CN112168136A - System and method for scan-free three-dimensional optical coherence tomography angiography and tissue structure imaging - Google Patents

Abstract

Translated fromChinese

本发明公开了一种无扫描三维光学相干层析血管造影与组织结构成像的系统与方法，包括低速扫频光源、分光片、视场偏转镜、高速二维相机、人眼成像模块、数据采集卡和计算机。本发明基于全场扫频光学相干层析成像技术，采用低速扫频光源对样品进行面照明、和采用高速二维相机采集一系列关于波数k的干涉光谱信号。对干涉光谱信号进行关于k的傅里叶逆变换来获得深度z方向信息，而横向x‑y面内为2D并行探测，故无需任何机械扫描即可获取3D信息，通过数据处理可获得3D或任意截面2D组织结构与血管造影图像。本发明同时提供血管造影和组织结构图像，信息更全面；具有稳定性高、成像速度快、结果准确、以及系统结构、控制和数据处理简单等优点。

The invention discloses a system and method for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging. card and computer. The invention is based on the full-field swept-frequency optical coherence tomography technology, uses a low-speed swept-frequency light source to illuminate the surface of the sample, and uses a high-speed two-dimensional camera to collect a series of interference spectral signals about the wave number k. The inverse Fourier transform about k is performed on the interference spectral signal to obtain the depth z-direction information, and the lateral x-y plane is 2D parallel detection, so the 3D information can be obtained without any mechanical scanning, and the 3D or 3D information can be obtained through data processing. Arbitrary section 2D tissue structure and angiographic images. The invention simultaneously provides angiography and tissue structure images with more comprehensive information, and has the advantages of high stability, fast imaging speed, accurate results, and simple system structure, control and data processing.

Description

Scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging system and method

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 system and a method for combining scanless three-dimensional angiography and tissue structure imaging based on a full-field frequency-sweeping optical coherence tomography technology.

Background

The blood circulation system in biological tissues is responsible for supplying nutrients and removing metabolites. The tissue structure and the vascular system are kept in a normal physiological state together, so that normal life activities can be maintained, and abnormal states such as pathological changes and the like can be caused. Various lesions can be represented on the tissue structure and/or the vascular system, the discovery and the diagnosis of the lesions can be realized by observing the lesions, and the combination of the tissue structure and the vascular system can realize more comprehensive and accurate disease diagnosis. Various high-resolution optical imaging methods are commonly used for structural imaging of biological tissues, and therefore, the description thereof is omitted, and the description mainly describes the observation of the vascular system by the optical methods.

Because the resolution of angiography methods such as ultrasonic wave and nuclear magnetic resonance is extremely low, and the requirement of early detection and accurate diagnosis of pathological changes cannot be met, optical angiography methods have been established in the fields of ophthalmology and the like instead of the methods. Taking the ocular fundus vascular system as an example, ocular fundus fluorescence angiography and indocyanine green angiography are currently widely used in clinic, and can be used for respectively observing the vascular network distribution of retina and choroid, and the obtained vascular images are clear and visible, but the methods also have the following defects: 1) the need to inject the dye intravenously, which is time consuming and may cause damage or discomfort to the body; 2) the leakage of the dye to surrounding tissues and the dyeing per se can lead the boundary of the falling of capillary vessels or the formation of new blood vessels to be blurred, thus being not beneficial to observation; 3) longitudinal resolution is weak and it is difficult to locate and view the vascularity of a particular layer.

Optical Coherence Tomography (OCT) without dye and with longitudinal resolution was used for angiography, resulting in Optical Coherence Tomography Angiography (OCTA) based on a motion contrast mechanism to generate angiographic results: the return light signal amplitude, phase, or both amplitude and phase change due to substances such as red blood cells flowing in the blood vessel, and the surrounding stationary tissue does not change, so that the blood vessel system can be separated from the surrounding tissue, and only the blood vessel network system can be displayed without tissue interference. OCTA has the advantages of no need of dye, high longitudinal decomposition capacity, high signal-to-noise ratio, high sensitivity, high speed and the like, and a plurality of commercial products are developed only in a short time of more than ten years, and are widely applied to basic research and clinical diagnosis of ophthalmology, so that the current situation fully shows the advantages and practical value of the technology.

The current OCTA technology is mostly based on Fourier-domain (FD-) OCT technology, as shown in fig. 1(a), and the process of obtaining contrast images is as follows: 1) performing Inverse Fast Fourier Transform (iFFT) on the acquired interference spectrum signal with respect to a wave number k to obtain all information in a depth z direction, namely A-scan information; 2) scanning along a transverse y axis, and combining the obtained multi-line A-scans information into two-dimensional (2D) information, namely B-scan information, in a longitudinal section y-z; 3) combining the obtained multiframe B-scans information into three-dimensional (3D) information of the sample by combining scanning along a transverse x axis; 4) carrying out contrast processing on adjacent A-scans or B-scans 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 and the 2D angiogram; 5) the 3D angiogram is digitally tomographically sliced to form an angiogram within the cross-section x-y (the vessels within the plane are in a continuous network-like distribution, rich in information). Therefore, the method has the problems of complex process, indirect formation and incapability of real-time visual observation as a result, slow speed and poor system stability caused by mechanical scanning and the like.

