A wearable dual-mode imaging probe device and a dual-mode imaging detection system

Abstract

The application relates to the field of biomedical imaging, and provides a wearable dual-mode imaging probe device and a dual-mode imaging detection system.The device comprises a single-mode optical fiber for receiving and transmitting first laser and second laser emitted by a laser emitter and receiving and transmitting a fluorescent signal generated by a measured object; a scanning assembly for reflecting and two-dimensionally raster scanning the laser; an objective lens for focusing a light beam to the measured object, generating a photoacoustic signal under excitation of a first laser related light beam, and generating a fluorescent signal under excitation of a second laser related light beam; an ultrasonic transducer for collecting the photoacoustic signal; a fluorescent signal collector coupled with the single-mode optical fiber and used for collecting the fluorescent signal transmitted by the single-mode optical fiber; and a connecting assembly arranged outside the objective lens and detachably fixed on a wearing assembly.The application can realize light weight and miniaturization, is suitable for an automatically moving measured object, and can simultaneously monitor neural activity and cerebral hemodynamic information of the measured object under various states.

Description

Technical Field

[0001] This application relates to the field of biomedical imaging, and in particular to a wearable dual-modal imaging probe device and a dual-modal imaging detection system. Background Technology

[0002] Neurovascular coupling (NVC) is a regulatory mechanism between neural activity and cerebral blood flow, ensuring adequate oxygen and energy supply to the brain under various functional states. Research on NVC is crucial for understanding the brain's metabolic needs, neurodegeneration, and the discovery of cerebral blood flow abnormalities.

[0003] In existing technologies, there are two main methods for detecting neural activity. The first is to determine neural activity through electroencephalogram (EEG) signals monitored by fluorescence imaging and electrophysiological techniques; the second is to infer neural activity based on cerebral hemodynamic information. The first method is susceptible to interference and cannot distinguish neural activity in different brain regions or at different depths, while the second method is difficult to quantify accurately. Cerebral hemodynamic information is obtained using functional magnetic resonance imaging (fMRI), functional ultrasound (fUS), laser speckle contrast imaging (LSCI), and photoacoustic microscopy (PAM). Therefore, existing technologies cannot simultaneously obtain both neural activity and cerebral hemodynamic information.

[0004] In addition, the acquisition of existing neural activity information and cerebral hemodynamic information is limited by the state of the subject being tested, and cannot simultaneously measure neural activity and cerebral hemodynamic information of different subjects under different states. Summary of the Invention

[0005] This application aims to solve the technical problem in the prior art that it is impossible to simultaneously measure the neural activity and cerebral hemodynamics of the subject under different states.

[0006] To address the aforementioned technical problems, the first aspect of the present invention provides a wearable dual-modal imaging probe device, comprising: a single-mode optical fiber, a scanning component, an objective lens, an ultrasonic transducer, a fluorescence signal collector, a connection component, and a wearable component;

[0007] The single-mode fiber-coupled laser transmitter is used to receive and transmit the first laser and the second laser emitted by the laser transmitter, as well as to receive and transmit the fluorescence signal generated by the object under test.

[0008] The scanning component is used to reflect and perform two-dimensional grating scanning on the laser emitted from the single-mode fiber.

[0009] The objective lens is used to focus the beam scanned by the two-dimensional grating onto the object under test. The object under test generates a photoacoustic signal under the excitation of the first laser correlation beam and a fluorescence signal under the excitation of the second laser correlation beam. The fluorescence signal at the focal plane passes through the objective lens and the scanning component in sequence and enters the single-mode optical fiber.

[0010] The ultrasonic transducer is disposed at the end of the objective lens near the object under test and is used to collect photoacoustic signals; the fluorescence signal collector is coupled to the single-mode optical fiber and is used to collect the fluorescence signal transmitted by the single-mode optical fiber.

[0011] The connecting component is disposed on the outside of the objective lens, the wearable component can be disposed on the object being tested, and the connecting component is detachably fixed to the wearable component.

[0012] In a further embodiment of this application, the wavelength of the first laser is 558 / 570±σ nanometers, where σ is a preset value, and the maximum excitation wavelength of the second laser is 488 nanometers.

[0013] As a further embodiment of this application, the wearable dual-modal imaging probe device further includes: an optical fiber collimator;

[0014] The fiber collimator is used to perform parallel conversion on the first laser and the second laser emitted from the single-mode fiber to obtain a parallel beam, which is then incident on the scanning component.

