All-optical opto-acoustic viscoelastic imaging device and method for sclera biomechanical detection

Abstract

The invention discloses an all-optical photoacoustic viscoelastic imaging device and method for sclera biomechanical detection.The device comprises a photoacoustic signal excitation module, a photoacoustic signal detection module, a pupil positioning module and an imaging platform, and the photoacoustic signal detection module is connected with the photoacoustic signal excitation module and the pupil positioning module; the imaging platform is respectively connected with the photoacoustic signal excitation module, the photoacoustic signal detection module and the pupil positioning module; the photoacoustic signal detection module comprises a detection light source assembly, a reference arm, a sample arm and a spectrograph, the detection light source assembly generates two paths of detection light, one path of detection light enters the reference arm and is reflected to the spectrograph by the reference arm, and the other path of detection light enters the sample arm after being combined with excitation light generated by the photoacoustic signal excitation module so as to obtain sample information. The method breaks through the limitation of traditional photoacoustic imaging, especially the limitation during deep tissue detection, viscoelastic information can be extracted from the cell level to the tissue level, and precise measurement of sclera biomechanical information is achieved.

Description

Technical Field

[0001] The invention relates to an all-optical photoacoustic viscoelastic imaging device and method for sclera biomechanics detection, belonging to the technical field of photoacoustic imaging. Background Art

[0002] The eye is one of the most important sensory organs of human beings. Through vision, individuals can perceive light, color and shape. The eye plays a vital role in learning, communication and daily life. The structure of the eye is complex, including the cornea, iris, lens, retina and sclera. The sclera is the outermost layer of the eye. It has a tough collagen connective tissue structure, which determines the size and shape of the eye and provides protection for the internal structure. The biomechanical properties of the sclera, especially its elasticity and viscosity, are crucial to the response of the eyeball to changes in internal and external pressure.

[0003] In recent years, the incidence of myopia has increased rapidly. It is estimated that by 2050, nearly half of the world's population will suffer from myopia, of which nearly 10% will be highly myopic. The main cause of myopia is the increase in axial length, which is closely related to the thinning and expansion of scleral tissue. With the development of myopia, the collagen fibers of the sclera become smaller and disordered, resulting in changes in mechanical properties, which reduces the strength of the sclera and causes deformation, leading to axial growth and changes in vision. Glaucoma is also an eye disease closely related to the biomechanical properties of the sclera, which is usually associated with increased intraocular pressure. Long-term high intraocular pressure can cause damage to the optic nerve and may lead to gradual loss of vision. As the main tissue that bears intraocular pressure, the biomechanical properties of the sclera have a significant impact on the optic nerve. Under high intraocular pressure conditions, the shape of the sclera, especially the posterior area, changes, and the sclera and the connective tissue of the optic nerve head squeeze each other, leading to axonal dysfunction or even death.

[0004] Changes in the mechanical properties of the sclera are closely related to the occurrence and development of eye diseases such as myopia and glaucoma. Studies have shown that the biomechanical properties of the sclera have become important biomarkers for predicting and diagnosing these diseases. Current research methods include in vitro measurements and in vivo measurements. In vitro measurement methods such as stretch strip tests, expansion tests, and indentation tests can reflect the mechanical properties of the sclera, but there are errors due to changes in the ocular environment. They are only used for in vitro experiments and cannot achieve in vivo measurements. Optical coherence tomography (OCT) and ultrasound elastography have made some progress in the measurement of sclera mechanics, but the accuracy of these methods needs to be further verified, and there are limitations in imaging depth and spatial resolution. In addition, most elastic imaging methods are based on linear elastic models, ignoring the viscous properties of the sclera as a viscoelastic material, and changes in viscosity are crucial to the development of the disease.

[0005] Photoacoustic imaging is an emerging biomedical imaging method that combines the high contrast of optical imaging and the high penetration depth of ultrasound imaging, and can provide high-resolution and high-contrast deep tissue imaging. Its application in eye imaging has made significant progress in eye structure imaging and functional imaging by utilizing its own high resolution and deep imaging depth, providing a new tool for the diagnosis and treatment of clinical eye diseases. Photoacoustic viscoelastic imaging is a new technology developed based on photoacoustic imaging. It can reveal the biomechanical properties of biological tissues and is of great significance in disease diagnosis.

