CN201026212Y - Non-destructive detection device for blood glucose based on optical coherence tomography fundus imaging - Google Patents

Abstract

The utility model discloses a method and a device for non-destructive detection of blood sugar by optical coherence tomography technology fundus imaging. Optical coherence tomography is applied to the tomographic imaging of the capillary layer of the human eye retina, and the blood sugar content of the human body is indirectly detected by analyzing the change of the scattering coefficient of the tissue in this layer, and finally the non-destructive detection of the human blood sugar is achieved. The device of the detection method adopts a fiber-optic optical coherence tomography system, which consists of a broadband light source, a 2×2 broadband fiber coupler, a phase modulator, a fast-scanning optical delay line, a polarization controller, a collimator, an objective lens, a detector, It is composed of an XY direction scanning component, a preamplifier, a data acquisition card, a computer, etc., and the tomographic image of the capillary layer of the human eye retina under different blood sugar concentrations can be obtained by using the above method. The utility model has the characteristics of non-destructive, tomographic and high-resolution, and can reflect the change of human blood sugar by identifying the change of light intensity information of the retinal capillary layer of the fundus.

Description

Non-destructive detection device for blood glucose based on optical coherence tomography fundus imaging

technical field

The utility model relates to a blood sugar non-destructive detection device based on optical coherence tomography technology fundus imaging.

Background technique

With the gradual improvement of people's living standards, people's physical labor has decreased significantly. At the same time, with the unreasonable diet structure, diabetes has become a major disease that affects people's health. The harm of diabetes is that the blood sugar content of the human body fluctuates too much, which leads to various concurrent diseases, such as cardiovascular and ophthalmological diseases. The size of the content is artificially injected with an appropriate amount of drugs to control the blood sugar content.

The existing blood glucose detection methods certified by the US FDA are all destructive or minimally destructive detection methods, such as the Onetouch blood glucose meter of Johnson & Johnson in the United States. These instruments need to collect a certain amount of blood samples from the human body to test the blood sugar content of the human body. Even a tiny amount of blood can be painful for a patient who needs to be tested several times a day. Compared with destructive testing, nondestructive testing methods have obvious advantages: (1) reduce the pain of daily blood sampling and measurement for patients, and improve the quality of life of patients; (2) can easily increase the number of blood sugar tests, improve the accuracy of blood sugar control, and reduce the risk of diabetes Risk of complications; (3) reduce the cost of each measurement. In view of the huge number of diabetics in the world, there is a large market space for non-destructive blood glucose detectors. Many large foreign companies and research institutions have devoted a lot of energy to research the non-destructive detection of human blood glucose. There are many methods studied abroad, such as near-infrared spectroscopy, optical rotation and polarization, Raman spectroscopy, photoacoustics, etc. Clinical application is not yet available.

Optical coherence tomography (OCT) is a newly developed tomographic technology, but it has shown strong strength in the non-destructive analysis and detection of tissue, so that it can achieve high precision and accuracy in the detection of biological tissue. resolution.

The unique optical properties of the human eye structure bring convenience to the optical imaging of the fundus structure. Light enters the pigmented layer, the outermost layer of the retina, from the pupil of the eye, and is reflected back to be detected by light-sensitive cells. The retinal structure of the fundus is well-structured and has a rich blood vessel network supply, which provides nutrients for the optic nerve and visual acuity cells.

The sub-hierarchy of the retinal and choroidal layers of the fundus is clear. There are two main blood supply layers:

(a) The choroid layer immediately adjacent to the retina. The choroid layer is rich in arterial and venous blood vessels and a specialized capillary layer that provides nutrients to the light-sensitive cells (rod cells and cone cells) in the outer layer of the retina.

(b) In the blood supply layer of the inner retina, the arteries and veins extend outward from the optic nerve mastoid, supplying nutrients to the tissues in the eye of the entire inner retinal layer.

