CN112168136B - Scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system and method - Google Patents
Scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system and method Download PDFInfo
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Abstract
The invention discloses a scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system and method. The invention is based on full-field sweep-frequency optical coherence tomography, adopts a low-speed sweep-frequency light source to carry out surface illumination on a sample, and adopts a high-speed two-dimensional camera to collect a series of interference spectrum signals related to wave number k. The interference spectrum signals are subjected to Fourier inversion on k to obtain depth z-direction information, and 2D parallel detection is performed in a transverse x-y plane, so that 3D information can be obtained without any mechanical scanning, and 3D or any cross-section 2D tissue structure and angiography images can be obtained through data processing. The invention provides angiography and tissue structure images at the same time, so that the information is more comprehensive; the method has the advantages of high stability, high imaging speed, accurate result, simple system structure, control and data processing and the like.
Description
Technical Field
The invention relates to the technical field of angiography and tissue structure imaging based on an optical coherence tomography technology, in particular to a scanning-free three-dimensional angiography and tissue structure imaging combined system and method based on a full-field sweep optical coherence tomography technology.
Background
The blood circulation system in biological tissues is responsible for supplying nutrients and carrying away metabolites. The tissue structure and the vascular system are kept in normal physiological state together, so that normal vital activities can be maintained, otherwise abnormal states such as lesions can be caused. Various lesions are represented on the tissue structure and/or the vascular system, the lesions can be found and diagnosed through observation of the lesions, and the tissue structure and the vascular system are combined to realize more comprehensive and accurate disease diagnosis. Various high resolution optical imaging methods are commonly used for imaging structures of biological tissues, and therefore, will not be described in detail, and the optical methods are mainly described herein in terms of observing the vascular system.
Because of the extremely low resolution of angiography methods such as ultrasound and nuclear magnetic resonance, which cannot meet the requirements of early detection and accurate diagnosis of lesions, optical angiography methods have become established in place of them in the fields of ophthalmology and the like. Taking fundus vascular system as an example, fundus fluorescence angiography and indocyanine green angiography are widely used methods clinically at present, and can observe the vascular network distribution of retina and choroid respectively, and the obtained vascular images are clearly visible, but the following defects exist: 1) The need to inject dye intravenously, this operation is time consuming and may cause injury or discomfort to the human body; 2) The dye leaks to the surrounding tissues and stains itself, which can obscure the boundary of capillary shedding or neovascularization, and is unfavorable for observation; 3) The longitudinal resolving power is weak and it is difficult to locate and observe the vascularity of a specific layer.
Optical coherence tomography (Optical coherence tomography, OCT) without dyes and with longitudinal resolution capability is used for angiography, resulting in Optical Coherence Tomography (OCT) based on motion contrast mechanisms to form angiography results: the blood vessel system can be separated from the surrounding tissue by causing the amplitude, phase or both amplitude and phase of the return light signal to change, while the surrounding stationary tissue does not change. OCTA has the advantages of no need of dye, high longitudinal decomposition capability, high signal to noise ratio, high sensitivity, rapidness and the like, and the current situation that a plurality of commercial products are developed only in a short period of more than ten years and are widely applied to basic research and clinical diagnosis of ophthalmology is fully demonstrated.
Most of the current OCTA techniques are based on Fourier-domain (FD-) OCT techniques, as shown in fig. 1 (a), which acquire a contrast image as follows: 1) Performing Inverse Fast Fourier Transform (iFFT) on the acquired interference spectrum signal with respect to the wave number k to obtain all information in the depth z direction, i.e., a-scan information; 2) Scanning along a transverse y axis, and combining the acquired multi-line A-scan information into two-dimensional (2D) information in a longitudinal section y-z, namely B-scan information; 3) Combining the scanning along the transverse x axis, and combining the obtained multi-frame B-scan information into three-dimensional (3D) information of the sample; 4) Performing contrast processing by using adjacent A-scan or B-scan information to obtain a 2D angiogram in a longitudinal section (the distribution of blood vessels in the section is discontinuous and the information is very little), and generating a 3D angiogram by using the 2D angiogram; 5) The 3D angiogram is subjected to digital tomography to form angiograms in cross section x-y (the blood vessels in this plane are distributed in a continuous network, and the information is rich). The method has the problems of complex process, indirect formation, incapability of visual observation in real time, slow speed and poor system stability caused by mechanical scanning, and the like.
In order to solve the above problems, the institute of photoelectric technology Yang Yaliang et al of the national academy of sciences propose an invention patent of a real-time angiography system and method based on full-field time domain OCT technology (chinese patent No. 201910233328.0), the principle of which is shown in fig. 1 (b). The method can obtain a 2D result in the cross section without scanning, can directly perform angiography observation, and avoids complex intermediate processes and motion artifacts caused by the complex intermediate processes. Besides the conventional angiography, the method has real-time characteristics, so that the method can dynamically image a certain layer of vascular system in a sample to obtain the kinetic information of the vascular system. Only one-dimensional mechanical scanning along the depth z is required to obtain a 3D angiography of the sample. Although this invention has many beneficial effects, the signal-to-noise ratio of the time domain OCT method itself is relatively low, and mechanical scanning along depth z still has problems of slow speed and poor stability.
