CN102028477A - Device and method for measuring fundus retinal blood oxygen saturation - Google Patents

Abstract

A method and apparatus for measuring the blood oxygen saturation of the retinal fundus, characterized in that: the method comprises the steps of taking an adaptive optics based laser confocal scanning ophthalmoscope (AOSLO) as a platform, selecting light with at least two different wavelengths as a light source of the AOSLO, correcting fundus aberrations by using the adaptive optics, and then sequentially imaging a retina. The deformable mirror is used for generating defocusing, so that the longitudinal chromatography of the retina is realized, and the same position of a retinal vascular layer is conveniently imaged. The resulting high resolution retinal images at multiple wavelengths are registered and multiple darkest points within the blood vessel and points in the tissue at a fixed distance from the darkest points are extracted along the blood vessel. And processing the data to obtain the blood oxygen saturation of the blood vessel. The invention corrects the fundus aberration by using the adaptive optics, and can obtain a retina high-resolution image; by processing the multi-wavelength image, the blood oxygen saturation of the arteriovenous vessels and capillary vessels of the fundus retina can be measured.

Description

Device and method for measuring fundus retinal blood oxygen saturation

technical field

The invention relates to a device and method for measuring blood oxygen saturation, in particular to a device and method for measuring blood oxygen saturation of retinal arteries, veins and capillaries.

Background technique

The confocal scanning laser ophthalmoscope (CSLO) uses laser light as the light source, and the laser beam forms a point light source through the illumination pinhole, and scans every point on the focal plane in the sample. The illuminated spot on the specimen is imaged at the probe pinhole. The illumination pinhole and detection pinhole are conjugate with respect to the focal plane of the objective lens, and points outside the focal plane will not be imaged at the detection pinhole, so that a confocal image of the optical cross-section of the sample is obtained, which greatly improves the system efficiency. resolution.

Adaptive optics (Adaptive Optics, AO) is a new optical technology developed in the past 20 years in the world. It uses optoelectronic devices to measure aberration and dynamic distortion in real time, uses fast electronic systems for calculation and control, and uses active devices for real-time aberration analysis. Calibration enables the optical system to automatically adapt to changes in external conditions and maintain a good working condition. It has important applications in high-resolution imaging observations.

Spectrophotometer refers to the technology that utilizes multiple spectral channels for image acquisition, display, processing and analytical interpretation. In terms of biomedical applications, blood oxygen saturation can be analyzed by using the difference in the absorption of different wavelengths of light by hemoglobin in blood.

Retinal images of the human eye are indispensable and important information in ophthalmology diagnosis and treatment. Medical research has shown that many retinal lesions can cause a large amount of oxygen consumption, such as diabetic retinopathy, glaucoma, and vascular obstruction. Observing the change of blood oxygen in the retina by a spectrophotometer can be used for early diagnosis and detection of these diseases, but there are various aberrations in the living human eye, which greatly limits the resolution and contrast of retinal imaging, and also greatly limits The resolution of blood oxygen measurement is improved. Fundus aberrations can be corrected using adaptive optics to obtain high-resolution retinal images. In Chinese Patent Application No. 201010197028.0, a reflective optics confocal scanning laser ophthalmoscope (AOSLO) based on adaptive optics is introduced. AOSLO combines adaptive optics technology and confocal scanning imaging technology to obtain high-resolution retinal images of the human eye in vivo, but cannot measure the blood oxygen saturation of the retinal fundus.

Contents of the invention

The technical problem to be solved by the present invention is: to overcome the deficiencies of the prior art, to provide a device and method for measuring the blood oxygen saturation of the fundus retina, and to process several high-resolution images of the fundus retina with different wavelengths by using spectrophotometer technology and AOSLO technology. Ratio images to measure the blood oxygen saturation of retinal blood vessels in the fundus.

