技术领域technical field
本发明涉及活体组织中微血流成像技术领域，特别是一种基于线性相关系数来重构三维微血流分布的方法及装置。The invention relates to the technical field of micro-blood flow imaging in living tissues, in particular to a method and device for reconstructing three-dimensional micro-blood flow distribution based on a linear correlation coefficient.
背景技术Background technique
人体组织和器官所需营养物质和氧气是通过血液循环输送的，而营养物质和氧气的交换是在毛细血管内进行的，并且微血流与人体的体温和血压等关键指标是相关联的，因此，对微血管的成像可以有助于对组织疾病诊断，如癌症，青光眼等。Nutrients and oxygen required by human tissues and organs are transported through blood circulation, while the exchange of nutrients and oxygen is carried out in capillaries, and micro-blood flow is related to key indicators such as body temperature and blood pressure. Therefore, imaging of microvessels can be helpful in the diagnosis of tissue diseases, such as cancer, glaucoma, etc.
光学相干层析术(Optical Coherence Tomography,OCT)是一种上世纪90年代提出的利用低相干光干涉成像的诊断技术。该技术具有高分辨率、无损伤和能够实时成像等优点。其中，频域相干层析术(Fourier Domain Optical Coherence Tomography,FDOCT)具有灵敏度高，噪声小和成像速度快等优点，所以FDOCT成为主要的研究方向之一。经过二十多年的发展，很多基于FDOCT系统的功能型OCT技术被人们提出。其中用于对人体血流速度成像的方法有相位分辨的多普勒OCT(PRODT)是一种不仅能够对组织中血管成像，还能根据两次连续A扫之间的相位信息精确的计算出血流速度值的方法。功率谱多普勒OCT和光学血管造影术(OMAG)是基于多普勒效应的额外的两种能够从组织信号中提取血流信号的方法，其中，功率谱多普勒OCT是通过分析运动粒子引起的总的后向散射光功率谱来实现提取血流动态信号的。而OMAG直接分析和处理一帧图像来提取血流信号的，这样可以减少由系统和样品引起的相位不稳定噪声。两种基于统计方差的方法来提取三维血流成像的方法是散斑方差(SVOCT)和相位方差(PVOCT)方法。SVOCT方法通过计算OCT样品强度信号中行间或帧间的方差来重构血流图像。PVOCT方法通过计算同一横向位置处连续多次B扫之间的相位差来重构血流图像，该方法已经被成功应用于眼科中，并且该方法能够对所有方向的血流信号进行成像。还有相关成像方法(cmOCT)利用连续两次B扫的结构信号中子窗口的相关系数来提取血流信号。Optical coherence tomography (Optical Coherence Tomography, OCT) is a diagnostic technique proposed in the 1990s using low-coherence light interference imaging. This technique has the advantages of high resolution, non-invasive and real-time imaging. Among them, frequency domain coherence tomography (Fourier Domain Optical Coherence Tomography, FDOCT) has the advantages of high sensitivity, low noise and fast imaging speed, so FDOCT has become one of the main research directions. After more than 20 years of development, many functional OCT technologies based on the FDOCT system have been proposed. Among them, the method used for imaging human blood flow velocity is phase-resolved Doppler OCT (PRODT), which can not only image blood vessels in tissues, but also accurately calculate the Method for blood velocity values. Power spectral Doppler OCT and optical angiography (OMAG) are two additional methods based on the Doppler effect that can extract blood flow signals from tissue signals. Among them, power spectral Doppler OCT is obtained by analyzing moving particle The resulting total backscattered optical power spectrum is used to extract blood flow dynamic signals. However, OMAG directly analyzes and processes a frame of images to extract blood flow signals, which can reduce phase instability noise caused by the system and samples. Two statistical variance-based methods to extract 3D blood flow imaging are the speckle variance (SVOCT) and phase variance (PVOCT) methods. The SVOCT method reconstructs blood flow images by calculating the variance between lines or frames in the intensity signal of OCT samples. The PVOCT method reconstructs blood flow images by calculating the phase difference between multiple consecutive B-scans at the same lateral position. This method has been successfully applied in ophthalmology, and this method can image blood flow signals in all directions. There is also a correlation imaging method (cmOCT) that uses the correlation coefficient of sub-windows in the structural signals of two consecutive B-scans to extract blood flow signals.