[0006] Researchers at home and abroad have also made many advances in the field of photoacoustic viscoelastic imaging, but the existing technology has some shortcomings, including the inability to detect in situ photoacoustic signals and their phases, lack of depth information, inability to achieve high-resolution viscoelastic imaging, and most methods only consider the elasticity of the tissue, ignoring the viscosity, and are unable to achieve simultaneous measurement. Summary of the invention

[0007] The purpose of the present invention is to solve the deficiencies of the above-mentioned prior art and to provide an all-optical photoacoustic viscoelastic imaging device for scleral biomechanical detection. The device uses frequency domain coherent optical technology as a detection method for photoacoustic signals, breaking through the limitation that traditional photoacoustic signals are affected by the transmission path and cannot obtain the true amplitude and phase information of deep tissues, and realizes quantitative imaging of multi-parameters of biomechanical properties, scattering and absorption structure information of scleral tissue, and clarifies the qualitative and quantitative relationship between photoacoustic viscoelastic information and the sclera at the cellular level and tissue level, which helps to better understand and diagnose the changes in the mechanical properties of the sclera during the occurrence and development of eye diseases such as myopia and glaucoma.

[0008] Another object of the present invention is to provide an all-optical photoacoustic viscoelastic imaging method.

[0009] The purpose of the present invention can be achieved by adopting the following technical solutions:

[0010] An all-optical photoacoustic viscoelastic imaging device for scleral biomechanics detection comprises a photoacoustic signal excitation module, a photoacoustic signal detection module, a pupil positioning module and an imaging platform, wherein the photoacoustic signal detection module is respectively connected to the photoacoustic signal excitation module and the pupil positioning module, and the imaging platform is respectively connected to the photoacoustic signal excitation module, the photoacoustic signal detection module and the pupil positioning module;

[0011] The photoacoustic signal detection module includes a detection light source assembly, a reference arm, a sample arm and a spectrometer. The detection light source assembly generates two detection lights. One detection light enters the reference arm and is reflected by the reference arm to the spectrometer. The other detection light is combined with the excitation light generated by the photoacoustic signal excitation module and enters the sample arm to obtain sample information.

[0012] Further, the detection light source assembly includes a broadband superluminescent diode light source, an isolator and a fiber coupler, the reference arm includes a first lens and a reflector, and the sample arm includes a second lens, a first dichroic mirror, a scanning galvanometer, a scanning lens, a tube lens, a second dichroic mirror and a first objective lens;

[0013] The broadband superluminescent diode light source enters the optical fiber coupler through the isolator and is divided into two detection lights. One detection light is reflected to the spectrometer after passing through the first lens and the reflector, and the other detection light is combined with the excitation light generated by the photoacoustic signal excitation module through the second lens and the first dichroic mirror, and then is used to detect the sample through the scanning galvanometer, the scanning lens, the tube mirror, the second dichroic mirror, and the first objective lens to obtain the information of the sample.

[0014] Furthermore, the spectrometer includes a first collimating lens, a grating, a third lens and a charge-coupled device. The reflected light in the reference arm and the sample arm converges in the fiber coupler. The optical path difference between the reference arm and the sample arm generates an interference signal within a coherent length, which enters the charge-coupled device through the first collimating lens, the grating and the third lens. The charge-coupled device transmits the detection light information to the imaging platform.

[0015] Furthermore, the photoacoustic signal excitation module includes an excitation light source assembly, a second objective lens, a second collimating lens, a first beam splitter and a photodetector. The excitation light generated by the excitation light source assembly is divided into two paths through the second objective lens, the second collimating lens and the first beam splitter. One path of excitation light is received by the photodetector and transmitted to the imaging platform, and the other path of excitation light is combined with the detection light generated by the detection light source assembly and enters the sample arm to excite the sample to generate a photoacoustic response signal.

[0016] Furthermore, the excitation light source assembly includes a laser, an electro-optic modulator and a spatial filter. The laser is periodically modulated by the electro-optic modulator to excite the sample to produce a periodic photoacoustic response. The spatial filter is used to filter stray light in the photoacoustic signal after modulation by the electro-optic modulator.

[0017] Furthermore, the pupil positioning module includes an LED light source, a second beam splitter, a fourth lens, a fifth lens and a camera. The visible light beam of the LED light source passes through the second beam splitter and coaxially illuminates the pupil via the fourth lens. The second beam splitter reflects the illuminated pupil image reflected back by the second dichroic mirror and reaches the camera via the fifth lens.