[0015] In a further embodiment of this application, the scanning component includes: a dual-axis microelectromechanical system scanner and a scanning lens;

[0016] The dual-axis microelectromechanical system scanner is used to reflect and perform two-dimensional grating scanning on the first and second lasers emitted from the single-mode fiber.

[0017] The scanning lens is used to generate a flat image plane based on the beam scanned by the two-dimensional grating.

[0018] In a further embodiment of this application, the fluorescence signal collector includes: an optical fiber coupler, a first dichroic mirror, and a photomultiplier tube;

[0019] The fiber coupler connects to the single-mode fiber;

[0020] The first dichroic mirror is used to reflect the fluorescence signal transmitted in the single-mode fiber to the photomultiplier tube; the first dichroic mirror is also used to transmit a first laser, which enters the single-mode fiber through an optical fiber coupler.

[0021] The photomultiplier tube is used to convert the fluorescence signal into an electrical signal and store it.

[0022] In a further embodiment of this application, the connecting component is provided with external threads on its outer side;

[0023] The wearable component includes a sleeve, at least one base plate, and screws;

[0024] The sleeve is provided with an internal thread, which, by engaging with the external thread, allows the sleeve to be fastened to the connecting assembly and the position of the focal point to be adjusted.

[0025] The screw is disposed on the sleeve to securely fix the sleeve to the connecting assembly;

[0026] The base plate is fixed to the sleeve and is designed for wearable installation on the object being tested.

[0027] As a further embodiment of this application, the wearable dual-modal imaging probe device further includes: a main body;

[0028] The shape of the main body is set according to the signal optical path;

[0029] The single-mode optical fiber is disposed within the main body, and the scanning component and the objective lens are disposed within the main body by screws.

[0030] A second aspect of the present invention provides a dual-modal imaging detection system, comprising: a first laser emitter, a second laser emitter, and any of the foregoing embodiments and the wearable dual-modal imaging probe device described above;

[0031] The first laser emitter is used to emit a first laser beam into the single-mode fiber, and the second laser emitter is used to emit a second laser beam into the single-mode fiber.

[0032] In a further embodiment of this application, the dual-modal imaging detection system further includes: a second dichroic mirror;

[0033] The second dichroic mirror is located on one side of the second laser emitter and is used to reflect the second laser into the single-mode fiber.

[0034] In a further embodiment of this application, the second dichroic mirror is located between the first dichroic mirror and the fiber coupler, and the second dichroic mirror is also used to transmit the first laser and fluorescence signals.

[0035] The wearable dual-modal imaging probe device and dual-modal imaging detection system provided in this application are lightweight and miniaturized, suitable for automatically moving test objects. They use a single single-mode optical fiber to achieve co-focusing of photoacoustic / fluorescence imaging excitation light and emission fluorescence, improving the compactness of the optical path and making the probe exquisite and small.

[0036] This application enables simultaneous monitoring of neural activity and cerebral hemodynamics in subjects under various states, including anesthesia, sleep, wakefulness, and free movement. Specifically, it achieves coaxial excitation of head-mounted photoacoustic microscopy and confocal fluorescence microscopy, along with simultaneous ultrasound detection and fluorescence collection, offering advantages such as high spatial resolution and high signal-to-noise ratio. Photoacoustic microscopy provides label-free structural and functional imaging of cerebral blood vessels, offering hemodynamic information such as cerebral blood supply and oxygenation. Confocal fluorescence microscopy, through fluorescence labeling, enables high-resolution imaging of individual neurons, recording individual neural activity and hemodynamic changes. This application provides a novel tool for neurovascular coupling research, contributing to the understanding of brain neural activity and cerebral blood flow.

[0037] To make the above and other objects, features and advantages of this application more apparent and understandable, preferred embodiments are described below in detail with reference to the accompanying drawings. Attached Figure Description

[0038] To more clearly illustrate the technical solutions in the embodiments of this application 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 this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0039] Figure 1 A perspective view of a wearable dual-modal imaging probe device according to an embodiment of this application is shown;

[0040] Figure 2 A three-dimensional structural diagram of a wearable dual-modal imaging probe device according to an embodiment of this application is shown;

[0041] Figure 3 Another perspective structural diagram of the wearable dual-modal imaging probe device according to an embodiment of this application is shown;

[0042] Figure 4 A cross-sectional schematic diagram of a wearable dual-modal imaging probe device according to an embodiment of this application is shown;

[0043] Figure 5 A schematic diagram of a dual-modal imaging detection system according to an embodiment of this application is shown;

[0044] Figure 6 A structural diagram of a computer device according to an embodiment of this application is shown;

[0045] Figure 7 A schematic diagram of the assembly structure of the wearable dual-modal imaging probe device according to an embodiment of this application is shown.