In order to solve the above problems, the institute of optoelectronics and technology of the Chinese academy of sciences, Yang Yao et al, proposed the invention patent "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). It can obtain 2D result in cross section without scanning, and can directly make angiographic observation, and can avoid complex intermediate process and motion false image resulted from it. The method can not only carry out conventional angiography, but also have real-time property, so that dynamic angiography can be carried out on a certain layer of vascular system in a sample to obtain dynamic information of the vascular system. Only one-dimensional mechanical scan along the depth z is required to obtain 3D angiographic results 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 the mechanical scanning along the depth z still has the problems of slow speed and poor stability.

If 3D and in-cross-section 2D angiography observations of a sample can be achieved without any mechanical scanning, the various drawbacks of the existing OCTA technology will be completely overcome and the application potential will be great. This desire is made possible by the Full-field swept-source (OCT) technique. The Swept-source (Swept-source) OCT technology in the FD-OCT technology adopts a high-speed Swept-source (the sweep rate of a commercial product is 10)¹～10²In the kHz range, experimental systems even up to tens of MHz level) to point focus illumination of the sample and acquisition of the interference spectral signals using a point detector, the processes of tissue structure imaging and angiography are the same as in the FD-OCT technique described previously. Unlike swept OCT, full-field swept OCT uses a slow swept source (wavelength sweep at 10⁰～10⁴nm/s magnitude range) for surface illumination of the sample, and a high-speed 2D camera (frame frequency needs to be 10)²In the order of Hz and above) continuously collecting a series of interference spectrum signals I with respect to wave number k_n(x_i,y_jK), N is 1, … N. For each position (x) in the horizontal direction_i,y_j) The position (x) is obtained by performing iFFT on an array of N sampled data of (x)_i,y_j) All information corresponding to the depth z direction; and 2D parallel detection imaging is performed 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, and reports on angiography and tissue structure imaging are not seen. Therefore, the invention provides an angiography and tissue structure imaging technology based on a full-field frequency-sweeping OCT technology, the principle of which is shown in figure 2, and the working process is as follows: from the amplitude or phase information in the 3D information obtained as described above, 3D can be generatedForming a 2D image of any section by a digital tomography slice; and carrying out contrast processing on the adjacent layers in the depth direction according to the 2D amplitude, the phase or the 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 technical problem to be solved by the invention is as follows: the defects of the prior art are overcome, and the system and the method for realizing 3D angiography and tissue structure imaging without any mechanical scanning are provided, and 2D images of any section can be conveniently acquired. The method is based on the full-field frequency-sweeping OCT technology, adopts a low-speed frequency-sweeping light source to perform surface illumination on a sample, and adopts a high-speed two-dimensional camera to acquire a series of interference spectrum signals related to wave number k. Performing iFFT on interference spectrum signals of each point (x, y) in the cross section by using the wave number k, and acquiring all information of the point corresponding to the depth z direction; and 2D parallel probe imaging in the cross section. Therefore, 3D information can be obtained without any mechanical scanning, and 2D and 3D tissue structures and angiography results can be conveniently obtained through data processing.

The technical scheme adopted by the invention for solving the technical problems is as follows: the system for non-scanning three-dimensional optical coherence tomography angiography and tissue structure imaging comprises a low-speed frequency-sweeping light source, a collimator, a beam splitter, a field-of-view 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 field-of-view guide sighting mark, 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 light splitting sheet: the sample light beam sequentially passes through a field deflection mirror and a beam reducer consisting of a first lens and a second lens and then enters a sample on a sample table; after passing through the dispersion balancer, the reference beam enters a reference mirror fixed on the translation stage; the sample light beam reflected or scattered by the sample and the reference light beam reflected by the reference mirror return to the light splitting sheet along the original path respectively; the sample light beam reflected by the light splitting sheet is superposed with the reference light beam penetrating through the light splitting sheet, and then enters the high-speed two-dimensional camera after passing through another beam reducer or beam expander formed by a third lens and a fourth lens;

the computer controls the field deflection mirror to change the direction of the sample beam, so that the sample beam irradiates the area 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 the computer controls the high-speed two-dimensional camera to synchronously acquire a series of interference spectrum signals; after the interference spectrum signal is converted into a digital signal by a data acquisition card, the digital signal is transmitted to a computer for processing;

when the imaging module is used for imaging the fundus of the human eye, the imaging module of the human eye is used: the sample light beam enters the fundus tissue after passing through a beam reducer consisting of a first lens and a human eye dioptric system; the visual field guides the visual target light emitted by the visual target, and the visual target light is collimated by the fifth lens, reflected by the dichroic mirror and focused on the fundus tissue by the human eye dioptric system; the computer controls the visual field to guide the lights at different positions of the sighting target to be lightened, and the eyeball direction can be adjusted by staring the lightened lights with human eyes, so that the sample light beams irradiate different to-be-imaged areas of the fundus tissue.

