An optical coherence tomography device for gynecological examination

Abstract

The present invention relates to an optical coherence tomography device for gynecological examination, comprising a computer, a broadband light source, an optical signal collection device, an optical fiber coupler, an integrated reference arm and a handheld probe, wherein the integrated reference arm comprises a controller, a polarization regulator and an optical delay device, the optical fiber connected to the end of the reference arm is a delay optical fiber, the delay optical fiber is wound around the polarization regulator for at least one turn and then connected to the optical delay device, the optical signal collection device is also connected to the computer, and the controller inside the integrated reference arm is connected to the computer. The present invention utilizes a computer and an optical fiber coupler to connect the integrated reference arm, the handheld probe and the optical signal collection device into a closed-loop system, which can compensate for the drift change of the optical signal in the system in real time, thereby improving the stability and availability of the optical coherence tomography (OCT) system.

Description

Technical Field

[0001] The present invention relates to the technical field of cervical examination, and in particular to an optical coherence tomography device for gynecological examination. Background Art

[0002] Cervical cancer is the third most common female malignancy in the world and the second most common malignancy in Chinese women. According to the World Health Organization (WHO), there are more than 470,000 new cases of cervical cancer worldwide each year, and China accounts for 28%. If there is a lack of appropriate and effective screening methods and prevention measures, the incidence of cervical cancer in Asia will increase by 40% by 2025.

[0003] Human papillomavirus (HPV) is the culprit of cervical cancer. It is an extremely common virus. Up to 75% of women will be infected with HPV at some stage in their lives. Most women can eliminate the virus with their own immunity; but if HPV infection persists for a long time, the cervix is ​​repeatedly infected, and cells often mutate and cause cancer. Persistent HPV infection is the main cause of cervical cancer and its precancerous lesions - cervical intraepithelial neoplasia (CIN), and the more severe the cervical lesions, the higher the high-risk HPV infection rate.

[0004] Fortunately, cervical cancer is the only malignant tumor with a clear etiology and a long, reversible precancerous lesion period during its development, which can be reduced through medical intervention. This means that cervical cancer is a largely preventable disease.

[0005] Currently, cervical cancer screening and diagnosis mainly adopts a "three-step" approach: the first step is cervical cytology (TCT) and / or HPV virus testing; the second step is colposcopy; and the third step is cervical pathological biopsy.

[0006] The existing three-step model has some limitations: First, it is divided into three steps, with many links, a long time, high uncertainty, and great psychological pressure on patients. Second, the final diagnosis depends on pathological biopsy, but biopsy is harmful, and the points that can be taken are limited, and sampling errors may cause missed detection. Third, biopsy may also cause infection. Fourth, some special populations are not suitable for the conventional three-step examination method, such as pregnant women or patients undergoing follow-up examinations after cervical surgery.

[0007] In terms of the vulva, common diseases include vulvar hypopigmentation, benign vulvar tumors, and malignant vulvar tumors. Currently, the most commonly used method for diagnosing vulvar lesions in clinical practice is routine gynecological examination, but the nature of the lesions cannot be accurately determined by naked eye observation alone. The diagnosis of vulvar lesions still depends on pathological biopsy, so the limitations of the above-mentioned pathological biopsy still exist.

[0008] OCT can obtain high-resolution images of in vivo tissues in real time and non-invasively without the need to collect or specially process tissue samples, thereby helping doctors obtain diagnostic evidence quickly and accurately, making up for the shortcomings of existing diagnostic methods and having great clinical application value.

[0009] Despite this, the application of OCT in gynecology was mainly limited to experimental research. The reasons are: first, the OCT previously used in gynecology was mostly a simple modification of the general OCT system, without comprehensive consideration of clinical needs, and could not really enter clinical use; second, from the perspective of resolution, the resolution of OCT previously used in gynecology was only about tens of microns, and the cell structure could not be seen, and the lesions could only be interpreted based on the gross morphology. However, for some types of lesions, it is necessary to judge by the morphology of the cells, otherwise confusion may occur. For example:

[0010] (1) Cervical inflammation tissue and low-grade lesion tissue

[0011] From a gross structural point of view, both cervical inflammation tissue and low-grade lesion tissue have clear stratified structures, with the upper layer being the epithelium composed of squamous cells and the lower layer being the matrix, separated by the basement membrane. The only difference is that low-grade lesion tissue has some hollowed-out cells in the epithelium due to HPV infection, characterized by enlarged nuclei, binucleation or multinucleation, and cavitation areas around the nucleus. These features can only be observed with high-resolution OCT with a resolution of less than 10 μm.

[0012] (2) Cervical columnar epithelial eversion and invasive carcinoma

[0013] Cervical columnar epithelial eversion and some invasive carcinomas both have papillary protrusions in their gross structure, which can be easily confused. However, the surface layer of the protrusions of columnar epithelial eversion is composed of a regular single layer of columnar epithelial cells, while the protrusions of invasive carcinoma do not have this structure. Therefore, the two can be distinguished by observing the single layer of columnar epithelial cells under high-resolution OCT.