在现有的技术中，由于PRODT是根据运动粒子的多普勒效应来对血流进行成像的，所以该方法无法测量出运动方向与光束方向垂直的运动粒子的速度。功率谱多普勒OCT方法是通过分析光谱分布来成像的，因此对于小血流信号的灵敏度不够。OMAG方法中，需要一些相位补偿方法来补偿运动伪影，这增加了系统的复杂度，并且需要大量的后续信号处理的时间。SVOCT方法重构的血流图像会受血管阴影和样品抖动的影响。PVOCT方法需要在同一横向位置处采集多次的B扫信号，所以成像速度限制了该方法在临床中的应用。而cmOCT方法中，信噪比与相关窗口的大小成正比，但增大相关窗口会使得小血管图像模糊。In the existing technology, since PRODT images the blood flow according to the Doppler effect of the moving particles, this method cannot measure the velocity of the moving particles whose moving direction is perpendicular to the beam direction. The power spectral Doppler OCT method is imaged by analyzing the spectral distribution, so it is not sensitive enough for small blood flow signals. In the OMAG method, some phase compensation methods are needed to compensate the motion artifacts, which increases the complexity of the system and requires a lot of time for subsequent signal processing. The blood flow image reconstructed by SVOCT method will be affected by vessel shadow and sample shake. The PVOCT method needs to acquire multiple B-scan signals at the same lateral position, so the imaging speed limits the clinical application of this method. In the cmOCT method, the signal-to-noise ratio is proportional to the size of the correlation window, but increasing the correlation window will blur the image of small blood vessels.
发明内容Contents of the invention
本发明的目的在于提供一种能够高灵敏度地提取并且重构三维微血流分布的基于线性相关系数来重构三维微血流分布的方法及装置，该方法还可以实现快速地对毛细血管成像。The purpose of the present invention is to provide a method and device for reconstructing three-dimensional micro-blood flow distribution based on linear correlation coefficient that can extract and reconstruct three-dimensional micro-blood flow distribution with high sensitivity, and the method can also realize rapid capillary imaging .
实现本发明目的的技术解决方案为：一种基于线性相关系数来重构三维微血流分布的方法，在频域光学相干层析系统中设置X扫描振镜和Y扫描振镜，其中，X扫描振镜为快扫方向、Y扫描振镜为慢扫方向，步骤如下：The technical solution to realize the purpose of the present invention is: a method for reconstructing three-dimensional micro-blood flow distribution based on linear correlation coefficient, setting X scanning galvanometer and Y scanning galvanometer in the frequency domain optical coherence tomography system, wherein, X The scanning galvanometer is in the fast scanning direction, and the Y scanning galvanometer is in the slow scanning direction. The steps are as follows:
步骤1，根据频域光学相干层析系统的横向分辨率确定快扫方向A扫的采样频率，使得横向分辨率为连续两次A扫之间平均距离的2.5～3.5倍；Step 1, according to the lateral resolution of the frequency-domain optical coherence tomography system, determine the sampling frequency of the A-scan in the fast-scan direction, so that the lateral resolution is 2.5 to 3.5 times the average distance between two consecutive A-scans;
步骤2，使Y扫描振镜的驱动信号为阶梯信号，每个幅度的保持时间为完成两次B扫的时间，而阶梯信号的步距电压为扫描光束移动横向分辨率大小的距离时对应的电压；Step 2, make the driving signal of the Y scanning galvanometer a step signal, the holding time of each amplitude is the time for completing two B scans, and the step voltage of the step signal is the corresponding distance when the scanning beam moves the horizontal resolution size Voltage;
步骤3，设置频域光学相干层析系统中CCD的外部触发信号，使该触发信号与X扫描振镜在起始位置的时刻同步，将CCD采集的信号传输到信号处理系统中，通过平均的方法计算每次B扫信号中干涉光谱的直流分量；Step 3, set the external trigger signal of the CCD in the frequency domain optical coherence tomography system, make the trigger signal synchronize with the time when the X scanning galvanometer is at the starting position, transmit the signal collected by the CCD to the signal processing system, and pass the average The method calculates the DC component of the interference spectrum in each B-scan signal;