[0018] Further, the imaging platform includes a computer and a field programmable gate array;

[0019] The computer is respectively connected to the photodetector of the photoacoustic signal excitation module, the charge coupled device of the spectrometer in the photoacoustic signal detection module, the camera of the pupil positioning module, and the field programmable gate array, and is used to generate a trigger signal of the field programmable gate array in response to the demand;

[0020] The field programmable gate array is respectively connected to the excitation light source assembly of the photoacoustic signal excitation module, the scanning galvanometer of the sample arm in the photoacoustic signal detection module, and the charge coupled device of the spectrometer, and is used to control the excitation light source assembly, the scanning galvanometer and the charge coupled device.

[0021] Another object of the present invention can be achieved by adopting the following technical solutions:

[0022] An all-optical photoacoustic viscoelastic imaging method is implemented based on the all-optical photoacoustic viscoelastic imaging device mentioned above, and the method comprises:

[0023] In the excitation light source component of the photoacoustic signal excitation module, the laser is modulated by an electro-optic modulator, and the reference trigger signal output by the electro-optic modulator is used as a synchronization signal of the excitation light;

[0024] The rising edge of the reference trigger signal is used to trigger the acquisition card of the photoacoustic signal detection module, generating N A-lines signals to trigger the charge coupled device of the spectrometer to record a periodic photoacoustic effect, record the response of M periods, and record N×M A-scan signals in total;

[0025] After M periods of photoacoustic response are collected at a transverse point, the scanning galvanometer of the sample arm is triggered to move one step along the X axis to record the periodic photoacoustic response of the next transverse point until a B-scan is completed;

[0026] After the scanning galvanometer X-axis completes the B-scan, it triggers the scanning galvanometer Y-axis to move one step to achieve the next B-scan, completing the two-dimensional scan of the entire scanning area to achieve three-dimensional imaging.

[0027] Furthermore, the method further comprises:

[0028] In the sample arm of the photoacoustic signal detection module, the scanning lens, the tube lens and the second dichroic mirror are replaced by two conical lens pairs for generating Bessel beams to achieve photoacoustic viscoelastic imaging of deep tissues.

[0029] Furthermore, the method further comprises:

[0030] In the sample arm of the photoacoustic signal detection module, the optical path of the reflective spatial light modulator is inserted between the first dichroic mirror and the scanning galvanometer, and the scanning lens, the tube mirror and the second dichroic mirror are removed to generate a non-diffracted light beam to achieve photoacoustic viscoelastic imaging of deep tissues.

[0031] The present invention has the following beneficial effects compared with the prior art:

[0032] 1. The present invention can solve the problem that the current photoacoustic viscoelastic imaging has no depth information and low spatial resolution. By improving the current photoacoustic viscoelastic ratio model and proposing a method for separating photoacoustic viscosity and elastic information, the viscosity and elastic parameters can be effectively separated, and the mechanical properties of the tissue can be accurately reflected. Through innovation in the imaging principle, an all-optical multimodal photoacoustic imaging technology that integrates photoacoustic viscoelasticity, absorption and scattering structural information is cleverly constructed. The absorption, scattering and viscoelastic information of the tissue can be obtained through a single scan, and the imaging detection of tissue structure and function can be realized at the same time.

[0033] 2. In view of the current insufficient means for detecting scleral biomechanics and incomplete mechanical information, which only have elastic information but lack viscosity information, the present invention utilizes the advantages of imaging depth and complete mechanical information of all-optical photoacoustic viscoelastic imaging technology and applies it to the precise measurement of scleral biomechanics, realizing multi-parameter quantitative imaging of the biomechanical properties, scattering and absorption structure information of scleral tissue, which is suitable for detecting changes in mechanical properties of eye diseases such as myopia and glaucoma, and will provide a new technical method with clinical application prospects for scleral biomechanics detection.

[0034] 3. The present invention realizes the extraction of viscoelastic information from the cell level to the tissue level by designing a photoacoustic viscoelastic imaging device adapted to the anterior and posterior segments of the eye, and develops a high-resolution mode and a high-depth viscoelastic imaging mode adapted to the anterior and posterior segments of the eye, which are used for detection at the cell level and tissue level, respectively, to meet the needs of different detection depths. The device includes modules such as photoacoustic signal excitation, acquisition, imaging scanning, and pupil positioning, and the imaging speed of the device is improved through FPGA programming.

