CN101243966B - A high-resolution fundus blood vessel flow velocity measurement system and measurement method - Google Patents

Abstract

The high-resolution fundus blood vessel flow velocity measurement system and measurement method are characterized in that: the beacon light source is focused on the fundus by the human eye through some optical elements to form a beacon light spot, and the light spot is retroreflected by the human eye to become parallel light, and then The wavefront phase corrector and a series of optical elements arrive at the wavefront sensor to realize the adaptive aberration correction process; the imaging light source is focused on the focal point of the human eye through some optical elements, and the tested human eye is collimated into parallel light to illuminate the fundus retina Blood flow microcirculation system; laser speckle interference is formed on the surface of the illuminated fundus blood vessels, and the interference field enters the wavefront phase corrector through some optical elements, and then after reflection, passes through a series of optical elements and is finally focused on the photodetector ; This process realizes the optical speckle imaging process; the corresponding measurement method utilizes the dynamic correction ability of the adaptive optics system to the aberration, so that the overall system can overcome the influence of the human eye aberration on the image acquisition of the laser speckle interference field, so that it can Acquire high-precision, high-resolution fundus flow velocity maps.

Description

A high-resolution fundus blood vessel flow velocity measurement system and measurement method

technical field

The invention belongs to the technical field of medical equipment manufacturing for retinal imaging of the human eye, and relates to a measurement method for a high-resolution fundus blood vessel flow velocity measurement system.

Background technique

Blood vessels are the most important metabolic channel of the human body. The disorder of the blood circulation system will inevitably lead to various diseases in the human body. Therefore, the detection of various functions of blood vessels has always been an important content of scientific research, and the monitoring of blood flow velocity is even more important. It is one of the long-term hot spots in the field of life science research.

Currently, there are three common in vivo blood flow velocimetry techniques: image processing-based velocimetry, laser Doppler technology, and laser speckle velocimetry; image-processing-based velocimetry is the earliest and simplest method. This method mainly obtains blood flow velocity information by calculating the position changes of the same vascular marker on two images at two time nodes before and after. The processing process of this method is very simple and intuitive, but its accuracy is not high. Laser Doppler technology is mainly based on the principle of Doppler frequency shift in physics, using the influence of moving objects on the frequency of incident electromagnetic waves to indirectly calculate the moving speed of objects. In principle, this method is the most accurate measurement technology at present, but in practical application, this method can only measure one blood vessel at a time. If you want to measure multiple blood vessels, you must use scanning technology, so it is limited application of this technology. Laser speckle test technology is a new speed measurement method derived from the statistical law of laser scattering field. The advantage of this method is that it can detect the blood flow velocity of the blood microcirculation system in real time and with high temporal and spatial resolution. Compared with the laser Doppler velocimetry technology, it can measure the blood flow distribution velocity of multiple blood vessels in a certain field of view without scanning, and this method is also applicable to opaque blood vessels.

Huazhong University of Science and Technology applied for invention patents (application numbers: 02138787.7, 200510120575.8) on the application of laser speckle velocimetry technology in the fields of mesentery and animal brain, but both of these two patents have certain shortcomings. The speed measurement of the mesenteric microcirculatory system in the body needs to be combined with endoscopic technology, which is invasive and will cause discomfort to the subject, so it is not suitable for long-term dynamic observation; the blood flow detection of the brain is only suitable for animals body, not for human use.

The human eye is the only deep tissue that can be directly observed on the human body surface. It has transparent refractive properties, and the human eye is not sensitive to infrared beams. Therefore, the use of low-dose infrared imaging light sources will not cause discomfort to the subject and is suitable for long-term dynamic observation. But the human eye is not an ideal optical system, it has a variety of wave aberrations, these aberrations vary from person to person, and cannot be compensated by a fixed method, so many existing ophthalmic imaging systems use thin beams (≤ 3mm) illumination imaging. However, the use of thin beams reduces the resolution of the overall optical system, making it impossible to achieve visual cell-level resolution. In patent numbers ZL99 1 15051.1, ZL991 15052.X, ZL99 1 15053.8, and ZL99 1 15054.6, a method of using adaptive optics to dynamically correct human eye aberrations was proposed to realize fundus imaging at the visual cell level. Therefore, if the two advanced technologies of laser speckle velocimetry and adaptive optics are organically combined, the shortcomings of the existing technology can be overcome, and long-term and high-resolution velocimetry of the microcirculation system of the living fundus can be realized.