[0046] Explanation of symbols in the attached drawings:

[0047] 101. Single-mode optical fiber;

[0048] 102. Scanning component;

[0049] 1021. Dual-axis MEMS scanner;

[0050] 1022. Scanning lens;

[0051] 103. Objective lens;

[0052] 104. Ultrasonic transducer;

[0053] 105. Fluorescence signal collector;

[0054] 1051. Fiber optic coupler;

[0055] 1052. First dichroic mirror;

[0056] 1053. Photomultiplier tube;

[0057] 1054. Filter;

[0058] 106. Connecting components;

[0059] 107. Wearable components;

[0060] 1071. Sleeve;

[0061] 1072. Screw;

[0062] 108. Fiber optic collimator;

[0063] 109. Main body;

[0064] 501. First laser emitter;

[0065] 502. Second laser emitter;

[0066] 503. Wearable dual-modal imaging probe device;

[0067] 504. Second dichroic mirror;

[0068] 602. Computer equipment;

[0069] 604, Processor;

[0070] 606. Memory;

[0071] 608. Drive mechanism;

[0072] 610. Input / output module;

[0073] 612. Input devices;

[0074] 614. Output devices;

[0075] 616. Presentation equipment;

[0076] 618. Graphical User Interface;

[0077] 620. Network interface;

[0078] 622. Communication link;

[0079] 624. Communication bus. Detailed Implementation

[0080] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0081] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of this application described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion; for example, a process, method, apparatus, product, or device that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or devices.

[0082] This specification provides the operational steps of the methods described in the embodiments or flowcharts, but based on conventional or non-inventive labor, more or fewer operational steps may be included. The order of steps listed in the embodiments is merely one possible execution order among many and does not represent the only possible execution order. In actual system or device products, the methods shown in the embodiments or drawings can be executed sequentially or in parallel.

[0083] It should be noted that in the embodiments of this application, certain software, components, models and other existing solutions in the industry may be mentioned. These should be regarded as exemplary and are only intended to illustrate the feasibility of implementing the technical solution of this application. However, it does not mean that the applicant has used or necessarily used the solution.

[0084] In existing technologies, there are two main methods for detecting neural activity:

[0085] The first method is to determine neural activity by monitoring electroencephalogram (EEG) signals through fluorescence imaging and electrophysiological techniques. The principle of fluorescence imaging is to label neurons by transfecting them with fluorescent proteins, and then use excitation light to generate fluorescence of a specific wavelength. The fluorescence signals are received and recorded by a photomultiplier tube (PMT) or CCD to form an image that reflects the characteristics of neuronal activity in the brain.

[0086] The second method involves inferring neural activity based on information about cerebral hemodynamics.

[0087] The first method of monitoring EEG signals has low spatial resolution, is susceptible to noise interference, and cannot accurately distinguish neural activity in different brain regions or at different depths, nor can it capture the electrical activity of individual neurons. The second method, which indirectly infers the strength of neural activity by recording changes in cerebral hemodynamic parameters through a single imaging modality, can only perform qualitative analysis and is difficult to perform accurate quantitative analysis.

[0088] In existing technologies, cerebral hemodynamic information is obtained using functional magnetic resonance imaging, functional ultrasound, laser speckle contrast imaging, photoacoustic microscopy, etc. Among them, photoacoustic microscopy benefits from the specific absorption of visible light by endogenous hemoglobin in blood vessels, which can achieve label-free high-resolution structural and functional imaging of brain blood vessels.

[0089] It is evident that existing technologies cannot simultaneously acquire neural activity and cerebral hemodynamic information. Furthermore, the acquisition of existing neural activity and cerebral hemodynamic information can only be performed under anesthesia or with the head fixed, meaning it is limited by the state of the subject and cannot measure neural activity and cerebral hemodynamic information under different states.

[0090] Furthermore, current fluorescence imaging typically relies on high-NA objectives to achieve high-resolution imaging and observe neurons. However, high-NA objectives usually have very limited working distances (millimeters, or even less than 1 mm). Traditional photoacoustic imaging, on the other hand, typically uses acoustic coupling prisms combined with large transducers for ultrasonic collection. The working space distances of these two methods are incompatible; therefore, a combined fluorescence and photoacoustic imaging solution is not currently available.