[0035] 4. The present invention verifies the accuracy and safety of photoacoustic viscoelastic imaging in in vitro samples and in vivo animal models, summarizes the biomechanical characteristics of normal and diseased sclera, compares the changes in scleral mechanical properties in myopia and glaucoma models, and establishes a scleral function evaluation system. By studying the pathology, structure and biomechanical changes of diseased sclera, a characteristic change database is established, providing an important reference for early diagnosis of the disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0037] Figure 1 Schematic diagram of the structure of the all-optical photoacoustic viscoelastic imaging device according to Example 1 of the present invention.

[0038] Figure 2 This is a timing diagram of the control signal of Example 1 of the present invention.

[0039] Figure 3 Schematic diagram of detection of the anterior scleral viscoelastic imaging mode of Example 1 of the present invention.

[0040] Figure 4 Schematic diagram of detection of the viscoelastic imaging mode of the posterior sclera of the eye according to Example 1 of the present invention.

[0041] Among them, 1-broadband superluminescent diode light source, 2-isolator, 3-fiber coupler, 4-first lens, 5-reflector, 6-second lens, 7-first dichroic mirror, 8-scanning galvanometer, 9-scanning lens, 10-tube lens, 11-second dichroic mirror, 12-first objective lens, 13-sample, 14-collimating lens, 15-grating, 16-third lens, 17-charge coupled device, 18-computer, 19-field programmable gate array, 20-laser, 21-electro-optic modulator, 22-spatial filter, 23-second objective lens, 24-collimating lens, 25-first beam splitter, 26-photodetector, 27-LED light source, 28-second beam splitter, 29-fourth lens, 30-fifth lens, 31-camera. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0043] It should be understood that when used in this specification and the appended claims, the terms "include" and "comprises" indicate the presence of described features, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or combinations thereof.

[0044] The description of the embodiments should be understood in conjunction with the attached drawings. The embodiments are only used to illustrate specific embodiments that can be used to implement the present invention, and do not limit the present invention. The directional terms mentioned in the present invention, such as "upper", "lower", "front", "back", "left", "right", "inner", "outer", "side", etc., are only referenced to the directions of the attached drawings. Therefore, the directional terms used are used to illustrate and understand the present invention, but not to limit the present invention.

[0045] Embodiment 1:

[0046] like Figure 1 As shown, this embodiment provides an all-optical photoacoustic viscoelastic imaging device for scleral biomechanics detection, which includes a photoacoustic signal excitation module, a photoacoustic signal detection module, a pupil positioning module and an imaging platform. The photoacoustic signal detection module is respectively connected to the photoacoustic signal excitation module and the pupil positioning module, and the imaging platform is respectively connected to the photoacoustic signal excitation module, the photoacoustic signal detection module and the pupil positioning module.

[0047] Furthermore, the photoacoustic signal detection module is a frequency domain optical coherence tomography (OCT) system, which includes a detection light source assembly, a reference arm, a sample arm and a spectrometer. The detection light source assembly generates two detection lights. One detection light enters the reference arm and is reflected by the reference arm to the spectrometer. The other detection light is combined with the excitation light generated by the photoacoustic signal excitation module and enters the sample arm to obtain sample information.

[0048] Furthermore, the detection light source assembly includes a broadband superluminescent diode light source (Super-luminescent diodes, referred to as SLD) 1, an isolator 2 and a fiber coupler 3, the reference arm includes a first lens 4 and a reflector 5, and the sample arm includes a second lens 6, a first dichroic mirror 7, a scanning galvanometer 8, a scanning lens 9, a tube lens 10, a second dichroic mirror 11 and a first objective lens 12; the broadband superluminescent diode light source 1 enters the fiber coupler 3 through the isolator 2 and is divided into two detection lights, one detection light is reflected to the spectrometer after passing through the first lens 4 and the reflector 5, and the other detection light passes through the second lens 6 and the excitation light generated by the photoacoustic signal excitation module, and then is combined with the first dichroic mirror 7, and then passes through the scanning galvanometer 8, the scanning lens 9, the tube lens 10, the second dichroic mirror 11, and the first objective lens 12 to detect the sample to obtain the information of the sample.