If the 3D and 2D angiography observation of the cross section of the sample can be realized without any mechanical scanning, various defects of the prior OCTA technology can be completely overcome, and the method has great application potential. Full-field sweep-source (OCT) technology makes this desire possible. Sweep-source (FD-OCT) OCT technique using high-speed Swept-lightSource (commercial product sweep rate at 10) 1 ～10 2 In the kHz order, the experimental system is even up to tens of MHz level) to perform point focus illumination on the sample and to acquire interference spectrum signals using a point detector, the process of tissue structure imaging and angiography is the same as the FD-OCT technique described above. Unlike swept OCT techniques, full-field swept OCT techniques employ a low-speed swept light source (wavelength swept speed at 10) 0 ～10 4 In the order of nm/s) for surface illumination of the sample, and using a high-speed 2D camera (frame rate at 10 2 Hz and above) continuously acquire a series of interference spectrum signals I with respect to wavenumber k n (x i ,y j K), n=1, … N. For each transverse position (x i ,y j ) The position (x) can be obtained by performing an iFFT on the wavenumber k in an array of N sample data i ,y j ) All information corresponding to the depth z direction; and 2D parallel detection imaging is adopted in the cross section, so that 3D information can be obtained without any mechanical scanning. At present, the technology is mainly used for 3D imaging of tissue structures, is not used for angiography, and is not reported for angiography and tissue structure imaging at the same time. Therefore, the invention provides an angiography and tissue structure imaging technology based on a full-field sweep OCT technology, the principle of which is shown in figure 2, and the working process is as follows: the amplitude or phase information in the obtained 3D information can be used for generating a 3D tissue structure image, and then a 2D image with any section is formed by digital chromatographic slicing; and carrying out contrast treatment on the adjacent layers in the depth direction by using 2D amplitude, phase or complex information in the cross section in the 3D information, so as to obtain a 2D contrast image in the cross section and generate a 3D contrast image.
Disclosure of Invention
The invention aims to solve the technical problems that: the system and the method for realizing 3D angiography and tissue structure imaging without mechanical scanning are provided, and can conveniently acquire 2D images with arbitrary sections. The invention is based on full-field sweep OCT technology, adopts a low-speed sweep light source to carry out surface illumination on a sample, and adopts a high-speed two-dimensional camera to collect a series of interference spectrum signals related to wave number k. Performing an iFFT on the interference spectrum signal of each point (x, y) in the cross section with respect to the wave number k to obtain all information of the point in the corresponding depth z direction; while in cross section 2D parallel probe imaging is performed. Therefore, 3D information can be obtained without any mechanical scanning, and then 2D and 3D tissue structures and angiography results can be conveniently obtained through data processing.
The technical scheme adopted for solving the technical problems is as follows: the scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system comprises a low-speed sweep light source, a collimator, a beam splitter, a view field deflection mirror, a first lens, a second lens, a sample stage, a dispersion balancer, a reference mirror, a translation stage, a third lens, a fourth lens, a high-speed two-dimensional camera, a human eye imaging module, a view field guiding visual target, a fifth lens, a dichroic mirror, a data acquisition card and a computer;
the light beam emitted by the low-speed sweep light source is collimated by the collimator and then is divided into a transmitted sample light beam and a reflected reference light beam by the beam splitting sheet: the sample beam sequentially passes through a view field deflection mirror and a beam shrinking device formed by a first lens and a second lens and then enters a sample arranged on a sample table; after passing through the dispersion balancer, the reference beam enters a reference mirror fixed on a translation stage; the sample beam reflected or scattered by the sample back and the reference beam reflected by the reference mirror return to the beam splitter along the original path respectively; the sample beam reflected by the beam splitting sheet is overlapped with the reference beam transmitted through the beam splitting sheet, and then enters the high-speed two-dimensional camera after passing through another beam shrinking device or beam expander formed by the third lens and the fourth lens;
the computer controls the view field deflection mirror to change the direction of the sample beam so that the sample beam irradiates the region to be imaged of the sample; the computer controls the translation stage to change the optical path of the reference beam so as to adjust the optical path difference between the sample beam and the reference beam; the low-speed sweep frequency light source starts to output light beams and simultaneously sends out trigger signals, and a computer is used for controlling the high-speed two-dimensional camera to synchronously acquire a series of interference spectrum signals; the interference spectrum signals are converted into digital signals through the data acquisition card and then transmitted to a computer for processing;
for ocular fundus imaging, then an ocular imaging module is used: the sample beam is incident to fundus tissue after passing through a beam shrinking device formed by a first lens and a human eye diopter system; the visual field guides the sighting target light emitted by the sighting target, and the sighting target light is focused on fundus tissues by a human eye diopter system after being collimated by a fifth lens and reflected by a dichroic mirror in sequence; the computer controls the view field to guide the lamps at different positions of the sighting target to be lighted, and the eyes can look at the lighted lamps to adjust the eyeball direction so as to enable the sample light beam to irradiate different regions to be imaged of fundus tissues.