[0091] To address the aforementioned technical problems, this application provides a wearable dual-modal imaging probe device, such as... Figures 1 to 4 As shown, it includes:

[0092] The device includes a single-mode fiber (SMF) 101, a scanning assembly 102, an objective lens 103, an ultrasonic transducer 104, a fluorescence signal collector 105, a connection assembly 106, and a wearable assembly 107.

[0093] A single-mode fiber optic cable 101 is coupled to a laser transmitter for receiving and transmitting a first laser and a second laser emitted by the laser transmitter, as well as receiving and transmitting a fluorescence signal generated by the object under test. In one specific embodiment, the wavelength of the first laser is 558 / 570 ± σ nanometers, where σ is a preset value. In practice, the value of σ can be selected within the range of 558 / 570 nanometers. The first laser selected within this range can excite photoacoustic signals from blood hemoglobin. The maximum excitation wavelength of the second laser is 488 nanometers, which has the highest excitation efficiency. In practice, the wavelength of the second laser can also be selected within the range of 488 nanometers. The object under test in this application is an object whose neural activity and cerebral hemodynamic information are to be determined.

[0094] The scanning component 102 is used to reflect and perform two-dimensional grating scanning on the laser emitted from the single-mode fiber 101. The laser emitted from the single-mode fiber 101 includes a first laser and a second laser. By scanning the laser with the scanning component 102, spot distortion can be reduced, and a flat image can be produced. To reduce the size of the probe device, the scanning component 102 is a miniaturized scanning lens.

[0095] Objective lens 103 is used to focus the beam scanned by the two-dimensional grating onto the object under test. The object under test generates a photoacoustic signal under the excitation of the first laser-correlated beam and a fluorescence signal under the excitation of the second laser-correlated beam. The fluorescence signal at the focal plane passes sequentially through objective lens 103 and scanning assembly 102 into single-mode fiber 101. In some real-time modes, objective lens 103 is selected with a high NA (0.5). The focal plane refers to the two-dimensional plane where the optical focal point is located after passing through the objective lens; the focal point is shown in the image. Figure 1 The enlarged illustration shows the optical fiber being focused behind the objective lens to form a focal point, and the focal point scanning plane forming the focal plane.

[0096] An ultrasonic transducer 104 is positioned at the end of the objective lens 103 closest to the object under test to collect photoacoustic signals. Specifically, the ultrasonic transducer 104 is a miniaturized ultrasonic transducer that employs off-axis detection of photoacoustic signals. This off-axis detection method using a miniaturized ultrasonic transducer effectively solves the problem of limited working distance. In practice, the ultrasonic transducer 104 is attached to the inside of the probe to avoid blocking the incident excitation light and to receive the acoustic signal generated by the excitation beam.

[0097] A fluorescence signal collector 105 is coupled to a single-mode fiber 101 and is used to collect the fluorescence signal transmitted by the single-mode fiber 101.

[0098] The connecting component 106 is disposed on the outside of the objective lens 103, and the wearable component 107 can be disposed on the test object. The connecting component 106 is detachably fixed to the wearable component 107. In specific implementation, the wearable component 107 and the connecting component 106 can be threaded or snapped together, and the wearable component 107 can be disposed on the test object by glue or dental cement.

[0099] This application features lightweight and miniaturization, making it suitable for automatically moving test objects. It uses a single single-mode optical fiber to achieve confocalization of photoacoustic / fluorescence imaging excitation light and emission fluorescence, improving the compactness of the optical path and making the probe exquisite and small.

[0100] This application enables simultaneous monitoring of neural activity and cerebral hemodynamics in subjects under various conditions. Specifically, single-mode fiber allows for coaxial excitation of head-mounted photoacoustic microscopy and confocal fluorescence microscopy, along with simultaneous ultrasound detection and fluorescence collection, eliminating the need for additional aperture elements. This makes optical path alignment more flexible, stable, and compact, laying the foundation for lightweight miniaturized probe design. Photoacoustic microscopy provides label-free structural and functional imaging of cerebral blood vessels, offering hemodynamic information such as cerebral blood supply and oxygenation. Confocal fluorescence microscopy, using fluorescent labeling, enables high-resolution imaging of individual neurons in the brain, recording neural activity information. This application provides a novel tool for neurovascular coupling research, contributing to the understanding of brain neural activity and cerebral blood flow.

[0101] In one embodiment of this application, as Figures 1 to 4 As shown, the wearable dual-modal imaging probe device also includes an optical fiber collimator 108, which is used to perform parallel conversion on the first laser and the second laser emitted from the single-mode optical fiber 101 to obtain a parallel beam, and the parallel beam is incident on the scanning component 102.

