Handheld multispectral photoacoustic imaging device and method for dry eye detection

Abstract

The invention discloses a handheld multispectral photoacoustic imaging device and method for dry eye detection. The device comprises a multispectral photoacoustic signal excitation module, an MEMS scanning imaging module and a data acquisition and control module, the multispectral photoacoustic signal excitation module is used for generating three laser beams with different wavelengths, and the three laser beams are coupled to enter the transmission optical fiber; the MEMS scanning imaging module is used for reflecting the laser of the transmission optical fiber, realizing optical scanning and excitation of a to-be-detected sample and converting a photoacoustic signal into an electric signal; and the data acquisition and control module is used for preprocessing the electric signal, performing analog-to-digital conversion on the preprocessed electric signal to form a digital signal, and synchronously controlling the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module. According to the invention, a'multi-modal imaging-multi-parameter evaluation 'system integrating structure, function and mechanical information is constructed, and support is provided for early diagnosis, typing evaluation and pathological mechanism research of xerophthalmia.

Description

Technical Field

[0001] This invention relates to a handheld multispectral photoacoustic imaging device and method for dry eye detection, belonging to the field of medical imaging technology. Background Technology

[0002] In recent years, with the widespread use of electronic products such as computers and mobile phones, people are spending increasingly more time using these devices. This leads to increased exposure of the eyes to blue light from screens, reduced blinking, and various environmental factors, resulting in a continuous increase in the number of people suffering from dry eye syndrome. Statistics show that approximately 30% of the world's population aged 50 and above suffers from dry eye syndrome, and the age of patients is trending younger, drawing significant attention.

[0003] Dry eye syndrome, a common ocular surface disease, can cause multidimensional pathophysiological changes in ocular surface tissues, mainly in the following aspects: 1) Dry eye syndrome promotes morphological changes in the palpebral conjunctival vascular network. Changes in conjunctival vascular structure are usually directly related to eye health problems. Studies have shown that the morphology (such as diameter and vascular density) and microcirculation (such as blood flow rate and velocity) of palpebral conjunctival vessels are altered in patients with dry eye syndrome. Therefore, the assessment of conjunctival microvessels and microcirculation may provide an indication of the chronic inflammatory state of dry eye and may be further developed into biomarkers for staging and treatment efficacy. 2) Dry eye syndrome causes abnormal fluctuations in blood oxygenation parameters in the palpebral conjunctival microcirculation. During the pathogenesis of dry eye syndrome, the ocular surface may become dry due to insufficient tear lubrication, leading to damage and inflammation of corneal epithelial cells. These changes may affect local oxygen supply, thereby exacerbating dry eye symptoms. This suggests that the assessment of blood oxygen saturation in the palpebral conjunctival vessels is helpful in detecting dry eye disease. 3) Meibomian gland dysfunction-type dry eye can cause pathological changes in the structure of the meibomian glands. Meibomian glands are the largest sebaceous glands in the human body, responsible for synthesizing and secreting key components of the tear film lipid layer. Meibomian gland dysfunction (MGD) manifests as meibomian gland duct obstruction or abnormal meibomian gland secretion, leading to the ocular surface's inability to maintain tear film stability, abnormally rapid tear evaporation, and increased tear osmotic pressure, resulting in dry eye disease. Typical signs of MGD mainly include meibomian gland openings, secretion characteristics, drainage capacity, and abnormal glandular structure. Therefore, analyzing the morphology of meibomian glands can provide important evidence for the diagnosis of dry eye disease; 4) In addition, patients with MGD-related dry eye syndrome exhibit significant changes in the biomechanical properties of the meibomian glands. In vivo confocal microscopy shows that MGD patients have increased inflammatory cells around the glands, aggravated fibrosis, leading to decreased glandular elasticity and increased rigidity. Therefore, assessing meibomian gland elasticity has important reference value for the diagnosis of dry eye.

[0004] Despite ongoing research into dry eye disease, clinical diagnosis still faces numerous challenges. Current mainstream detection methods include dry eye questionnaires, tear film stability testing, tear secretion testing, and ophthalmic imaging examinations. While these methods can detect dry eye to some extent, they still have significant limitations, primarily in the following aspects: First, questionnaires heavily rely on patients' subjective feelings, leading to biased results and failing to objectively reflect ocular pathological changes; second, tear film stability testing is insensitive to mild dry eye, requires precise operation, and is significantly affected by external factors; tear secretion testing (such as the Schirmer test) has poor repeatability; ophthalmic imaging examinations (such as laser corneal confocal microscopy) have limited imaging range and lack quantitative analysis software, and some methods (such as meibomian gland imaging) may not fully reflect the functional status of the meibomian glands.