[0014] (3) Vulvar condyloma acuminatum and papilloma

[0015] Vulvar condyloma acuminatum and papilloma both have papillary protrusions in their gross structure, which can be easily confused. Vulvar condyloma acuminatum is caused by HPV virus infection and is similar to low-grade cervical lesions, with koilocytes, while papilloma does not have this feature. Therefore, under high-resolution OCT, the two can be distinguished by observing koilocytes with enlarged nuclei and perinuclear halos.

[0016] Optical coherence tomography (OCT) is a high-resolution non-invasive optical imaging technology. Its basic principle is low-coherence light interference technology. It uses low-coherence near-infrared light to illuminate biological tissues, and obtains two-dimensional cross-sectional images or three-dimensional reconstructed images of biological tissues with micron-level resolution by interferometric measurement of the scattered light signals. In OCT, image contrast is generated by changes in the optical refractive index of tissue structures. No exogenous contrast agent is required, and the imaging depth in the tissue is about 2-3mm. OCT is very suitable for tissue surface imaging, such as retinal imaging. With the development of OCT probe catheter technology in recent years, OCT has been increasingly used in the field of endoscopy, mainly for high-resolution imaging of superficial tissues in the body, including cardiovascular, digestive tract, lungs, larynx, and urogenital systems. At present, the application of OCT in gynecology is mainly in the laboratory research stage, and commercial applications have just started, mainly for screening and diagnosis of cervix and vulva. Summary of the invention

[0017] In order to solve the above technical problems, the present invention provides an optical coherence tomography device for gynecological examination.

[0018] The technical solution of the present invention is: an optical coherence tomography device for gynecological examination, comprising a computer, a broadband light source, an optical signal acquisition device, an optical fiber coupler, an integrated reference arm and a handheld probe, wherein the optical fiber coupler is a 2x2 optical fiber coupler, and the four ports of the optical fiber coupler are respectively an input end, a reference arm end, a sample arm end and an output end, and the input end, the reference arm end, the sample arm end and the output end are respectively connected to the broadband light source, the integrated reference arm, the handheld probe and the optical signal acquisition device through optical fibers, the integrated reference arm comprises a controller, a polarization regulator and an optical delay device, the optical fiber connected to the reference arm end is a delay optical fiber, and the delay optical fiber is connected to the optical delay device after being wound around the polarization regulator for at least one turn, the optical signal acquisition device is also connected to the computer, and the controller inside the integrated reference arm is connected to the computer.

[0019] Preferably, the polarization adjuster includes a deflection adjustment motor and a deflection adjustment rocker arm, the deflection adjustment rocker arm is connected to the output shaft of the deflection adjustment motor through a crank, the delay optical fiber is wound on the deflection adjustment rocker arm, and fixing seats for fixing the optical fiber are arranged on both sides of the deflection adjustment rocker arm, and the delay optical fiber is wound on the front and rear of the deflection adjustment rocker arm and fixed respectively.

[0020] Preferably, the optical delay device includes a first collimator and a delay component, the optical fiber is a delay optical fiber and is connected to the collimator optical fiber port of the first collimator, the delay component includes a sliding reflection angle cone and a fixed reflection angle cone, the sliding reflection angle cone is installed on a slider that slides along a linear slide rail, the slider is fixedly connected to the adjusting nut of the screw nut pair, the adjusting screw of the screw nut pair is connected to the output shaft of the optical delay motor, the light beam outlet of the first collimator faces the sliding reflection angle cone, the fixed reflection angle cone is installed between the sliding reflection angle cone and the first collimator and is close to the first collimator, the distance between the center line of the fixed reflection angle cone and the center line of the sliding reflection angle cone is equal to the distance between the center line of the fixed reflection angle cone and the center line of the first collimator, and the center line of the fixed reflection angle cone, the center line of the sliding reflection angle cone, and the center line of the first collimator are located in the same plane.

[0021] Preferably, the integrated reference arm also includes an adjustable optical attenuator, which includes an attenuation motor and an attenuation plate, wherein the attenuation plate is connected to the output shaft of the attenuation motor, the attenuation plate is an eccentrically arranged semicircular structure, and the attenuation plate is located in front of the first collimator.

[0022] Preferably, the center of the attenuation plate and the output shaft of the attenuation motor are eccentrically arranged along the straight edge of the attenuation plate, and the arc edge of the attenuation plate is located directly in front of the first collimating mirror.

[0023] Preferably, the integrated reference arm comprises a closed shell, the deflection adjustment motor, the fixed seat, the optical delay motor, the linear slide rail, the attenuation motor, the fiber coupler and the first collimator are all fixed at the bottom of the shell, a fiber optic positioning groove is provided at the bottom of the shell, the controller is a drive controller installed inside the shell and controls the deflection adjustment motor, the optical delay motor and the attenuation motor, and a power interface and a USB interface connected to the drive controller are provided on the side wall of the shell.