The wavelength sweep frequency speed of the low-speed sweep frequency light source is 10⁰～10⁴The magnitude range of nm/s and the sweep frequency speed can be adjusted.

The splitting ratio of the splitting sheet is about 50:50 in a wide waveband range.

The first lens, the second lens, the third lens, the fourth lens and the fifth lens are all wide-band achromatic lenses.

The dispersion balancer is used for compensating dispersion caused by the first lens and the second lens; when the dispersion balancer is used for imaging the fundus of the human eye, the dispersion balancer is used for compensating dispersion caused by the first lens, the dichroic mirror and human eye tissues.

The frame frequency of the high-speed two-dimensional camera needs to be 10²In Hz and above.

A method of scanless three-dimensional optical coherence tomography angiography and tissue structure imaging, comprising the steps of:

step 1: starting a system and setting parameters;

step 2: operating the field deflection mirror to move the illumination spot to the area F to be imaged of the sample_r(x_i,y_j) I, j is 1, …, M is the number of sampling points along the x axis and the y axis in the cross section, and r is the number of the imaging area; when imaging the fundus of the eye, the visual field guide sighting mark is operated to move the illumination facula to the region F to be imaged of the fundus tissue_r(x_i,y_j)；

And step 3: the optical path difference between the sample light beam and the reference light 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: the corresponding position of the reference mirror in the sample arm is brought as close as possible to the sample, but outside the sample surface, so that the pair I in step 6_n’(x_i,y_jK) separating the image of the sample generated after performing an Inverse Fast Fourier Transform (iFFT) from the image of the mirror, and retaining and displaying only the image of the sample;

and 4, step 4: the low-speed sweep frequency light source starts to work, and the high-speed two-dimensional camera synchronously acquires a series of interference spectrum signals I related to wave number k_n(x_i,y_jK), N is 1, …, N is the number of sampling points with respect to the wavenumber k;

and 5: for each point (x) in the cross section_i,y_j) Interference spectrum signal I formed by N sampling data_n(x_i,y_jK), carrying out background subtraction, wave number k homogenization resampling, spectrum shaping, dispersion compensation and other treatment to obtain I_n’(x_i,y_j,k)；

Step 6: to I_n’(x_i,y_jK) performs iFFT on the wave number k, resulting in a cross section defined by each point (x) in the cross section_i,y_j) 3D information composed of corresponding depth z-space information

And 7: using amplitude A (x)_i,y_j,z_s) (usually logarithmic) or phase

Information, 3D or arbitrary cross-sectional 2D tissue structure images of the sample or fundus tissue can be generated;

and 8: for a certain depth z_s2D amplitude A (x) of adjacent layer_i,y_j,z_s) Or phase

Or a plurality of

Information is processed by radiography to obtain the depth z of the sample or the fundus tissue_sA 2D angiographic image in cross section of (a); continuously carrying out contrast processing on the 2D information of the adjacent layers in the depth z direction to obtain a 3D angiography image of the sample or the fundus tissue;

and step 9: operating the field-of-view deflection mirror to move the illumination spot to the next region F to be imaged of the sample_r(x_i,y_j) R is r + 1; when the fundus of the eye is imaged, the visual field guide sighting mark is operated to move the illumination facula to the next to-be-imaged area F of the fundus tissue_r(x_i,y_j) R is r + 1; repeating the steps 3 to 8 until the imaging of all the areas to be imaged is completed; if desired, the imaging area F can be made_r(x_i,y_j) Continuously moving and overlapping a small part of edges of the images, and forming a large-field image by splicing the images of all imaging area results.

Compared with the prior art, the invention has the beneficial effects that:

1) the invention can realize the 3D and any section 2D observation of the blood vessel system and the tissue structure without any mechanical scanning, thereby greatly improving the system stability and the imaging speed. Take the example that the 3D image is composed of 512x512x512 pixels and the frame frequency of the high-speed two-dimensional camera is 400 Hz: the 512 points in the z direction means that 1024 interference spectrum signals need to be collected continuously, and the time required for signal collection is only 2.56 s. Compared with the frequency-sweeping OCT technology, the frequency-sweeping speed of the frequency-sweeping light source needs to be 102.4kHz if signal acquisition of the same point number is completed in the same time, and the speed is common in frequency-sweeping OCT, but mechanical scanning along the transverse y axis and the transverse x axis is needed, so that the stability of the system is reduced and the control becomes complicated.