[0005] Domestic and international researchers have made some progress in photoacoustic eye imaging, but mainly focused on improving and optimizing imaging technology. There has been no significant progress in clinical translation, such as the portability of imaging systems and the clinical problems they can solve. Summary of the Invention

[0006] The purpose of this invention is to address the shortcomings of the prior art by providing a handheld multispectral photoacoustic imaging device for dry eye detection. This device utilizes multispectral excitation and dynamic photoacoustic signal analysis to establish a multimodal analytical model of ocular surface vascular morphology, meibomian gland structure, and their functional parameters (including blood oxygen saturation, and biomechanical properties of blood vessels and glands). This achieves integrated and simultaneous extraction of structural imaging and functional parameters, overcoming the technical limitations of existing dry eye detection methods that separate structural and functional information and lack biomechanical assessment. It constructs a "multimodal imaging-multiparameter assessment" system that integrates structural, functional, and mechanical information, providing support for the early diagnosis, classification assessment, and pathological mechanism research of dry eye syndrome.

[0007] Another object of the present invention is to provide a multispectral photoacoustic imaging method based on the above-mentioned handheld multispectral photoacoustic imaging device.

[0008] The objective of this invention can be achieved by adopting the following technical solutions:

[0009] A handheld multispectral photoacoustic imaging device for dry eye detection includes a multispectral photoacoustic signal excitation module, a MEMS scanning imaging module, and a data acquisition and control module.

[0010] The multispectral photoacoustic signal excitation module includes a first laser signal excitation unit and a second laser signal excitation unit. The first laser signal excitation unit is used to generate a first specific wavelength laser, and the second laser signal excitation unit is used to generate a second specific wavelength laser and a third specific wavelength laser. The first specific wavelength laser, the second specific wavelength laser and the third specific wavelength laser are coupled into the transmission optical fiber.

[0011] The MEMS scanning imaging module is used to reflect the laser in the transmission fiber to realize optical scanning and excitation of the sample under test, and to convert the photoacoustic signal into an electrical signal.

[0012] The data acquisition and control module is used to preprocess the electrical signal, convert the preprocessed electrical signal into a digital signal by analog-to-digital conversion, and synchronously control the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

[0013] Furthermore, the first laser signal excitation unit includes a first pulsed laser, a first linear polarizer, a first half-wave plate, a first fiber coupler, a first polarization-maintaining fiber, a first collimating lens, a first bandpass filter, a first reflecting mirror, and a first dichroic mirror;

[0014] The laser output from the first pulsed laser passes through the first linear polarizer and the first half-wave plate for polarization control in sequence, is injected into the first polarization-maintaining fiber by the first fiber coupler, and generates a broadband laser spectrum through the nonlinear optical effect in the first polarization-maintaining fiber. After being collimated by the first collimating lens, the first specific wavelength is selected by the first bandpass filter and guided to the first dichroic mirror by the first reflecting mirror.

[0015] Furthermore, the second laser signal excitation unit includes a second pulsed laser, a beam splitter, a second dichroic mirror, a second reflector, a second linear polarizer, a second half-wave plate, a second fiber coupler, a second polarization-maintaining fiber, a second collimating lens, a second bandpass filter, a third reflector, and a third dichroic mirror.

[0016] The laser output from the second pulsed laser is split into two paths by a beam splitter. One path uses the center wavelength of the second pulsed laser as the second specific wavelength and is directly output to the second dichroic mirror as the fundamental frequency. The other path is reflected by the second mirror and then passes through the second linear polarizer and the second half-wave plate for polarization control. It is then injected into the second polarization-maintaining fiber by the second fiber coupler. A broadband laser spectrum is generated through the nonlinear optical effect in the second polarization-maintaining fiber. After being collimated by the second collimating mirror, the third specific wavelength is selected by the second bandpass filter and guided to the third dichroic mirror by the third mirror.

[0017] Furthermore, the MEMS scanning imaging module includes a third collimating lens, an objective lens, a MEMS micro-vibration mirror, and an ultrasonic transducer;

[0018] The laser beam transmitted through the optical fiber is collimated into a parallel beam by a third collimating lens. The parallel beam is focused by the objective lens and reflected by the MEMS micro-mirror to achieve two-dimensional scanning deflection. The beam is transmitted through a transparent ultrasonic transducer and focused on a predetermined target area of ​​the sample to be tested, thereby realizing optical scanning and excitation of the sample to be tested and converting the photoacoustic signal into an electrical signal.