[0024] Preferably, the optical fiber connected to the input end is an input optical fiber connected to a broadband light source optical fiber, the optical fiber connected to the sample arm end is a sample optical fiber connected to a handheld probe, the optical fiber connected to the output end is an optical signal collection optical fiber connected to an optical signal collection device, the sample optical fiber and the optical signal collection optical fiber extend from an optical fiber output port on the side wall of the shell, the input optical fiber is connected to a fiber optic connector on the side wall of the shell, half of the fiber optic connector is located inside the shell and connected to the input optical fiber, and the other half is located outside the shell and connected to the broadband light source optical fiber.

[0025] Preferably, the handheld probe includes a second collimator, a reflector, a scanning galvanometer and a probe tube, the second collimator is connected to the sample optical fiber, the divergent light beam emitted by the sample optical fiber is refracted by the collimating lens of the second collimator to form nearly parallel light, the nearly parallel light emitted by the second collimator passes through a section of optical path and then is reflected by the scanning galvanometer to enter the probe tube, the scanning galvanometer is a two-dimensional galvanometer for circular scanning, the surface of the scanning galvanometer is a plane mirror coated with a high-reflection film, 2n+1 lenses are arranged in the probe tube, an inclined window is arranged at the tail of the probe tube, the end of the probe tube is an oblique opening sealed with the window, the window is a plano-convex lens, and the nearly parallel light entering the probe tube passes through the lens in the probe tube and is focused on the outer surface of the window.

[0026] Preferably, the lower side of the oblique opening is inclined inwardly.

[0027] Preferably, a reflecting mirror is arranged between the second collimating mirror and the scanning galvanometer mirror.

[0028] The beneficial effects of the present invention are:

[0029] The present invention focuses on solving the problems faced by the use of optical coherence tomography (OCT) in the field of gynecology, fully considers the use environment of gynecological clinics, optimizes the design of the OCT system, and meets the use requirements of general gynecological examinations. At the same time, through excellent optical design, the resolution is reduced to below 5μm, and the cellular level imaging of cervical tissue is realized on the human body for the first time, which brings the image quality of gynecological OCT to a new level. Clinical research has verified that this OCT system can achieve a high degree of accuracy in the identification of gynecological cervical and vulvar lesions, and has obtained results that are highly consistent with pathological biopsy (more than 85%).

[0030] The present invention can utilize a computer and an integrated reference arm to control and adjust the optical path entering the integrated reference arm, extend the light travel distance through an optical delay device, and achieve a good coupling interference effect for the light returned from the integrated reference arm and a handheld probe to the optical fiber coupler. The interference optical path is output to an optical signal acquisition device, and the internal stress of the optical fiber is changed through a polarization adjuster, thereby changing the refraction state of the light, thereby performing polarization control on the light.

[0031] The present invention also provides an adjustable optical attenuator in the integrated reference arm, which can enable the collimated light beam emitted by the first collimator in the integrated reference arm to pass through the outer circumference of the attenuation plate, so that part of the light beam is blocked by the outer circumference of the attenuation plate. The attenuation plate is an eccentrically arranged semicircular structure, and the area of ​​the light beam blocked by the attenuation plate can be changed by rotating the attenuation plate, thereby achieving the purpose of continuously adjusting the light attenuation.

[0032] The present invention uses a computer and an integrated reference arm to electrically control a polarization adjuster, an adjustable optical attenuator and an optical delay device to adjust the optical path of the delay optical fiber in the integrated reference arm in real time, so that it corresponds to the optical path of the sample optical fiber, thereby causing the light returned by the delay optical fiber and the sample optical fiber to interfere in the optical fiber coupler, thereby improving the stability of the optical path of the optical signal acquisition optical fiber output.

[0033] The integrated reference arm of the present invention combines a polarization regulator, an adjustable optical attenuator and an optical delay device with a simple and ingenious design, has high integration and is easy to maintain.

[0034] The handheld probe of the present invention has ultra-high resolution and realizes the cellular level imaging of cervical tissue in vivo for the first time. The use of a plano-convex lens as a window greatly reduces aberration and improves resolution.

[0035] The scanning galvanometer in the present invention is a two-dimensional galvanometer for circular scanning. The circular scanning avoids sudden acceleration and deceleration and has a larger effective imaging area under the same hardware conditions (such as the light aperture).

[0036] The present invention uses a computer and a fiber optic coupler to connect an integrated reference arm, a handheld probe, and an optical signal collection device into a closed-loop system, which can compensate for the drift changes of the optical signal in the system in real time, thereby improving the stability and availability of the OCT system. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 It is a schematic diagram of the external structure of the present invention;

[0038] Figure 2 It is a principle block diagram of the present invention;

[0039] Figure 3 It is a top view schematic diagram of the internal structure of the integrated reference arm;

[0040] Figure 4 is a schematic diagram of the three-dimensional structure of the housing of the integrated reference arm;

[0041] Figure 5 It is a schematic diagram of the structure of the attenuation plate in the integrated reference arm;

[0042] Figure 6 This is the control principle block diagram of the drive controller;

[0043] Figure 7 This is the circuit schematic diagram of the drive controller;