[0102] In this embodiment, the use of the fiber optic collimator 108 can reduce the divergence angle, making it easier for the subsequent scanning components to perform beam scanning.

[0103] In one embodiment of this application, such as Figure 1 As shown, the scanning assembly 102 includes a dual-axis microelectromechanical system scanner 1021 and a scanning lens 1022.

[0104] The dual-axis microelectromechanical system scanner 1021 is used to reflect and perform two-dimensional grating scanning on the first and second lasers emitted from the single-mode fiber 101.

[0105] The scanning lens 1022 is used to generate a flat image plane based on the beam scanned by the two-dimensional grating.

[0106] In one embodiment of this application, as Figure 5 As shown, the fluorescence signal collector 105 includes: an optical fiber coupler 1051, a first dichroic mirror 1052, and a photomultiplier tube 1053.

[0107] Fiber optic coupler 1051 connects to single-mode fiber 101.

[0108] The first dichroic mirror 1052 is used to reflect the fluorescence signal transmitted through the single-mode fiber 101 to the photomultiplier tube 1053. The first dichroic mirror 1052 is also used to transmit a first laser beam, which enters the single-mode fiber 101 through the fiber coupler 1051. Specifically, as... Figure 5 As shown, a first laser is emitted by a first laser emitter 501. In some embodiments, the first laser emitter 501 is a 558 / 570nm nanosecond pulsed laser.

[0109] The photomultiplier tube 1053 is used to convert fluorescence signals into electrical signals and store them.

[0110] In a specific implementation, the fluorescence signal collector 105 further includes a filter 1054, which is disposed between the first dichroic mirror 1052 and the photomultiplier tube 1053.

[0111] In one embodiment of this application, the ultrasonic transducer is a miniaturized ultrasonic transducer with dimensions of 0.4mm × 0.5mm. By detecting photoacoustic signals using a miniaturized ultrasonic transducer, its compact size perfectly solves the short working distance limitation imposed by high-NA objectives in fluorescence imaging modes. In specific implementations, the ultrasonic transducer can also be expanded by splicing multiple transducers, which has the potential to extend the imaging field of view.

[0112] In one embodiment of this application, as Figure 1 , Figure 3 and Figure 4 As shown, the outer side of the connecting component 106 is provided with an external thread. In one specific embodiment, the external thread is a fine thread, such as M5.5, with a pitch of 0.5 mm.

[0113] The wearable component 107 includes a sleeve 1071, at least one base plate, and screws 1072.

[0114] The sleeve 1071 is provided with an internal thread, which, through its engagement with the external thread of the connecting component 106, allows the sleeve 1071 to be fastened to the connecting component 106 and to adjust the position of the focusing point.

[0115] Screw 1072 is disposed on sleeve 1071 to securely fix sleeve 1071 to connecting assembly 106. In one specific embodiment, screw 1072 is a hexagonal flat-head set screw, thereby securing sleeve 1071 and preventing shaking and drift of the imaging scene when the object under test moves freely.

[0116] The base plate is fixed to the sleeve 1071 and is used for wearable installation on the object being tested.

[0117] This application uses custom-machined fine-pitch threads as the assembly connection between the imaging probe and the mouse headgear. By manually rotating the sleeve, the fine-pitch threads allow for precise adjustment of the focal plane position during imaging. Furthermore, the threaded connection facilitates repeated disassembly and assembly, enabling long-term, multi-day imaging monitoring. Additionally, using finer-pitch threads with even finer pitch allows for more precise focus adjustment. Simultaneously, the probe can be repeatedly disassembled and reassembled by tightening the threads.

[0118] In practice, in order to make the wearable dual-modal imaging probe device applicable to a variety of test objects, it is equipped with base plates of various sizes, and the base plates are connected to the sleeve by means of snap-fit, threads, etc.

[0119] In one embodiment of this application, as Figures 2 to 4 As shown, the wearable dual-modal imaging probe device also includes a main body 109. The shape of the main body 109 is set according to the optical path of the signal. A single-mode optical fiber 101 is disposed within the main body 109, and the scanning assembly 102 and the objective lens 103 are disposed within the main body 109 by screws.

[0120] This embodiment can improve the compactness of the optical path, making the probe exquisite and small.

[0121] In one embodiment of this application, a dual-modal imaging detection system is also provided, such as... Figure 5 As shown, it includes: a first laser emitter 501, a second laser emitter 502, and a wearable dual-modal imaging probe device 503, wherein the internal structure of the wearable dual-modal imaging probe device 503 is as follows. Figures 1 to 4 As shown.