步骤4，将每次A扫信号与直流分量相减后再通过傅里叶变换获取样品的复解析信号，然后提取出慢扫方向上同一位置处连续两次B扫的实部信号，再通过计算局部窗口内线性相关系数的方法来重构三维微血流分布。Step 4: Subtract each A-scan signal from the DC component and then obtain the complex analysis signal of the sample through Fourier transform, then extract the real part signals of two consecutive B-scans at the same position in the slow-scan direction, and then pass The method of calculating the linear correlation coefficient in the local window is used to reconstruct the three-dimensional micro-flow distribution.
一种基于线性相关系数来重构三维微血流分布的装置，包括激光光源、光纤耦合器、第一准直透镜、色散补偿棱镜、第一汇聚透镜、平面反射镜、第二准直透镜、X扫描振镜、Y扫描振镜、第二汇聚透镜、被测组织、第三准直透镜、光栅、傅里叶透镜、CCD、信号处理系统；A device for reconstructing three-dimensional micro-blood flow distribution based on a linear correlation coefficient, including a laser light source, a fiber coupler, a first collimating lens, a dispersion compensation prism, a first converging lens, a plane mirror, a second collimating lens, X scanning galvanometer, Y scanning galvanometer, second converging lens, measured tissue, third collimating lens, grating, Fourier lens, CCD, signal processing system;
所述激光光源发出的光经过光纤耦合器后分为两束，一束为参考光，参考光经过第一准直透镜准直后通过色散补偿棱镜，再通过第一汇聚透镜汇聚到平面反射镜上；另一束为样品光，样品光经过第二准直透镜后由X扫描振镜和Y扫描振镜反射，再由第二汇聚透镜汇聚到被测组织上，后向散射光沿原光路返回到光纤耦合器中，参考光与样品光在光纤耦合器中发生干涉，干涉光通过第三准直透镜后形成准直光，该准直光由光栅衍射分光后通过傅里叶透镜，汇聚在CCD上，CCD采集的干涉光谱信号由信号处理系统来重构组织中的三维微血流分布。The light emitted by the laser light source is divided into two beams after passing through the fiber coupler, one beam is the reference beam, the reference beam is collimated by the first collimating lens, passes through the dispersion compensating prism, and then converges to the plane reflector through the first converging lens The other beam is the sample light, the sample light is reflected by the X scanning galvanometer and the Y scanning galvanometer after passing through the second collimating lens, and then converged to the measured tissue by the second converging lens, and the backscattered light follows the original optical path Returning to the fiber coupler, the reference light and the sample light interfere in the fiber coupler, and the interfering light passes through the third collimating lens to form collimated light, which is diffracted by the grating and then passed through the Fourier lens to converge On the CCD, the interference spectrum signal collected by the CCD is reconstructed by the signal processing system to reconstruct the three-dimensional micro-blood flow distribution in the tissue.
本发明与现有技术相比，显著优点为：(1)该发明大大提高了提取动态信号的灵敏度，可以对毛细血管中的血流成像；(2)该方法在Y方向上的采样密度不需要过采样，从而提高成像速度；(3)由于相位对运动粒子位移灵敏较高，可以较小的相关窗口来提取出血流信号，从而减小了计算机的计算量和计算时间。Compared with the prior art, the present invention has the following significant advantages: (1) the invention greatly improves the sensitivity of extracting dynamic signals, and can image blood flow in capillaries; (2) the sampling density of the method in the Y direction is not Oversampling is needed to increase the imaging speed; (3) Since the phase is highly sensitive to the displacement of moving particles, the blood flow signal can be extracted with a smaller correlation window, thereby reducing the calculation amount and calculation time of the computer.