Technical solution of the present invention: a device for measuring retinal blood oxygen saturation of the fundus, comprising:

(1) A device capable of producing light of at least two specific wavelengths;

(2) Optical system and control system of confocal laser scanning ophthalmoscope (AOSLO) based on adaptive optics;

(3) Devices for detecting light of the above-mentioned specific wavelength;

(4) Data acquisition device;

(5) Data processing device, that is, a device for determining blood oxygen saturation;

A device that can generate at least two different wavelengths of light generates multiple specific wavelengths of light, and the generated light is used as the light source of the optical system and control system of AOSLO in turn, and the retina of the human eye is observed with this device; the light reflected by the retina is obtained by The device that detects light detects, and then collects the detected light signal by the data acquisition device; AOSLO's optical system and control system can use adaptive optics to correct fundus aberrations, and perform high-resolution imaging of living retinas. At the same time, adaptive optics can Using a deformable mirror to generate defocus, realize the longitudinal tomography of the retina, so that the light of different wavelengths can image the same position of the retina; the light of different wavelengths can image the blood vessels at the same position of the retina, and after the images of different wavelengths are registered by the data processing device, Calculate the oxygen saturation of the blood vessel.

A device and method for measuring fundus retinal blood oxygen saturation are as follows:

(1) Using a device that can generate at least two different wavelengths of light, sequentially generate at least two specific wavelengths of light, these specific wavelengths of light include at least one wavelength of light with a large difference in the extinction coefficient of redox protein and reduced hemoglobin That is, a light sensitive to blood oxygen saturation;

(2) The light of multiple wavelengths produced by a device capable of producing at least two different wavelengths of light is sequentially used as the light source of the optical system and control system of AOSLO, and the fundus retina is observed with this device;

(3) Using AOSLO's optical system and control system to use adaptive optics to generate defocus, so that different wavelengths of light can image the same layer in the retinal vascular layer;

(4) Utilize the optical detection device to detect the signal, and collect it by the data acquisition device, and then input it into the data processing device;

(5) The data processing device registers the collected images of different wavelengths, so as to extract multi-wavelength information at the same position of the retina;

(6) The data processing device searches for the darkest point in the multiple blood vessels and points in the tissue at a fixed distance from the darkest point along the blood vessel in any one of the above-mentioned different wavelength images, and extracts the gray information of these points, Calculate the oxygen saturation of the blood vessel.

Compared with the prior art, the present invention has the following advantages:

(1) The present invention can non-destructively measure the blood oxygen saturation of the fundus retina by using spectral technology.

(2) The current measuring devices for blood oxygen in retinal blood vessels can only measure the blood oxygen saturation of large blood vessels in the fundus. The invention adopts the self-adaptive optics technology, significantly improves the resolution of the image, can measure the blood oxygen saturation of finer structures, and can measure the blood oxygen saturation of the fundus capillaries.

(3) Using a deformable mirror to generate defocus, longitudinal tomography can be performed on the retina, so that light of different wavelengths can image the same layer of retinal blood vessels, avoiding complicated achromatic operations.

(4) The method of sequentially imaging the retina with different wavelengths of light not only avoids the optical splitting and multi-channel simultaneous detection required for simultaneous multi-wavelength imaging, but also makes reasonable use of light energy.

Description of drawings

Fig. 1 is the flowchart of the method for measuring the blood oxygen saturation of fundus retina;

Fig. 2 is the extinction coefficient of oxygenated hemoglobin and reduced hemoglobin;

Fig. 3 is the constituent structural diagram of the fundus retinal blood oxygen saturation measuring device of the present invention;

Fig. 4 is a flow chart of multi-wavelength image registration process;

Fig. 5 is a working flow diagram of the device for measuring fundus retinal blood oxygen saturation.

Among them, 1 and 2 are SLD light sources, 3 and 4 are collimating lenses, 5 and 6 are optical filters, 7, 8, and 24 are beam splitters, and 9, 10, 12, 13, 15, 16, 18, and 20 are spherical surfaces Mirrors, 19 and 21 are plane mirrors, 11 is a deformable mirror, 17 is a Y-direction scanning mirror, 14 is an X-direction scanning mirror, 22 is an optometry lens, 23 is a human eye, 26 is a focusing lens, 27 is a pinhole, 28 It is a photomultiplier tube (PMT), 29 is a signal conditioning circuit and an image acquisition card, 25 is a Hartmann sensor, and 30 and 31 are computers. 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 25, 26, 27, 31 are the optical system and control system of AOSLO.

