Photoacoustic small animal head-mounted imaging system and method

By combining micro-nano optical lenses and transparent ultrasonic transducers in the photoacoustic small animal head-mounted imaging system, the problem of difficulty in achieving high-resolution and high-speed imaging of the whole cerebral cortex is solved in the prior art, and a uniform resolution of large field of view is achieved. Neurological activity monitoring is suitable for basic scientific research.

CN119385522APending Publication Date: 2025-02-07GUANGDONG GENERAL HOSPITAL
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Patent Information

Application Number
CN202411846803.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-16
Publication Date
2025-02-07

AI Technical Summary

Technical Problem

Existing photoacoustic imaging technology is difficult to achieve high-resolution high-speed imaging of the entire cerebral cortex of awake small animals, especially under large field of vision and arc-shaped characteristics of the brain, with uneven resolution and large equipment size.

Method used

The photoacoustic small animal head-mounted imaging system is used to combine micro-nano optical lenses and transparent ultrasonic transducers to generate a high-resolution excitation beam with a large depth of field through micro-nano optical lenses, and to receive photoacoustic signals using transparent ultrasonic transducers. Achieve interference-free large field of view and high resolution high-speed neural activity monitoring in free-action mice.

Benefits of technology

Overcoming the limitations of head-mounted imaging with small field of vision, uneven resolution and large equipment weight, it has achieved uniform resolution and high-quality neural activity imaging of the entire cerebral cortex of small animals, which is suitable for basic scientific research fields.

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Abstract

The invention discloses a photoacoustic small animal head-mounted imaging method and system. The device comprises a free motion mode photoelectric transmission module, a signal excitation and receiving module, a scanning control module, a miniature fixed supporting structure and an image reconstruction module. The free motion mode photoelectric transmission module comprises a single mode fiber, a collimator, a fixer, a multi-channel hollow brushless electric slip ring and a signal transmission line; the signal excitation and receiving module comprises a micro-nano optical lens, a transparent ultrasonic transducer, an amplifier and a filter. The micro-nano optical lens and the transparent ultrasonic transducer are combined and applied to the small animal head-mounted imaging system for the first time, large-depth-of-field high-resolution excitation photoacoustic is generated through the micro-nano optical lens, and the transparent ultrasonic transducer receives signals, so that the limitations of small visual field, non-uniform resolution, heavy mass and large size of head-mounted imaging are overcome; neural activity imaging covering the visual field of the whole cerebral cortex of the small animal is provided, and the method can be widely applied to the basic scientific research field.
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Description

Technical Field

[0001] The present invention relates to the research field of photoacoustic endoscopy, and in particular to a photoacoustic small animal head-mounted imaging system and method. Background Art

[0002] Monitoring the neural activity of the cerebral cortex of awake small animals is crucial to neuroscience research. During the research process, keeping the animals awake has obvious advantages because it can more accurately reflect the natural physiological state of the animals and avoid the interference of anesthesia on neural activity. Brain cortical imaging in the awake state can provide more realistic and reliable data, helping scientists to deeply understand the neural function and behavioral performance of animals.

[0003] In order to overcome this limitation, various methods have been proposed, and a variety of imaging methods have been used for cortical imaging of awake small animals, such as optical imaging, ultrasound imaging, and photoacoustic imaging. Among them, photoacoustic imaging technology combines the advantages of optics and ultrasound, has high selectivity, resolution, and deep penetration, and can achieve high-resolution imaging of the cerebral cortex of awake small animals. However, there are still limitations. The current imaging field of these methods is limited to a certain small area, and it is impossible to image the entire cortex with a large field of view, and the arched features of the brain cannot achieve uniform resolution imaging. Although there are technologies that solve the imaging limitations of large fields of view and brain arcs, they are limited to large microscopes that fix the mouse head. At present, high-resolution and high-speed imaging of the entire cerebral cortex of freely moving mice is still a challenge. Summary of the invention