[0019] Furthermore, the data acquisition and control module includes a data preprocessing unit, a data acquisition unit, and a synchronization control unit;

[0020] The data preprocessing unit is used to preprocess the electrical signals;

[0021] The data acquisition unit is used to perform analog-to-digital conversion on the preprocessed electrical signal to form a digital signal;

[0022] The synchronization control unit is used to receive the global trigger pulse signal sent by the data acquisition unit and synchronously control the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

[0023] Furthermore, the data preprocessing unit includes a signal amplifier, which performs amplitude amplification and signal-to-noise ratio optimization preprocessing on the electrical signal.

[0024] Furthermore, the data acquisition unit includes a data acquisition card and a computer. The data acquisition card performs analog-to-digital conversion on the preprocessed electrical signal to form a digital signal, and then uploads the digital signal to the computer.

[0025] Furthermore, the synchronization control unit includes a field-programmable gate array (FPGA), which receives a global trigger pulse signal sent by the data acquisition unit, activates the internally preset synchronization control logic, and synchronously controls the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module according to the preset timing sequence.

[0026] Another objective of this invention can be achieved by adopting the following technical solution:

[0027] A multispectral photoacoustic imaging method, implemented based on the aforementioned handheld multispectral photoacoustic imaging device, the method comprising:

[0028] In the first laser signal excitation unit, the laser output from the first pulsed laser passes through the first linear polarizer and the first half-wave plate in sequence for polarization control, is injected into the first polarization-maintaining fiber by the first fiber coupler, and generates a broadband laser spectrum through the nonlinear optical effect in the first polarization-maintaining fiber. After being collimated by the first collimating lens, the first specific wavelength is selected by the first bandpass filter and guided to the first dichroic mirror by the first reflecting mirror.

[0029] In the second laser signal excitation unit, the laser output from the second pulse laser is split into two paths by a beam splitter. One path is directly output to the second dichroic mirror as the fundamental frequency light, and the other path is reflected by the second mirror and then polarized by the second linear polarizer and the second half-wave plate. It is then injected into the second polarization-maintaining fiber by the second fiber coupler. A broadband laser spectrum is generated through the nonlinear optical effect in the second polarization-maintaining fiber. After being collimated by the second collimating mirror, the second specific wavelength is selected by the second bandpass filter and guided to the third dichroic mirror by the third mirror.

[0030] Through the spatial beam combining effect of the first, second, and third dichroic mirrors, the first specific wavelength laser, the second specific wavelength laser, and the third specific wavelength laser achieve coaxial output and couple into the transmission optical fiber.

[0031] In the MEMS scanning imaging module, the laser beam transmitted through the optical fiber is collimated into a parallel beam by the third collimating lens. The parallel beam is focused by the objective lens and reflected by the MEMS micro-mirror to achieve two-dimensional scanning deflection. The beam is transmitted through a transparent ultrasonic transducer and focused on the predetermined target area of ​​the sample to be tested, thereby realizing optical scanning and excitation of the sample to be tested and converting the photoacoustic signal into an electrical signal.

[0032] In the data acquisition and control module, the electrical signal is preprocessed, and the preprocessed electrical signal is converted from analog to digital to form a digital signal, which simultaneously controls the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

[0033] Furthermore, the synchronous control multispectral photoacoustic signal excitation module and the MEMS scanning imaging module include:

[0034] The system receives a global trigger pulse signal from the data acquisition unit, initiates a preset synchronization control logic, and generates and outputs three timing control signals according to a preset timing sequence. Two of these signals are used to drive the first and second pulse lasers to emit lasers at a specified frequency and pulse width, while the other signal is used to control the MEMS micromirror in the MEMS scanning imaging module to execute a preset scanning trajectory.

[0035] The present invention has the following advantages over the prior art:

[0036] 1. This invention achieves high-resolution imaging and simultaneous dual-modal detection of the three-dimensional structure of the meibomian gland in vivo: Utilizing photoacoustic imaging technology, this invention leverages its unique advantage of high-resolution three-dimensional tomographic imaging capabilities to achieve non-invasive, high-resolution imaging of the three-dimensional ductal structure of the meibomian gland in vivo. This overcomes the limitations of traditional methods that only provide two-dimensional morphological information, providing crucial three-dimensional spatial information support for comprehensively assessing the morphological structure and functional status of the meibomian gland. Furthermore, it simultaneously performs quantitative measurements of glandular tissue elasticity. This technology can sensitively capture key pathological features such as microscopic changes in glandular structure, abnormal lipid metabolism, and decreased tissue mechanical properties in the early stages before clinical symptoms fully manifest, providing important structural and functional evidence for the early screening and accurate diagnosis of dry eye syndrome.