Contents of the invention

The technical problem to be solved by the present invention is to overcome the technical defects in the existing laser speckle velocimetry technology such as intrusion, inability to observe for a long time, and inability to use with the human body, as well as the common low resolution phenomenon in the existing ophthalmic imaging system ; A high-resolution fundus vascular flow velocity measurement system is proposed, which can organically combine two advanced technologies of laser speckle velocimetry and adaptive optics, overcome the influence of dynamic aberration on the wide-beam illumination imaging of the human eye, and realize microscopic fundus measurement. In vivo long-term, high-resolution flow measurement of the circulatory system.

The technical solution adopted by the present invention to solve the technical problem is: a high-resolution fundus blood vessel flow velocity measurement system, which is characterized in that: the light beam emitted by the beacon light source 7 becomes a parallel light beam after being collimated by the objective lens 6, and then passes through the first After being reflected by the second beam splitter 3 and the first beam splitter 2, the human eye 1 under test focuses the fundus to form a beacon spot; the beacon spot emits a reflected light beam that passes through the human eye and becomes parallel light, and passes through the first beam splitter. The plate 2 is transmitted into the first beam aperture matching system 8, and then enters the wavefront phase corrector 10 in parallel, and the beam enters the second beam aperture matching system 11 after being reflected, and then passes through the first mirror 13 and the third beam splitter After 14 reflections, enter the wavefront sensor 15;

Simultaneously, after passing through the objective lens 4, the light beam emitted by the imaging light source 5 first passes through the second beam splitter 3 and then is reflected by the first beam splitter 2. Straight parallel light illuminates the blood flow microcirculation system of the fundus retina; the illuminated fundus blood vessel surface forms laser speckle interference, and the interference field is transmitted through the first beam splitter 2 into the first beam aperture matching system 8 in turn, and then parallel The incident light enters the wavefront phase corrector 10, and the light beam enters the second beam aperture matching system 11 after being reflected, and then reflected by the first reflector 13, and then transmitted through the third beam splitter 14 and then incident on the second reflector 16, Finally, the reflected beam is focused onto the photodetector 19 by the imaging objective lens 17; the first confocal filter pinhole 9 and the second confocal filter pinhole 12 are used in the system to filter stray light; Adjust the imaging range.

The wavefront sensor 15 is conjugate to the pupil of the human eye 1 to be tested.

The photodetector 19 is conjugated to the retinal blood vessel layer of the human eye 1 to be tested.

The imaging light source 5 and the beacon light source 7 are light sources of different wavelength bands.

The first confocal filter pinhole 9 and the second confocal filter pinhole 12 are respectively located on the intermediate focal planes of the first beam aperture matching system 8 and the second beam aperture matching system 11 to form a confocal filter.

The beam splitter 14 is an anti-reflection coating for the wavelength of the imaging beam, and an anti-reflection coating for the wavelength of the beacon beam.

The wavefront phase corrector 10 is a liquid crystal device, or a micromechanical film deformation mirror, or a surface micromechanical deformation mirror.

The photodetector 19 is a CCD sensor, or a CMOS sensor, or a PDA sensor.

The adjustable field diaphragm 18 is located between the imaging objective lens 17 and the photodetector 19 to adjust the imaging area, or is located between the objective lens 4 and the imaging light source 5 to achieve the same function.

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

1. The method involved in the present invention is a non-invasive imaging technology, and its test object is the human eye, and low-power infrared light is used as the imaging light beam, so even a long-term dynamic observation will not cause the measured patient's discomfort;

2. Adaptive optics technology is adopted in the measurement system of the present invention, so wide-beam illumination and imaging can be used to achieve the resolution of visual cells; it has the characteristics of high resolution;

3. Compared with other blood flow velocimetry methods, the present invention can measure the velocity of an object in a certain area at the same time, avoiding the use of complex scanning techniques, so it has the characteristics of high speed and high precision.

Description of drawings

Fig. 1 is the schematic diagram of high-resolution fundus blood vessel velocity measurement system of the present invention;

Figure 2 is a schematic diagram of sub-aperture segmentation of a laser speckle interference image;

In Figure 1: 1 is the human eye under test, 2 is the beam splitter, 3 is the beam splitter, 4 is the objective lens, 5 is the imaging light source, 6 is the collimating objective lens, 7 is the beacon light source, 8 is the beam aperture matching system, 9 Pinhole for confocal filtering, 10 for wavefront phase corrector, 11 for beam aperture matching system, 12 for pinhole for confocal filtering, 13 for mirror, 14 for beam splitter, 15 for wavefront sensor, 16 for mirror , 17 is an imaging objective lens, 18 is an adjustable field diaphragm, and 19 is a photodetector.