[0004] The main purpose of the present invention is to overcome the shortcomings and deficiencies of the prior art and to provide a photoacoustic small animal head-mounted imaging system and method, which is based on the ability to generate micro-nano optical lenses and transparent ultrasonic transducers to produce an excitation light beam with a large depth of field, a small beam waist radius and an ultra-large field of view coverage, while maintaining miniaturization and lightweight, thereby achieving non-interference, large field of view, high-resolution and high-speed neural activity monitoring of freely moving mice.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] In a first aspect, the present invention provides a photoacoustic small animal head-mounted imaging system, comprising a free-motion mode photoelectric transmission module, a signal excitation and receiving module, a scanning control module, a micro-fixed support structure, and an image reconstruction module; the free-motion mode photoelectric transmission module performs signal excitation, signal reception, and transmission of sampling signals and scanning control module command signals, and finally inputs the signals into an image reconstruction module to achieve image reconstruction;

[0007] The free motion mode optoelectronic transmission module comprises a pulse laser, a single-mode optical fiber, a beam expansion and collimation unit, an optical fiber coupler, a first collimation unit, a second collimation unit, a fixture, a multi-channel hollow brushless electric slip ring and a signal transmission line; the optical fiber coupler couples the pulse laser beam passing through the beam expansion and collimation unit into the single-mode optical fiber; the first collimation unit is placed at the optical output end of the single-mode optical fiber and fixed by a fixture for forward optical transmission, and adjusts the output light of the single-mode optical fiber into collimated light; the second collimation unit is coaxially placed opposite to the first collimation unit and fixed to the stator of the multi-channel hollow brushless electric slip ring, and couples the collimated light output by the first collimation unit into the single-mode optical fiber again; the stator of the multi-channel hollow brushless electric slip ring is fixed to the second collimation unit and can rotate freely;

[0008] The signal excitation and receiving module includes a micro-nano optical lens, a transparent ultrasonic transducer, an amplifier and a filter; the micro-nano optical lens determines the focal length according to the designed diffraction structure and is located at the output end of the single-mode optical fiber. The single-mode optical fiber outputs divergent light and enters the micro-nano optical lens, wherein a lens or a lens group is arranged between the optical fiber end and the micro-nano optical lens for light collimation; the light beam shaped by the micro-nano optical lens is irradiated onto the sample through the transparent ultrasonic transducer; the micro-nano optical lens and the transparent ultrasonic transducer are both placed in a micro fixed support structure; the sample signal passes through the amplifier and the filter once;

[0009] The scanning control module includes a micro-MEMS, a MEMS driver and an FPGA; the micro-MEMS performs resonance scanning through a given pulse signal of the FPGA and the control of the MEMS driver;

[0010] The micro-fixation support structure is connected to a detachable small animal brain fixation base;

[0011] The image reconstruction module includes an acquisition card and a computer. The computer stores and processes the acquired data to complete the photoacoustic image reconstruction.

[0012] As a preferred technical solution, in the free motion mode optoelectronic transmission module, the final output end of the single-mode optical fiber is fixed to a micro-fixed support structure, and the divergent light output by the single-mode optical fiber is reflected and scanned by the micro-MEMS through the micro-nano optical lens and irradiated onto the sample through the transparent ultrasonic transducer, thereby exciting a photoacoustic signal and being received by the transparent ultrasonic transducer.

[0013] As a preferred technical solution, the signal transmission line of the free motion mode photoelectric transmission module includes a transparent ultrasonic transducer and a MEMS signal transmission line, both of which are transmitted through a multi-channel hollow brushless electric slip ring to follow the free movement and rotation of the small animal.

[0014] As a preferred technical solution, the micro-nano optical lens is designed and prepared through a diffraction optical design scheme to deform a Gaussian beam into a telephoto beam with a large depth of field and high resolution for output.