2) The invention can provide the result of angiography and tissue structure imaging at the same time, has more comprehensive information and is more beneficial to the discovery and diagnosis of pathological changes. The lesion which can not be discovered only by adopting a single imaging mode can be possibly revealed by the combination of the two; the combination of the two makes it possible to make the diagnosis doubtful.

3) The invention has the advantages that 2D parallel detection imaging is carried out in the cross section, signals of all the points are collected simultaneously, false images caused by mutual jumping among different pixel points are avoided, and the result is more accurate. This is of great significance for vascular systems with pronounced distribution characteristics within 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 tissue structure imaging and angiography based on FD-OCT technique;

FIG. 2 is a schematic diagram of tissue structure imaging and angiography based on the full-field swept OCT technique proposed by the present invention;

FIG. 3 is a schematic diagram of the system architecture of the present invention;

FIG. 4 is a schematic view of the control system of the present invention;

fig. 5 is a flow chart of a method of operation of the present invention.

In the figure: 1. the system comprises a low-speed sweep light source, 2, a collimator, 3, a beam splitter, 4, a field-of-view deflection mirror, 5, a first lens, 6, a second lens, 7, a sample, 8, a sample stage, 9, a dispersion balancer, 10, a reference mirror, 11, a translation stage, 12, a third lens, 13, a fourth lens, 14, a high-speed two-dimensional camera, 15, a human eye imaging module, 16, a field-of-view guide sighting mark, 17, a fifth lens, 18, a dichroic mirror, 19, a human eye refraction system, 20, fundus tissues, 21, a data acquisition card, 22 and a computer.

Detailed Description

The invention is further described with reference to the following figures and specific examples.

As shown in fig. 3, the system for scanless three-dimensional optical coherence tomography angiography and tissue structure imaging includes a low-speed frequency-sweepinglight source 1, a collimator 2, a beam splitter 3, a field-of-view deflecting mirror 4, afirst lens 5, a second lens 6, asample stage 8, a dispersion balancer 9, areference mirror 10, atranslation stage 11, athird lens 12, afourth lens 13, a high-speed two-dimensional camera 14, a humaneye imaging module 15, a field-of-viewguide sighting mark 16, afifth lens 17, adichroic mirror 18, adata acquisition card 21, and acomputer 22.

The light beam emitted by the low-speedsweep 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 afield deflection mirror 4 and a beam reducer consisting of afirst 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 is incident on areference mirror 10 fixed to atranslation stage 11. The wavelength sweep speed of the low-speedsweep light source 1 is 10⁰～10⁴The magnitude range of nm/s and the sweep frequency speed can be adjusted. The splitting ratio of the splitting sheet 3 is about 50:50 in a wide wavelength band. The sample beam reflected or scattered back by the sample 7 and the reference beam reflected by thereference mirror 10 are respectively returned to the spectroscopic plate 3 along the original paths. The sample beam reflected by the spectroscope 3 and the reference beam transmitted through the spectroscope 3 are superposed, and then, after passing through another beam contracting or expanding device constituted by athird lens 12 and afourth lens 13, the sample beam and the reference beam are incident on a high-speed two-dimensional camera 14. The frame rate of the high-speed two-dimensional camera 14 needs to be 10²In Hz and above.

For imaging the fundus of the eye, theeye imaging module 15 is used. The sample beam passes through a beam reducer composed of thefirst lens 5 and the eyedioptric system 19 and then enters thefundus tissue 20. The visual field guides the sighting target light emitted by thesighting target 16, and after being collimated by thefifth lens 17 and reflected by thedichroic mirror 18 in sequence, the sighting target light is focused on thefundus tissue 20 by the human eyedioptric system 19.

Thefirst lens 5, the second lens 6, thethird lens 12, thefourth lens 13, and thefifth lens 17 are all broadband achromatic lenses. The dispersion balancer 9 is used for balancing dispersion caused by thefirst lens 5 and the second lens 6, and is used for balancing dispersion caused by thefirst lens 5, thedichroic mirror 18, and human eye tissues when imaging a human eye fundus. The beam reducer consisting of thefirst lens 5 and the second lens 6 can determine the size of a field of view of the sample beam incident on the sample 7; the beam reducer composed of thefirst lens 5 and the human eyedioptric system 19 can determine the size of the field of view of the sample beam incident on thefundus tissue 20; another beam reducer or expander, which is composed of thethird lens 12 and thefourth lens 13, determines the size of the image plane on which the light beam is incident on the high-speed two-dimensional camera 14.