[0122] The first laser transmitter 501 is used to emit a first laser beam into a single-mode fiber, and the second laser transmitter 502 is used to emit a second laser beam into a single-mode fiber.

[0123] In practice, the single-mode optical fiber of the wearable dual-modal imaging probe device 503 has a certain length, which ensures that the mouse's activity is not restricted.

[0124] In a further embodiment of this application, the dual-modal imaging detection system further includes a second dichroic mirror.

[0125] The second dichroic mirror is located on one side of the second laser emitter and is used to reflect the second laser into the single-mode fiber.

[0126] In specific implementation, such as Figure 5 As shown, the second dichroic mirror 504 is located between the first dichroic mirror 1052 and the fiber coupler 1051. The second dichroic mirror 504 is also used to transmit the first laser and fluorescence signals.

[0127] This embodiment can improve the compactness of the optical path, making the probe exquisite and small.

[0128] The wearable dual-modal imaging probe device and dual-modal imaging detection system provided in this application have been simulated and modeled in three dimensions using optical design software. The optical design meets the optical imaging principle, and the mechanical processing meets the processing technology. The stable and reliable photoacoustic / fluorescence dual-modal imaging performance has been verified in imaging experiments. It can realize high-resolution imaging of hemodynamic information of neurons in the brain and surrounding blood vessels of mice in a conscious and freely moving state.

[0129] In a specific embodiment of this application, based on the foregoing embodiments, the following optical path design, mechanical processing design, and acoustic detection design were performed, specifically:

[0130] (1) Optical path design: The photoacoustic microscopy imaging beam and the confocal fluorescence imaging beam are coupled to the same single-mode fiber. After the single-mode fiber emits multi-wavelength lasers (488nm / 558nm / 570nm), it is collimated using a custom-made micro fiber collimator with a diameter of 3mm. Then it is reflected by a dual-axis microelectromechanical system scanner and scanned by a scanning lens for two-dimensional grating scanning. Finally, it is focused onto biological tissue by a miniaturized high-NA objective lens to excite photoacoustic and fluorescence signals. The excited fluorescence returns along the original optical path. Since only the fluorescence at the focal plane can be collected and transmitted through the single-mode fiber, it is detected by a photomultiplier tube after being emitted along the single-mode fiber. Therefore, the confocalization of the excitation light and the emission light is achieved through a single single-mode fiber, which improves the imaging resolution and makes the optical path alignment more flexible, stable and compact.

[0131] Miniaturized high-NA objectives can achieve better optical focusing and thus higher resolution imaging. Imaging a single neuron requires a high-NA objective.

[0132] Confocal microscopy blocks fluorescence signals from entering the fiber and returning to the PMT, enabling optical slicing, acquiring clear images of samples at different depths, and improving longitudinal (depth) resolution.

[0133] (2) Machining: Based on the optical path design structure, a three-dimensional solid model is created using SolidWorks. Geometric dimensions and tolerances are used to ensure machining and assembly accuracy, such as... Figure 7As shown, the entire main body 109, connecting assembly 106, and wearable assembly 107 are manufactured using five-axis computer numerical control (CNC) machining. Due to the lightweight and high-strength mechanical properties of polyetheretherketone (PEEK) material, 30% carbon fiber reinforced PEEK material is selected as the material for the sleeves in the main body and wearable assembly.

[0134] Meanwhile, to meet the needs of continuous multi-day long-term imaging scenarios, the probe assembly is designed to be detachable. The dual-axis MEMS scanner is connected to the probe body via M1.2 slotted flathead screws. The scanning lens, objective lens, and miniature fiber optic collimator are secured with M1.2 stainless steel slotted flathead screws. The outer periphery of the connecting component 106 is designed with custom-machined fine threads (M5.5, 0.5mm pitch), which mate with the internally threaded sleeve connected to the metal base plate in the wearable component, facilitating disassembly and assembly. Furthermore, the fine thread allows for precise manual rotation of the probe to adjust the optical focus (0.5mm per rotation). After determining the imaging focal plane, tightening the M2 internal hexagon flathead set screw on the side of the fixing sleeve securely fixes the probe, preventing shaking and drift of the imaging field of view when the mouse moves freely.

[0135] (3) Acoustic detection: To adapt to the working distance (1mm) of the miniaturized high NA objective lens, a customized 0.4mm×0.5mm flat field non-focusing miniature transducer (center frequency of 55MHz, -6dB bandwidth of 70%) is attached to the inside of the probe. The photoacoustic signal is received by off-axis alignment, which can effectively avoid the obstruction of excitation light and emission fluorescence.