[0015] As a preferred technical solution, the transparent ultrasonic transducer is prepared by piezoelectric materials such as lithium niobate or PVDF film and transparent electrodes such as indium tin oxide or silver nanowires to form a piezoelectric receiving device with high light transmittance for receiving photoacoustic signals generated by pulsed light excitation.

[0016] As a preferred technical solution, in the scanning control module, the MEMS is fixed in a micro-support structure and placed between the micro-nano optical lens and the transparent transducer or between the single-mode optical fiber and the micro-nano optical lens according to the imaging field of view; the MEMS drive control signal line is led out by a soft flat cable and transmitted through a multi-channel hollow brushless electric slip ring.

[0017] As a preferred technical solution, the small animal brain base is fixed to the small animal brain through a fixing agent; the single-mode optical fiber, micro-nano optical lens, transparent ultrasonic transducer and micro-MEMS are fixed in a micro-fixed support structure.

[0018] As a preferred technical solution, the shape of the small animal brain fixing base matches the curvature and field of view of the entire small animal cerebral cortex; the micro-fixed support structure is fixed on the small animal brain fixing base, the small animal brain fixing base and the micro-fixed support structure can be disassembled and fixed, and the gaps between the small animal brain fixing base and the micro-fixed support structure and the brain are filled with ultrasonic gel.

[0019] As a preferred technical solution, the amplifier and filter parameter models are designed according to the response sensitivity, main frequency and bandwidth of the transparent ultrasonic transducer; and are used to process the electrical signal generated by the transparent ultrasonic transducer.

[0020] In a second aspect, the present invention provides an imaging method of a photoacoustic small animal head-mounted imaging system, comprising the following steps:

[0021] (1) Fixation of the head-mounted system: The small animal brain fixation base is fixed to the brain of the small animal of interest by dental cement, and then filled with ultrasound gel, and the micro-fixation support structure is fixed to the small animal brain fixation base;

[0022] (2) Excitation and transmission: The pulsed laser is incident into the single-mode optical fiber through the beam expansion collimation unit and the fiber coupler, and is transmitted in the single-mode optical fiber. The parallel light is emitted through the first collimation unit, and then enters the single-mode optical fiber for transmission through the freely rotatable second collimation unit. The light output from the single-mode optical fiber is focused by the micro-nano optical lens, and is reflected by the micro-MEMS. After passing through the transparent ultrasonic transducer, the focused light is irradiated onto the freely moving sample to excite the photoacoustic signal. The signal with uniform resolution over a large field of view is obtained through grating scanning of the beam with a large depth of field.

[0023] (3) Data acquisition: The photoacoustic signal generated by the sample absorbing light energy is transmitted to the transparent ultrasonic transducer through the sound propagation medium and then received. Then, the signal is transmitted through the acquisition signal line, multi-channel hollow brushless electric slip ring, amplifier, filter, and finally to the data acquisition card, and the signal is converted by the AC / DC conversion module on the signal acquisition circuit.

[0024] (4) Image reconstruction and display: The computer stores and processes the collected data to complete the photoacoustic image reconstruction.

[0025] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0026] The present invention combines micro-nano optical lenses and transparent ultrasonic transducers for the first time and applies them to a head-mounted imaging system for small animals. The metasurface generates high-resolution excitation photoacoustics with a large depth of field, and the transparent ultrasonic transducer receives the signal. This overcomes the limitations of head-mounted imaging, such as small field of view, uneven resolution, and heavy mass and large volume. It provides high-quality neural activity imaging with uniform resolution covering the entire cerebral cortex field of small animals, and can be widely used in basic scientific research. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0028] Figure 1 This is a schematic diagram of the structure of a photoacoustic small animal head-mounted imaging system according to an embodiment of the present invention;

[0029] Figure 2 It is a schematic diagram of the overall device of an embodiment of the present invention;

[0030] Figure 3 The figure is a flowchart of the photoacoustic small animal head-mounted imaging system according to an embodiment of the present invention.