[0037] 2. This invention adopts a handheld photoacoustic diagnostic paradigm that integrates "structure-function-mechanics", breaking through the limitations of existing dry eye diagnostic technologies that only provide single-dimensional information (such as meibomian gland photography which only shows structure and tear film detection which only assesses function). Through multi-modal fusion imaging, it simultaneously acquires gland morphology and structure (density of glandular branches), microcirculation blood oxygen (inflammatory markers), and tissue elasticity (degree of fibrosis), achieving a complete analysis of the etiology of dry eye.

[0038] 3. This invention overcomes the problem of high-precision imaging of deep tissues in portable devices by proposing a “MEMS-transparent sensor” coupling design. Specifically, it utilizes MEMS micromirrors to achieve micron-level precision scanning, breaking through the size limitations of traditional photoacoustic probes. It develops a transparent sensor to overcome the limitations of photoacoustic path separation in traditional probes, establishes an integrated coaxial light and sound path of “excitation-reception”, eliminates optical obstruction, and achieves blind-zone-free imaging of the entire eyelid layer (from the epidermis to the deep meibomian gland). Attached Figure Description

[0039] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0040] Figure 1 This is a schematic diagram of the handheld multispectral photoacoustic imaging device for dry eye detection according to Embodiment 1 of the present invention.

[0041] Figure 2 This is a schematic diagram of the handheld portion of the handheld multispectral photoacoustic imaging device for dry eye detection according to Embodiment 1 of the present invention.

[0042] Figure 3 This is an image showing the imaging result of Embodiment 2 of the present invention.

[0043] Among them, 1-first pulsed laser, 2-first linear polarizer, 3-first half-wave plate, 4-first fiber coupler, 5-first polarization-maintaining fiber, 6-first collimating lens, 7-first filter, 8-first reflecting mirror, 9-second pulsed laser, 10-beam splitter, 11-second dichroic mirror, 12-first dichroic mirror, 13-second reflecting mirror, 14-second linear polarizer, 15-second half-wave plate, 16-second fiber coupler, 17-second polarization-maintaining fiber, 18-second collimating lens, 19-second filter, 20-third reflecting mirror, 21-third dichroic mirror, 22-third fiber coupler, 23-third collimating lens, 24-objective lens, 25-MEMS micro-mirror, 26-field programmable gate array, 27-ultrasonic transducer, 28-signal amplifier, 29-data acquisition card, 30-computer, 31-sample to be tested. Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0045] It should be understood that, when used in this specification and the appended claims, the terms "comprising" and "including" indicate the presence of the described features, integrals, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

[0046] 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.

[0047] Example 1:

[0048] like Figure 1 As shown, this embodiment provides a handheld multispectral photoacoustic imaging device for dry eye detection. The device includes a multispectral photoacoustic signal excitation module, a MEMS scanning imaging module, and a data acquisition and control module. The specific descriptions of each module are as follows:

[0049] The multispectral photoacoustic signal excitation module can generate three laser beams of different wavelengths, which are combined and transmitted through optical fiber to achieve specific excitation of different absorption groups (such as lipids and hemoglobin) in meibomian glands and conjunctival blood vessels. It includes a first laser signal excitation unit and a second laser signal excitation unit. The first laser signal excitation unit is used to generate a first specific wavelength laser, and the second laser signal excitation unit is used to generate a second specific wavelength laser and a third specific wavelength laser. The multi-wavelength laser, including the first specific wavelength laser, the second specific wavelength laser, and the third specific wavelength laser, is coupled into the transmission optical fiber.