[0044] Figure 8 It is the schematic diagram of the stepper motor driving circuit in the driving controller;

[0045] Fig. 9 This is the circuit schematic diagram of the USB adapter chip in the driver controller;

[0046] Fig.10 This is the schematic diagram of the power supply circuit in the drive controller;

[0047] Fig.11 It is a structural schematic diagram of a handheld probe;

[0048] Fig.12 This is a comparison diagram of the lateral resolution measured by the present invention on the USAF1951 resolution plate;

[0049] Fig.12 a in the figure is the actual measured lateral resolution of the USAF1951 resolution plate by the present invention;

[0050] Fig.12 Middle b is the standard pattern of USAF 1951 resolution plate;

[0051] Fig.13 This is the longitudinal resolution test result of the present invention;

[0052] Fig.14 The image is obtained by performing OCT scanning on in vivo human cervical tissue in the present invention.

[0053] In the figure: 1—drive controller; 2—deflection adjustment motor; 3—deflection adjustment rocker arm; 4—fixed seat; 5—fiber coupler; 6—fiber positioning slot; 8—attenuation motor; 9—collimation fiber port; 10—first collimator; 11—optical delay motor; 12—photoelectric switch; 13—linear slide rail; 14—adjustment nut; 15—sliding reflection cone; 16—slider; 17—attenuation plate; 18—fixed reflection cone; 20—power interface; 21—USB interface; 22—housing; 23—fiber connector; 24—fiber output port; 25, sample fiber; 26, second collimator; 27, reflector; 28, scanning galvanometer; 29, probe tube; 30, lens; 31, window; 32, sample tissue; 33, fuselage; 34, bracket; 35, display; 36, casters; 37, handheld probe; 38, operation panel; 39, storage box; 40, keyboard; 41, mouse. DETAILED DESCRIPTION

[0054] The specific implementation of the present invention is shown in Figure 1-Figure 14 :

[0055] The technical solution of the present invention is:

[0056] An optical coherence tomography device for gynecological examination, such as Figure 2-Figure 6, including a computer, a broadband light source, an optical signal acquisition device, an optical fiber coupler 5, an integrated reference arm and a handheld probe, the optical fiber coupler 5 is a 2x2 optical fiber coupler 5, the four ports of the optical fiber coupler 5 are respectively an input end, a reference arm end, a sample arm end and an output end, the input end, the reference arm end, the sample arm end and the output end are respectively connected to the broadband light source, the integrated reference arm, the handheld probe and the optical signal acquisition device through optical fibers, the integrated reference arm includes a controller, a polarization regulator and an optical delay device, the optical fiber connected to the reference arm end is a delay optical fiber, the delay optical fiber is connected to the optical delay device after being wound around the polarization regulator for at least one turn, the optical signal acquisition device is also connected to the computer, the controller inside the integrated reference arm is connected to the computer, the polarization regulator includes a deflection adjustment motor 2 and a deflection adjustment rocker arm 3, the deflection adjustment rocker arm 3 is connected to the output shaft of the deflection adjustment motor 2 through a crank, the delay optical fiber is wound around the deflection adjustment rocker arm 3, and a fixing seat 4 for fixing the optical fiber is arranged on both sides of the deflection adjustment rocker arm 3, the delay optical fiber is wound around the front of the deflection adjustment rocker arm 3, The optical delay device comprises a first collimator 10 and a delay component, the optical fiber is a delay optical fiber and is connected to the collimator optical fiber port 9 of the first collimator 10, the delay component comprises a sliding reflection angle cone 15 and a fixed reflection angle cone 18, the sliding reflection angle cone 15 is installed on a slider 16 sliding along a linear slide rail 13, the slider 16 is fixedly connected to an adjusting nut 14 of a lead screw nut pair, the adjusting lead screw of the lead screw nut pair is connected to an output shaft of an optical delay motor 11, a light beam outlet of the first collimator 10 faces the sliding reflection angle cone 15, the fixed reflection angle cone 18 is installed between the sliding reflection angle cone 15 and the first collimator 10 and is close to the first collimator 10, the distance between the center line of the fixed reflection angle cone 18 and the center line of the sliding reflection angle cone 15 is equal to the distance between the center line of the fixed reflection angle cone 18 and the center line of the first collimator 10, the center line of the fixed reflection angle cone 18, the center line of the sliding reflection angle cone 15, and the center line of the first collimator 10 are located in the same plane.

[0057] The integrated reference arm in the present invention also includes an adjustable optical attenuator, which includes an attenuation motor 8 and an attenuation plate 17. The attenuation plate 17 is connected to the output shaft of the attenuation motor 8. The attenuation plate 17 is an eccentrically arranged semicircular structure. The attenuation plate 17 is located in front of the first collimator 10. The center of the circle of the attenuation plate 17 and the output shaft of the attenuation motor 8 are eccentrically arranged along the straight edge of the attenuation plate 17. The arc edge of the attenuation plate 17 is located directly in front of the first collimator 10. The collimated light beam emitted by the first collimator 10 in the integrated reference arm passes through the outer circumference of the attenuation plate 17, so that part of the light beam is blocked by the outer circumference of the attenuation plate 17. The attenuation plate 17 is an eccentrically arranged semicircular structure. The area of ​​the light beam blocked by the attenuation plate 17 can be changed by rotating the attenuation plate 17, thereby achieving the purpose of continuously adjusting the light attenuation. Figure 5 , the center B of the attenuation plate 17 is offset to one side relative to the center A of the output shaft of the attenuation motor 8.