[0031] Explanation of the accompanying numbers: 1-single-mode optical fiber, 2-micro fixed support structure, 3-micro-nano optical lens, 4-micro MEMS, 5-transparent ultrasonic transducer, 6-signal transmission line, 7-small animal brain fixing base, 8-sample, 9-collimator, 10-multi-channel hollow brushless electric slip ring, 11-camera, 12-fixture, 13-head-mounted system, 14-pulse laser, 15-amplifier, 16-filter, 17-acquisition card, 18-computer, 19-FPGA, 20-MEMS driver. DETAILED DESCRIPTION

[0032] In order to enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without making creative work are within the scope of protection of the present application.

[0033] Reference to "embodiments" in this application means that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of the phrase in various locations in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described in this application may be combined with other embodiments.

[0034] A micro-nano optical lens for a photoacoustic small animal head-mounted imaging system of the present invention comprises a free-motion mode photoelectric transmission module, a signal excitation and receiving module, a scanning control module, a micro-fixed support structure and an image reconstruction module; the free-motion mode photoelectric transmission module performs signal excitation, signal reception, and transmission of sampling signals and scanning control module command signals, and finally inputs the signals into an image reconstruction module to achieve image reconstruction.

[0035] In a specific embodiment, Figure 1 As shown, the signal excitation and receiving module includes: a micro-nano optical lens 3, a transparent ultrasonic transducer 5, an amplifier 15 and a filter 16; the micro-nano optical lens 3 is designed and prepared through a diffraction optical design scheme, and the Gaussian beam is deformed into a long-focus beam with a large depth of field and high resolution for output. The transparent ultrasonic transducer 5 is prepared by piezoelectric materials such as lithium niobate or PVDF film and transparent electrodes such as indium tin oxide or silver nanowires to form a piezoelectric receiving device with high light transmittance, which is used to receive the photoacoustic signal generated by pulsed light excitation. The parameter models of the amplifier 15 and the filter 16 can be designed according to the response sensitivity, main frequency and bandwidth of the transparent ultrasonic transducer to process the electrical signal generated by the transparent ultrasonic transducer 5.

[0036] Furthermore, the micro-nano optical lens determines the focal length according to the diffraction structure designed by it, and is located at the output end of the single-mode optical fiber. The single-mode optical fiber outputs divergent light and enters the micro-nano optical lens, wherein a lens or a lens group can be set between the optical fiber end and the micro-nano optical lens for light collimation. The light beam shaped by the micro-nano optical lens is irradiated onto the sample through the transparent ultrasonic transducer. The micro-nano optical lens and the transparent ultrasonic transducer are both placed in a micro fixed support structure. The sample signal passes through the amplifier and the filter once.

[0037] In a specific embodiment, Figure 1 As shown, the scanning control module includes: a micro MEMS 4, a MEMS driver 20, and an FPGA 19; the micro MEMS 4 performs resonance scanning through a given pulse signal of the FPGA 19 and the control of the MEMS driver 20.

[0038] In a specific embodiment, Figure 1 As shown, the micro-fixed support structure 2 includes: a small animal brain fixing base 7 and an imaging module base; the small animal brain base 7 is fixed to the small animal brain by biological fixing agents such as dental cement, and the imaging module base mainly provides position fixation for the single-mode optical fiber 1, the micro-nano optical lens 3, the transparent ultrasonic transducer 5 and the micro MEMS 4.

[0039] In a specific embodiment, Figure 2 The free motion mode optoelectronic transmission module includes a pulse laser 14, a single-mode optical fiber 1, an optical fiber coupler, a collimator 9, a fixture 12, a multi-channel hollow brushless electric slip ring 10 and a signal transmission line 6; the collimator 9 includes a beam expansion collimation unit (such as a beam expansion collimation lens or a lens group), a first collimation unit (such as a collimator or a collimation lens) and a second collimation unit (such as a collimator or a collimation lens).