Detailed ways

The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.

The overall structure of the system is shown in Figure 1. There are two processes in the actual operation of the system: laser speckle imaging and adaptive optical aberration correction.

(1) Adaptive optical aberration correction:

In the actual detection of the subject, the beam emitted by the beacon light source 7 becomes a parallel beam after being collimated by the objective lens 6, and then reflected by the beam splitter 3 and the beam splitter 2 respectively, and then the subject's eye 1 focuses on the fundus , forming a beacon light spot; the light beam reflected back by the light spot becomes parallel light after passing through the human eye, transmits through the beam splitter 2 and enters the aperture matching system 8, and then enters the wavefront phase corrector 10 in parallel, and the light beam is reflected Enter the aperture matching system 11, and then enter the wavefront sensor 15 after being reflected by the mirror 13 and the beam splitter 14; the wavefront sensor 15 calculates the wavefront aberration of the beacon beam, which represents the human eye at this moment. the aberrations; then through further calculations, the control parameters of the wavefront phase corrector 10 are obtained to correct the incident wavefront, thereby compensating for the aberrations of the human eye, so that the resolution of the entire optical system reaches the diffraction limit.

(2) Laser Speckle Imaging

After passing through the objective lens 4, the light beam emitted by the imaging light source 5 first passes through the beam splitter 3 and then is reflected by the beam splitter 2, then focuses on the front focus of the human eye 1 under test, and then is collimated by the human eye 1 into parallel illumination The blood flow microcirculation system of the bright retina; the surface of the illuminated fundus blood vessels forms laser speckle interference, and the interference field is transmitted through the beam splitter 2 in turn, enters the aperture matching system 8, and then enters the wavefront phase corrector 10 in parallel. The light beam enters the aperture matching system 11 after being reflected, is reflected by the mirror 13, is transmitted through the beam splitter 14, and is incident on the mirror 16. Finally, the reflected beam is focused by the imaging objective lens 17 onto the photodetector 19, and is imaged The field of view diaphragm 18 is inserted between the objective lens 17 and the photodetector 19, and the imaging area can be adjusted by adjusting the field of view diaphragm 18. Finally, the laser speckle interference field signal obtained on the photodetector 19 is sent to a computer for data processing; The field diaphragm 18 here can also be located between the objective lens 4 and the imaging light source 5 , and the same function can also be realized through adjustment.

On the intermediate focal planes of the beam aperture matching system 8 and the beam aperture matching system 11, there are respectively a first confocal filtering pinhole 9 and a second confocal filtering pinhole 12, which realize the function of a confocal filter and are used to eliminate impurities. Astigmatism is filtered.

The signal processing of the speckle interference field is mainly based on the method of probability and statistics, and the contrast of the speckle interference field is defined here:

$<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; C</span>}<span\; class="notranslate">\; =</span>\frac{\mathrm{<span\; class="notranslate">\; \&sigma;</span>}}{<span\; class="notranslate">\; \&lang;</span>\mathrm{<span\; class="notranslate">\; I</span>}<span\; class="notranslate">\; \&rang;</span>}$

Among them, σ is the average standard deviation of the light intensity of the interference field, and in an ideal situation, σ is equal to the average light intensity <I> of the interference light field. So ideally the contrast ratio C is 1. But when the measured object is in motion, C≤1.

According to statistical optics, we can get:

$\frac{{\mathrm{<span\; class="notranslate">\; \&sigma;</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}}{<span\; class="notranslate">\; \&lang;</span>\mathrm{<span\; class="notranslate">\; I</span>}<span\; class="notranslate">\; \&rang;</span>}<span\; class="notranslate">\; =</span>{<span\; class="notranslate">\; [</span>\frac{{\mathrm{<span\; class="notranslate">\; \&tau;</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}}{\mathrm{<span\; class="notranslate">\; 2</span>}\mathrm{<span\; class="notranslate">\; T</span>}}<span\; class="notranslate">\; \{</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; exp</span>}<span\; class="notranslate">\; (</span>\frac{<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; 2</span>}\mathrm{<span\; class="notranslate">\; T</span>}}{{\mathrm{<span\; class="notranslate">\; \&tau;</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; \}</span><span\; class="notranslate">\; ]</span>}^{\frac{\mathrm{<span\; class="notranslate">\; 1</span>}}{\mathrm{<span\; class="notranslate">\; 2</span>}}}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; 2</span>}<span\; class="notranslate">\; )</span>$

Where T is the exposure time of the photodetector and τ _c is the correlation time.