附图说明Description of drawings
图1为本发明基于线性相关系数来重构三维微血流分布的装置的结构示意图。FIG. 1 is a schematic structural diagram of a device for reconstructing a three-dimensional micro-blood flow distribution based on a linear correlation coefficient according to the present invention.
具体实施方式Detailed ways
在介绍本发明的技术方案之前，先对本发明的构思做一分析如下：Before introducing the technical scheme of the present invention, the design of the present invention is analyzed as follows:
结合图1，CCD 15接收到的干涉信号经过傅里叶变换后的复解析信号可以表示为Combined with Fig. 1, the complex analysis signal after the Fourier transform of the interference signal received by the CCD 15 can be expressed as
其中，x，y，z表示笛卡尔坐标系，x轴表示快扫方向，y轴表示慢扫方向，z轴表示深度方向，A(x,y,z)表示样品的强度信号，表示由样品结构决定的初始相位信号。在慢扫方向的同一位置，系统连续采集两次B扫信号，在这两次B扫信号中，对静态组织信号来说，强度信号A(x,y,z)和相位信号没有变化，但是对于动态血流信号来说，两次B扫信号之间的强度信号好相位信号都有所改变。其中对于轴向速度分量，粒子的运动会引入一由于多普勒相应而引起的相位差；由于干涉信号中相位对于粒子位移的灵敏度比光源的中心波长还小很多，而血红细胞的直径为10微米左右，所以血红细胞的横向移动同样会引起复解析信号中相位的变化，并且该变化是随机的。所以公式1进一步表示为：Among them, x, y, z represent the Cartesian coordinate system, the x-axis represents the fast-scan direction, the y-axis represents the slow-scan direction, the z-axis represents the depth direction, A(x, y, z) represents the intensity signal of the sample, Indicates the initial phase signal determined by the sample structure. At the same position in the slow-scan direction, the system continuously collects two B-scan signals. In these two B-scan signals, for static tissue signals, the intensity signal A(x,y,z) and the phase signal There is no change, but for the dynamic blood flow signal, both the intensity signal and the phase signal between the two B-scan signals have changed. Among them, for the axial velocity component, the motion of the particle will introduce a phase difference due to the Doppler response; because the sensitivity of the phase in the interference signal to the particle displacement is much smaller than the central wavelength of the light source, and the diameter of the red blood cell is 10 microns Left and right, so the lateral movement of red blood cells will also cause a phase change in the complex analysis signal, and the change is random. So Equation 1 is further expressed as:
其中，n表示样品的折射率，k表示波数，δz表示血红细胞在横向移动过程中引入的轴向位移的变化，v(x,y,z)表示血红细胞的运动速度，θ表示血红细胞运动方向与探测光束之间的夹角，t表示时间。根据静态组织信号和血流动态信号对复解析信号的影响，可以将慢扫方向上同一位置的两次B扫信号通过计算局部窗口线性相关系数的方法来提取动态信号，计算方法表示为：Among them, n represents the refractive index of the sample, k represents the wave number, δz represents the change of the axial displacement introduced by the red blood cell during the lateral movement, v(x, y, z) represents the movement speed of the red blood cell, and θ represents the movement of the red blood cell The angle between the direction and the detection beam, t represents the time. Complex analysis signal based on static tissue signal and blood flow dynamic signal The impact of the two B-scan signals at the same position in the slow-scan direction can be used to extract the dynamic signal by calculating the linear correlation coefficient of the local window. The calculation method is expressed as:
其中，M和N分别表示相关窗口横向和纵向的大小，p和q分别表示窗口内的像素序数，表示该窗口内实部信号的平均值，real(·)表示求复解析信号的实部。将相关窗口在xz截面内平移后可以得到一幅相关图像，其中相关系数的范围为0～±1，分别表示弱相关(动态血流信号)和强相关(静态组织信号)。Among them, M and N represent the horizontal and vertical sizes of the relevant window, respectively, and p and q represent the ordinal number of pixels in the window, respectively, Indicates the average value of the real part signal in the window, and real(·) means to find the real part of the complex analytical signal. After the correlation window is translated in the xz section, a correlation image can be obtained, and the correlation coefficient ranges from 0 to ±1, which respectively represent weak correlation (dynamic blood flow signal) and strong correlation (static tissue signal).