[0040] Furthermore, the optical fiber coupler couples the pulsed laser beam passing through the beam expansion and collimation unit into the single-mode optical fiber;

[0041] Furthermore, the first collimating unit is placed at the light output end of the single-mode optical fiber and fixed by a fixture, and is used for forward light transmission to adjust the output light of the single-mode optical fiber into collimated light;

[0042] Furthermore, the second collimation unit is placed coaxially opposite to the first collimation unit and fixed to the stator of the multi-channel hollow brushless electric slip ring, and the collimated light output by the first collimation unit is coupled into the single-mode optical fiber again; the stator of the multi-channel hollow brushless electric slip ring is fixed to the second collimation unit and can rotate freely.

[0043] like Figure 3As shown, the image reconstruction module includes an acquisition card 17 and a computer 18. The computer stores and processes the acquired data to complete the photoacoustic image reconstruction.

[0044] In a specific embodiment, the signal excitation and receiving module, the design of the micro-nano optical lens 3 can be based on a long-focus design scheme such as the Bessel beam principle or the multi-focus principle to design a large depth of field beam, and can use collimated light or divergent light as input light.

[0045] In a specific embodiment, the signal excitation and receiving module, the transparent ultrasonic transducer 5 can be a planar transducer or a curved arc-shaped transducer adapted to the curvature of the brain, and the size covers the required imaging field of view.

[0046] In a specific embodiment, the scanning control module, the micro-MEMS 4 is placed behind the micro-nano optical lens 3 and before the transparent ultrasonic transducer 5 to scan the light beam focused by the micro-nano optical lens 3;

[0047] In a specific embodiment, in the free motion mode optoelectronic transmission module, the final output end of the single-mode optical fiber 1 is fixed to the imaging module base 2, and the divergent light output by the single-mode optical fiber 1 is reflected and scanned by the micro-MEMS 4 through the micro-nano optical lens 3 and irradiated onto the sample through the transparent ultrasonic transducer 5, thereby exciting a photoacoustic signal and being received by the transparent ultrasonic transducer 5.

[0048] In a specific embodiment, the micro-fixed support structure, the shape of the small animal brain fixed base 7 matches the curvature and field of view of the entire small animal cerebral cortex; the imaging module base 2 is fixed on the small animal brain fixed base 7, and the two can be separated and fixed, and the gap between the two and the sample 8 is filled with ultrasound gel, pure water and other media that can transmit sound.

[0049] In a specific embodiment, the signal transmission line of the free motion mode photoelectric transmission module includes a transparent ultrasonic transducer and a MEMS signal transmission line 8, both of which are transmitted through a multi-channel hollow brushless electric slip ring 10, and can follow the free movement and rotation of the small animal.

[0050] In another embodiment of the present application, an imaging method of a photoacoustic small animal head-mounted imaging system based on a micro-nano optical lens and a transparent ultrasonic transducer is provided, comprising the following steps:

[0051] First, a pretreatment step is performed to fix the small animal brain fixing base 7 to the brain of the small animal of interest through dental cement, and then filled with ultrasonic gel, and the micro-fixation support structure 2 is fixed to the small animal brain fixing base.

[0052] Then, the pulse laser 18 is turned on, and the pulse laser is incident into the single-mode optical fiber through the fixed reverse collimator 9, transmitted in the single-mode optical fiber 1, and emits parallel light through the fixed forward collimator 9, and then enters the single-mode optical fiber 1 again through the freely rotatable reverse collimator 9 for transmission. The light output from the single-mode optical fiber 1 is focused by the micro-nano optical lens 3, and reflected by the micro-MEMS 4. After passing through the transparent ultrasonic transducer 5, the focused light is irradiated onto the freely moving sample 8 to excite the photoacoustic signal, and the large field of view uniform resolution signal is obtained by grating scanning of the large depth of field light beam.