[0050] Furthermore, the first laser signal excitation unit includes a first pulsed laser 1, a first linear polarizer 2, a first half-wave plate 3, a first fiber coupler 4, a first polarization-maintaining fiber 5, a first collimating lens 6, a first bandpass filter 7, a first reflecting mirror 8, and a first dichroic mirror 12. The center wavelength of the first pulsed laser is 1064 nm, the center wavelength of the first bandpass filter 7 is 1220 nm, and the bandwidth is 50 nm. The laser output from the first pulsed laser 1 is polarized by passing through the first linear polarizer 2 and the first half-wave plate 3 in sequence, and is injected into the first polarization-maintaining fiber 5 by the first fiber coupler 4. The laser spectrum is generated by the nonlinear optical effect in the first polarization-maintaining fiber 5. After collimation by the first collimating lens 6, the first specific wavelength (i.e., 1220 nm) is selected by the first bandpass filter 7 and guided to the first dichroic mirror 12 by the first reflecting mirror 8.

[0051] Furthermore, the second laser signal excitation unit includes a second pulsed laser 9, a beam splitter 10, a second dichroic mirror 11, a second reflecting mirror 13, a second linear polarizer 14, a second half-wave plate 15, a second fiber coupler 16, a second polarization-maintaining fiber 17, a second collimating mirror 18, a second bandpass filter 19, a third reflecting mirror 20, and a third dichroic mirror 21. The center wavelength of the second pulsed laser is 532 nm, and the center wavelength of the second bandpass filter 19 is 580 nm with a bandwidth of 50 nm. The laser output from the second pulsed laser 9 is split into two paths by the beam splitter 10, one of which uses the center wavelength of the second pulsed laser 9 as the second specific wavelength (i.e., 532 nm). The light (nm) is directly output as the fundamental frequency to the second dichroic mirror 11. Another path is reflected by the second mirror 13 and then polarized by the second linear polarizer 14 and the second half-wave plate 15. It is then injected into the second polarization-maintaining fiber 17 by the second fiber coupler 16. The broadband laser spectrum is generated by the nonlinear optical effect in the second polarization-maintaining fiber 17. After being collimated by the second collimating mirror 18, the third specific wavelength (i.e., 580nm) is selected by the second bandpass filter 19 and guided to the third dichroic mirror 21 by the third mirror 20.

[0052] Furthermore, through the spatial beam combining effect of the first dichroic mirror 12, the second dichroic mirror 11, and the third dichroic mirror 21, the first specific wavelength laser, the second specific wavelength laser, and the third specific wavelength laser achieve coaxial output, and then enter the transmission optical fiber after being coupled by the third optical fiber coupler 22.

[0053] Furthermore, the MEMS scanning imaging module is the handheld part of the handheld multispectral photoacoustic imaging device in this embodiment. It integrates a MEMS micromirror 25, which precisely controls the laser focus to perform high-speed, programmed scanning within the tissue through its two-dimensional deflection, thereby replacing the bulky traditional mechanical scanning mechanism; such as Figure 2 As shown, the MEMS scanning imaging module specifically includes a third collimating lens 23, an objective lens 24, a MEMS micro-mirror 25, and an ultrasonic transducer 27. The ultrasonic transducer 27 is a transparent ultrasonic transducer. The laser beam transmitted through the optical fiber is collimated into a parallel beam by the third collimating lens 23. The parallel beam is converged by the objective lens 24 and reflected by the MEMS micro-mirror 25 to achieve two-dimensional scanning deflection. The beam is transmitted through the transparent ultrasonic transducer 27 and focused on the predetermined target area of ​​the sample 31 to be tested, thereby realizing optical scanning and excitation of the sample to be tested and converting the photoacoustic signal into an electrical signal.

[0054] To achieve precise spatial matching between optical excitation and ultrasonic detection, this embodiment employs a transparent ultrasonic transducer as the core detection unit. Specifically, its optical transparency allows the excitation laser beam to penetrate its working area with low loss and be precisely focused on the sample. Simultaneously, this focal point lies precisely within the transducer's ultrasonic detection focal range. This perfect spatial alignment ensures maximum efficiency in both excitation and detection, significantly improving the intensity and signal-to-noise ratio of the photoacoustic signal. Furthermore, this design avoids the complex off-axis optical path required by traditional non-transparent transducers due to optical path obstruction, simplifying the device structure and laying a solid foundation for miniaturization and weight reduction.

