All-optical photoacoustic viscoelastic imaging apparatus and method for sclera biomechanical testing

Abstract

The application discloses a kind of full-optical photoacoustic viscoelastic imaging device and method for sclera biomechanics detection, the device includes photoacoustic signal excitation module, photoacoustic signal detection module, pupil positioning module and imaging platform, photoacoustic signal detection module is connected with photoacoustic signal excitation module, pupil positioning module respectively, imaging platform is connected with photoacoustic signal excitation module, photoacoustic signal detection module, pupil positioning module respectively;Photoacoustic signal detection module includes detection light source assembly, reference arm, sample arm and spectrometer, detection light source assembly generates two detection lights, one enters reference arm, is reflected to spectrometer by reference arm, another road and the excitation light of photoacoustic signal excitation module combined beam enters sample arm, to obtain the information of sample.The application breaks through the limitation of traditional photoacoustic imaging, especially when detecting deep tissue, can extract viscoelastic information from cell level to tissue level, realize the accurate measurement of sclera biomechanics information.

Description

TECHNICAL FIELD

[0001] The present application relates to a full-optical photoacoustic viscoelastic imaging device and method for sclera biomechanical detection, belonging to the technical field of photoacoustic imaging. BACKGROUND

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

[0003] In recent years, the incidence of myopia has been rapidly increasing, and it is estimated that nearly half of the global population will be myopic by 2050, of which nearly 10% will be high myopia. The main cause of myopia is the increase in axial length, which is closely related to the thinning and expansion of the scleral tissue. As myopia progresses, the collagen fibers in the sclera become smaller and disordered, leading to changes in mechanical properties, which reduces the strength of the sclera and causes deformation, further leading to axial length growth and changes in vision. Glaucoma is also an eye disease closely related to the biomechanical properties of the sclera, usually associated with increased intraocular pressure. Long-term high intraocular pressure can cause damage to the optic nerve, which can lead to gradual loss of vision. The sclera, as the main tissue bearing the intraocular pressure, its biomechanical properties have a significant impact on the optic nerve. In the case of high intraocular pressure, the shape of the sclera, especially the posterior region, changes, and the connective tissue between the sclera and the optic nerve head is squeezed, leading to axon dysfunction or even death.

[0004] Changes in the mechanical properties of the sclera are closely related to the development of eye diseases such as myopia and glaucoma. Studies have shown that the biomechanical properties of the sclera have become an important biomarker for predicting and diagnosing these diseases. Current research methods include in vitro and in vivo measurements. In vitro measurement methods such as stretch band experiments, inflation experiments, and indentation experiments, although they can reflect the mechanical properties of the sclera, have errors due to changes in the eyeball environment, and are only used for in vitro experiments, which cannot be measured in vivo. Optical coherence tomography (OCT) and ultrasonic elastography have made some progress in scleral mechanical measurement, but the accuracy of these methods needs to be further verified, and there are limitations in imaging depth and spatial resolution. In addition, most of the elastic imaging methods are based on the linear elastic model, ignoring the viscous properties of the sclera as a viscoelastic material, while the changes in viscosity are crucial for disease development.

[0005] Photoacoustic imaging technology is an emerging biomedical imaging method, which combines the high contrast of optical imaging and the high penetration depth of ultrasonic 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, providing new tools for the diagnosis and treatment of clinical eye diseases. Photoacoustic viscoelastic imaging technology is a new technology based on photoacoustic imaging, which can reveal the biomechanical properties of biological tissues and has important significance in disease diagnosis.

[0006] Researchers at home and abroad have also made many progress 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, the lack of depth information, the inability to achieve high-resolution viscoelastic imaging, and the fact that most methods only consider the elasticity of the tissue and ignore the viscosity, and cannot be measured simultaneously. SUMMARY

[0007] The purpose of the present application is to solve the above-mentioned shortcomings of the prior art, and to provide a full-optical photoacoustic viscoelastic imaging device for sclera biomechanics detection. The device uses frequency domain coherent optical technology as a method for detecting photoacoustic signals, breaking through the limitation that traditional photoacoustic signals cannot obtain the true amplitude and phase information of deep tissues due to the influence of the transmission path, and realizing the quantitative imaging of multiple parameters of the biomechanical properties, scattering and absorption structure information of the sclera tissue. The qualitative and quantitative relationship between photoacoustic viscoelastic information and the sclera at the cellular and tissue levels is elucidated, which helps to better understand and diagnose the changes in the mechanical properties of the sclera in the development process of myopia, glaucoma and other eye diseases.