[0053] Secondly, after the signal is excited, the signal is collected. The photoacoustic signal generated by the sample 8 absorbing the light energy is transmitted to the transparent ultrasonic transducer 5 through the sound propagation medium and received, and then passed through the acquisition signal line 8, the multi-channel hollow brushless electric slip ring 10, the amplifier 15, the filter 16, and finally the signal is transmitted to the data acquisition card 17, and the signal is converted by the AC / DC conversion module on the signal acquisition circuit.

[0054] Finally, the collected signals are reconstructed and displayed, and the computer 18 stores and processes the collected data to complete the photoacoustic image reconstruction.

[0055] Those skilled in the art can understand that all or part of the processes in the above-mentioned embodiment methods can be completed by instructing the relevant hardware through a computer program, and the program can be stored in a non-volatile computer-readable storage medium. When the program is executed, it can include the processes of the embodiments of the above-mentioned methods. Among them, any reference to memory, storage, database or other media used in the embodiments provided in this application can include non-volatile and / or volatile memory. Non-volatile memory may include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM) or flash memory. Volatile memory may include random access memory (RAM) or external cache memory. As an illustration and not limitation, RAM is available in many forms, such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDRSDRAM), enhanced SDRAM (ESDRAM), synchronous link (Synchlink) DRAM (SLDRAM), memory bus (Rambus) direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM).

[0056] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0057] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. Micro-nano optical lens for photoacoustic small animal head-mounted imaging system, characterized in that: It includes a free motion mode photoelectric transmission module, a signal excitation and receiving module, a scanning control module, a micro-fixed support structure and an image reconstruction module; the free motion mode photoelectric transmission module performs signal excitation, signal reception, and transmission of sampling signals and scanning control module command signals, and finally inputs the signals into the image reconstruction module to realize image reconstruction; The free motion mode optoelectronic transmission module comprises a pulse laser, a single-mode optical fiber, a beam expansion and collimation unit, an optical fiber coupler, a first collimation unit, a second collimation unit, a fixture, a multi-channel hollow brushless electric slip ring and a signal transmission line; the optical fiber coupler couples the pulse laser beam passing through the beam expansion and collimation unit into the single-mode optical fiber; the first collimation unit is placed at the optical output end of the single-mode optical fiber and fixed by a fixture for forward optical transmission, and adjusts the output light of the single-mode optical fiber into collimated light; the second collimation unit is coaxially placed opposite to the first collimation unit and fixed to the stator of the multi-channel hollow brushless electric slip ring, and couples the collimated light output by the first collimation unit into the single-mode optical fiber again; the stator of the multi-channel hollow brushless electric slip ring is fixed to the second collimation unit and can rotate freely; The signal excitation and receiving module includes a micro-nano optical lens, a transparent ultrasonic transducer, an amplifier and a filter; the micro-nano optical lens determines the focal length according to the designed diffraction structure and is located at the output end of the single-mode optical fiber. The single-mode optical fiber outputs divergent light and enters the micro-nano optical lens, wherein a lens or a lens group is arranged between the optical fiber end and the micro-nano optical lens for light collimation; the light beam shaped by the micro-nano optical lens is irradiated onto the sample through the transparent ultrasonic transducer; the micro-nano optical lens and the transparent ultrasonic transducer are both placed in a micro fixed support structure; the sample signal passes through the amplifier and the filter once; The scanning control module includes a micro-MEMS, a MEMS driver and an FPGA; the micro-MEMS performs resonance scanning through a given pulse signal of the FPGA and the control of the MEMS driver; The micro-fixation support structure is connected to a detachable small animal brain fixation base; The image reconstruction module includes an acquisition card and a computer. The computer stores and processes the acquired data to complete the photoacoustic image reconstruction.

2. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: In the free motion mode photoelectric transmission module, the final output end of the single-mode optical fiber is fixed to a micro-fixed support structure, and the divergent light output by the single-mode optical fiber is reflected and scanned by the micro-MEMS through the micro-nano optical lens and irradiated onto the sample through the transparent ultrasonic transducer, thereby stimulating a photoacoustic signal, which is received by the transparent ultrasonic transducer.

3. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: The signal transmission line of the free motion mode photoelectric transmission module includes a transparent ultrasonic transducer and a MEMS signal transmission line, both of which are transmitted through a multi-channel hollow brushless electric slip ring to follow the free movement and rotation of the small animal.

4. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: The micro-nano optical lens includes a metasurface lens, a metastructure lens and a diffraction optical lens, which uses a sub-wavelength-scale nanostructure to manipulate the phase, amplitude and polarization of light, or etches a microstructure on the surface to design and prepare the propagation direction and shape of the light beam through the diffraction and interference of light, and deforms the Gaussian light beam into a telephoto light beam with a large depth of field and high resolution for output.

5. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: The transparent ultrasonic transducer is prepared by lithium niobate or PVDF film and indium tin oxide or silver nanowires to form a piezoelectric receiving device with high light transmittance, which is used to receive photoacoustic signals generated by pulse light excitation.

6. The micro-nano optical lens of the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: In the scanning control module, the MEMS is fixed in a micro-support structure and is placed between the micro-nano optical lens and the transparent transducer or between the single-mode optical fiber and the micro-nano optical lens according to the imaging field of view; the MEMS drive control signal line is led out by a soft flat cable and transmitted through a multi-channel hollow brushless electric slip ring.

7. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: The small animal brain base is fixed to the small animal brain through a fixing agent; the single-mode optical fiber, micro-nano optical lens, transparent ultrasonic transducer and micro-MEMS are fixed in a micro-fixed supporting structure.

8. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: The shape of the small animal brain fixing base matches the curvature and field of view of the entire small animal cerebral cortex; the micro-fixation support structure is fixed on the small animal brain fixing base, the small animal brain fixing base and the micro-fixation support structure can be disassembled and fixed, and the gap between the small animal brain fixing base and the micro-fixation support structure and the brain is filled with ultrasonic gel.

9. The micro-nano optical lens for the photoacoustic small animal head-mounted imaging system according to claim 1, characterized in that: The amplifier and filter parameter models are designed according to the response sensitivity, main frequency and bandwidth of the transparent ultrasonic transducer; and are used to process the electrical signal generated by the transparent ultrasonic transducer.

10. The imaging method of the photoacoustic small animal head-mounted imaging system according to any one of claims 1 to 9, characterized in that: The steps include: (1) Fixation of the head-mounted system: The small animal brain fixation base is fixed to the brain of the small animal of interest by dental cement, and then filled with ultrasound gel, and the micro-fixation support structure is fixed to the small animal brain fixation base; (2) Excitation and transmission: The pulsed laser is incident into the single-mode optical fiber through the beam expansion collimation unit and the fiber coupler, and is transmitted in the single-mode optical fiber. The parallel light is emitted through the first collimation unit, and then enters the single-mode optical fiber for transmission through the freely rotatable second collimation unit. The light output from the single-mode optical fiber is focused by the micro-nano optical lens, and is reflected by the micro-MEMS. After passing through the transparent ultrasonic transducer, the focused light is irradiated onto the freely moving sample to excite the photoacoustic signal. The signal with uniform resolution over a large field of view is obtained through grating scanning of the beam with a large depth of field. (3) Data acquisition: The photoacoustic signal generated by the sample absorbing light energy is transmitted to the transparent ultrasonic transducer through the sound propagation medium and then received. Then, the signal is transmitted through the acquisition signal line, multi-channel hollow brushless electric slip ring, amplifier, filter, and finally to the data acquisition card, and the signal is converted by the AC / DC conversion module on the signal acquisition circuit. (4) Image reconstruction and display: The computer stores and processes the collected data to complete the photoacoustic image reconstruction.