According to Mie theory, the refractive index difference between the scatterer and the medium in which the scatterer is located will be reflected by the scattering coefficient of the scattering system. The change of blood glucose concentration will change the refractive index of the tissue body fluid, and then affect the overall scattering coefficient of the tissue body. The relationship between the scattering coefficient and the difference in refractive index inside and outside the cell can be expressed as follows:

${{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}}^{<span\; class="notranslate">\; \&prime;</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 3.28</span>}\mathrm{<span\; class="notranslate">\; \&pi;</span>}{\mathrm{<span\; class="notranslate">\; <figure-callout\; id="2"\; label="r"\; filenames="Y20062014129600101.png"\; state="\{\{state\}\}">r</figure-callout></span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}{<span\; class="notranslate">\; (</span>\frac{\mathrm{<span\; class="notranslate">\; 2</span>}\mathrm{<span\; class="notranslate">\; \&pi;r</span>}}{\mathrm{<span\; class="notranslate">\; \&lambda;</span>}}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 0.37</span>}}{<span\; class="notranslate">\; (</span>\frac{{\mathrm{<span\; class="notranslate">\; no</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}}{{\mathrm{<span\; class="notranslate">\; no</span>}}_{\mathrm{<span\; class="notranslate">\; medium</span>}}}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 2.09</span>}}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span>$

Among them, r is the radius of the scattering sphere, ρ _s is the number of scattering spheres per unit volume, λ is the wavelength of the incident light, n _s is the refractive index of the intracellular substance, n _medium is the refractive index of the extracellular body fluid, and n _s >n _medium . As the blood sugar concentration increases, n _medium will become larger, so the scattering coefficient represented by the above formula will become smaller. Conversely, the smaller the blood sugar concentration, the smaller the n _medium , and the larger the scattering coefficient.

The utility model detects the backscattering signal of the tissue, and the slope of its intensity curve characterizes the size of the scattering coefficient of the tissue. The attenuation of light in a medium with scattering and absorption can be approximated as:

$\mathrm{<span\; class="notranslate">\; I</span>}<span\; class="notranslate">\; =</span>{\mathrm{<span\; class="notranslate">\; I</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}<span\; class="notranslate">\; \&CenterDot;</span>{\mathrm{<span\; class="notranslate">\; Ae</span>}}^{<span\; class="notranslate">\; -</span>{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}\mathrm{<span\; class="notranslate">\; d</span>}}$

As the blood glucose concentration of the tissue changes, the slope of the exponential attenuation of the intensity signal in the tissue reflects the size of u _s . Therefore, the intensity signal curve of the tissue detected by OCT can be obtained according to the value of the slope of the curve. The size of the coefficient can indirectly obtain the size of the blood glucose concentration in the tissue.

Contents of the invention

The purpose of the utility model is to provide a blood sugar non-destructive detection device for fundus imaging by optical coherence tomography. Optical coherence tomography (OCT) is used to perform tomographic imaging on the capillary layer of the human eye retina, and to indirectly detect the blood sugar content of the human body by analyzing the change in the scattering coefficient of the tissue in this layer, and finally achieve the non-destructive detection of human blood sugar.

In order to achieve the above object, the technical solution adopted in the utility model is:

1. Optical coherence tomography fundus imaging non-destructive detection method for blood sugar

Using optical coherence tomography to perform tomographic imaging on the capillary layer of the human eye retina, and indirectly detect the blood sugar content of the human body by analyzing the change of the scattering coefficient of the tissue in this layer, and finally achieve the non-destructive detection of human blood sugar; the specific steps of the method as follows:

1) When a beam of light enters the tissue body, the slope of the exponential attenuation of the intensity signal of the light in the tissue body reflects the information of the tissue body. The intensity signal curve of the tissue body is detected by OCT, and the scattering coefficient can be obtained according to the value of the slope of the curve Since the change of blood glucose concentration will change the refractive index of the tissue body fluid, and then affect the overall scattering coefficient of the tissue body, so by detecting the backscattering signal of the tissue body, the slope of its intensity curve represents the scattering coefficient of the tissue body size;

2) After entering the OCT system, the backscattered light at a specific measured position of the capillary layer of the human eye interferes with the sample light when it merges at the fiber coupler, and scans the slice through the XY direction scanning component to obtain the The multi-point modulation signal of a specific layer is then converted into an electrical signal by the detector and the preamplifier. The data acquisition card converts the signal into a digital signal, and the image is reconstructed by the computer. Through data processing, the tissue blood sugar can be obtained indirectly. The size of the concentration content.

2. Optical coherence tomography fundus imaging non-destructive detection device for blood sugar

The low-coherent light of the broadband light source enters the 2×2 broadband fiber coupler through the optical fiber, and enters the reference arm and the sample arm respectively after being split. Fast scanning system composed of Fourier transform lens and vibrating mirror; one path entering the sample arm is projected onto the sample cell through polarization controller, collimating mirror, XY direction scanning component, collimating mirror and objective lens in turn; two paths of reflected light pass through 2 After the interference occurs when the ×2 broadband fiber couplers converge, they are connected to the detector and the preamplifier, and are electrically connected to the data acquisition card and the computer in turn.