[0008] Another purpose of the present application is to provide a full-optical photoacoustic viscoelastic imaging method.

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

[0010] A full-optical photoacoustic viscoelastic imaging device for sclera biomechanics detection, comprising a photoacoustic signal excitation module, a photoacoustic signal detection module, a pupil positioning module and an imaging platform, the photoacoustic signal detection module is connected with the photoacoustic signal excitation module and the pupil positioning module respectively, and the imaging platform is connected with the photoacoustic signal excitation module, the photoacoustic signal detection module and the pupil positioning module respectively.

[0011] The photoacoustic signal detection module comprises 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 the information of the sample.

[0012] Further, the probe light source assembly comprises a broadband superluminescent diode light source, an isolator and a fiber coupler, the reference arm comprises a first lens and a mirror, and the sample arm comprises a second lens, a first dichroic mirror, a scanning galvanometer, a scanning lens, a cylindrical lens, a second dichroic mirror and a first objective lens.

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

[0014] Further, the spectrometer comprises 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 of the reference arm and the sample arm occurs within a coherence length to generate an interference signal, which enters the charge coupled device through the first collimating lens, the grating and the third lens, and the charge coupled device transmits the probe light information to the imaging platform.

[0015] Further, the photoacoustic signal excitation module comprises 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 of which is received by the photodetector and transmitted to the imaging platform, and the other of which is combined with the probe light generated by the probe light source assembly and then enters the sample arm to excite the sample to generate a photoacoustic response signal.

[0016] Further, the excitation light source assembly comprises 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, and the spatial filter is used to filter stray light in the photoacoustic signal after the modulation of the electro-optic modulator.

[0017] Further, the pupil positioning module comprises 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 illuminates the pupil coaxially through the fourth lens, and the image of the illuminated pupil reflected by the second dichroic mirror reaches the camera through the fifth lens.

[0018] Further, the imaging platform comprises a computer and a field programmable gate array.

[0019] The computer is connected with the photoelectric detector 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 respectively, and is used for generating a trigger signal of the field programmable gate array in response to a requirement.

[0020] The field programmable gate array is connected with 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 respectively, and is used for controlling the excitation light source assembly, the scanning galvanometer and the charge coupled device.

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

[0022] A full-optical photoacoustic viscoelastic imaging method is realized based on the full-optical photoacoustic viscoelastic imaging device, and the method comprises the following steps:

[0023] In the excitation light source assembly of the photoacoustic signal excitation module, the laser is modulated through an electro-optic modulator, and a 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 triggers the acquisition card of the photoacoustic signal detection module to generate N A-lines signals, and the charge coupled device of the spectrometer is triggered to record a periodic photoacoustic effect, and the response of M cycles is recorded, and a total of N*M A-scan signals are recorded.

[0025] After the photoacoustic response of M cycles at a transverse point is collected, the scanning galvanometer X axis of the sample arm is triggered to move one step, so that the recording of the periodic photoacoustic response of the next transverse point is realized, and until a B-scan is completed.

[0026] After the scanning galvanometer X axis completes the B-scan, the scanning galvanometer Y axis is triggered to move one step, so that the next B-scan is scanned, and two-dimensional scanning of the entire scanning area is completed, so as to realize three-dimensional imaging.

[0027] Further, the method further comprises:

[0028] In the sample arm of the photoacoustic signal detection module, the scanning lens, the cylindrical lens and the second dichroic mirror are replaced by two pairs of conical lenses, which are used to generate a Bessel beam to realize photoacoustic viscoelastic imaging of deep tissues.

[0029] Further, 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 cylindrical lens and the second dichroic mirror are removed, which are used to generate a non-diffractive beam to realize photoacoustic viscoelastic imaging of deep tissues.

[0031] The present application has the following beneficial effects relative to the prior art:

[0032] 1、The present application can solve the problem of no depth information and low spatial resolution in current photoacoustic viscoelastic imaging, by improving the current photoacoustic viscoelastic model and proposing a method for separating photoacoustic viscosity and elasticity information, the viscosity and elasticity parameters can be effectively separated, and the mechanical properties of the tissue can be accurately reflected. Through the innovation of imaging principle, the full-optical multi-modal photoacoustic imaging technology integrating photoacoustic viscoelasticity, absorption and scattering structural information is ingeniously constructed, and the absorption, scattering and viscoelastic information of the tissue can be obtained through one scan, and the imaging detection of tissue structure and function is realized.