The wavelength sweep speed of the low-speed sweep light source is 10 0 ～10 4 The scanning speed can be adjusted in the nm/s magnitude range.
The splitting ratio of the splitting sheet is about 50:50 in a broadband range.
The first lens, the second lens, the third lens, the fourth lens and the fifth lens are all broadband achromats.
The dispersion balancer is used for compensating the dispersion caused by the first lens and the second lens; for imaging the fundus of the human eye, a dispersion balancer is used to compensate for the dispersion caused by the first lens, the dichroic mirror and the human eye tissue.
The frame frequency of the high-speed two-dimensional camera is required to be 10 2 Hz and above.
A method for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging, comprising the steps of:
step 1: starting the system and setting parameters;
step 2: operating the field deflection mirror to move the illumination spot to the region F to be imaged of the sample r (x i ,y j ) I, j=1, …, M being the number of sampling points along the x-axis and y-axis in the cross section, r being the number of imaging regions; when imaging the eyeground of human eyes, the visual field is operated to guide the optotype so that the illumination light spot moves to the region F to be imaged of the eyeground tissue r (x i ,y j )；
Step 3: the optical path difference between the sample beam and the reference beam is adjusted through the translation stage, so that strongest and sparsest interference fringes appear in a software real-time display window of the high-speed two-dimensional camera, namely: positioning a reference mirror in a sample armAs close to the sample as possible but outside the sample surface, so that in step 6 the sample is subjected to a test n ’(x i ,y j K) separating the sample image and the mirror image generated after the Inverse Fast Fourier Transform (iFFT) is performed, and only retaining and displaying the sample image;
step 4: the low-speed sweep-frequency light source starts to work, and the high-speed two-dimensional camera synchronously collects a series of interference spectrum signals I about wave number k n (x i ,y j K), n=1, …, N being the number of sampling points with respect to the wave number k;
step 5: for each point (x i ,y j ) Interference spectrum signal I consisting of N sampled data n (x i ,y j K), performing background subtraction, wavenumber k homogenization resampling, spectral shaping, or dispersion compensation to obtain I n ’(x i ,y j ,k)；
Step 6: pair I n ’(x i ,y j K) performing an iFFT on the wavenumber k to obtain a value obtained from each point (x i ,y j ) 3D information composed of corresponding depth z space information
Step 7: by amplitude A (x i ,y j ,z s ) (usually taking the logarithm) or the phaseThe information can generate a 3D or arbitrary section 2D tissue structure image of the sample or fundus tissue;
step 8: for a certain depth z s 2D amplitude a (x) i ,y j ,z s ) Or phase ofOr a plurality of The information is subjected to contrast treatment, and a sample or fundus tissue can be obtained at the depth z s A cross-sectional intra-2D angiographic image at; continuously carrying out contrast treatment on the 2D information of the adjacent layers in the depth z direction, so as to obtain a 3D angiography image of the sample or fundus tissue;
step 9: operating the field deflection mirror to move the illumination spot to the next region F to be imaged r (x i ,y j ) R=r+1; when imaging the ocular fundus of human eye, the visual field is operated to guide the optotype to move the illumination light spot to the next region F to be imaged of the ocular fundus tissue r (x i ,y j ) R=r+1; repeating the steps 3 to 8 until imaging of all the areas to be imaged is completed; the imaging region F can also be made to r (x i ,y j ) Continuously moving and overlapping with a small portion of the edges, and forming a large field of view image by stitching the resulting images of all imaging regions.
Compared with the prior art, the invention has the beneficial effects that:
1) According to the invention, 3D and 2D observation of any section of a vascular system and a tissue structure can be realized without any mechanical scanning, so that the system stability and the imaging speed are greatly improved. Taking the example that the 3D image is composed of 512x512x512 pixels and the frame rate of the high-speed two-dimensional camera is 400 Hz: the z-direction 512 points means that 1024 interference spectrum signals need to be continuously acquired, and the time required for signal acquisition is only 2.56s. Compared with the sweep OCT technology, the sweep rate of the sweep light source is 102.4kHz when the signal acquisition of the same number of points is completed in the same time, and the sweep rate is common in the sweep OCT technology, but mechanical scanning along the transverse y axis and the transverse x axis is required, so that the stability of the system is reduced and the control is complicated.
2) The invention can provide angiography and tissue structure imaging results at the same time, has more comprehensive information and is more beneficial to the discovery and diagnosis of lesions. Lesions which cannot be found by a single imaging mode are possible to be revealed by the combination of the two; lesions that cannot be diagnosed with only a single imaging modality may be determined by a combination of both.