[0049] Furthermore, the spectrometer includes a first collimating lens 14, a grating 15, a third lens 16 and a charge coupled device (CCD) 17. The reflected light in the reference arm and the sample arm converges in the fiber coupler 3. The optical path difference between the reference arm and the sample arm generates an interference signal within a coherent length, which enters the charge coupled device 17 through the first collimating lens 14, the grating 15 and the third lens 16. The charge coupled device 17 transmits the detection light information to the imaging platform.

[0050] Furthermore, the photoacoustic signal excitation module includes an excitation light source assembly, a second objective lens 23, a second collimating lens 24, a first beam splitter 25 and a photodetector 26. The excitation light generated by the excitation light source assembly is divided into two paths by the second objective lens 23, the second collimating lens 24 and the first beam splitter 25. One path of excitation light is received by the photodetector 26 and transmitted to the imaging platform, and the other path of excitation light is combined with the detection light beam generated by the detection light source assembly and enters the sample arm to excite the sample to generate a photoacoustic response signal.

[0051] Furthermore, the excitation light source assembly includes a laser 20, an electro-optic modulator (EOM) 21 and a spatial filter 22. The laser 20 is periodically modulated by the electro-optic modulator 21 to excite the absorber (i.e., the sample being tested) to produce a periodic photoacoustic response. A phase-sensitive frequency-domain optical coherence tomography system (i.e., a photoacoustic signal detection module) is used to detect this periodic photoacoustic response to obtain the amplitude and phase information of the photoacoustic signal deep in the tissue. The spatial filter 22 is used to filter out unnecessary stray light in the photoacoustic signal after modulation by the electro-optic modulator to ensure the quality of the photoacoustic signal.

[0052] Furthermore, the pupil positioning module is mainly used to locate the pupil during photoacoustic viscoelastic imaging of the posterior segment of the eye, and includes an LED light source 27, a second beam splitter 28, a fourth lens 29, a fifth lens 30 and a camera 31. The visible light beam of the LED light source 27 passes through the second beam splitter 28 and coaxially illuminates the pupil via the fourth lens 29. The second beam splitter 28 reflects the illuminated pupil image reflected back by the second dichroic mirror 11 and reaches the camera 31 via the fifth lens 30.

[0053] Furthermore, the imaging platform includes a computer 18 and a field programmable gate array (FPGA) 19; the computer 18 is respectively connected to the photodetector 26 of the photoacoustic signal excitation module, the charge coupled device 17 in the spectrometer of the photoacoustic signal detection module, the camera 31 of the pupil positioning module, and the field programmable gate array 19, so as to generate a trigger signal of the field programmable gate array 19 in response to the demand; the field programmable gate array 19 is respectively connected to the laser 20 in the excitation light source assembly, the electro-optic modulator 21, the scanning galvanometer 8 in the sample arm, and the charge coupled device 17 in the spectrometer, so as to control the laser 20, the electro-optic modulator 21, the scanning galvanometer 8 and the charge coupled device 17.

[0054] In this embodiment, the central wavelength of the broadband superluminescent diode light source 1 is 1300nm, and the bandwidth is ≥100nm; the line speed of the charge coupled device 17 is ≥200KHz; the photoacoustic excitation wavelength is 500-1100nm; the computer 18 adopts a CPU-GPU-CPU architecture, the CPU controls the software, allocates 3 threads to collect 3 groups of module data, the GPU processes images in parallel, and transmits them to the CPU for image display.

[0055] The all-optical photoacoustic viscoelastic imaging device of this embodiment improves the photoacoustic viscoelastic ratio model, deeply studies the mechanical response of viscoelastic materials under different excitation modes and excitation frequencies, and establishes a more accurate viscoelastic measurement method. In the theoretical model, based on the relationship between stress and strain in the Kelvin-Voigt model, it is found that strain has the same frequency of change as stress, but has a phase delay relative to stress, and the phase delay is directly related to the viscoelasticity of the medium. Under a certain frequency, the phase delay of different biological tissues is different. By scanning the sample, the viscoelastic ratio image reflecting the mechanical properties can be obtained, revealing the quantitative relationship between the viscoelastic ratio and the phase delay, ensuring the accurate evaluation of the mechanical properties of different biological tissues.