[0033] 2、The present application aims at the insufficient detection means and incomplete mechanical information of the sclera biomechanics, only elastic information is obtained, and the viscosity information is lacked, the full-optical photoacoustic viscoelastic imaging technology is applied to the precise measurement of sclera biomechanics, the multi-parameter quantitative imaging of the sclera tissue biomechanics, scattering and absorption structural information is realized, and the mechanical property changes of myopia, glaucoma and other eye diseases are detected, so that a new technical method with clinical application prospect is provided for the sclera biomechanics detection.

[0034] 3、The present application realizes the extraction of viscoelastic information from the cell level to the tissue level by designing a photoacoustic viscoelastic imaging device suitable for the anterior segment and the posterior segment of the eye, and the photoacoustic viscoelastic imaging suitable for the anterior segment and the posterior segment of the eye is developed, a high-resolution mode and a high-depth viscoelastic imaging mode are developed for cell level and tissue level detection respectively, and the needs of different detection depths are met. The device includes photoacoustic signal excitation, collection, imaging scanning, pupil positioning and other modules, and the imaging speed of the device is improved through FPGA programming.

[0035] 4、The present application verifies the accuracy and safety of photoacoustic viscoelastic imaging in ex vivo samples and live animal models, summarizes the biomechanical characteristics of normal and pathological sclera, compares the changes of sclera mechanical properties in myopia and glaucoma models, and establishes a sclera function evaluation system. By studying the pathology, structure and biomechanical changes of pathological sclera, a characteristic change database is established, which provides an important reference for early diagnosis of diseases. DETAILED DESCRIPTION

[0036] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor based on the drawings shown.

[0037] Figure 1 It is a full-optical photoacoustic viscoelastic imaging device structure schematic diagram of the embodiment 1 of the present application.

[0038] Figure 2 It is a timing diagram of the control signal of the embodiment 1 of the present application.

[0039] Figure 3 It is a detection schematic diagram of the anterior segment sclera viscoelastic imaging mode of the embodiment 1 of the present application.

[0040] Figure 4 It is a detection schematic diagram of the posterior segment sclera viscoelastic imaging mode of the embodiment 1 of the present application.

[0041] Wherein, 1-wideband superluminescent diode light source, 2-isolator, 3-fiber coupler, 4-first lens, 5-mirror, 6-second lens, 7-first dichroic mirror, 8-scanning galvanometer, 9-scanning lens, 10-barrel 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-space filter, 23-second objective lens, 24-collimating lens, 25-first beam splitter, 26-photoelectric detector, 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 scheme and advantages of the embodiments of the present application more clear, the technical scheme in the embodiments of the present application will be described clearly and completely below in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the present application.

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

[0044] The description of the embodiments should be understood in conjunction with the accompanying drawings. The embodiments are only used to illustrate specific ways in which the present invention can be implemented and do not constitute a limitation on the present invention. The directional terms mentioned in the present invention, such as "up," "down," "front," "back," "left," "right," "inner," "outer," and "side," are only for reference to the accompanying drawings. Therefore, the directional terms used are for the purpose of explaining and understanding the present invention, and not for limiting the present invention.

[0045] Example 1:

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

[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 beams. One detection beam enters the reference arm and is reflected by the reference arm to the spectrometer. The other detection beam is combined with the excitation beam generated by the photoacoustic signal excitation module and then enters the sample arm to obtain information about the sample.

[0048] Furthermore, the detection light source assembly includes a broadband super-luminescent diode (SLD) light source 1, an isolator 2, and an optical 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 super-luminescent diode light source 1 enters the optical fiber coupler 3 through the isolator 2 and is split into two detection beams. One detection beam is reflected to the spectrometer after passing through the first lens 4 and the reflector 5. The other detection beam passes through the second lens 6 and is combined with the excitation light generated by the photoacoustic signal excitation module at the first dichroic mirror 7. Then, it 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 and obtain sample information.

[0049] Further, the spectrometer comprises 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 of the reference arm and the sample arm interferes within a coherence length to generate an interference signal, which enters the charge coupled device 17 through the first collimating lens 14, the grating 15 and the third lens 16, and the charge coupled device 17 transmits the detected light information to the imaging platform.

[0050] Further, the photoacoustic signal excitation module comprises 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 split into two paths by the second objective lens 23, the second collimating lens 24 and the first beam splitter 25, one path of the excitation light is received by the photodetector 26 and transmitted to the imaging platform, and the other path of the excitation light is combined with the probe light generated by the probe light source assembly and then enters the sample arm to excite the sample to generate a photoacoustic response signal.