The control system of the present invention is shown in fig. 4. Thecomputer 22 controls thefield deflection mirror 4 to change the direction of the sample beam so that the sample beam impinges on the area of the sample 7 to be imaged. Thecomputer 22 controls thetranslation 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-speedsweep light source 1 starts to output light beams and simultaneously sends out trigger signals, and thecomputer 22 controls the high-speed two-dimensional camera 14 to synchronously acquire a series of interference spectrum signals. The interference spectrum signal is converted into a digital signal by thedata acquisition card 21, and then transmitted to thecomputer 22 for processing. When the eye-based eye fundus imaging system is used for imaging the eye fundus, thecomputer 22 controls the lighting of the lamps at different positions of the visual fieldguide sighting target 16, and the eye direction can be adjusted by the lighting lamps when the eye stares at the eyes, so that the sample light beams irradiate different to-be-imaged areas of theeye fundus tissues 20.

The flow of the method for scanless three-dimensional optical coherence tomography angiography and tissue structure imaging is shown in fig. 5. The method comprises the following steps:

step 1: starting a system and setting parameters;

step 2: operating the field-of-view deflecting mirror 4 to illuminateThe light spot is moved to the area F to be imaged of the sample 7_r(x_i,y_j) I, j is 1, …, M is the number of sampling points along the x axis and the y axis in the cross section, and r is the number of the imaging area; when imaging the fundus of the eye, the visualfield guide optotype 16 is operated to move the illumination spot to the region F to be imaged of the fundus tissue 20_r(x_i,y_j)；

And step 3: the optical path difference between the sample beam and the reference beam is adjusted by thetranslation stage 11, so that the strongest and sparsest interference fringes appear in the software real-time display window of the high-speed two-dimensional camera 14, namely: the corresponding position of thereference mirror 10 in the sample arm is brought as close as possible to the sample 7, but outside the surface of the sample 7, so that the pair I in step 6_n’(x_i,y_jK) separating the image of the sample generated after performing an Inverse Fast Fourier Transform (iFFT) from the image of the mirror, and retaining and displaying only the image of the sample;

and 4, step 4: the low-speedsweep light source 1 starts to work, and the high-speed two-dimensional camera 14 synchronously acquires a series of interference spectrum signals I related to wave number k_n(x_i,y_jK), N is 1, …, N is the number of sampling points with respect to the wavenumber k;

and 5: for each point (x) in the cross section_i,y_j) Interference spectrum signal I formed by N sampling data_n(x_i,y_jK), carrying out background subtraction, wave number k homogenization resampling, spectrum shaping, dispersion compensation and other treatment to obtain I_n’(x_i,y_j,k)；

Step 6: to I_n’(x_i,y_jK) performs iFFT on the wave number k, resulting in a cross section defined by each point (x) in the cross section_i,y_j) 3D information composed of corresponding depth z-space information

And 7: using amplitude A (x)_i,y_j,z_s) (usually logarithmic) or phase

Information, can give birth toForming a 3D or arbitrary section 2D tissue structure image of the sample 7 or thefundus tissue 20;

and 8: for a certain depth z_s2D amplitude A (x) of adjacent layer_i,y_j,z_s) Or phase

Or a plurality of

Information is processed by imaging to obtain the depth z of the sample 7 or the fundus tissue 20_sA 2D angiographic image in cross section of (a); continuously performing contrast processing on the aforementioned 2D information of adjacent layers in the depth z direction to obtain a 3D angiographic image of the sample 7 or thefundus tissue 20;

and step 9: the field-of-view deflecting mirror 4 is operated to move the illumination spot to the next area F to be imaged of the sample 7_r(x_i,y_j) R is r + 1; when imaging the fundus of the eye, the visualfield guide optotype 16 is operated to move the illumination spot to the next region F to be imaged of the fundus tissue 20_r(x_i,y_j) R is r + 1; repeating the steps 3 to 8 until the imaging of all the areas to be imaged is completed; if desired, the imaging area F can be made_r(x_i,y_j) Continuously moving and overlapping a small part of edges of the images, and forming a large-field image by splicing the images of all imaging area results.

As an example, the low-speed sweptoptical source 1 may be a Broadsweeper product available from Superlum, Ireland (www.superlumdiodes.com), such as a BS-840-1-HP product, with 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 may be an ORCA-flash 4.0V 3 CMOS digital Camera available from hamamatsu corporation, which is operable in a near infrared band (quantum efficiency at 840nm is approximately 40%) suitable for imaging biological tissues or fundus oculi, and when a Camera Link data transmission method is used, a frame frequency at sampling of 512 × 512 pixels (which is obtained by combining 4 × 4 pixels from 2048 × 2048 pixels) may reach 400 Hz. The wavelength sweep speed of the low-speedsweep light source 1 needs to be matched with the frame frequency of the high-speed two-dimensional camera 14: taking the example of a 3D image consisting of 512 × 512 pixels, the z-direction 512 pixels means that 1024 interference spectrum signals need to be continuously collected. If the frame frequency of the camera is 400Hz, the time required for completing signal acquisition is 2.56 s; the low-speedsweep light source 1 needs to complete the scanning within the wavelength range of 75nm within the time, the wavelength sweep speed is about 30nm/s, and the selected device meets the requirements within the product parameter range. The rest are conventional devices and can be purchased in the market.