3) The invention carries out 2D parallel detection imaging in the cross section, signals of all points are collected simultaneously, and false images caused by mutual jump among different pixel points are avoided, so that the result is more accurate. This is of great importance for distributing the vascular system with distinct characteristics in the cross-section.
4) The invention has the advantages of simple system structure, control and data processing, low cost and the like. The scanning mechanism and the control circuit thereof are not needed, the light path and the control system are greatly simplified, and the cost is reduced. In the aspect of data processing, various intermediate processes and operations such as data storage management and the like required by the prior art are avoided.
Drawings
FIG. 1 is a schematic diagram of a prior art FD-OCT-based tissue structure imaging and angiography technique;
FIG. 2 is a schematic diagram of tissue structure imaging and angiography based on full-field swept OCT technology according to the present invention;
FIG. 3 is a schematic diagram of the system architecture of the present invention;
FIG. 4 is a schematic diagram of a control system of the present invention;
fig. 5 is a flow chart of the method of operation of the present invention.
In the figure: 1. a low-speed sweep frequency light source, a collimator, a beam splitter, a view field deflection mirror, a first lens, a second lens, a sample stage, a dispersion balancer, a reference mirror, a translation stage, a third lens and a fourth lens, wherein the low-speed sweep frequency light source, the collimator, the beam splitter, the view field deflection mirror, the first lens, the second lens, the sample and the third lens are arranged in sequence, and the sample stage, the dispersion balancer, the reference mirror, the translation stage and the third lens are arranged in sequence. The system comprises a first lens, a second lens, a third lens, a fourth lens, a high-speed two-dimensional camera, a human eye imaging module, a visual field guiding visual target, a fifth lens, a dichroic mirror, a human eye diopter system, a fundus tissue, a data acquisition card and a computer.
Detailed Description
The invention is further described below with reference to the drawings and specific examples.
As shown in fig. 3, the system for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging provided by the invention comprises a low-speed sweep light source 1, a collimator 2, a beam splitter 3, a field deflection mirror 4, a first lens 5, a second lens 6, a sample stage 8, a dispersion balancer 9, a reference mirror 10, a translation stage 11, a third lens 12, a fourth lens 13, a high-speed two-dimensional camera 14, a human eye imaging module 15, a field guiding optotype 16, a fifth lens 17, a dichroic mirror 18, a data acquisition card 21 and a computer 22.
The light beam emitted by the low-speed sweep light source 1 is collimated by the collimator 2 and then is divided into a transmitted sample light beam and a reflected reference light beam by the light splitting sheet 3: the sample beam sequentially passes through a view field deflection mirror 4 and a beam shrinking device formed by a first lens 5 and a second lens 6 and then enters a sample 7 arranged on a sample stage 8; after passing through the dispersion balancer 9, the reference beam is incident on a reference mirror 10 fixed on a translation stage 11. The wavelength sweep speed of the low-speed sweep light source 1 is 10 0 ～10 4 The scanning speed can be adjusted in the nm/s magnitude range. The ratio of the light splitting sheet 3 is about 50:50 in a broad band range. The sample beam reflected or scattered by the sample 7 and the reference beam reflected by the reference mirror 10 are returned to the spectroscopic plate 3 along the original paths, respectively. The sample beam reflected by the beam splitter 3 and the reference beam transmitted through the beam splitter 3 overlap, and then pass through another beam expander or beam expander composed of the third lens 12 and the fourth lens 13, and then enter the high-speed two-dimensional camera 14. The frame rate of the high-speed two-dimensional camera 14 is required to be 10 2 Hz and above.
For imaging the fundus of the human eye, the human eye imaging module 15 is used. The sample beam passes through a beam reducer composed of the first lens 5 and the human eye refractive system 19, and then enters the fundus tissue 20. The visual field directs the target light from the target 16, which is in turn collimated by the fifth lens 17 and reflected by the dichroic mirror 18, and is focused by the eye refractive system 19 onto the fundus tissue 20.
The first lens 5, the second lens 6, the third lens 12, the fourth lens 13 and the fifth lens 17 are all broadband achromats. The dispersion balancer 9 is for balancing the dispersion caused by the first lens 5 and the second lens 6, and for balancing the dispersion caused by the first lens 5, the dichroic mirror 18, and human eye tissue when the human eye fundus images. A beam reducer consisting of a first lens 5 and a second lens 6, which can determine the size of a field of view of a sample beam incident on a sample 7; a beam reducer consisting of the first lens 5 and the eye refractive system 19 can determine the size of the field of view of the sample beam incident on the fundus tissue 20; the other beam expander or beam expander formed by the third lens 12 and the fourth lens 13 can determine the image plane size of the light beam incident on the high-speed two-dimensional camera 14.