[0051] Further, the excitation light source assembly comprises 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 periodic photoacoustic response of the absorbing body (i.e. the sample to be detected), the phase-sensitive frequency domain optical coherence tomography system (i.e. the photoacoustic signal detection module) is used to detect the periodic photoacoustic response to obtain the amplitude and phase information of the photoacoustic signal in the deep tissue, and the spatial filter 22 is used to filter unnecessary stray light in the photoacoustic signal modulated by the electro-optic modulator to ensure the quality of the photoacoustic signal.

[0052] Further, the pupil positioning module is mainly used for positioning the pupil during the photoacoustic viscoelastic imaging of the posterior segment of the eye, and comprises 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 illuminates the pupil coaxially through the fourth lens 29, and the illuminated pupil image reflected by the second dichroic mirror 11 is reflected by the second beam splitter 28 and reaches the camera 31 through the fifth lens 30.

[0053] Further, the imaging platform comprises a computer 18 and a filed programmable gate array (FPGA) 19; the computer 18 is connected with the photoelectric detector 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 FPGA 19 respectively, and is used for generating a trigger signal of the FPGA 19 in response to a requirement; the FPGA 19 is connected with 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 respectively, and is used for controlling the laser 20, the electro-optic modulator 21, the scanning galvanometer 8 and the charge coupled device 17.

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

[0055] The full-optical photoacoustic viscoelastic imaging device of the embodiment improves a photoacoustic viscoelastic ratio model, deeply studies the mechanical response of a viscoelastic substance 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 the strain has the same frequency of change as the stress, but has a phase delay relative to the stress, and the phase delay is directly related to the viscoelasticity of the medium. Under the condition that the frequency is constant, the phase delay of different biological tissues is different, and the viscoelastic ratio image reflecting the mechanical properties can be obtained by scanning the sample, the quantitative relationship between the viscoelastic ratio and the phase delay is revealed, and the accurate evaluation of the mechanical properties of different biological tissues is ensured.

[0056] The full-optical photoacoustic viscoelastic imaging device of the embodiment proposes a model for separating photoacoustic viscosity and elasticity, combines the photoacoustic field described based on the Navier’s equation with the wave equation, and expresses the photoacoustic elasticity by analyzing the displacement field of the photoacoustic wave in the longitudinal wave and transverse wave modes according to the rising time required from the displacement zero point to the maximum vibration displacement. According to the quantitative relationship between the viscoelastic ratio and the phase delay, the viscosity and elasticity information of the tissue is decomposed, the shortcomings of the existing photoacoustic imaging technology in separating the viscosity and elasticity information are overcome, and the measurement accuracy of the mechanical properties of biological tissues is significantly improved.

[0057] The full-optical photoacoustic viscoelastic imaging device of the embodiment can detect the amplitude and phase information of the photoacoustic signal of deep tissue with high sensitivity by adopting the frequency domain optical coherence tomography technology, 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 the photoacoustic responses and extract the amplitude and phase information of the photoacoustic signal of deep tissue, thereby ensuring accurate measurement of the biomechanical properties of the sclera.

[0058] The full-optical photoacoustic viscoelastic imaging device of the embodiment ensures synchronization of the photoacoustic signal excitation module and the photoacoustic signal detection module and accurate detection of the photoacoustic response process, realizes timing logic control of excitation and acquisition, as shown in Figure 2 After the device is started, the excitation light source assembly of the photoacoustic signal excitation module is modulated by the electro-optical modulator, and since there is only a fixed time delay between the reference trigger signal output by the electro-optical modulator and the light 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 rising edge of the reference trigger signal triggers the acquisition card of the photoacoustic signal detection module to generate N A-line signals, which trigger the charge-coupled device of the spectrometer to record a periodic photoacoustic effect, and M cycles of response are recorded, so that a total of N*M A-scan signals need to be recorded. After M cycles of photoacoustic response of a lateral point are collected, the scanning galvanometer X axis of the sample arm is triggered to move one step 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, complete the two-dimensional scanning of the entire scanning area, and achieve the purpose of three-dimensional imaging.

[0059] The full-optical photoacoustic viscoelastic imaging device of the embodiment designs high-resolution and deep imaging modes suitable for the anterior segment and the posterior segment of the eye according to the imaging requirements of different eye regions. The anterior segment mode realizes high-resolution imaging at the cellular level through a high-power objective lens and is mainly used for detecting 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 and greatly expand the application range of the photoacoustic viscoelastic imaging technology.