[0056] The all-optical photoacoustic viscoelastic imaging device of this embodiment proposes a model for separating photoacoustic viscosity and elasticity. Based on the photoacoustic field described by Navier's equation combined with the wave equation, the photoacoustic elasticity can be described by analyzing the displacement field of the photoacoustic wave in the longitudinal and transverse wave modes according to the rise time required from the zero displacement to the maximum vibration displacement. According to the above-mentioned quantitative relationship between the viscoelastic ratio and the phase delay, the viscosity and elasticity information of the tissue are decomposed, which overcomes the shortcomings of the existing photoacoustic imaging technology in separating the viscosity and elasticity information and significantly improves the measurement accuracy of the mechanical properties of biological tissues.

[0057] The all-optical photoacoustic viscoelastic imaging device of this embodiment adopts frequency-domain optical coherence tomography technology, and the device can detect the amplitude and phase information of photoacoustic signals in deep tissues with high sensitivity, thereby realizing high-resolution viscoelastic imaging; specifically, the laser and the electro-optical modulator generate periodic photoacoustic responses, and the frequency-domain optical coherence tomography system is used to detect these photoacoustic responses and extract the amplitude and phase information of photoacoustic signals in deep tissues, thereby ensuring accurate measurement of the biomechanical properties of the sclera.

[0058] The all-optical photoacoustic viscoelastic imaging device of this embodiment ensures the synchronization of the photoacoustic signal excitation module and the photoacoustic signal detection module, and can accurately detect the photoacoustic response process, and realizes the excitation and acquisition timing logic control, such as Figure 2 As shown; after the device is started, in the excitation light source component of the photoacoustic signal excitation module, the laser is modulated by the electro-optic modulator. Since there is only a fixed time delay between the reference trigger signal output by the electro-optic modulator and the optical signal of the continuously modulated pump laser, the reference information can be used as the synchronization signal of the excitation light. In order to synchronize the detection unit and the excitation unit and record the periodic photoacoustic response (M cycles), the reference trigger signal rising edge triggers the acquisition card of the photoacoustic signal detection module, generates N A-lines signals to trigger the charge coupled device of the spectrometer to record a periodic photoacoustic effect, and records the response of M cycles, so a total of N×M A-scan signals need to be recorded; after the photoacoustic response of M cycles at a lateral point is collected, the scanning galvanometer of the sample arm is triggered to move one step on the X-axis to realize the recording of the periodic photoacoustic response of the next lateral point until a B-scan is completed; after the scanning galvanometer X-axis completes the B-scan, the scanning galvanometer Y-axis is triggered to move one step to realize the scanning of the next B-scan, and the two-dimensional scanning of the entire scanning area is completed, so as to achieve the purpose of realizing three-dimensional imaging.

[0059] The all-optical photoacoustic viscoelastic imaging device of this embodiment is designed with high-resolution and deep imaging modes adapted to the anterior and posterior segments of the eye in response to the imaging requirements of different eye regions. The anterior segment mode achieves high-resolution imaging at the cellular level through a high-power objective lens, and is mainly used to detect the biomechanical properties of local lesions; the posterior segment mode improves the detection sensitivity and imaging depth of the photoacoustic signal through the application of Bessel beams, and is suitable for deep detection of thick scleral tissue; these designs ensure the imaging requirements of the device at different detection depths, greatly expanding the application scope of the photoacoustic viscoelastic imaging technology.

[0060] Furthermore, in this embodiment, the optical path is modified to adapt to the anterior segment and posterior segment scleral viscoelastic imaging modes, the anterior segment high-resolution viscoelastic imaging mode, such as Figure 3As shown in the figure, like the optical resolution photoacoustic microscope, the anterior segment high-resolution photoacoustic viscoelastic imaging probe is composed of a high-power objective lens and focuses the excitation light and the detection light beam. It is mainly used for high-resolution imaging detection of local lesions such as anterior segment scleral biomechanics imaging, and is also used for in vitro and in vivo cell micromechanics imaging.

