging system according to embodiments of the present invention, fusion of imaging in conjunction with three-dimensional morphosis imaging and functional imaging and two kinds of images, both can to the stereochemical structure functional imaging of soft tissue especially cerebral tissue and brain stem tissue, frequency domain optical-coherence tomography and fluorescent high spectral image can be gathered again respectively, the realtime imaging in art can also be gathered simultaneously.The pathological changes identification suitable in neurosurgery of this system and detection, have that volume is little, it is flexible, easy to operate to use, integrated level is high, resolution is high, cost is low, good stability, reliability high and the advantage of noinvasive imaging.
In describing the invention, it will be appreciated that, term " " center ", " longitudinal direction ", " transverse direction ", " length ", " width ", " thickness ", " on ", D score, " front ", " afterwards ", " left side ", " right side ", " vertically ", " level ", " top ", " end " " interior ", " outward ", " clockwise ", " counterclockwise ", " axially ", " radially ", orientation or the position relationship of the instruction such as " circumference " are based on orientation shown in the drawings or position relationship, it is for only for ease of the description present invention and simplifies description, rather than the device of instruction or hint indication or element must have specific orientation, with specific azimuth configuration and operation, therefore it is not considered as limiting the invention.
Additionally, term " first ", " second " are only for descriptive purposes, and it is not intended that indicate or imply relative importance or the implicit quantity indicating indicated technical characteristic.Thus, define " first ", the feature of " second " can express or implicitly include at least one this feature.In describing the invention, " multiple " are meant that at least two, for instance two, three etc., unless otherwise expressly limited specifically.
In the present invention, unless otherwise clearly defined and limited, the term such as term " installation ", " being connected ", " connection ", " fixing " should be interpreted broadly, for instance, it is possible to it is fixing connection, it is also possible to be removably connect, or integral;Can be mechanically connected, it is also possible to be electrical connection;Can be joined directly together, it is also possible to be indirectly connected to by intermediary, it is possible to be connection or the interaction relationship of two elements of two element internals, unless otherwise clear and definite restriction.For the ordinary skill in the art, it is possible to understand above-mentioned term concrete meaning in the present invention as the case may be.
In the present invention, unless otherwise clearly defined and limited, fisrt feature second feature " on " or D score can be that the first and second features directly contact, or the first and second features are by intermediary mediate contact.And, fisrt feature second feature " on ", " top " and " above " but fisrt feature directly over second feature or oblique upper, or be merely representative of fisrt feature level height higher than second feature.Fisrt feature second feature " under ", " lower section " and " below " can be fisrt feature immediately below second feature or obliquely downward, or be merely representative of fisrt feature level height less than second feature.
In the description of this specification, specific features, structure, material or feature that the description of reference term " embodiment ", " some embodiments ", " example ", " concrete example " or " some examples " etc. means in conjunction with this embodiment or example describe are contained at least one embodiment or the example of the present invention.In this manual, the schematic representation of above-mentioned term is necessarily directed to identical embodiment or example.And, the specific features of description, structure, material or feature can combine in one or more embodiments in office or example in an appropriate manner.Additionally, when not conflicting, the feature of the different embodiments described in this specification or example and different embodiment or example can be carried out combining and combining by those skilled in the art.
Although above it has been shown and described that embodiments of the invention, it is understandable that, above-described embodiment is illustrative of, it is impossible to be interpreted as limitation of the present invention, and above-described embodiment can be changed, revises, replace and modification by those of ordinary skill in the art within the scope of the invention.

Claims (10)

1. a stereochemical structure function imaging system, it is characterised in that including:
Frequency domain optical-coherence tomography subsystem, described frequency domain light coherence tomography subsystem adopts low-coherent light as light source, and described light source is input to bonder by after Polarization Controller, by returning to described bonder after described bonder light splitting to reference arm and sample arm to form coherent states field, and spectrogrph and CCD is adopted to gather described coherent states field storage and display in external host;
Fluorescence imaging and spectrum analysis subsystem, described fluorescence imaging and spectrum analysis subsystem have multiple optional light source, the light path of the plurality of optional light source is adjusted, obtain the light source of predetermined power, and by the light source couples of described predetermined power to the sample arm of described frequency domain optical-coherence tomography subsystem;And
Front end Scan Architecture subsystem, described front end Scan Architecture subsystem for by the light source of described fluorescence imaging and spectrum analysis subsystem and the sample of described coherence in frequency domain fault imaging subsystem optically coupling in same light path, use two-dimensional scanning mirrors that emergent light scans the dot matrix image to form two-dimensional structure, and the dot matrix image composition according to described two-dimensional structure comprises surface fluorescence spectral signal and structure tomography stereo-picture.
2. stereochemical structure function imaging system according to claim 1, it is characterized in that, the size of described stereo-picture is determined by microscopical enlargement ratio, the surface image spatial resolution of described stereo-picture is determined by described microscopical enlargement ratio and spot size, and the surface image longitudinal resolution of described stereo-picture is determined by the coherence length of laser of described frequency domain optical-coherence tomography subsystem.
3. stereochemical structure function imaging system according to claim 1, it is characterised in that described fluorescence imaging and spectrum analysis subsystem include photomultiplier tube detectors and imaging spectrometer, wherein,
Described imaging spectrometer is for carrying out light splitting by fluorescence signal by grating, and the fluorescence signal after light splitting is transferred to external host storage and display by described photomultiplier tube detectors.
4. stereochemical structure function imaging system according to claim 1, it is characterised in that described fluorescence imaging and spectrum analysis subsystem have first to fourth light source interface, wherein,
Described first to fourth light source interface correspondence connects first to fourth fluorescence excitation light source of different wave length.
5. stereochemical structure function imaging system according to claim 4, it is characterised in that described first to fourth fluorescence excitation light source is connected with described front end Scan Architecture subsystem by optical fiber, wherein,
Described front end Scan Architecture subsystem includes the first wave filter, the second wave filter, power attenuator and fluorescence excitation light-receiving unit, wherein,
Described first wave filter is connected with described fluorescence excitation light-receiving unit, the optical signal of fluorescence excitation light source described in high pass, the sample reflection light of high anti-described frequency domain optical-coherence tomography subsystem.
6. stereochemical structure function imaging system according to claim 5, it is characterised in that described fluorescence excitation light-receiving unit is made up of spectrogrph and photomultiplier tube detectors.
7. stereochemical structure function imaging system according to claim 5, it is characterized in that, described sample light directly arrives described front end Scan Architecture subsystem after optical fiber connects, by arriving sample through overscanning object lens after being connected to galvanometer after described second wave filter and described first wave filter, wherein, the sample light of the high anti-described frequency domain optical-coherence tomography subsystem of described first wave filter, the exciting light of high anti-described fluorescence imaging and spectrum analysis subsystem, the light source of frequency domain optical-coherence tomography subsystem described in described second wave filter high pass, the light source light of high anti-described fluorescence imaging and spectrum analysis subsystem.
8. stereochemical structure function imaging system according to claim 1, it is characterised in that the light source of described frequency domain light coherence tomography subsystem is bandwidth light source, and the centre wavelength of described bandwidth light source is 1310nm, and the bandwidth of described bandwidth light source is 60nm.
9. stereochemical structure function imaging system according to claim 1, it is characterised in that the splitting ratio of described bonder is 50:50, the signal of described light source is divided into reference light and sample light by described bonder.
10. stereochemical structure function imaging system according to claim 7, it is characterised in that described front end Scan Architecture subsystem is made up of one-dimensional or 2-D vibration mirror system.
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