The beneficial effect that the utility model has compared with background technology is:

(1) Optical coherence tomography (OCT) is used to non-destructively detect human blood sugar levels on fundus imaging. Compared with OCT detection on skin, it has the following advantages:

a. Although the skin has a relatively large detection depth (1-2mm) for the detection light wavelength (1310nm), the cuticle on the surface of the skin has a relatively large attenuation of the light signal, but the eyes are almost transparent to the detection light. The depth can reach 2-3cm.

b. There are a large number of large tissues such as hair follicles and fat in the dermis that interfere with OCT detection signals, while the retinal structure is relatively uniform, and its layered structure is very obvious, which can be more effectively detected for the characteristics of OCT tomography.

c. The blood supply system of the human eye is richer than the blood supply system of the skin, and the change of blood sugar content has a great influence on the change of tissue scattering coefficient, which is beneficial to the detection.

(2) By using OCT to detect changes in the scattering coefficient to indirectly detect the blood sugar content of the human body. Compared with other non-destructive detection methods, this method has the characteristics of high precision, high sensitivity, and high anti-interference brought by chromatography.

(3) By establishing the scattering model of the capillary layer of the fundus, the microsphere simulation system that can simulate the change of the tissue scattering coefficient can be carried out by detecting the change of the sugar concentration in the model.

(4) Since the structure of the device is non-contact measurement, which is similar to eye examination, it is easy to be accepted and convenient to use and operate.

Description of drawings

Fig. 1 is the structural diagram of the nondestructive detection device for blood sugar based on optical coherence tomography technology of the present invention for fundus imaging;

Fig. 2 is a curve diagram of OCT signal and fitting intensity;

Fig. 3 is a comparison diagram of OCT signal intensity curves of solutions with different refractive indices.

In the figure: 1. Broadband light source, 2. Optical fiber, 3. 2×2 broadband fiber coupler, 4. Phase modulator, 5. Fast scanning system, 5-1. Collimating mirror, 5-2. Diffraction grating, 5 -3. Fourier transform lens, 5-4. Galvanometer, 6. Polarization controller, 7. Collimator and objective lens, 8. Detector and preamplifier, 9. Data acquisition card, 10. Scanning in XY direction Components, 11, computer, 12, sample cell.

Detailed ways

According to Mie theory, the refractive index difference between the scatterer and the medium in which the scatterer is located will be reflected by the scattering coefficient of the scattering system. The change of blood glucose concentration will change the refractive index of the tissue body fluid, and then affect the overall scattering coefficient of the tissue body. The relationship between the scattering coefficient and the difference in refractive index inside and outside the cell can be expressed as follows:

${{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}}^{<span\; class="notranslate">\; \&prime;</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 3.28</span>}\mathrm{<span\; class="notranslate">\; \&pi;</span>}{\mathrm{<span\; class="notranslate">\; <figure-callout\; id="2"\; label="r"\; filenames="Y20062014129600101.png"\; state="\{\{state\}\}">r</figure-callout></span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}{<span\; class="notranslate">\; (</span>\frac{\mathrm{<span\; class="notranslate">\; 2</span>}\mathrm{<span\; class="notranslate">\; \&pi;r</span>}}{\mathrm{<span\; class="notranslate">\; \&lambda;</span>}}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 0.37</span>}}{<span\; class="notranslate">\; (</span>\frac{{\mathrm{<span\; class="notranslate">\; no</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}}{{\mathrm{<span\; class="notranslate">\; no</span>}}_{\mathrm{<span\; class="notranslate">\; medium</span>}}}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 2.09</span>}}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span>$

Among them, r is the radius of the scattering sphere, ρ _s is the number of scattering spheres per unit volume, λ is the wavelength of the incident light, n _s is the refractive index of the intracellular substance, n _medium is the refractive index of the extracellular body fluid, and n _s >n _medium . As the blood sugar concentration increases, n _medium will become larger, so the scattering coefficient represented by the above formula will become smaller. Conversely, the smaller the blood sugar concentration, the smaller the n _medium , and the larger the scattering coefficient.