[0058] The integrated reference arm of the present invention comprises a closed shell 22, the deflection adjustment motor 2, the fixing seat 4, the optical delay motor 11, the linear slide rail 13, the attenuation motor 8, the fiber coupler 5 and the first collimator 10 are all fixed at the bottom of the shell 22, and the bottom of the shell 22 is provided with a fiber positioning groove 6. The controller inside the integrated reference arm is a drive controller installed inside the shell and controlling the deflection adjustment motor, the optical delay motor and the attenuation motor. The side wall of the shell 22 is provided with a power interface 20 and a USB interface 21 connected to the drive controller 1. The optical fiber connected to the input end is an input optical fiber connected to a broadband light source optical fiber, and the optical fiber connected to the sample arm end is a sample optical fiber 25 connected to a handheld probe. The optical fiber connected to the output end is an optical signal collection optical fiber connected to an optical signal collection device. The sample optical fiber 25 and the optical signal collection optical fiber extend from the optical fiber output port 24 on the side wall of the shell 22. The input optical fiber is connected to the optical fiber connector 23 on the side wall of the shell 22. Half of the optical fiber connector 23 is located inside the shell 22 and connected to the input optical fiber, and the other half is located outside the shell 22 and connected to the broadband light source optical fiber. Three photoelectric switches 12 are also arranged at the bottom of the shell 22. The three photoelectric switches 12 are distributed below the deflection adjustment rocker arm 3, on the left side of the linear slide rail 13, and below the attenuation plate 17. The three photoelectric switches 12 are distributed and connected to the control circuits of the deflection adjustment motor 2, the optical delay motor 11, and the attenuation motor 8 to play a limiting role.

[0059] In the present invention, the deflection motor 2, the optical delay motor 11 and the attenuation motor 8 are all stepper motors controlled by the drive controller 1. The drive controller 1 adopts the STM32F103VE chip. The drive controller 1 is connected to the stepper motor drive circuit. The specific connection is as follows: Figure 7 and 8, the USB adapter chip circuit and power supply circuit of the driving controller 1 are as follows Fig. 9 and 10 .

[0060] The delay optical fiber connected to the reference arm end of the fiber coupler in the present invention is connected to the optical delay device to extend the light travel. The light beam emitted from the reference arm end is collimated by the delay optical fiber to the first collimator 10, and then propagates to the sliding reflection angle cone 15. The light beam is reflected by the sliding reflection angle cone 15 and then returns in the opposite direction. Since the incident light beam slightly deviates upward from the center of the sliding reflection angle cone 15, the returned light beam has a translation downward, and the reflected light beam is antiparallel to the incident light beam and has an equal distance relative to the center of the sliding reflection angle cone 15. The reflected light beam continues to propagate to the center of the fixed reflection angle cone 18, and the light beam reflected by the fixed reflection angle cone 18 returns completely along the original path to the reference arm end of the fiber coupler, wherein the sliding reflection angle cone 15 and the fixed reflection angle cone 18 are parallel to each other. The incident angle cone 18 preferably uses a total internal reflection angle cone, and the incident surface can be coated with an anti-reflection film to improve the light transmission efficiency. The sliding reflection angle cone 15 can be moved back and forth along the linear slide rail 13 driven by the optical delay motor 11 to change the optical path of the light beam at the reference arm end and match the optical path of the light beam at the sample arm end, thereby achieving a good interference effect and then output to the optical signal acquisition device through the optical signal acquisition optical fiber. The internal stress of the optical fiber is changed by a polarization regulator in the middle, thereby changing the refraction state of the light, thereby controlling the polarization of the light. The position state of the optical fiber in the integrated reference arm will directly affect the interference signal, so the optical fiber is fixed by the optical fiber positioning groove 6 at the bottom of the shell 22 to prevent the optical fiber from moving uncontrolled.

[0061] The handheld probe of the present invention comprises a second collimator 26, a reflector 27, a scanning galvanometer 28 and a probe tube 29. The second collimator 26 is connected to the sample optical fiber 25. The divergent light beam emitted by the sample optical fiber 25 is refracted by the collimator lens of the second collimator 26 to form a nearly parallel light. The nearly parallel light emitted by the second collimator 26 passes through a section of the optical path and then is reflected by the scanning galvanometer 28 to enter the probe tube 29. The scanning galvanometer 28 is a two-dimensional galvanometer for annular scanning. The surface of the scanning galvanometer 28 is a plane mirror coated with a high-reflection film. 2n+1 lenses 3 are arranged in the probe tube 29. 0, an inclined window 31 is arranged at the tail of the probe tube 29, the end of the probe tube 29 is an inclined opening sealed with the window 31, the window 31 is a plano-convex lens with a convex surface on the inner side and a flat surface on the outer side, the outer side surface of the window 31 is flush with the surface of the inclined opening, the nearly parallel light entering the probe tube 29 is focused onto the outer surface of the window 31 after passing through the lens 30 in the probe tube 29, the lower direction of the inclined opening is inclined inward, a reflector 27 is arranged between the second collimator 26 and the scanning galvanometer 28, the reflector 27 is a plane mirror, a prism or a total reflection prism coated with a high reflection film.