[0060] Further, 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, as shown in Figure 3As shown, like the optical resolution photoacoustic microscope, the high-resolution photoacoustic viscoelastic imaging probe of the anterior segment of the eye is composed of a high-power objective lens, and focuses the excitation light and the detection beam, and is mainly used for high-resolution imaging detection of local lesions such as sclera biomechanical imaging of the anterior segment of the eye, and is also used for ex vivo and in vivo cell micromechanics imaging.

[0061] Further, a deep imaging depth viscoelastic imaging mode of the posterior segment of the eye is as shown in the figure. Figure 4 As shown, because the sclera of the posterior segment of the eye can be up to 1 mm thick, and the sclera is milky white, in order to further improve the photoacoustic signal detection sensitivity, suppress the background noise, improve the photoacoustic imaging depth of the posterior segment of the eye, and meet the requirement that the excitation light spot size needs to be consistent in the photoacoustic viscosity and elasticity separation process, the following two schemes are adopted to realize the photoacoustic viscoelastic imaging of deep tissues.

[0062] 1) Scheme one: a cone lens pair is used to generate a Bessel beam to excite and receive photoacoustic signals, the Bessel beam is a kind of beam with non-diffraction and self-healing characteristics, and can keep the beam size within a certain range without spreading on the propagation path, so it is widely used in optical imaging devices to reduce scattering distortion, can improve the imaging depth, and the previous research has proved that the Bessel beam can effectively improve the imaging depth; the specific implementation scheme is: the scanning lens 9, the barrel lens 10 and the second dichroic mirror 11 are replaced by two cone lens pairs for generating a Bessel beam.

[0063] 2) Scheme two: a Bessel beam and other non-diffraction beams are generated by using a spatial light modulator, the advantage of generating non-diffraction beams by the spatial light modulation is that the phase template can be adjusted according to the actual situation, so that a suitable non-diffraction beam is obtained to meet the imaging detection requirement; the specific implementation scheme is: a reflective spatial light modulator is inserted into the classical optical path 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, for generating a Bessel beam and other non-diffraction beams, and the scanning lens 9, the barrel lens 10 and the second dichroic mirror 11 are removed.

[0064] In summary, the present application overcomes the limitations of traditional technology in deep tissue imaging by integrating photoacoustic imaging and frequency domain coherent optical technology, based on the viscoelasticity ratio theoretical model of the Kelvin-Voigt model, Navier's equation and the like, the amplitude and phase relationship of the photoacoustic signal is analyzed, the multi-parameter quantitative imaging of the biomechanical properties, scattering and absorption structure information of the sclera tissue from the cell level to the tissue level is realized, through the development of a high-resolution and deep penetration mode photoacoustic viscoelastic imaging device suitable for the anterior segment and the posterior segment of the eye, the imaging accuracy and applicability are improved; at the same time, combined with the experimental verification of the animal model, the application potential of the technology in the research and diagnosis of myopia, glaucoma and other eye diseases is significantly embodied, and has a broad clinical application prospect.

[0065] The above merely describes preferred embodiments of the present application, but the protection scope of the present application is not limited thereto, and any person skilled in the art, within the scope disclosed by the present application, can make equivalent replacements or changes according to the technical scheme and inventive concept of the present application, and all of them shall fall within the protection scope of the present application.