The utility model detects the backscattering signal of the tissue, and the slope of its intensity curve characterizes the size of the scattering coefficient of the tissue. The attenuation of light in a medium with scattering and absorption can be approximated as:

$\mathrm{<span\; class="notranslate">\; I</span>}<span\; class="notranslate">\; =</span>{\mathrm{<span\; class="notranslate">\; I</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}<span\; class="notranslate">\; \&Center\; Dot;</span>{\mathrm{<span\; class="notranslate">\; Ae</span>}}^{<span\; class="notranslate">\; -</span>{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}\mathrm{<span\; class="notranslate">\; d</span>}}$

As the blood glucose concentration of the tissue changes, the slope of the exponential attenuation of the intensity signal in the tissue reflects the size of u _s . Therefore, the intensity signal curve of the tissue detected by OCT can be obtained according to the value of the slope of the curve. The size of the coefficient can indirectly obtain the size of the blood glucose concentration in the tissue.

The device of the present utility model is shown in Figure 1, and it is by broadband light source 1, optical fiber, 2 * 2 broadband optical fiber couplers 3, phase modulator 4, fast scanning system 5, polarization controller 6, collimating mirror and objective lens 7, Detector and preamplifier 8, data acquisition card 9, XY direction scanning component 10, computer 11. The low-coherent light of broadband light source 1 enters the 2×2 broadband fiber coupler 3 through the optical fiber 2, and enters the reference arm and the sample arm respectively after being split. 5-1, fast scanning system 5 composed of diffraction grating 5-2, Fourier transform lens 5-3 and vibrating mirror 5-4; the way into the sample arm is scanned in turn by polarization controller 6, collimating mirror, XY direction The component 10 and the objective lens 7 are projected on the sample cell 12; after the two reflected lights are combined by the 2×2 broadband fiber coupler 3 and interfere with each other, they are connected to the detector and the preamplifier 8, and are connected to the data acquisition card 9 and the computer 11 in turn. connect.

The backscattered light at a specific measured position of the capillary layer of the human retina, after entering the OCT system, interferes with the sample light when it merges at the fiber coupler, and scans the layer through the XY direction scanning component to obtain the specific layer The multi-point modulation signal is then converted into an electrical signal by the detector and the preamplifier; the data acquisition card converts the signal into a digital signal, and the image reconstruction is performed by the computer.

Figure 2 is the OCT image of the model and its depth signal intensity curve after horizontal average processing. The exponential slope of the curve reflects the size of the scattering coefficient. According to the exponential slope of the OCT signal and the system resolution, the specific scattering coefficient can be calculated.

Figure 3 shows the OCT depth signal curves of polystyrene microsphere suspensions with different sugar concentrations. The curves in the figure show that the relationship of the scattering coefficients of the six samples is 3-1>3-2>3-3>3 -4>3-5>3-6, consistent with the theoretical calculation results. The experimental data in the figure proves that OCT can detect the change of model scattering coefficient caused by the change of 5% sugar concentration, thus verifying the feasibility of using OCT method to detect human blood sugar content.

(1) OCT scattering detection of fundus capillary layer

The scattering method is more suitable for tissue body parts with rich capillaries and obvious scattering. There are two blood supply layers in the fundus, which are respectively located in front of and behind the photosensitive cell layer. big. Therefore, it is the main content of the utility model to find the two blood supply layers accurately and quickly, and obtain the backscattering signal with good repeatability.

Considering the mutual interference of multiple scattered lights in the OCT signal, the actual relationship to be established is much more complicated. The acquisition of the OCT signal curve needs to be obtained by processing the original OCT signal data. Since OCT detects backscattered coherent light signals, the scattered light intensity information of different depth layers can be obtained through the axial scanning of the scanning arm. After multiple horizontal averages, a uniform and stable OCT scattering intensity curve with depth as an independent variable can be obtained. Since the sublayers of the fundus retina have relatively large changes in thickness with different positions, the horizontal averaging needs to consider the depth difference of the target layer at different positions.

(2) OCT scattering detection of blood in the central retinal vein

In view of the relatively thick retinal blood vessels (generally the largest diameter can reach 150um), there are relatively thick veins and blood vessels at the optic nerve head. Compared with the um-level resolution of OCT, it is enough for detection, and the scattering coefficient of blood is relatively large. Scattering due to changes in blood glucose concentration will be more pronounced. Therefore, to find the ideal blood vessel to be measured, on the premise of obtaining the signal, find a reasonable detection point in the blood vessel to obtain the best correlation.