[0062] The probe of the present invention has ultra-high resolution, such as Fig.14 , for the first time, in vivo cellular-level imaging of cervical tissue was achieved. The use of a plano-convex lens as window 31 greatly reduced aberrations and improved resolution.

[0063] In the present invention, the optical signal is emitted from the optical fiber coupler 5 and transmitted to the scanning probe through the sample optical fiber 25. After passing through a series of optical paths of the probe to reach the sample tissue 32, the optical signal reflected by the sample tissue 32 returns through the original path and is then transmitted back to the optical fiber coupler 5 by the sample optical fiber 25. Since the core diameter of the sample optical fiber 25 port is very small, in addition to playing the role of optical transmission, the sample optical fiber 25 port also plays the role of emission and collection pinhole filtering required for confocal scanning.

[0064] The second collimator 26 in the present invention includes one or a group of lenses 30, which is used to transform the divergent light output by the sample optical fiber 25 into collimated light that is nearly parallel. When the light signal returns, the second collimator 26 also plays a focusing role, focusing the returned light signal to a very small area, thereby coupling it into the sample optical fiber 25. The second collimator 26 and the sample optical fiber 25 can be coordinated in a fixed structure, so that the port of the sample optical fiber 25 is located on the focal plane of the second collimator 26; or it can be an adjustable structure, through which the distance between the port of the sample optical fiber 25 and the second collimator 26 can be adjusted manually or electrically, thereby optimizing the imaging quality or confocal focal plane scanning.

[0065] There may be no or one or more reflectors 27 between the second collimator 26 and the galvanometer, and between the galvanometer and the probe tube 29; the reflector 27 does not change the divergence or convergence state of the light beam, but only changes the propagation direction of the light beam, so as to design the probe structure, for example, to design it into a shape suitable for hand-holding, or to meet the incident angle requirements of the optical element, the reflector 27 may be a plane mirror, a prism, or a total reflection prism coated with a high reflection film.

[0066] The scanning galvanometer 28 is a type of reflector 27 whose angle is adjustable within a certain range. The mirror angle is controlled by an electronic system to change the direction of the reflected light beam, and finally realize the translation scanning of the focus point on the focal plane of the probe. The scanning galvanometer 28 of the handheld probe in the present invention is a two-dimensional galvanometer for circular scanning. The scanning galvanometer 28 in the present invention applies sine or cosine signals in two scanning directions respectively to form a circular trajectory. After scanning one circle, the circular radius is changed to continue scanning, and a trajectory similar to concentric circles is formed within a certain radius range. Compared with linear scanning, the main advantage of this circular scanning method is that under linear scanning, the galvanometer has a large acceleration and deceleration process at the beginning and end of each line scan, which will cause this part of the image to be distorted, thereby reducing the effective imaging area; circular scanning avoids sudden acceleration and deceleration, and has a larger effective imaging area under the same hardware conditions (such as the aperture).

[0067] The probe tube 29 in the present invention is sealed at both ends, and the material of the probe tube 29 meets the biocompatibility requirements of medical products. The window 31 at the tail of the probe tube 29 is the last optical element of the light beam exit probe, and at the same time ensures the sealing of the top of the probe. The window 31 is tilted, and its normal direction forms a small angle with the optical axis. This is to reduce the light signal directly reflected by the interface of the window 31 from entering the light path and interfering with the light signal returned by the sample tissue 32. The tilted plane mirror will introduce large aberrations during imaging and reduce the imaging quality. The window 31 using a plano-convex lens can suppress this aberration to a large extent and obtain a higher lateral resolution.