[0055] Furthermore, the data acquisition and control module is responsible for receiving, amplifying, and digitizing the electrical signals converted by the ultrasonic transducer 27, and for synchronously controlling the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module. The data acquisition and control module includes a data preprocessing unit, a data acquisition unit, and a synchronization control unit. The data preprocessing unit is used to preprocess the electrical signals, the data acquisition unit is used to perform analog-to-digital conversion on the preprocessed electrical signals to form digital signals, and the synchronization control unit is used to receive the global trigger pulse signal sent by the data acquisition unit and synchronously control the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

[0056] Furthermore, the data preprocessing unit includes a signal amplifier 28, which performs amplitude amplification and signal-to-noise ratio optimization preprocessing on the electrical signal converted by the ultrasound transducer 27; the data acquisition unit includes a data acquisition card 29 and a computer 30. The sampling rate of the data acquisition card 29 is 250 MHz. The preprocessed electrical signal is further precisely sampled and converted from analog to digital by the data acquisition card 29 to form a digital signal. This digital signal is uploaded to the computer 30 to complete subsequent imaging, reconstruction or quantitative analysis. Ultimately, it can simultaneously acquire and reconstruct images reflecting various characteristics of biological tissues, including but not limited to: high-resolution two-dimensional / three-dimensional morphological structure of meibomian glands, quantitative distribution of elastic modulus in their mechanical properties, and macroscopic structure, vascular wall elasticity and blood oxygen saturation of palpebral conjunctival vessels.

[0057] The handheld multispectral photoacoustic imaging device of this embodiment provides a powerful tool for in vivo and quantitative assessment of meibomian gland function. It not only theoretically achieves multispectral analysis of lipid components and blood oxygen saturation and precise modeling of biomechanical properties, but also technically achieves high-resolution, multi-parameter handheld imaging by integrating MEMS scanning and a transparent ultrasound transducer.

[0058] Furthermore, to ensure strict synchronization between spectral laser excitation, MEMS micromirror 25 scanning, and data acquisition card 29, a synchronization control unit includes a field-programmable gate array (FPGA) 26. A computer 30 sends a global trigger pulse signal to the FPGA 26 to activate its internal preset synchronization control logic. The FPGA 26 generates and outputs three timing control signals according to a preset timing sequence. Two of these signals drive the first and second pulse lasers to emit laser light at a specified frequency and pulse width, while the third signal controls the MEMS micromirror... The galvanometer 25 executes a preset scanning trajectory; the synchronous pulse signal generated by the pulsed laser (first pulsed laser 1 and second pulsed laser 9) each time it emits light is fed back to the data acquisition card 29 as its external trigger source to precisely control the opening time of the acquisition window. The field programmable gate array 26, through its highly stable internal clock management unit, performs unified scheduling and precise delay compensation for the timing of laser excitation, galvanometer movement and data acquisition, thereby ensuring that the entire device achieves synchronous operation at the microsecond level or even higher precision in the time dimension, effectively avoiding data acquisition misalignment or signal distortion caused by timing deviation.

[0059] In this embodiment, after introducing the field-programmable gate array 26, the emission of laser pulses, the deflection angle of the MEMS micro-mirror 25, and the sampling time of the data acquisition card 29 are centrally and precisely scheduled through the unified clock tree inside the field-programmable gate array 26. The device can thereby achieve precise spatiotemporal matching between the laser focus position, the ultrasonic signal generation, and the data acquisition time, thus providing reliable raw data for reconstructing high-fidelity multi-parameter images. This timing control method not only fundamentally avoids problems such as image blurring, ghosting, or geometric distortion caused by timing mismatch, but also ensures the long-term operational stability and data consistency of the device under high-speed scanning, ultimately guaranteeing the efficient and accurate extraction of multi-parameter information such as meibomian gland morphology, elasticity, and conjunctival vascular oxygen saturation.

[0060] Example 2:

[0061] Based on the handheld multispectral photoacoustic imaging device for dry eye detection disclosed in Embodiment 1, this embodiment uses the handheld multispectral photoacoustic imaging device to perform in vivo imaging of rabbit palpebral conjunctival vessels. The specific steps are as follows: The probe end of the MEMS scanning imaging module of the handheld multispectral photoacoustic imaging device is attached to the surface of the rabbit eyelid, and the device posture is adjusted so that the excitation beam is focused on the target blood vessel area; after the system is started, the synchronous control unit generates a global trigger signal through the field programmable gate array (FPGA) to drive the multispectral photoacoustic signal excitation module to output a laser of a set wavelength, which enters the MEMS scanning imaging module after beam combining and transmission; after collimation and focusing, the laser is reflected by the MEMS micro-mirror for high-speed two-dimensional scanning, and after penetrating the transparent ultrasonic transducer, it converges on the palpebral conjunctival blood vessel tissue, exciting and generating photoacoustic signals; the photoacoustic signals are received by the same transparent ultrasonic transducer and converted into electrical signals, which are then amplified and acquired before being uploaded to the computer for image reconstruction and processing.