Detailed ways

The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments. In this embodiment, the confocal scanning ophthalmoscope (AOSLO) based on adaptive optics is used as a platform, and the retinal blood oxygen saturation of the fundus is measured using spectral technology. The process is shown in Figures 1 and 5; the specific steps are as follows:

(1) A device 32 capable of generating light of at least two specific wavelengths is composed of SLD light sources 1,2, collimator lenses 3,4 and optical filters 5,6. The central wavelengths of SLD light sources 1 and 2 are 680nm and 796nm respectively. After being collimated by collimating lenses 3 and 4, filters 5 and 6 are used to filter out two wavelengths of light with central wavelengths of 680nm and 796nm and a bandwidth of 7nm respectively. , where 796nm light is insensitive to blood oxygen saturation, and 680nm light is sensitive to blood oxygen saturation;

(2) the light of 680nm is used as the light source of AOSLO optical system and control system 25, AOSLO optical system and control system 32 comprise beam splitter 7,8,24, spherical reflector 9,10,12,13,15,16,18 , 20, plane mirrors 19, 21, deformable mirror 11, X-direction scanning mirror 14, Y-direction scanning mirror 17, optometry lens 22, Hartmann sensor 25, focusing lens 26, pinhole 27, computer 31.

The light of 680nm passes through the spectroscopic mirrors 7 and 8 in sequence, and then is sequentially received by the spherical mirrors 9 and 10, the deformable mirror 11, the spherical mirrors 12 and 13, the scanning mirror 14 in the X direction, the spherical mirrors 15 and 16, and the scanning mirror 17 in the Y direction. , spherical reflector 18, plane reflector 19, spherical reflector 20, and plane reflector 21 reflect, and finally pass through the optometry lens 22 and converge at one point on the retina 23 of the living human eye. In the optical path, scanning of a certain area of the living human eye retina 23 is completed through the X-direction scanning mirror 14 and the Y-direction scanning mirror 17 . The light reflected by the retina 23 of the living human eye returns according to the original optical path, passes through the beam splitter 8, and is divided into two paths by the beam splitter 24. One path of light is detected by the Hartmann sensor 25, and after the signal is processed by the computer 31, the deformation environment 5 of the unit 37 is controlled to correct the fundus aberration. Another path of light passes through the focusing lens 26 and the pinhole 27 and is detected by the light detecting device 33 .

(3) Using the deformable mirror 11 to generate defocus, the retina can be layered longitudinally, and the image of the retinal blood vessel layer can be observed;

(4) The photomultiplier tube 28 is selected as the means 33 for detecting light. Use the photomultiplier tube 28 to detect the light of 680nm, through the data acquisition device 34, i.e. the signal conditioning circuit and the image acquisition card 29, the two-way signal is shaped and amplified, and the collected data is input into the data processing device 35, i.e. the computer 30;

(5) Using 796nm light as the light source of AOSLO, after correcting the aberration of the human eye, a high-resolution retinal image is obtained;

(6) Utilize the deformable mirror 11 to produce defocus, and collect the image again at the same position where the last image (680nm is collected as the image of the AOSLO light source) is collected;

其中p_AB(i，j)为图像A和B的联合概率密度，p_A(i，j)和p_B(i，j)分别为图像A、B的概率密度。p_AB(i，j)用两幅图像的联合直方图来表示，同时p_A(i，j)和p_B(i，j)分别用两幅图像的直方图来表示。互信息表示两幅图像的相似度，互信息越大，两幅图像相似度越高，配准的效果越好。将一幅图像做仿射变换，计算变换后与另一幅图像的互信息。不断变换仿射变换的参数，寻找互信息极大值即可完成配准。图像中一点(x，y)^T经仿射变换到点(x′，y′)^T的变换公式为：

其中参数

为满秩矩阵，a₁₁，a₁₂，a₂₁，a₂₂四个参数共同表示图像的旋转、缩放、剪切，参数t_x表示图像水平方向平移，参数t_y表示图像垂直方向平移。(7) Writing software in the computer 30 to process multi-wavelength images, the specific method is as follows: firstly, the collected images of 680nm and 796nm are registered using a method based on mutual information. The mutual information of two images A and B is defined as:

Where p _AB (i, j) is the joint probability density of images A and B, p _A (i, j) and p _B (i, j) are the probability densities of images A and B, respectively. p _AB (i, j) is represented by the joint histogram of the two images, while p _A (i, j) and p _B (i, j) are represented by the histograms of the two images respectively. Mutual information indicates the similarity between two images, the greater the mutual information, the higher the similarity between the two images, and the better the registration effect. Perform an affine transformation on an image, and calculate the mutual information between the transformed image and another image. The registration can be completed by continuously changing the parameters of the affine transformation and finding the maximum value of the mutual information. The transformation formula of a point (x, y) ^T in the image to a point (x′, y′) ^T after affine transformation is:

where parameters

It is a full-rank matrix. The four parameters a ₁₁ , a ₁₂ , a ₂₁ , and a ₂₂ together represent the rotation, scaling, and shearing of the image. The parameter t _x represents the horizontal translation of the image, and the parameter _ty represents the vertical translation of the image.

The registration process is shown in Figure 4. After the registration of the collected retinal images of 680nm and 796nm is completed, multiple darkest points are searched along the blood vessel direction in the 680nm image, and points in the tissue at a fixed distance from each darkest point are found. Assume that the brightness of a certain darkest point is I, and the brightness of a point in the tissue at a fixed distance from this darkest point is I ₀ . Then calculate the logarithm of the ratio of I ₀ and I of the two images of 680nm and 796nm at the same position Then calculate the OD ratio of the two images of 680nm and 796nm ODR=OD ₆₈₀ /OD ₇₉₆ , where OD ₆₈₀ is the logarithm of the ratio of I ₀ and I of the 680nm image, and OD ₇₉₆ is the ratio of I ₀ and I of the 796nm image logarithm of . Select multiple darkest points to calculate ODR and then take the average to improve the measurement accuracy of ODR. ODR has a linear relationship with blood oxygen saturation, and ODR can represent the blood oxygen saturation at this position in the blood vessel.

While the invention has been illustrated and described with reference to the specification and specific embodiments of the invention, it will be understood to those skilled in the art that various changes in form and details may be made therein without departing from the teachings. The spirit and scope of the present invention are defined by the appended claims.

Parts not described in detail in the present invention belong to the well-known technology in the art.

Claims (5)