Instep 8 of the method, it is mentioned that the 2D amplitude, or phase, or complex information of adjacent slices along the depth z needs to be processed for imaging to obtain an angiographic result. The correlation mapping method based on amplitude information proposed by Jonathan et al (E Jonathan, et al. correlation mapping method for generating a micro circulation from Optical Coherence Tomography (OCT) intensity images. journal of Biophotonics,2011,4(9): 583-. And generating a blood vessel distribution image by calculating the signal correlation between adjacent C-scans, wherein the calculation formula of a correlation coefficient cm (x, y) is as follows:

in the formula: m and N are the grid size of C-scan,

and

respectively adjacent C-sweeps amplitude signal A_U(x, y) and A_V(x, y) and subscripts U and V are the numbers of adjacent layers. This grid is shifted over the whole image to obtain a two-dimensional correlation coefficient cm (x, y) map. The graph contains correlation values from 0 to + -1, with 0 indicating a weak correlation and + -1 indicating a strong correlation. The strongly correlated one is a static tissue background, and the weakly correlated one is a moving tissue. By selecting the appropriateThe relative coefficient value can separate the vascular system from the surrounding tissues, filter the tissue information interference and only display the vascular system.

The foregoing detailed description is intended to be illustrative of the invention and is not to be construed as limiting the invention. Any modification and variation of the present invention within the spirit of the present invention and the scope of the claims will fall within the scope of the present invention.

Claims (7)