下面结合附图和具体实施方式对本发明做进一步说明。The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.
结合图1，本发明基于线性相关系数来重构三维微血流分布的装置，包括激光光源1、光纤耦合器2、第一准直透镜3、色散补偿棱镜4、第一汇聚透镜5、平面反射镜6、第二准直透镜7、X扫描振镜8、Y扫描振镜9、第二汇聚透镜10、被测组织11、第三准直透镜12、光栅13、傅里叶透镜14、CCD 15、信号处理系统16；1, the present invention reconstructs the three-dimensional micro-blood flow distribution device based on the linear correlation coefficient, including a laser light source 1, a fiber coupler 2, a first collimating lens 3, a dispersion compensation prism 4, a first converging lens 5, a plane Mirror 6, second collimating lens 7, X scanning vibrating mirror 8, Y scanning vibrating mirror 9, second converging lens 10, measured tissue 11, third collimating lens 12, grating 13, Fourier lens 14, CCD 15, signal processing system 16;
所述激光光源1发出的光经过光纤耦合器2后分为两束，一束为参考光，参考光经过第一准直透镜3准直后通过色散补偿棱镜4，再通过第一汇聚透镜5汇聚到平面反射镜6上；另一束为样品光，样品光经过第二准直透镜7后由X扫描振镜8和Y扫描振镜9反射，再由第二汇聚透镜10汇聚到被测组织11上，后向散射光沿原光路返回到光纤耦合器2中，参考光与样品光在光纤耦合器2中发生干涉，干涉光通过第三准直透镜12后形成准直光，该准直光由光栅13衍射分光后通过傅里叶透镜14，汇聚在CCD 15上，CCD 15采集的干涉光谱信号由信号处理系统16来重构组织中的三维微血流分布。所述样品光在X扫描振镜8与Y扫描振镜9上的两光斑之间的距离小于第二汇聚透镜10的焦距的1/10，并且两光斑的中点应该放置在第二汇聚透镜10的焦点上。The light emitted by the laser light source 1 is divided into two beams after passing through the fiber coupler 2, one beam is a reference beam, the reference beam passes through the dispersion compensation prism 4 after being collimated by the first collimating lens 3, and then passes through the first converging lens 5 Converge on the plane mirror 6; the other beam is the sample light, the sample light is reflected by the X scanning vibrating mirror 8 and the Y scanning vibrating mirror 9 after passing through the second collimating lens 7, and then converged to the measured surface by the second converging lens 10 On the tissue 11, the backscattered light returns to the fiber coupler 2 along the original optical path, the reference light and the sample light interfere in the fiber coupler 2, and the interfering light passes through the third collimating lens 12 to form collimated light. The direct light is diffracted by the grating 13 and then passed through the Fourier lens 14 and converged on the CCD 15. The interference spectrum signal collected by the CCD 15 is reconstructed by the signal processing system 16 to reconstruct the three-dimensional micro-blood flow distribution in the tissue. The distance between the two light spots of the sample light on the X scanning galvanometer 8 and the Y scanning galvanometer 9 is less than 1/10 of the focal length of the second converging lens 10, and the midpoint of the two light spots should be placed on the second converging lens 10 on focus.