The control system of the present invention is shown in fig. 4. The computer 22 controls the field deflection mirror 4 to change the direction of the sample beam so that the sample beam irradiates the region to be imaged of the sample 7. The computer 22 controls the translation stage 11 to change the optical path length of the reference beam to adjust the optical path length difference between the sample beam and the reference beam. The low-speed sweep light source 1 starts to output light beams and simultaneously sends out trigger signals, and the computer 22 controls the high-speed two-dimensional camera 14 to synchronously acquire a series of interference spectrum signals. The interference spectrum signals are converted into digital signals through the data acquisition card 21 and then transmitted to the computer 22 for processing. When the device is used for imaging the fundus of a human eye, the computer 22 controls the visual field to guide the lights at different positions of the visual target 16 to be turned on, and the turned-on lights can be used for adjusting the eyeball direction when the human eye stares at the turned-on lights so as to enable sample light beams to irradiate different areas to be imaged of fundus tissues 20.
The flow of the scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging method is shown in figure 5. The method comprises the following steps:
step 1: starting the system and setting parameters;
step 2: the view deflection mirror 4 is operated to move the illumination spot to the region F to be imaged of the sample 7 r (x i ,y j ) I, j=1, …, M being the number of sampling points along the x-axis and y-axis in the cross section, r being the number of imaging regions; when imaging the fundus of a human eye, the field of view is operated to direct the optotype 16 so that the illumination spot is moved to the region F to be imaged of the fundus tissue 20 r (x i ,y j )；
Step 3: the optical path difference between the sample beam and the reference beam is adjusted by the translation stage 11, so that strongest and sparsest interference fringes appear in a software real-time display window of the high-speed two-dimensional camera 14, namely: the reference mirror 10 is positioned as close as possible to the sample 7 in the sample arm but outside the surface of the sample 7 so that the reference mirror is positioned at the position corresponding to the position of the sample arm in the step 6 n ’(x i ,y j K) sample image and mirror produced after performing Inverse Fast Fourier Transform (iFFT)Phase separation, while only preserving and displaying the sample image;
step 4: the low-speed sweep-frequency light source 1 starts to work, and the high-speed two-dimensional camera 14 synchronously collects a series of interference spectrum signals I about the wave number k n (x i ,y j K), n=1, …, N being the number of sampling points with respect to the wave number k;
step 5: for each point (x i ,y j ) Interference spectrum signal I consisting of N sampled data n (x i ,y j K), performing background subtraction, wavenumber k homogenization resampling, spectral shaping, or dispersion compensation to obtain I n ’(x i ,y j ,k)；
Step 6: pair I n ’(x i ,y j K) performing an iFFT on the wavenumber k to obtain a value obtained from each point (x i ,y j ) 3D information composed of corresponding depth z space information
Step 7: by amplitude A (x i ,y j ,z s ) (usually taking the logarithm) or the phaseInformation, 3D or arbitrary section 2D tissue structure images of the sample 7 or fundus tissue 20 can be generated;
step 8: for a certain depth z s 2D amplitude a (x) i ,y j ,z s ) Or phase ofOr a plurality of The information is subjected to contrast processing, and the sample 7 or the fundus tissue 20 can be obtained at the depth z s A cross-sectional intra-2D angiographic image at; continuously to the depth z directionThe aforementioned 2D information of the adjacent layers is subjected to a contrast treatment, and a 3D angiographic image of the sample 7 or fundus tissue 20 can be obtained;
step 9: the view deflecting mirror 4 is operated to move the illumination spot to the next region F to be imaged of the sample 7 r (x i ,y j ) R=r+1; when imaging the fundus of a human eye, the field of view is operated to direct the optotype 16 so that the illumination spot moves to the next region F to be imaged of the fundus tissue 20 r (x i ,y j ) R=r+1; repeating the steps 3 to 8 until imaging of all the areas to be imaged is completed; the imaging region F can also be made to r (x i ,y j ) Continuously moving and overlapping with a small portion of the edges, and forming a large field of view image by stitching the resulting images of all imaging regions.
By way of example, the low-speed swept light source 1 may employ a broadsweep product from Ireland Superlum (www.superlumdiodes.com), such as the BS-840-1-HP product, having a center wavelength of about 840nm, a wavelength sweep range of about 75nm, and a wavelength sweep speed of 2-10000 nm/s (tunable). The high-speed two-dimensional Camera 14 can be an ORCA-flash 4.0V 3 CMOS digital Camera of the japan bingo company, which can operate in a near infrared band (quantum efficiency at 840nm is close to 40%) suitable for biological tissue or fundus imaging, and when a Camera Link data transmission mode is adopted, the frame rate of 512x512 pixels (which is formed by combining 2048x2048 pixels by 4x4 pixels) can reach 400Hz. The wavelength sweep speed of the low-speed sweep light source 1 needs to be matched with the frame frequency of the high-speed two-dimensional camera 14: taking a 3D image composed of 512x512x512 pixels as an example, the z-direction 512 pixels means 1024 interference spectrum signals need to be continuously acquired. The frame frequency of the camera is 400Hz, and the time required for completing signal acquisition is 2.56s; the scanning of the wavelength range of 75nm is completed in the time of the low-speed scanning light source 1, so that the wavelength scanning speed is about 30nm/s, and the selected device meets the requirements within the product parameter range. The rest are conventional devices and are commercially available.