The utility model is based on the optical coherence tomography technology, and the blood sugar non-destructive detection method of fundus imaging comprises the following steps:

(1) The low-coherent light from the broadband light source is incident on the 2×2 broadband fiber coupler, and enters the reference arm and the sample arm respectively after being split.

(2) The light entering the reference arm first passes through the phase modulator (Phase modulator), and then enters the rapid scanning optical delay line (Rapid Scanning Optical Delay Line, RSOD) composed of collimating mirror, diffraction grating, Fourier transform lens and galvanometer ).

(3) The light incident on the sample arm is projected on the capillary layer of the fundus retina through the collimating lens and the objective lens after passing through the polarization controller.

(4) The light returned from the reference arm and the sample arm, if the experienced optical path difference is within the coherence length of the light source, interference will occur when they meet at the fiber coupler. Click to modulate the signal.

(5) The generated interference signal is transmitted to the data acquisition card after passing through the detector and the preamplifier, and the subsequent processing and image reconstruction are carried out by the computer, so as to obtain the tomographic image of the capillary layer of the fundus retina.

The light emitted by the broadband light source used in the utility model is low coherence light, its central wavelength λ=1310nm, and the bandwidth Δλ=65nm.

The device scans the sample in the Z direction through RSOD, and selects the sample scanning mode for XY direction scanning, which is realized by using a two-dimensional electric micro-displacement platform.

The utility model adopts the carrier frequency technology of the interference signal, and sets the phase modulation frequency of the PM in the reference arm at 500KHz, so that the signal and the low-frequency noise can be effectively separated in the frequency domain.

The utility model adopts a low-noise preamplifier to implement circuit filtering and subsequent software digital filtering.

The device is composed of various components connected, among which: the broadband light source 1 is a light source with a central wavelength λ=1310nm and a bandwidth Δλ=65nm produced by B & W Tek.; The quartz optical fiber of the lens (core diameter 0.1mm, numerical aperture 0.37); 2×2 broadband fiber coupler 3 chooses a broadband fiber coupler with a spectral ratio of 50/50 and a bandwidth of 80nm produced by Hangzhou Futong Company; the phase modulator 4 chooses JDS The product that Uniphase Company produces; Fast scanning system 5 is connected successively by collimating mirror 5-1, diffraction grating 5-2, Fourier transform lens 5-3, vibrating mirror 5-4 and constitutes, and wherein collimating mirror 5-1 and It is connected to the phase modulator 4 through optical coupling; one end of the polarization controller 6 is connected to the 2×2 broadband fiber coupler 3 through optical fiber, and the other end is connected to the collimator 7 through optical coupling; the collimator and objective lens 7 can be selected from Zhejiang Shun Conventional product of Yu Group; Detector and preamplifier 8 select the product of Hamamatsu Company of Japan for use; Data acquisition card 9 selects the Compusscopepel2100 type high-speed acquisition card (acquisition rate is 10MHz) of Gage Applied Company for use; XY direction scanning assembly 10 is a two-dimensional The three-dimensional electric micro-displacement platform can make the sample pool 12 do a small displacement on the two-dimensional plane; the computer 11 can be a Pentium 586 or above microcomputer, and is equipped with a GPIB card; the sample pool 12 is made of plexiglass material, and opened on both sides There are a pair of windows, inlaid with quartz windows, the thickness of which is 1mm, the simulated medium in the sample cell is polystyrene microsphere suspension, and the simulated target tissue is a colloidal cube (5mm×5mm×5mm), used to Replacing the retinal capillary layer of the human fundus.

Claims (1)

1. The blood sugar nondestructive testing device of the optical coherence tomography eyeground imaging is characterized in that: the method comprises the following steps that low-coherence light of a broadband light source (1) enters a 2 x 2 broadband optical fiber coupler (3) through an optical fiber (2), is split and then respectively enters a reference arm and a sample arm, enters one path of the reference arm, passes through a phase modulator (4), and then enters a fast scanning system (5) which sequentially consists of a collimating lens (5-1), a diffraction grating (5-2), a Fourier transform lens (5-3) and a vibrating lens (5-4); one path entering the sample arm is projected to a sample cell (12) through a polarization controller (6), a collimating mirror, an XY direction scanning component (10), the collimating mirror and an objective lens (7) in sequence; after two paths of reflected light generate interference when being converged by the 2 multiplied by 2 broadband optical fiber coupler (3), the two paths of reflected light are connected into a detector and a preamplifier (8) and are electrically connected with a data acquisition card (9) and a computer (11) in sequence.

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