[0062] like Figure 3 As shown, the imaging results indicate that the palpebral conjunctival vascular images acquired by this device have micron-level spatial resolution, with clear and complete vascular morphology and structure, and distinguishable fine branches. This embodiment verifies the feasibility and effectiveness of this handheld multispectral photoacoustic imaging device in performing high-resolution structural imaging in living tissue.

[0063] In summary, this invention, based on photoacoustic microscopy, successfully overcomes the limitations of existing dry eye detection methods that separate morphological and functional information. It deeply integrates photoacoustic physical effects, analyzing the relationship between the amplitude and spectrum of photoacoustic signals (achieving quantitative composition based on Lambert-Beer's law) and the relationship between amplitude and temporal characteristics (inverting elasticity based on mechanical models such as Navier's equation). Ultimately, on an integrated handheld platform, it simultaneously achieves high-resolution two-dimensional / three-dimensional structural imaging of the meibomian glands, quantitative elastic modulus, and precise multi-parameter measurement of the structure, vascular elasticity, and blood oxygen saturation of the palpebral conjunctival vessels. Therefore, through this integrated "structure-function-mechanics" handheld photoacoustic diagnostic paradigm, it provides a novel technical means for early screening, accurate classification, and efficacy evaluation of dry eye syndrome, possessing broad clinical application and market prospects.

[0064] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope disclosed in the present invention, based on the technical solution and inventive concept of the present invention, shall fall within the scope of protection of the present invention.

Claims

1. A handheld multispectral photoacoustic imaging device for dry eye detection, characterized in that, It includes a multispectral photoacoustic signal excitation module, a MEMS scanning imaging module, and a data acquisition and control module; The multispectral photoacoustic signal excitation module includes a first laser signal excitation unit and a second laser signal excitation unit. The first laser signal excitation unit is used to generate a first specific wavelength laser, and the second laser signal excitation unit is used to generate a second specific wavelength laser and a third specific wavelength laser. The first specific wavelength laser, the second specific wavelength laser and the third specific wavelength laser are coupled into the transmission optical fiber. The MEMS scanning imaging module is used to reflect the laser in the transmission fiber to realize optical scanning and excitation of the sample under test, and to convert the photoacoustic signal into an electrical signal. The data acquisition and control module is used to preprocess the electrical signal, convert the preprocessed electrical signal into a digital signal by analog-to-digital conversion, and synchronously control the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

2. The handheld multispectral photoacoustic imaging device according to claim 1, characterized in that, The first laser signal excitation unit includes a first pulsed laser, a first linear polarizer, a first half-wave plate, a first fiber coupler, a first polarization-maintaining fiber, a first collimating lens, a first bandpass filter, a first reflecting mirror, and a first dichroic mirror; The laser output from the first pulsed laser passes through the first linear polarizer and the first half-wave plate for polarization control in sequence, is injected into the first polarization-maintaining fiber by the first fiber coupler, and generates a laser spectrum through the nonlinear optical effect in the first polarization-maintaining fiber. After being collimated by the first collimating lens, the first specific wavelength is selected by the first bandpass filter and guided to the first dichroic mirror by the first reflecting mirror.

3. The handheld multispectral photoacoustic imaging device according to claim 1, characterized in that, The second laser signal excitation unit includes a second pulsed laser, a beam splitter, a second dichroic mirror, a second reflector, a second linear polarizer, a second half-wave plate, a second fiber coupler, a second polarization-maintaining fiber, a second collimating lens, a second bandpass filter, a third reflector, and a third dichroic mirror. The laser output from the second pulsed laser is split into two paths by a beam splitter. One path uses the center wavelength of the second pulsed laser as the second specific wavelength and is directly output to the second dichroic mirror as the fundamental frequency. The other path is reflected by the second mirror and then passes through the second linear polarizer and the second half-wave plate for polarization control. It is then injected into the second polarization-maintaining fiber by the second fiber coupler. A broadband laser spectrum is generated through the nonlinear optical effect in the second polarization-maintaining fiber. After being collimated by the second collimating mirror, the third specific wavelength is selected by the second bandpass filter and guided to the third dichroic mirror by the third mirror.