In step 8 of the method it is mentioned that 2D amplitude, or phase, or complex information of adjacent layers along the depth z is subjected to a contrast treatment to obtain angiographic results. The relevant mapping method based on amplitude information, proposed by Jonathan et al (E Jonathan, et al Correlation mapping method for generating microcirculation morphology from Optical Coherence Tomography (OCT) intension images. Journal of Biophotonics,2011,4 (9): 583-587), is described here as an example. The vascularity image is generated by calculating the signal correlation between adjacent C-scan, and the calculation formula of the correlation coefficient cm (x, y) is:
wherein: m and N are the grid sizes of the C-scan,and->Respectively adjacent C-scan amplitude signals A U (x, y) and A V The average intensity of (x, y), subscripts U and V are the numbers of adjacent layers. The grid is moved over the whole image to obtain a two-dimensional correlation coefficient cm (x, y) map. The figure contains correlation coefficient values from 0 to + -1, 0 indicating weak correlation and + -1 indicating strong correlation. The strong correlation is static tissue background, and the weak correlation is motion tissue. By selecting appropriate correlation coefficient values, the vascular system can be separated from surrounding tissue and tissue information disturbances can be filtered out, showing only the vascular system.
The foregoing detailed description is provided to illustrate the invention, not to limit the invention. Any modifications and changes made to the present invention fall within the spirit of the invention and the scope of the appended claims.
Claims (7)
1. A scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system, which is characterized in that: the device comprises a low-speed sweep frequency light source (1), a collimator (2), a beam splitter (3), a view field deflection mirror (4), a first lens (5), a second lens (6), a sample stage (8), a dispersion balancer (9), a reference mirror (10), a translation stage (11), a third lens (12), a fourth lens (13), a high-speed two-dimensional camera (14), a human eye imaging module (15), a view field guiding optotype (16), a fifth lens (17), a dichroic mirror (18), a data acquisition card (21) and a computer (22);
the light beam emitted by the low-speed sweep light source (1) is collimated by the collimator (2) and then is divided into a transmitted sample light beam and a reflected reference light beam by the light splitting sheet (3): the sample light beam sequentially passes through a view field deflection mirror (4) and a beam shrinking device formed by a first lens (5) and a second lens (6), and then enters a sample (7) arranged on a sample table (8); after passing through the dispersion balancer (9), the reference beam enters a reference mirror (10) fixed on a translation stage (11); the sample beam reflected or scattered by the sample (7) and the reference beam reflected by the reference mirror (10) are returned to the beam splitter (3) along the original path respectively; the sample beam reflected by the beam-splitting sheet (3) is overlapped with the reference beam transmitted by the beam-splitting sheet (3), and then enters the high-speed two-dimensional camera (14) after passing through another beam expander or beam expander formed by the third lens (12) and the fourth lens (13);
a computer (22) controls the view deflection mirror (4) to change the direction of the sample light beam so that the sample light beam irradiates the region to be imaged of the sample (7); a computer (22) controls the translation stage (11) to change the optical path length of the reference beam so as to adjust the optical path length difference between the sample beam and the reference beam; the low-speed sweep frequency light source (1) starts to output light beams and simultaneously sends out trigger signals, and a computer (22) is used for controlling the high-speed two-dimensional camera (14) to synchronously acquire a series of interference spectrum signals; the interference spectrum signals are converted into digital signals through a data acquisition card (21) and then transmitted to a computer (22) for processing;
for ocular fundus imaging, an ocular imaging module (15) is used: the sample beam passes through a beam contractor formed by the first lens (5) and the human eye diopter system (19) and then enters fundus tissue (20); the visual field guides the visual target light emitted by the visual target (16), and after being collimated by the fifth lens (17) and reflected by the dichroic mirror (18), the visual target light is focused on fundus tissues (20) by the human eye diopter system (19); the computer (22) controls the view field to guide the lamps at different positions of the sighting target (16) to be lightened, and the direction of the eyeballs can be adjusted by staring at the lightened lamps so that sample light beams irradiate different areas to be imaged of fundus tissues (20);
the scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system works in the following manner:
step 1: starting the system and setting parameters;
step 2: operating the field deflection mirror (4) to move the illumination spot to the region of the sample (7) to be imagedF r (x i , y j ) I, j=1, ⋯, M is the inner edge of the cross sectionxShaft and method for producing the sameyThe sampling point number of the axis, r is the number of the imaging area; when imaging the fundus of a human eye, the field of view is operated to direct the optotype (16) so that the illumination spot is moved to the region of the fundus tissue (20) to be imagedF r (x i , y j )；
Step 3: the optical path difference between the sample beam and the reference beam is adjusted through the translation stage (11), so that strongest and sparsest interference fringes appear in a software real-time display window of the high-speed two-dimensional camera (14), namely: the reference mirror (10) is positioned as close to the sample (7) as possible in the sample arm but outside the surface of the sample (7) so that the alignment in step 6I n ’(x i , y j , k) The sample image generated after the Inverse Fast Fourier Transform (iFFT) is separated from the mirror image, and only the sample image is retained and displayed;
step 4: the low-speed sweep frequency light source (1) starts to work, and the high-speed two-dimensional camera (14) synchronously collects wave numberskIs a series of interference spectrum signalsI n (x i , y j , k) N=1, ⋯, N is the number of waveskIs a sampling point number of (a);
step 5: for each point in the cross sectionx i , y j ) Interference spectrum signal composed of N sampling dataI n (x i , y j ,k) Performing subtractionBackground, wave numberkHomogenizing resampling, spectral shaping, or dispersion compensating to obtainI n ’(x i , y j , k)；
Step 6: for a pair ofI n ’(x i , y j , k) Implementation of the wave numberkObtain iFFT of each point in cross sectionx i , y j ) Corresponding depthz3D information composed of spatial informationI(x i , y j , z s )=A(x i , y j , z s )·exp[-i·φ(x i , y j , z s )]，s=1,⋯, N/2；
Step 7: by amplitude of vibrationA(x i , y j , z s ) Or phase ofφ(x i , y j , z s ) Information, 3D or arbitrary section 2D tissue structure images of the sample (7) or fundus tissue (20) can be generated;
step 8: for a certain depthz s 2D amplitude of adjacent layersA(x i , y j , z s ) Or phase ofφ(x i , y j , z s ) Or a plurality ofA(x i , y j , z s )·exp[-i·φ(x i , y j , z s )]The information is subjected to contrast treatment, and the depth of the sample (7) or the fundus tissue (20) can be obtainedz s A cross-sectional intra-2D angiographic image at; continuous pair depthzCarrying out contrast treatment on the 2D information of the adjacent layers in the direction, and obtaining a 3D angiography image of the sample (7) or fundus tissue (20);
step 9: operating the field deflection mirror (4) to move the illumination spot to the next region to be imaged of the sample (7)F r (x i , y j ) R=r+1; when imaging the fundus of a human eye, the field of view directing sighting target (16) is operated to shift the illumination spotTo the next region to be imaged of fundus tissue (20)F r (x i , y j ) R=r+1; repeating the steps 3 to 8 until imaging of all the areas to be imaged is completed; if desired, the imaging region can also be madeF r (x i , y j ) Continuously moving and overlapping with a small portion of the edges, and forming a large field of view image by stitching the resulting images of all imaging regions.
2. The scanless three-dimensional optical coherence tomography angiography and tissue structure imaging system of claim 1, wherein: the wavelength sweep speed of the low-speed sweep light source (1) is 10 0 ~10 4 The scanning speed can be adjusted in the nm/s magnitude range.
3. The scanless three-dimensional optical coherence tomography angiography and tissue structure imaging system of claim 1, wherein: the light splitting ratio of the light splitting sheet (3) is 50:50 in a broadband range.
4. The scanless three-dimensional optical coherence tomography angiography and tissue structure imaging system of claim 1, wherein: the first lens (5), the second lens (6), the third lens (12), the fourth lens (13) and the fifth lens (17) are all broadband achromats.
5. The scanless three-dimensional optical coherence tomography angiography and tissue structure imaging system of claim 1, wherein: the dispersion balancer (9) is used for balancing the dispersion caused by the first lens (5) and the second lens (6); for ocular fundus imaging, a dispersion balancer (9) is used for balancing dispersion caused by a first lens (5), a dichroic mirror (18) and ocular tissues.
6. Scanning-free three-dimensional optical coherence tomography angiography and tissue according to claim 1A system for imaging a structure, characterized by: the frame frequency of the high-speed two-dimensional camera (14) is required to be 10 2 Hz and above.