Translated fromChinese

1.无扫描三维光学相干层析血管造影与组织结构成像的系统，其特征在于：包括低速扫频光源(1)、准直器(2)、分光片(3)、视场偏转镜(4)、第一透镜(5)、第二透镜(6)、样品台(8)、色散平衡器(9)、参考镜(10)、平移台(11)、第三透镜(12)、第四透镜(13)、高速二维相机(14)、人眼成像模块(15)、视场引导视标(16)、第五透镜(17)、二向色镜(18)、数据采集卡(21)和计算机(22)；1. A system for non-scanning three-dimensional optical coherence tomography angiography and tissue structure imaging, characterized in that: comprising a low-speed frequency sweep light source (1), a collimator (2), a beam splitter (3), a field of view deflection mirror (4) ), first lens (5), second lens (6), sample stage (8), dispersion balancer (9), reference mirror (10), translation stage (11), third lens (12), fourth lens Lens (13), high-speed two-dimensional camera (14), human eye imaging module (15), field-of-view guidance optotype (16), fifth lens (17), dichroic mirror (18), data acquisition card (21) ) and a computer (22);低速扫频光源(1)发出的光束，经准直器(2)准直后，被分光片(3)分成透射的样品光束和反射的参考光束：样品光束依次经过视场偏转镜(4)、和由第一透镜(5)与第二透镜(6)构成的缩束器后，入射置于样品台(8)上的样品(7)；参考光束经过色散平衡器(9)后，入射固定在平移台(11)上的参考镜(10)；由样品(7)后向反射或散射的样品光束、和由参考镜(10)反射的参考光束，分别沿原路返回至分光片(3)；被分光片(3)反射的样品光束和透过分光片(3)的参考光束重合，然后经过由第三透镜(12)和第四透镜(13)构成的另一缩束器或扩束器后，入射高速二维相机(14)；The light beam emitted by the low-speed frequency swept light source (1) is collimated by the collimator (2), and then divided into the transmitted sample beam and the reflected reference beam by the beam splitter (3): the sample beam passes through the field of view deflection mirror (4) in turn , and the beam reducer formed by the first lens (5) and the second lens (6), the sample (7) placed on the sample stage (8) is incident; after the reference beam passes through the dispersion balancer (9), the incident The reference mirror (10) fixed on the translation stage (11); the sample beam reflected or scattered by the sample (7) and the reference beam reflected by the reference mirror (10) are respectively returned to the beam splitter ( 3); the sample beam reflected by the beam splitter (3) coincides with the reference beam transmitted through the beam splitter (3), and then passes through another beam reducer composed of the third lens (12) and the fourth lens (13) or After the beam expander, the incident high-speed two-dimensional camera (14);计算机(22)控制视场偏转镜(4)来改变样品光束的方向，使样品光束照射在样品(7)的待成像区域；计算机(22)控制平移台(11)来改变参考光束的光程，以调节样品光束与参考光束之间的光程差；低速扫频光源(1)开始输出光束的同时还发出触发信号，通过计算机(22)去控制高速二维相机(14)同步采集一系列干涉光谱信号；干涉光谱信号经过数据采集卡(21)转化为数字信号后，传输至计算机(22)进行处理；The computer (22) controls the field deflection mirror (4) to change the direction of the sample beam, so that the sample beam is irradiated on the area to be imaged of the sample (7); the computer (22) controls the translation stage (11) to change the optical path of the reference beam , to adjust the optical path difference between the sample beam and the reference beam; the low-speed frequency sweep light source (1) starts to output the beam and also sends out a trigger signal, and the computer (22) controls the high-speed two-dimensional camera (14) to synchronously collect a series of interference spectrum signal; after the interference spectrum signal is converted into a digital signal by the data acquisition card (21), it is transmitted to the computer (22) for processing;用于人眼眼底成像时，则使用人眼成像模块(15)：样品光束经过由第一透镜(5)与人眼屈光系统(19)构成的缩束器后，入射眼底组织(20)；视场引导视标(16)发出的视标光，依次被第五透镜(17)准直和二向色镜(18)反射后，被人眼屈光系统(19)聚焦在眼底组织(20)上；计算机(22)控制视场引导视标(16)不同位置的灯点亮，人眼盯视点亮的灯即可调节眼球方向，以使样品光束照射在眼底组织(20)不同的待成像区域。When it is used for imaging of the human eye fundus, the human eye imaging module (15) is used: after the sample beam passes through the beam reducer formed by the first lens (5) and the human eye refractive system (19), it enters the fundus tissue (20) ; The visual target light emitted by the visual field guiding target (16), after being collimated by the fifth lens (17) and reflected by the dichroic mirror (18) in turn, is focused on the fundus tissue by the human eye refractive system (19). 20); the computer (22) controls the field of view to guide lights at different positions of the optotype (16) to light up, and the human eye can adjust the direction of the eyeball by staring at the lighted lights, so that the sample beam is irradiated on the fundus tissue (20) differently the area to be imaged.2.根据权利要求1所述的无扫描三维光学相干层析血管造影与组织结构成像的系统，其特征在于：所述的低速扫频光源(1)的波长扫频速度在10⁰～10⁴nm/s量级范围，扫频速度可调节。2 . The system for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging according to claim 1 , wherein the wavelength sweep speed of the low-speed frequency-sweep light source ( 1 ) is between 10⁰ and 10^{4 .} The range of nm/s magnitude, the sweep speed can be adjusted.3.根据权利要求1所述的无扫描三维光学相干层析血管造影与组织结构成像的系统，其特征在于：所述的分光片(3)的分光比，在宽波段范围内约为50:50。3. the system of non-scanning three-dimensional optical coherence tomography angiography and tissue structure imaging according to claim 1, is characterized in that: the spectroscopic ratio of described spectroscopic sheet (3) is about 50 in wide-band range: 50.4.根据权利要求1所述的无扫描三维光学相干层析血管造影与组织结构成像的系统，其特征在于：所述的第一透镜(5)、第二透镜(6)、第三透镜(12)、第四透镜(13)和第五透镜(17)，均为宽波段消色差透镜。4. The system for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging according to claim 1, characterized in that: the first lens (5), the second lens (6), the third lens ( 12), the fourth lens (13) and the fifth lens (17), all of which are broadband achromatic lenses.5.根据权利要求1所述的无扫描三维光学相干层析血管造影与组织结构成像的系统，其特征在于：所述的色散平衡器(9)，用于平衡由第一透镜(5)和第二透镜(6)引起的色散；用于人眼眼底成像时，色散平衡器(9)用于平衡由第一透镜(5)、二向色镜(18)和人眼组织引起的色散。5. The system for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging according to claim 1, wherein the dispersion balancer (9) is used to balance the first lens (5) and the tissue structure imaging system. Dispersion caused by the second lens (6); when used in human eye fundus imaging, the dispersion balancer (9) is used to balance the dispersion caused by the first lens (5), the dichroic mirror (18) and human eye tissue.6.根据权利要求1所述的无扫描三维光学相干层析血管造影与组织结构成像的系统，其特征在于：所述的高速二维相机(14)的帧频需在10²Hz及以上量级。6. The system for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging according to claim 1, wherein the frame frequency of the high-speed two-dimensional camera (14) needs to be¹⁰ Hz and above class.7.无扫描三维光学相干层析血管造影与组织结构成像的方法，其特征在于：包括以下步骤：7. The method for scanning-free three-dimensional optical coherence tomography angiography and tissue structure imaging, characterized in that it comprises the following steps:步骤1：启动系统，设置参数；Step 1: Start the system and set the parameters;步骤2：操作视场偏转镜(4)，使照明光斑移至样品(7)的待成像区域F_r(x_i,y_j)，i,j＝1,…,M，M为横截面内沿x轴和y轴的采样点数，r为成像区域的编号；当对人眼眼底成像时，操作视场引导视标(16)，使照明光斑移至眼底组织(20)的待成像区域F_r(x_i,y_j)；Step 2: Operate the field of view deflection mirror (4) to move the illumination spot to the area to be imaged F_r (x_i , y_j ) of the sample (7), i,j=1,...,M, where M is the cross section The number of sampling points along the x-axis and the y-axis, r is the number of the imaging area; when imaging the human eye fundus, operate the field of view to guide the optotype (16), so that the illumination spot moves to the area to be imaged F of the fundus tissue (20)._r (x_i ,y_j );步骤3：通过平移台(11)调节样品光束与参考光束之间的光程差，使高速二维相机(14)的软件实时显示窗口中出现最强和最稀疏的干涉条纹、即：使参考镜(10)在样品臂中的对应位置尽量接近样品(7)、但又位于样品(7)表面之外，以使步骤6中对I_n’(x_i,y_j,k)实施快速傅里叶逆变换(iFFT)后产生的样品像和镜像相分离，而只保留和显示样品像；Step 3: Adjust the optical path difference between the sample beam and the reference beam through the translation stage (11), so that the strongest and the sparsest interference fringes appear in the real-time display window of the software of the high-speed two-dimensional camera (14), that is: make the reference The corresponding position of the mirror (10) in the sample arm is as close as possible to the sample (7), but is located outside the surface of the sample (7), so that the_{FFT of In'(x i,} y_j ,k) is performed in step 6. The sample image and the mirror image generated after inverse Liye transform (iFFT) are separated, and only the sample image is retained and displayed;步骤4：低速扫频光源(1)开始工作，高速二维相机(14)同步采集关于波数k的一系列干涉光谱信号I_n(x_i,y_j,k)，n＝1,…,N，N为关于波数k的采样点数；Step 4: The low-speed swept frequency light source (1) starts to work, and the high-speed two-dimensional camera (14) synchronously collects a series of interference spectral signals I_n (x_i , y_j , k) about the wave number k, n=1,...,N , N is the number of sampling points about the wave number k;步骤5：对横截面内每一点(x_i,y_j)、由N个采样数据构成的干涉光谱信号I_n(x_i,y_j,k)，进行减背景、波数k均匀化重采样、光谱整形、或色散补偿等处理，得到I_n’(x_i,y_j,k)；Step 5_: Perform background_subtraction ,_wavenumberk homogenization_resampling , Spectral shaping, or dispersion compensation, etc., to obtain In '(x_i , y_j ,_k );步骤6：对I_n’(x_i,y_j,k)实施关于波数k的iFFT，得到由横截面内每一点(x_i,y_j)对应的深度z空间信息构成的3D信息