Claims

1. A full-optical photoacoustic viscoelastic imaging device for sclera biomechanical detection, characterized in that, The application relates to a photoacoustic signal detection device, which comprises a photoacoustic signal excitation module, a photoacoustic signal detection module, a pupil positioning module and an imaging platform. The photoacoustic signal detection module comprises a detection light source assembly, a reference arm, a sample arm and a spectrometer; the detection light source assembly generates two detection light beams; one detection light beam enters the reference arm and is reflected by the reference arm to the spectrometer; the other detection light beam is combined with the excitation light generated by the photoacoustic signal excitation module and then enters the sample arm to obtain sample information. The detection light source assembly comprises a broadband superluminescent diode light source, an isolator and a fiber coupler; the reference arm comprises a first lens and a mirror; and the sample arm comprises a second lens, a first dichroic mirror, a scanning galvanometer, a scanning lens, a cylindrical lens, a second dichroic mirror and a first objective lens. The broadband superluminescent diode light source enters the fiber coupler through the isolator and is divided into two detection light beams; one detection light beam is reflected by the first lens and the mirror to the spectrometer; the other detection light beam is combined with the excitation light generated by the photoacoustic signal excitation module at the first dichroic mirror, and then passes through the scanning galvanometer, the scanning lens, the cylindrical lens, the second dichroic mirror and the first objective lens to detect the sample and obtain sample information. The spectrometer comprises 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 interference signals within a coherence length; the interference signals pass through the first collimating lens, the grating and the third lens to enter the charge coupled device; and the charge coupled device transmits the detection light information to the imaging platform. In the sample arm of the photoacoustic signal detection module, the scanning lens, the cylindrical lens and the second dichroic mirror are replaced by two pairs of tapered lenses to generate Bessel beams, so as to realize photoacoustic viscoelastic imaging of deep tissues; or in the sample arm of the photoacoustic signal detection module, a reflective spatial light modulator is inserted into the light path between the first dichroic mirror and the scanning galvanometer, and the scanning lens, the cylindrical lens and the second dichroic mirror are removed, so as to generate non-diffracted beams to realize photoacoustic viscoelastic imaging of deep tissues.

2. The all-optical photoacoustic viscoelasticity imaging apparatus of claim 1, wherein, The photoacoustic signal excitation module comprises 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 passes through the second objective lens, the second collimating lens and the first beam splitter and is divided into two excitation light beams; one excitation light beam is received by the photodetector and transmitted to the imaging platform; and the other excitation light beam is combined with the detection light generated by the detection light source assembly and then enters the sample arm to excite the sample to generate photoacoustic response signals.

3. The all-optical photoacoustic viscoelasticity imaging apparatus according to claim 2, characterized by, The excitation light source assembly comprises 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 periodic photoacoustic responses; and the spatial filter is used for filtering stray light in the photoacoustic signals modulated by the electro-optic modulator.

4. The all-optical photoacoustic viscoelasticity imaging apparatus of claim 1, wherein, The pupil positioning module comprises an LED light source, a second beam splitter, a fourth lens, a fifth lens and a camera, a visible light beam of the LED light source passes through the second beam splitter and coaxially illuminates the pupil through the fourth lens, the second beam splitter reflects the illuminated pupil image reflected by the second dichroic mirror to the camera through the fifth lens.

5. The all-optical photoacoustic viscoelasticity imaging apparatus according to any one of claims 1 to 4, characterized by, The imaging platform comprises a computer and a field programmable gate array; The computer is connected with 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 respectively, and is used for generating a trigger signal responding to the field programmable gate array; The field programmable gate array is connected with 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 respectively, and is used for controlling the excitation light source assembly, the scanning galvanometer and the charge coupled device.

6. An all-optical photoacoustic viscoelastic imaging method, implemented based on the all-optical photoacoustic viscoelastic imaging device of any one of claims 1-5, characterized in that, The method comprises: In the excitation light source assembly of the photoacoustic signal excitation module, a laser is modulated by an electro-optical modulator, and a reference trigger signal output by the electro-optical modulator is used as a synchronization signal of excitation light; A rising edge of the reference trigger signal triggers an acquisition card of the photoacoustic signal detection module to generate N A-line signals, and a charge coupled device of the spectrometer is triggered to record a periodic photoacoustic effect, and M cycles of responses are recorded, and a total of NXM A-scan signals are recorded; After M cycles of photoacoustic responses of a transverse point are collected, the scanning galvanometer X axis is triggered to move one step, and the recording of periodic photoacoustic responses of the next transverse point is realized, 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, and the scanning of the next B-scan is realized, and two-dimensional scanning of the entire scanning area is completed to realize three-dimensional imaging.

7. The all-optical photoacoustic viscoelasticity imaging method of claim 6, wherein, The method further comprises: In the sample arm of the photoacoustic signal detection module, two pairs of conical lenses are used to replace the scanning lens, the cylindrical lens and the second dichroic mirror to generate a Bessel beam, so as to realize photoacoustic viscoelastic imaging of deep tissues.

8. The all-optical photoacoustic viscoelasticity imaging method of claim 6, wherein, The method further comprises: In the sample arm of the photoacoustic signal detection module, a reflective spatial light modulator is inserted into the optical path between the first dichroic mirror and the scanning galvanometer, and the scanning lens, the cylindrical lens and the second dichroic mirror are removed, and a non-diffracted beam is generated to realize photoacoustic viscoelastic imaging of deep tissues.

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