[0068] When the present invention is in use, the sample tissue 32 is tightly attached to the surface of the window 31 of the handheld probe. In order to avoid cross infection, a very thin transparent isolation cover can be put on the outside of the probe; the probe covers a scanning area each time it collects, and the operator selects different points of the patient for multiple scans to cover more areas. The second collimator 26 in the probe is composed of an optical fiber interface and a collimator lens. The optical fiber interface is connected to the optical fiber of the imaging device. The divergent light beam emitted by the optical fiber is refracted by the collimator lens to form a nearly parallel light. The nearly parallel light irradiates the central area of ​​the scanning galvanometer 28 after passing through a section of the optical path. The surface of the scanning galvanometer 28 is a plane mirror coated with a high-reflection film. The nearly parallel light is reflected by the scanning galvanometer 28 and enters the probe tube 29. 2n+1 lenses 30 are arranged in the probe tube 29. By adjusting the spacing between the lenses 30, the light beam is focused on the outer surface of the window 31 at the tail end of the probe tube 29. When the scanning galvanometer 28 is driven by an electrical signal to scan, the incident angle of the nearly parallel light changes, and the focusing point on the outer surface of the window 31 The position changes accordingly, so as to achieve sampling at different positions of the sample. After the light emitted from the fiber coupler 5 reaches the sample tissue 32 through a series of optical paths of the probe, the signal reflected by the sample tissue 32 returns through the original path, and is then transmitted back to the fiber coupler 5 by the sample optical fiber 25. Then, it interferes with the light returned by the reference arm and is transmitted to the optical signal acquisition device. The optical signal acquisition device includes a spectrometer and an acquisition card. The spectrometer includes a collimator, a diffraction element, a focusing lens, and a high-speed linear camera. The spectral range of the spectrometer corresponds to the spectral range of the light source. The light output by the fiber coupler 5 is transmitted to the spectrometer. The acquisition card samples the signal received by the spectrometer camera and transmits it to the computer. The computer is connected to the signal generator, and the signal generator is connected to the acquisition card and the handheld probe. The signal generator generates a camera acquisition trigger signal and transmits it to the acquisition card. The signal generator generates a galvanometer control signal and transmits it to the scanning galvanometer 28 in the handheld probe. The signal generator coordinates the timing of each control and acquisition process.

[0069] The present invention constitutes a whole, such as Figure 1The computer host, broadband light source, and integrated reference arm are installed inside the fuselage 33. There are casters 36 at the bottom of the fuselage 33 for easy movement in the clinic. When moved to a suitable position, the casters 36 can be locked. The computer monitor 35 is installed on the top of the fuselage for real-time observation of image data. The monitor 35 is installed on a rotatable bracket 34. The doctor can adjust the angle of the monitor according to his or her own situation. The middle part of the fuselage is an operation panel 38, on which a keyboard 40 and a mouse 41 are also placed. One side of the panel is a storage box 39 for convenient storage of small objects, and the other side is a probe rack. The handheld probe 37 can be placed on the probe rack when not in use. A cable protection sleeve with a sample optical fiber 25 and a signal line is provided at the tail of the handheld probe. The handheld probe is connected to the integrated reference arm through the sample optical fiber 25 and to the signal generator through the signal line. There are a power cord socket and a USB socket on the back of the fuselage, which can be plugged into a foot pedal. The foot pedal can be used to trigger data collection when both hands are occupied.

[0070] The basic working principle of optical coherence tomography (OCT) is low-coherence light interference technology. The light source used needs to have both low temporal coherence and high spatial coherence. Low temporal coherence is to reduce the coherence length and achieve high longitudinal resolution; while high spatial coherence is to focus the light spot to a very small point and achieve high lateral resolution. Lower temporal coherence means that the light source is a broadband light source. Assuming that the light source spectrum line type is Gaussian, the relationship between the bandwidth of the light source and the longitudinal resolution is:

[0071]

[0072] Among them, Δz represents the longitudinal resolution, λ represents the central wavelength of the light source, and Δλ represents the bandwidth of the light source. It can be seen that the wider the bandwidth of the light source, the higher the longitudinal resolution of OCT. In the OCT system of the present invention, the light source we use is an SLD or supercontinuum light source with a central wavelength of about 850nm and a bandwidth of more than 155nm, so theoretically the longitudinal resolution can reach about 2μm (in air) or 1.5μm (in tissue).

[0073] The current common gynecological detection methods can only see the situation on the surface of the tissue, but cannot understand the tissue structure under the surface. The OCT device of the present invention can be used for gynecological cervical and vulva examinations, helping doctors understand the structural changes at the cellular level under the epidermis, providing a basis for more accurate diagnosis. The device has ultra-high resolution and realizes the cellular level imaging of cervical tissue in vivo for the first time. Fig.12 The figure shows the result of the lateral resolution measured by this equipment, the target is the USAF1951 resolution test plate. From the result, it can be seen that the lateral resolution at least reaches the 3rd element of the 7th group of the resolution plate, the corresponding line pair number is 161 lp / mm, and the corresponding line width is 3.1μm; Fig.13 To test the longitudinal resolution, we used flat glass as a sample, measured the line width at the glass-air interface, and converted it to the depth in the tissue according to the refractive index of the biological tissue (n=1.38). According to the test results, the longitudinal resolution in the biological tissue is about 1.8μm, corresponding to the longitudinal resolution in the air is about 2.5μm, which is slightly larger than the theoretical value. This is because the light source spectrum is not a true Gaussian, and the residual dispersion in the system will also slightly widen the line width. We further used the OCT system to perform OCT scanning imaging of in vivo human cervical tissue, and the results are shown in the figure. Fig.14 As shown, from the picture we can clearly distinguish the epidermal cells of cervical tissue.