Step 6: Perform iFFT on In '(x_i , y_j , k) with respect to wavenumber k, and obtain 3D information composed of depth z space information corresponding to each point (x_i , y_j) in the cross section

步骤7：利用振幅A(x_i,y_j,z_s)(通常取对数)或相位

信息，可生成样品(7)或眼底组织(20)的3D或任意截面2D组织结构图像；Step 7: Use Amplitude A(x_i ,y_j ,z_s ) (usually logarithmic) or Phase

information, which can generate a 3D or arbitrary cross-sectional 2D tissue structure image of the sample (7) or the fundus tissue (20);步骤8：对某一深度z_s处相邻层的2D振幅A(x_i,y_j,z_s)、或相位

或复数

信息进行造影处理，可获得样品(7)或眼底组织(20)在深度z_s处的横截面内2D血管造影图像；连续对深度z方向相邻层的前述2D信息进行造影处理，可获得样品(7)或眼底组织(20)的3D血管造影图像；Step 8: 2D amplitude A(x_i , y_j , z_s ), or phase for adjacent layers at a depth z_s

or plural

Perform contrast processing on the information to obtain a 2D angiographic image in the cross-section of the sample (7) or the fundus tissue (20) at the depth z_s ; continuously perform contrast processing on the aforementioned 2D information of the adjacent layers in the depth z direction to obtain the sample (7) or a 3D angiographic image of the fundus tissue (20);步骤9：操作视场偏转镜(4)，使照明光斑移至样品(7)的下一待成像区域F_r(x_i,y_j)，r＝r+1；当对人眼眼底成像时，操作视场引导视标(16)，使照明光斑移至眼底组织(20)的下一待成像区域F_r(x_i,y_j)，r＝r+1；重复步骤3至步骤8，直至完成对所有待成像区域的成像；如有需要，也可使成像区域F_r(x_i,y_j)连续移动、并相互有少部分边缘重叠，通过对所有成像区域结果的图像拼接来形成大视场图像。Step 9: Operate the field of view deflecting mirror (4) to move the illumination spot to the next area to be imaged F_r (x_i , y_j ) of the sample (7), r=r+1; when imaging the fundus of the human eye , operate the field of view to guide the optotype (16) to move the illumination spot to the next area to be imaged_Fr (x_i , y_j ) of the fundus tissue (20), r=r+1; repeat steps 3 to 8, Until the imaging of all the areas to be imaged is completed; if necessary, the imaging area_Fr (x_i , y_j ) can also be moved continuously, and a small part of the edges overlap each other, which is formed by stitching the results of all the imaging areas. Large field of view image.

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