[0061] Further, deep imaging of the posterior segment of the eye using deep viscoelastic imaging mode, such as Figure 4 As shown in the figure, since the thickness of the sclera of the posterior segment of the eye can reach 1mm and the sclera is milky white, in order to further improve the sensitivity of photoacoustic signal detection, suppress background noise, increase the depth of photoacoustic imaging of the posterior segment of the eye, and meet the requirement that the excitation spot size must be kept consistent during photoacoustic viscosity and elastic separation, the following two schemes are used to achieve photoacoustic viscoelastic imaging of deep tissues.

[0062] 1) Solution 1: Use the Bessel beam generated by a conical lens pair to excite and receive photoacoustic signals. The Bessel beam is a beam with non-diffraction and self-healing properties. It can keep the beam size within a certain range without spreading on the propagation path. Therefore, it is widely used in optical imaging devices to reduce scattering distortion and improve imaging depth. Previous studies have proved that the Bessel beam can effectively improve the imaging depth. The specific implementation plan is: replace the scanning lens 9, the tube lens 10 and the second dichroic mirror 11 with two conical lens pairs to generate the Bessel beam.

[0063] 2) Solution 2: Use a spatial light modulator to generate non-diffraction light beams such as Bessel beams. The advantage of using spatial light modulation to generate non-diffraction light beams is that the phase template can be adjusted according to actual conditions to obtain a suitable non-diffraction light beam to meet the imaging detection requirements. The specific implementation plan is: insert a classical optical path of a reflective spatial light modulator between the first dichroic mirror 7 and the scanning galvanometer 8, which is composed of a polarizer, a wave plate, a spatial light modulator, a lens and a pinhole, and is used to generate non-diffraction light beams such as Bessel beams, and remove the scanning lens 9, the tube lens 10 and the second dichroic mirror 11.

[0064] In summary, the present invention overcomes the limitations of traditional technologies in deep tissue imaging by integrating photoacoustic imaging with frequency domain coherent optical technology. Based on the viscoelastic ratio theoretical model of the Kelvin-Voigt model, Navier's equation, etc., the amplitude and phase relationship of the photoacoustic signal is analyzed to achieve multi-parameter quantitative imaging of the biomechanical properties, scattering and absorption structure information of the sclera tissue from the cellular level to the tissue level. By developing a high-resolution and deep-penetration mode photoacoustic viscoelastic imaging device suitable for the anterior and posterior segments of the eye, the accuracy and applicability of imaging are improved. At the same time, combined with experimental verification of animal models, the application potential of this technology in the research and diagnosis of eye diseases such as myopia and glaucoma has been significantly reflected, and it has broad clinical application prospects.

[0065] The above is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical solution and inventive concept of the present invention within the scope disclosed by the present invention, which shall fall within the protection scope of the present invention.

Claims

1. An all-optical photoacoustic viscoelastic imaging device for scleral biomechanics detection, characterized in that: It includes a photoacoustic signal excitation module, a photoacoustic signal detection module, a pupil positioning module and an imaging platform, wherein the photoacoustic signal detection module is respectively connected to the photoacoustic signal excitation module and the pupil positioning module, and the imaging platform is respectively connected to the photoacoustic signal excitation module, the photoacoustic signal detection module and the pupil positioning module; The photoacoustic signal detection module includes a detection light source assembly, a reference arm, a sample arm and a spectrometer. The detection light source assembly generates two detection lights. One detection light enters the reference arm and is reflected by the reference arm to the spectrometer. The other detection light is combined with the excitation light generated by the photoacoustic signal excitation module and enters the sample arm to obtain sample information.

2. The all-optical photoacoustic viscoelastic imaging device according to claim 1, characterized in that: The detection light source assembly includes a broadband superluminescent diode light source, an isolator and a fiber coupler, the reference arm includes a first lens and a reflector, and the sample arm includes a second lens, a first dichroic mirror, a scanning galvanometer, a scanning lens, a tube lens, a second dichroic mirror and a first objective lens; The broadband superluminescent diode light source enters the optical fiber coupler through the isolator and is divided into two detection lights. One detection light is reflected to the spectrometer after passing through the first lens and the reflector, and the other detection light is combined with the excitation light generated by the photoacoustic signal excitation module through the second lens and the first dichroic mirror, and then is used to detect the sample through the scanning galvanometer, the scanning lens, the tube mirror, the second dichroic mirror, and the first objective lens to obtain the information of the sample.