[0136] The distance between the transducer and the focal point is where its response sensitivity is strongest, that is, where the sound field intensity of the transducer is greatest. This distance is related to the size of the transducer; for a 0.4mm × 0.5mm transducer, the distance is approximately 2mm.

[0137] This application enables the development of a lightweight and miniaturized head-mounted photoacoustic / confocal fluorescence dual-modal microscopy probe. It utilizes a single-mode optical fiber to achieve confocalization of the excitation light and emitted fluorescence for photoacoustic / fluorescence imaging, improving optical path compactness and making the probe exquisitely small. Furthermore, it can simultaneously acquire high-resolution information on neural activity and cerebral hemodynamics in awake, freely moving mice, which is of great significance for research on neurovascular coupling and the mechanisms of brain diseases.

[0138] In one embodiment of this application, a computer device is also provided, such as... Figure 6As shown, computer device 602 is used to control the operation of the wearable dual-modal imaging probe device, the first laser emitter, and the second laser emitter, and / or to analyze and process the collected fluorescence signals and photoacoustic signals. Specifically, computer device 602 may include one or more processors 604, such as one or more central processing units (CPUs), each of which can implement one or more hardware threads. Computer device 602 may also include any memory 606 for storing any kind of information such as code, settings, data, etc. Non-limitingly, for example, memory 606 may include any type of RAM, any type of ROM, flash memory, hard disk, optical disk, etc. More generally, any memory can use any technology to store information. Furthermore, any memory can provide volatile or non-volatile retention of information. Furthermore, any memory can represent a fixed or removable component of computer device 602. In one case, when processor 604 executes associated instructions stored in any memory or combination of memories, computer device 602 can perform any operation of the associated instructions. The computer device 602 also includes one or more drive mechanisms 608 for interacting with any memory, such as a hard disk drive mechanism, an optical disk drive mechanism, etc.

[0139] Computer device 602 may also include an input / output module 610 (I / O) for receiving various inputs (via input device 612) and providing various outputs (via output device 614). A specific output mechanism may include a presentation device 616 and an associated graphical user interface (GUI) 618. In other embodiments, the input / output module 610 (I / O), input device 612, and output device 614 may be omitted, and the device may function solely as a computer device within a network. Computer device 602 may also include one or more network interfaces 620 for exchanging data with other devices via one or more communication links 622. One or more communication buses 624 couple the components described above together.

[0140] Communication link 622 can be implemented in any way, such as via a local area network, a wide area network (e.g., the Internet), a point-to-point connection, or any combination thereof. Communication link 622 may include any combination of hardwired links, wireless links, routers, gateway functions, name servers, etc., governed by any protocol or combination of protocols.

[0141] It should also be understood that, in the embodiments of this application, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this application generally indicates that the preceding and following related objects have an "or" relationship.

[0142] Those skilled in the art will recognize that the units and algorithm steps of the various examples described in conjunction with the embodiments disclosed in this application can be implemented in electronic hardware, computer software, or a combination of both. To clearly illustrate the interchangeability of hardware and software, the composition and steps of each example have been generally described in terms of functionality in the foregoing description. Whether these functions are implemented in hardware or software depends on the specific application and design constraints of the technical solution. Those skilled in the art can use different methods to implement the described functions for each specific application, but such implementation should not be considered beyond the scope of this application.

[0143] Those skilled in the art will clearly understand that, for the sake of convenience and brevity, the specific working processes of the systems, devices, and units described above can be referred to the corresponding processes in the foregoing method embodiments, and will not be repeated here.

[0144] In the embodiments provided in this application, it should be understood that the disclosed systems, apparatuses, and methods can be implemented in other ways. For example, the apparatus embodiments described above are merely illustrative; for instance, the division of units is only a logical functional division, and in actual implementation, there may be other division methods. For example, multiple units or components may be combined or integrated into another system, or some features may be ignored or not executed. Furthermore, the couplings or direct couplings or communication connections shown or discussed may be indirect couplings or communication connections through some interfaces, apparatuses, or units, or they may be electrical, mechanical, or other forms of connection.

[0145] The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the units can be selected to achieve the purpose of the embodiments of this application, depending on actual needs.

[0146] Furthermore, the functional units in the various embodiments of this application can be integrated into one processing unit, or each unit can exist physically separately, or two or more units can be integrated into one unit. The integrated unit can be implemented in hardware or as a software functional unit.