1. A device for measuring fundus retinal blood oxygen saturation, characterized in that it comprises: a device (32) capable of generating light of at least two different wavelengths, at least one of which should be blood oxygen saturation sensitive; Optical system and control system of adaptive optics confocal scanning laser ophthalmoscope (AOSLO) based on adaptive optics (33); means for detecting light (34); Data acquisition device (35); A data processing device (36), i.e. a device for determining blood oxygen saturation; A device (32) capable of producing at least two different wavelengths of light generates light of multiple specific wavelengths, and the generated light is used as the light source of the optical system and control system (33) of AOSLO in turn, and the retina of the living human eye is observed; the retina The reflected light is detected by the device for detecting light (34), and then the detected optical signal is collected by the data acquisition device (35); the optical system and control system (33) of AOSLO use adaptive optics to correct the fundus aberration, High-resolution imaging of the living retina, while using the deformable mirror to generate defocus, realize the longitudinal tomography of the retina, so that the light of different wavelengths can image the same position of the retina; the light of different wavelengths can image the blood vessels at the same position of the retina, and the data processing The device (36) calculates the blood oxygen saturation of the blood vessel after registering images of different wavelengths. 2. The device for measuring retinal blood oxygen saturation according to claim 1, characterized in that: said AOSLO optical system and control system (33) include three beam splitters (7, 8, 24), eight spherical reflectors (9, 10, 12, 13, 15, 16, 18, 20), two plane mirrors (19, 21), deformable mirror (11), scanning mirror in X direction (14), scanning mirror in Y direction (17) , a trial lens (22), a Hartmann sensor (25), a focusing lens (26), a pinhole (27) and a computer (31); the light produced by the device (32) that can produce at least two specific wavelengths of light first passes through The beam splitter (7, 8) is then sequentially replaced by a spherical reflector (9, 10), a deformable mirror (11), a spherical reflector (12, 13), an X-direction scanning mirror (14), a spherical reflector (15, 16) ), Y-direction scanning mirror (17), spherical reflector (18), plane reflector (19), spherical reflector (20), plane reflector (21) reflection, finally after passing through the optometry lens (22), in the living body The human eye retina (23) converges at one point; scanning a certain area of the living human eye retina (23) is completed through the X-direction scanning mirror (14) and the Y-direction scanning mirror (17) in the light path. The light reflected by the retina (23) of the living human eye returns according to the original optical path. After passing through the beam splitter (8), it is divided into two paths by the beam splitter (24). One path of light is detected by the Hartmann sensor (25). (31) Control the deformed environment after processing (5) Correct the aberration of the fundus, and the other light is detected by the light detecting device (34) after passing through the focusing lens (26) and the pinhole (27). 3. The device for measuring retinal blood oxygen saturation according to claim 1, characterized in that: said one device (32) capable of producing at least two specific wavelengths of light consists of SLD light sources (1, 2), two collimated Lens (3, 4) and two filters (5, 6); the central wavelengths of the two SLD light sources (1, 2) are 680nm and 796nm respectively, after being collimated by collimating lenses (3, 4) , use filters (5, 6) to filter out two wavelengths of light with a center wavelength of 680nm and a bandwidth of 796nm and a bandwidth of 7nm, wherein the light of 796nm is not sensitive to blood oxygen saturation, and the light of 680nm is sensitive to blood oxygen saturation. Oxygen saturation sensitive light. 4. The device for measuring retinal blood oxygen saturation according to claim 1, characterized in that: the implementation process of the data processing device (36) is: firstly adopt the method based on mutual information to gather images of 680nm and 796nm Perform registration; after completing the registration of the collected retinal images of 680nm and 796nm, search for multiple darkest points along the blood vessel direction in the 680nm image, and find points in the tissue at a fixed distance from each darkest point; Assuming that the brightness of a certain darkest point is I, and the brightness of a point in the tissue at a fixed distance from the darkest point is I ₀ , the comparison of the ratios of I ₀ and I of the two images of 680nm and 796nm at the same position is calculated respectively. number

Calculate the OD ratio of the two images of 680nm and 796nm ODR=OD ₆₈₀ /OD ₇₉₆ , where OD ₆₈₀ is the logarithm of the ratio of I ₀ and I of the 680nm image, and OD ₇₉₆ is the ratio of I ₀ and I of the 796nm image The logarithm of the logarithm, select multiple darkest points to calculate ODR and then take the average to improve the measurement accuracy of ODR; ODR has a linear relationship with blood oxygen saturation, and the blood oxygen saturation at this position in the blood vessel can be obtained through ODR. 5. A method for measuring fundus retinal blood oxygen saturation, characterized in that the implementation steps are as follows: (1) Using a device that can generate at least two different wavelengths of light, sequentially generate at least two specific wavelengths of light, these specific wavelengths of light include at least one wavelength of light with a large difference in the extinction coefficient of redox protein and reduced hemoglobin That is, a light sensitive to blood oxygen saturation; (2) The light of multiple wavelengths produced by a device capable of producing at least two different wavelengths of light is sequentially used as the light source of the optical system and control system of AOSLO, and the fundus retina is observed with this device; (3) The optical system and control system of AOSLO use adaptive optics to generate defocus, so that the light of different wavelengths can image the same layer in the retinal vascular layer; (4) Utilize the light detection device to detect the reflected light of the retina, collect it by the data acquisition device, and then input it into the data processing device; (5) The data processing device registers the collected images of different wavelengths, so as to extract multi-wavelength information at the same position of the retina; (6) The data processing device searches for the darkest point in the multiple blood vessels and points in the tissue at a fixed distance from the darkest point along the blood vessel in any one of the above-mentioned different wavelength images, and extracts the gray information of these points, Calculate the oxygen saturation of the blood vessel.

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