T _c =1/(ak ₀ V) (3)

Where a is a physical constant related to the scattering characteristics of the measured object, k ₀ is the wave number of the incident laser, and V is the average velocity of the measured object.

During the system data processing process, the photodetector 19 array shown in Figure 2 is divided into sub-aperture regions each having N×N pixel numbers, and the contrast ratio of the sub-regions is calculated using formula 1, and this value is assigned to the sub-regions The central pixel of the pixel, and then obtain the velocity value of the pixel according to formula 2 and formula 3, and the entire velocity image can be obtained by looping through the entire image.

When performing laser speckle imaging directly on the fundus, due to the existence of human eye aberration, it will inevitably affect the resolution of the system, so that high-resolution speckle images cannot be obtained. Resolution extraction is realized on the basis that the aberration of the human eye has been corrected by the adaptive optics system.

In summary, through the organic combination of adaptive optical aberration correction technology and laser speckle velocimetry technology, the influence of human eye aberration on laser speckle interference field imaging can be overcome, and high-resolution laser speckle interference field imaging can be obtained. Based on the field image, high-precision fundus retinal blood vessel flow velocity map is obtained, so as to realize high-resolution and high-precision flow velocity measurement of the fundus microcirculation system.

Claims (9)

1. A high-resolution fundus blood vessel flow velocity measurement system is characterized in that: the light beam sent by the beacon light source (7) becomes a parallel light beam after being collimated by the objective lens (6), and then passes through the second beam splitter (3) and the After being reflected by the first beam splitter (2), the tested human eye (1) focuses on the fundus to form a beacon light spot; the reflected light beam from the beacon light spot becomes parallel light after passing through the human eye, and passes through the first beam splitter (2) Transmitted into the first beam aperture matching system (8), then parallel incident into the wavefront phase corrector (10), the beam enters the second beam aperture matching system (11) after reflection, and then passes through the first reflection After being reflected by the mirror (13) and the third beam splitter (14), it enters the wavefront sensor (15); After passing through the objective lens (4), the light beam emitted by the imaging light source (5) first passes through the second beam splitter (3) and then is reflected by the first beam splitter (2), focusing on the front focus of the human eye (1) under test , and then the tested human eye (1) is collimated into parallel light to illuminate the blood flow microcirculation system of the fundus retina; the surface of the illuminated fundus blood vessels forms laser speckle interference, and the interference field passes through the first beam splitter (2 ) is transmitted into the first beam aperture matching system (8), and then enters the wavefront phase corrector (10) in parallel, and the beam enters the second beam aperture matching system (11) after reflection, and then passes through the first mirror (13 ) reflection, and then incident on the second mirror (16) after being transmitted by the third beam splitter (14), and finally the reflected light beam is focused onto the photodetector (19) by the imaging objective lens (17); the first common light beam is used in the system The focal filter pinhole (9) and the second confocal filter pinhole (12) realize the filtering of stray light; the field of view diaphragm (18) is adjusted to adjust the imaging range. 2. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the wavefront sensor (15) is conjugate to the pupil of the measured human eye (1). 3. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the photodetector (19) is conjugated to the retinal blood vessel layer of the human eye (1) to be measured. 4. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the imaging light source (5) and the beacon light source (7) adopt light sources of different wave bands, and the imaging light source (5) adopts For low-power infrared light, the beacon light source (7) uses an infrared light source with a different central wavelength from that of the imaging light source (5). 5. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the first confocal filtering pinhole (9) and the second confocal filtering pinhole (12) are respectively located at the first A confocal filter is formed on the intermediate focal planes of the beam aperture matching system (8) and the second beam aperture matching system (11). 6. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the third beam splitter (14) is an anti-reflection film to the wavelength of the imaging beam, and is an anti-reflection film to the wavelength of the beacon beam. membrane. 7. The high-resolution heel vessel flow velocity measurement system according to claim 1, characterized in that: the wavefront phase corrector (10) is a liquid crystal device, or a micromechanical thin film deformation mirror, or a surface micromechanical deformation mirror. 8. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the photodetector (19) is a CCD sensor, or a CMOS sensor, or a PDA sensor. 9. The high-resolution fundus blood vessel flow velocity measurement system according to claim 1, characterized in that: the adjustable field diaphragm (18) is located between the imaging objective lens (17) and the photodetector (19), Adjust the imaging area, or be located between the objective lens (4) and the imaging light source (5) to achieve the same function.

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