Claims

1. An optical coherence tomography device for gynecological examination, comprising a computer, a broadband light source, an optical signal acquisition device, a fiber coupler, an integrated reference arm and a handheld probe, characterized in that: The fiber coupler is a 2x2 fiber coupler, and the four ports of the fiber coupler are respectively an input end, a reference arm end, a sample arm end and an output end. The input end, the reference arm end, the sample arm end and the output end are respectively connected to a broadband light source, an integrated reference arm, a handheld probe and an optical signal acquisition device through optical fibers. The integrated reference arm includes a controller, a polarization regulator and an optical delay device. The optical fiber connected to the reference arm end is a delay optical fiber. The delay optical fiber is connected to the optical delay device after being wound around the polarization regulator for at least one turn. The optical signal acquisition device is also connected to a computer. The controller inside the integrated reference arm is connected to the computer. The polarization regulator includes a deflection adjustment motor and a deflection adjustment rocker arm. The deflection adjustment rocker arm is connected to the output shaft of the deflection adjustment motor through a crank. The delay optical fiber is wound around the deflection adjustment rocker arm. Fixing seats for fixing the optical fiber are arranged on both sides of the deflection adjustment rocker arm. The delay optical fiber is wound around the deflection adjustment rocker arm and fixed before and after it is respectively fixed. The optical delay device includes a first collimator and a delay component. The optical fiber is a delay optical fiber and is connected to the first collimator. collimated optical fiber port, the delay component includes a sliding reflection angle cone and a fixed reflection angle cone, the sliding reflection angle cone is installed on a slider sliding along a linear slide rail, the slider is fixedly connected to the adjusting nut of the lead screw nut pair, the adjusting lead screw of the lead screw nut pair is connected to the output shaft of the optical delay motor, the light beam outlet of the first collimator faces the sliding reflection angle cone, the fixed reflection angle cone is installed between the sliding reflection angle cone and the first collimator and is close to the first collimator, the distance between the center line of the fixed reflection angle cone and the center line of the sliding reflection angle cone is equal to the distance between the center line of the fixed reflection angle cone and the center line of the first collimator, the center line of the fixed reflection angle cone, the center line of the sliding reflection angle cone, and the center line of the first collimator are located in the same plane, the integrated reference arm also includes an adjustable optical attenuator, the adjustable optical attenuator includes an attenuation motor and an attenuation plate, the attenuation plate is connected to the output shaft of the attenuation motor, the attenuation plate is an eccentrically arranged semicircular structure, and the attenuation plate is located in front of the first collimator.

2. The optical coherence tomography device for gynecological examination according to claim 1, characterized in that: The center of the attenuation plate and the output shaft of the attenuation motor are eccentrically arranged along the straight edge of the attenuation plate, and the arc edge of the attenuation plate is located directly in front of the first collimating mirror.

3. The optical coherence tomography device for gynecological examination according to claim 2, characterized in that: The integrated reference arm includes a closed shell, and the deflection adjustment motor, the fixed seat, the optical delay motor, the linear slide rail, the attenuation motor, the fiber coupler and the first collimator are all fixed on the bottom of the shell. The bottom of the shell is provided with a fiber positioning groove. The controller is a drive controller installed inside the shell and controls the deflection adjustment motor, the optical delay motor and the attenuation motor. The side wall of the shell is provided with a power interface and a USB interface connected to the drive controller.

4. The optical coherence tomography device for gynecological examination according to claim 3, characterized in that: The optical fiber connected to the input end is an input optical fiber connected to a broadband light source optical fiber, the optical fiber connected to the sample arm end is a sample optical fiber connected to a handheld probe, the optical fiber connected to the output end is an optical signal collection optical fiber connected to an optical signal collection device, the sample optical fiber and the optical signal collection optical fiber extend from an optical fiber output port on a side wall of the shell, the input optical fiber is connected to an optical fiber connector on the side wall of the shell, half of the optical fiber connector is located inside the shell and connected to the input optical fiber, and the other half is located outside the shell and connected to the broadband light source optical fiber.

5. The optical coherence tomography device for gynecological examination according to any one of claims 1 to 4, characterized in that: The handheld probe includes a second collimator, a reflector, a scanning galvanometer and a probe tube. The second collimator is connected to the sample optical fiber. The divergent light beam emitted by the sample optical fiber is refracted by the collimating lens of the second collimator to form nearly parallel light. The nearly parallel light emitted by the second collimator passes through a section of optical path and then is reflected by the scanning galvanometer to enter the probe tube. The scanning galvanometer is a two-dimensional galvanometer for circular scanning. The surface of the scanning galvanometer is a plane mirror coated with a high-reflection film. 2n+1 lenses are arranged in the probe tube. An inclined window is arranged at the tail of the probe tube. The end of the probe tube is an oblique opening sealed with the window. The window is a plano-convex lens. The nearly parallel light entering the probe tube is focused on the outer surface of the window after passing through the lens in the probe tube.

6. The optical coherence tomography device for gynecological examination according to claim 5, characterized in that: The lower side of the oblique opening is inclined inward.

7. The optical coherence tomography device for gynecological examination according to claim 6, characterized in that: A reflecting mirror is arranged between the second collimating mirror and the scanning galvanometer mirror.

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