[0147] If the integrated unit is implemented as a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of this application, in essence, or the part that contributes to the prior art, or all or part of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of this application. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0148] This application uses specific embodiments to illustrate the principles and implementation methods of this application. The description of the above embodiments is only for the purpose of helping to understand the method and core ideas of this application. At the same time, for those skilled in the art, there will be changes in the specific implementation methods and application scope based on the ideas of this application. Therefore, the content of this specification should not be construed as a limitation of this application.

Claims

1. A wearable dual-modal imaging probe device, characterized in that, include: Single-mode fiber, scanning assembly, objective lens, ultrasonic transducer, fluorescence signal collector, connection assembly, and wearable assembly; The single-mode fiber-coupled laser transmitter is used to receive and transmit the first laser and the second laser emitted by the laser transmitter, as well as to receive and transmit the fluorescence signal generated by the object under test. The scanning component is used to reflect and perform two-dimensional grating scanning on the laser emitted from the single-mode fiber. The objective lens is used to focus the beam scanned by the two-dimensional grating onto the object under test. The object under test generates a photoacoustic signal under the excitation of the first laser correlation beam and a fluorescence signal under the excitation of the second laser correlation beam. The fluorescence signal at the focal plane passes through the objective lens and the scanning component in sequence and enters the single-mode optical fiber. The ultrasonic transducer is disposed at the end of the objective lens near the object under test and is used to collect photoacoustic signals; the fluorescence signal collector is coupled to the single-mode optical fiber and is used to collect the fluorescence signal transmitted by the single-mode optical fiber. The connecting component is disposed on the outside of the objective lens, the wearable component can be disposed on the object being tested, and the connecting component is detachably fixed to the wearable component.

2. The apparatus as claimed in claim 1, characterized in that, The wavelength of the first laser is 558 / 570±σ nanometers, where σ is a preset value, and the maximum excitation wavelength of the second laser is 488 nanometers.

3. The apparatus as described in claim 1, characterized in that, Also includes: Fiber optic collimator; The fiber collimator is used to perform parallel conversion on the first laser and the second laser emitted from the single-mode fiber to obtain a parallel beam, which is then incident on the scanning component.

4. The apparatus as claimed in claim 1, characterized in that, The scanning components include: a dual-axis microelectromechanical system scanner and a scanning lens; The dual-axis microelectromechanical system scanner is used to reflect and perform two-dimensional grating scanning on the first and second lasers emitted from the single-mode fiber. The scanning lens is used to generate a flat image plane based on the beam scanned by the two-dimensional grating.

5. The apparatus as claimed in claim 1, characterized in that, The fluorescence signal collector includes: an optical fiber coupler, a first dichroic mirror, and a photomultiplier tube; The fiber coupler connects to the single-mode fiber; The first dichroic mirror is used to reflect the fluorescence signal transmitted in the single-mode fiber to the photomultiplier tube; the first dichroic mirror is also used to transmit a first laser, which enters the single-mode fiber through an optical fiber coupler. The photomultiplier tube is used to convert the fluorescence signal into an electrical signal and store it.

6. The apparatus as claimed in claim 1, characterized in that, The outer side of the connecting component is provided with external threads; The wearable component includes a sleeve, at least one base plate, and screws; The sleeve is provided with an internal thread, which, by engaging with the external thread, allows the sleeve to be fastened to the connecting assembly and the position of the focusing point to be adjusted. The screw is disposed on the sleeve to securely fix the sleeve to the connecting assembly; The base plate is fixed to the sleeve and is designed for wearable installation on the object being tested.

7. The apparatus as claimed in claim 1, characterized in that, Also includes: main body; The shape of the main body is set according to the optical path of the signal; The single-mode optical fiber is disposed within the main body, and the scanning component and the objective lens are disposed within the main body by screws.

8. A dual-modal imaging detection system, characterized in that, include: The first laser emitter, the second laser emitter, and the wearable dual-modal imaging probe device according to any one of claims 1 to 7; The first laser emitter is used to emit a first laser beam into the single-mode fiber, and the second laser emitter is used to emit a second laser beam into the single-mode fiber.

9. The system as described in claim 8, characterized in that, Also includes: Second dichroic mirror; The second dichroic mirror is located on one side of the second laser emitter and is used to reflect the second laser into the single-mode fiber.

10. The system as described in claim 9, characterized in that, The second dichroic mirror is located between the first dichroic mirror and the fiber coupler, and the second dichroic mirror is also used to transmit the first laser and fluorescence signals.

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