本发明基于线性相关系数来重构三维微血流分布的方法，在频域光学相干层析系统中设置X扫描振镜和Y扫描振镜，其中，X扫描振镜为快扫方向、Y扫描振镜为慢扫方向，步骤如下：The method for reconstructing the three-dimensional micro-blood flow distribution based on the linear correlation coefficient of the present invention is to set an X-scanning galvanometer and a Y-scanning galvanometer in the frequency-domain optical coherence tomography system, wherein the X-scanning galvanometer is in the fast-scanning direction and the Y-scanning The galvanometer is in the slow sweep direction, the steps are as follows:
步骤1，根据频域光学相干层析系统的横向分辨率确定快扫方向A扫的采样频率，使得横向分辨率为连续两次A扫之间平均距离的2.5～3.5倍；Step 1, according to the lateral resolution of the frequency-domain optical coherence tomography system, determine the sampling frequency of the A-scan in the fast-scan direction, so that the lateral resolution is 2.5 to 3.5 times the average distance between two consecutive A-scans;
步骤2，使Y扫描振镜的驱动信号为阶梯信号，每个幅度的保持时间为完成两次B扫的时间，而阶梯信号的步距电压为扫描光束移动横向分辨率大小的距离时对应的电压；Step 2, make the driving signal of the Y scanning galvanometer a step signal, the holding time of each amplitude is the time for completing two B scans, and the step voltage of the step signal is the corresponding distance when the scanning beam moves the horizontal resolution size Voltage;
步骤3，设置频域光学相干层析系统中CCD的外部触发信号，使该触发信号与X扫描振镜在起始位置的时刻同步，将CCD采集的信号传输到信号处理系统中，通过平均的方法计算每次B扫信号中干涉光谱的直流分量；Step 3, set the external trigger signal of the CCD in the frequency domain optical coherence tomography system, make the trigger signal synchronize with the time when the X scanning galvanometer is at the starting position, transmit the signal collected by the CCD to the signal processing system, and pass the average The method calculates the DC component of the interference spectrum in each B-scan signal;
步骤4，将每次A扫信号与直流分量相减后再通过傅里叶变换获取样品的复解析信号，如公式(2)所示，然后提取出慢扫方向上同一位置处连续两次B扫的实部信号，再通过计算局部窗口内线性相关系数的方法来重构三维微血流分布，计算方法如公式(3)所示。Step 4, subtract each A-scan signal from the DC component and then obtain the complex analysis signal of the sample through Fourier transform, as shown in formula (2), and then extract two consecutive B The real part of the signal is scanned, and then the three-dimensional micro-blood flow distribution is reconstructed by calculating the linear correlation coefficient in the local window. The calculation method is shown in formula (3).
本发明对活体组织血流成像装置及方法中利用了血流信号对复解析信号中幅度和相位的影响，通过相关的方法来提取血流信号；该方法具有高灵敏度的优点，可以快速地对微血流进行成像。The present invention utilizes the influence of the blood flow signal on the amplitude and phase of the complex analysis signal in the living tissue blood flow imaging device and method, and extracts the blood flow signal through a related method; the method has the advantage of high sensitivity and can quickly detect Microvascular imaging.
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| CN201510014527.4ACN104545872B (en) | 2015-01-12 | 2015-01-12 | Method and device for reconstructing three-dimensional micro blood flow distribution on basis of linearly dependent coefficients |
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| CN201510014527.4ACN104545872B (en) | 2015-01-12 | 2015-01-12 | Method and device for reconstructing three-dimensional micro blood flow distribution on basis of linearly dependent coefficients |
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| CN104545872Atrue CN104545872A (en) | 2015-04-29 |
| CN104545872B CN104545872B (en) | 2017-04-19 |
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| CN201510014527.4AExpired - Fee RelatedCN104545872B (en) | 2015-01-12 | 2015-01-12 | Method and device for reconstructing three-dimensional micro blood flow distribution on basis of linearly dependent coefficients |
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