4. The handheld multispectral photoacoustic imaging device according to claim 1, characterized in that, The MEMS scanning imaging module includes a third collimating lens, an objective lens, a MEMS micro-vibration mirror, and an ultrasonic transducer. The laser beam transmitted through the optical fiber is collimated into a parallel beam by a third collimating lens. The parallel beam is focused by the objective lens and reflected by the MEMS micro-mirror to achieve two-dimensional scanning deflection. The beam is transmitted through a transparent ultrasonic transducer and focused on a predetermined target area of ​​the sample to be tested, thereby realizing optical scanning and excitation of the sample to be tested and converting the photoacoustic signal into an electrical signal.

5. The handheld multispectral photoacoustic imaging device according to claim 1, characterized in that, The data acquisition and control module includes a data preprocessing unit, a data acquisition unit, and a synchronization control unit; The data preprocessing unit is used to preprocess the electrical signals; The data acquisition unit is used to perform analog-to-digital conversion on the preprocessed electrical signal to form a digital signal; The synchronization control unit is used to receive the global trigger pulse signal sent by the data acquisition unit and synchronously control the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

6. The handheld multispectral photoacoustic imaging device according to claim 5, characterized in that, The data preprocessing unit includes a signal amplifier, which performs amplitude amplification and signal-to-noise ratio optimization preprocessing on the electrical signal.

7. The handheld multispectral photoacoustic imaging device according to claim 5, characterized in that, The data acquisition unit includes a data acquisition card and a computer. The data acquisition card performs analog-to-digital conversion on the preprocessed electrical signal to form a digital signal, and then uploads the digital signal to the computer.

8. The handheld multispectral photoacoustic imaging device according to claim 5, characterized in that, The synchronization control unit includes a field-programmable gate array (FPGA). The FPGA receives a global trigger pulse signal sent by the data acquisition unit, activates the internally preset synchronization control logic, and synchronously controls the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module according to the preset timing sequence.

9. A multispectral photoacoustic imaging method, implemented based on the handheld multispectral photoacoustic imaging device according to any one of claims 1-8, characterized in that, The method includes: In the first laser signal excitation unit, the laser output from the first pulsed laser passes through the first linear polarizer and the first half-wave plate in sequence for polarization control, is injected into the first polarization-maintaining fiber by the first fiber coupler, and generates a broadband laser spectrum through the nonlinear optical effect in the first polarization-maintaining fiber. After being collimated by the first collimating lens, the first specific wavelength is selected by the first bandpass filter and guided to the first dichroic mirror by the first reflecting mirror. In the second laser signal excitation unit, the laser output from the second pulse laser is split into two paths by a beam splitter. One path uses the center wavelength of the second pulse laser as the second specific wavelength and is directly output to the second dichroic mirror as the fundamental frequency light. The other path is reflected by the second mirror and then passes through the second linear polarizer and the second half-wave plate for polarization control. It is then injected into the second polarization-maintaining fiber by the second fiber coupler. A broadband laser spectrum is generated through the nonlinear optical effect in the second polarization-maintaining fiber. After being collimated by the second collimating mirror, the third specific wavelength is selected by the second bandpass filter and guided to the third dichroic mirror by the third mirror. Through the spatial beam combining effect of the first, second, and third dichroic mirrors, the first specific wavelength laser, the second specific wavelength laser, and the third specific wavelength laser achieve coaxial output and couple into the transmission optical fiber. In the MEMS scanning imaging module, the laser beam transmitted through the optical fiber is collimated into a parallel beam by the third collimating lens. The parallel beam is focused by the objective lens and reflected by the MEMS micro-mirror to achieve two-dimensional scanning deflection. The beam is transmitted through a transparent ultrasonic transducer and focused on the predetermined target area of ​​the sample to be tested, thereby realizing optical scanning and excitation of the sample to be tested and converting the photoacoustic signal into an electrical signal. In the data acquisition and control module, the electrical signal is preprocessed, and the preprocessed electrical signal is converted from analog to digital to form a digital signal, which simultaneously controls the multispectral photoacoustic signal excitation module and the MEMS scanning imaging module.

10. The multispectral photoacoustic imaging method according to claim 9, characterized in that, The synchronous control multispectral photoacoustic signal excitation module and MEMS scanning imaging module include: The system receives a global trigger pulse signal from the data acquisition unit, initiates a preset synchronization control logic, and generates and outputs three timing control signals according to a preset timing sequence. Two of these signals are used to drive the first and second pulse lasers to emit lasers at a specified frequency and pulse width, while the other signal is used to control the MEMS micromirror in the MEMS scanning imaging module to execute a preset scanning trajectory.

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