3. The all-optical photoacoustic viscoelastic imaging device according to claim 1, characterized in that: The spectrometer includes a first collimating lens, a grating, a third lens and a charge-coupled device. The reflected light in the reference arm and the sample arm converges in the fiber coupler. The optical path difference between the reference arm and the sample arm generates an interference signal within a coherent length, which enters the charge-coupled device through the first collimating lens, the grating and the third lens. The charge-coupled device transmits the detection light information to the imaging platform.

4. The all-optical photoacoustic viscoelastic imaging device according to claim 1, characterized in that: The photoacoustic signal excitation module includes an excitation light source assembly, a second objective lens, a second collimating lens, a first beam splitter and a photodetector. The excitation light generated by the excitation light source assembly is divided into two paths through the second objective lens, the second collimating lens and the first beam splitter. One path of excitation light is received by the photodetector and transmitted to the imaging platform, and the other path of excitation light is combined with the detection light generated by the detection light source assembly and enters the sample arm to excite the sample to generate a photoacoustic response signal.

5. The all-optical photoacoustic viscoelastic imaging device according to claim 4, characterized in that: The excitation light source assembly includes a laser, an electro-optic modulator and a spatial filter. The laser is periodically modulated by the electro-optic modulator to excite the sample to generate a periodic photoacoustic response. The spatial filter is used to filter stray light in the photoacoustic signal modulated by the electro-optic modulator.

6. The all-optical photoacoustic viscoelastic imaging device according to claim 1, characterized in that: The pupil positioning module includes an LED light source, a second beam splitter, a fourth lens, a fifth lens and a camera. The visible light beam of the LED light source passes through the second beam splitter and coaxially illuminates the pupil via the fourth lens. The second beam splitter reflects the illuminated pupil image reflected back by the second dichroic mirror and reaches the camera via the fifth lens.

7. The all-optical photoacoustic viscoelastic imaging device according to any one of claims 1 to 6, characterized in that: The imaging platform includes a computer and a field programmable gate array; The computer is respectively connected to the photodetector of the photoacoustic signal excitation module, the charge coupled device of the spectrometer in the photoacoustic signal detection module, the camera of the pupil positioning module, and the field programmable gate array, and is used to generate a trigger signal of the field programmable gate array in response to the demand; The field programmable gate array is respectively connected to the excitation light source assembly of the photoacoustic signal excitation module, the scanning galvanometer of the sample arm in the photoacoustic signal detection module, and the charge coupled device of the spectrometer, and is used to control the excitation light source assembly, the scanning galvanometer and the charge coupled device.

8. An all-optical photoacoustic viscoelastic imaging method, implemented based on the all-optical photoacoustic viscoelastic imaging device according to any one of claims 1 to 8, characterized in that: The method comprises: In the excitation light source component of the photoacoustic signal excitation module, the laser is modulated by an electro-optic modulator, and the reference trigger signal output by the electro-optic modulator is used as a synchronization signal of the excitation light; The rising edge of the reference trigger signal is used to trigger the acquisition card of the photoacoustic signal detection module, generating N A-lines signals to trigger the charge coupled device of the spectrometer to record a periodic photoacoustic effect, record the response of M periods, and record N×M A-scan signals in total; After M periods of photoacoustic response are collected at a transverse point, the scanning galvanometer of the sample arm is triggered to move one step along the X axis to record the periodic photoacoustic response of the next transverse point until a B-scan is completed; After the scanning galvanometer X-axis completes the B-scan, it triggers the scanning galvanometer Y-axis to move one step to achieve the next B-scan, completing the two-dimensional scan of the entire scanning area to achieve three-dimensional imaging.

9. The all-optical photoacoustic viscoelastic imaging method according to claim 8, characterized in that: The method further comprises: In the sample arm of the photoacoustic signal detection module, the scanning lens, the tube lens and the second dichroic mirror are replaced by two conical lens pairs for generating Bessel beams to achieve photoacoustic viscoelastic imaging of deep tissues.

10. The all-optical photoacoustic viscoelastic imaging method according to claim 8, characterized in that: The method further comprises: In the sample arm of the photoacoustic signal detection module, the optical path of the reflective spatial light modulator is inserted between the first dichroic mirror and the scanning galvanometer, and the scanning lens, the tube mirror and the second dichroic mirror are removed to generate a non-diffracted light beam to achieve photoacoustic viscoelastic imaging of deep tissues.

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