7. The scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging method is characterized by comprising the following steps of: the method utilizes a scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system and comprises a low-speed sweep light source (1), a collimator (2), a beam splitter (3), a view field deflection mirror (4), a first lens (5), a second lens (6), a sample stage (8), a dispersion balancer (9), a reference mirror (10), a translation stage (11), a third lens (12), a fourth lens (13), a high-speed two-dimensional camera (14), a human eye imaging module (15), a view field guiding optotype (16), a fifth lens (17), a dichroic mirror (18), a data acquisition card (21) and a computer (22);
the light beam emitted by the low-speed sweep light source (1) is collimated by the collimator (2) and then is divided into a transmitted sample light beam and a reflected reference light beam by the light splitting sheet (3): the sample light beam sequentially passes through a view field deflection mirror (4) and a beam shrinking device formed by a first lens (5) and a second lens (6), and then enters a sample (7) arranged on a sample table (8); after passing through the dispersion balancer (9), the reference beam enters a reference mirror (10) fixed on a translation stage (11); the sample beam reflected or scattered by the sample (7) and the reference beam reflected by the reference mirror (10) are returned to the beam splitter (3) along the original path respectively; the sample beam reflected by the beam-splitting sheet (3) is overlapped with the reference beam transmitted by the beam-splitting sheet (3), and then enters the high-speed two-dimensional camera (14) after passing through another beam expander or beam expander formed by the third lens (12) and the fourth lens (13);
a computer (22) controls the view deflection mirror (4) to change the direction of the sample light beam so that the sample light beam irradiates the region to be imaged of the sample (7); a computer (22) controls the translation stage (11) to change the optical path length of the reference beam so as to adjust the optical path length difference between the sample beam and the reference beam; the low-speed sweep frequency light source (1) starts to output light beams and simultaneously sends out trigger signals, and a computer (22) is used for controlling the high-speed two-dimensional camera (14) to synchronously acquire a series of interference spectrum signals; the interference spectrum signals are converted into digital signals through a data acquisition card (21) and then transmitted to a computer (22) for processing;
for ocular fundus imaging, an ocular imaging module (15) is used: the sample beam passes through a beam contractor formed by the first lens (5) and the human eye diopter system (19) and then enters fundus tissue (20); the visual field guides the visual target light emitted by the visual target (16), and after being collimated by the fifth lens (17) and reflected by the dichroic mirror (18), the visual target light is focused on fundus tissues (20) by the human eye diopter system (19); the computer (22) controls the view field to guide the lamps at different positions of the sighting target (16) to be lightened, and the direction of the eyeballs can be adjusted by staring at the lightened lamps so that sample light beams irradiate different areas to be imaged of fundus tissues (20); the method comprises the following steps:
step 1: starting the system and setting parameters;
step 2: operating the field deflection mirror (4) to move the illumination spot to the region of the sample (7) to be imagedF r (x i , y j ) I, j=1, ⋯, M is the inner edge of the cross sectionxShaft and method for producing the sameyThe sampling point number of the axis, r is the number of the imaging area; when imaging the fundus of a human eye, the field of view is operated to direct the optotype (16) so that the illumination spot is moved to the region of the fundus tissue (20) to be imagedF r (x i , y j )；
Step 3: the optical path difference between the sample beam and the reference beam is adjusted through the translation stage (11), so that strongest and sparsest interference fringes appear in a software real-time display window of the high-speed two-dimensional camera (14), namely: the reference mirror (10) is positioned as close to the sample (7) as possible in the sample arm but outside the surface of the sample (7) so that the alignment in step 6I n ’(x i , y j , k) The sample image generated after the Inverse Fast Fourier Transform (iFFT) is separated from the mirror image, and only the sample image is retained and displayed;
step 4: low speed sweep frequency light source (1)Starting to work, the high-speed two-dimensional camera (14) synchronously collects wave numberskIs a series of interference spectrum signalsI n (x i , y j , k) N=1, ⋯, N is the number of waveskIs a sampling point number of (a);
step 5: for each point in the cross sectionx i , y j ) Interference spectrum signal composed of N sampling dataI n (x i , y j ,k) Background and wave number reduction is carried outkHomogenizing resampling, spectral shaping, or dispersion compensating to obtainI n ’(x i , y j , k)；
Step 6: for a pair ofI n ’(x i , y j , k) Implementation of the wave numberkObtain iFFT of each point in cross sectionx i , y j ) Corresponding depthz3D information composed of spatial informationI(x i , y j , z s )=A(x i , y j , z s )·exp[-i·φ(x i , y j , z s )]，s=1,⋯, N/2；
Step 7: by amplitude of vibrationA(x i , y j , z s ) Or phase ofφ(x i , y j , z s ) Information, 3D or arbitrary section 2D tissue structure images of the sample (7) or fundus tissue (20) can be generated;
step 8: for a certain depthz s 2D amplitude of adjacent layersA(x i , y j , z s ) Or phase ofφ(x i , y j , z s ) Or a plurality ofA(x i , y j , z s )·exp[-i·φ(x i , y j , z s )]The information is subjected to contrast treatment, and the depth of the sample (7) or the fundus tissue (20) can be obtainedz s A cross-sectional intra-2D angiographic image at; continuous pair depthzCarrying out contrast treatment on the 2D information of the adjacent layers in the direction, and obtaining a 3D angiography image of the sample (7) or fundus tissue (20);
step 9: operating the field deflection mirror (4) to move the illumination spot to the next region to be imaged of the sample (7)F r (x i , y j ) R=r+1; when imaging the fundus of a human eye, the field of view is operated to direct the optotype (16) so that the illumination spot is moved to the next region to be imaged of the fundus tissue (20)F r (x i , y j ) R=r+1; repeating the steps 3 to 8 until imaging of all the areas to be imaged is completed; if desired, the imaging region can also be madeF r (x i , y j ) Continuously moving and overlapping with a small portion of the edges, and forming a large field of view image by stitching the resulting images of all imaging regions.
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