Photoacoustic brain imaging system and imaging method based on PVDF-ITO transparent transducer skull window

Abstract

The application discloses a photoacoustic brain imaging system and imaging method based on a PVDF-ITO transparent transducer skull window, and the system comprises an arc-shaped transparent transducer, a transparent transducer skull window and a photoacoustic brain imaging system. The arc-shaped transparent transducer is composed of an ITO electrode, PVDF piezoelectric material, a silver wire, an epoxy resin backing layer and an arc-shaped structure matching layer. The transparent transducer skull window is connected with the arc-shaped transparent transducer and the scalp through a transducer connecting ring and is sealed and fixed. The photoacoustic brain imaging system comprises an optical excitation scanning module and a signal processing reconstruction module. The optical excitation scanning module is driven by a two-dimensional galvanometer to realize non-contact rapid scanning of a double-wavelength excitation light source on the surface of the transparent transducer. The signal processing reconstruction module restores the photoacoustic signals received by the transducer skull window into a photoacoustic brain image. The application has the advantages that the transparent skull window is converted into an active sensing device, and the dual functions of an optical transparent imaging window and ultrasonic transducer detection are realized.

Description

Technical Field

[0001] This invention relates to the field of photoacoustic imaging technology, specifically to a photoacoustic brain imaging system and method based on a PVDF-ITO transparent transducer cranial window. Background Technology

[0002] Cranial windows are widely used in traditional optical imaging fields such as two-photon fluorescence microscopy, optical coherence tomography, and laser speckle contrast imaging. Transparent imaging cranial windows not only overcome the light scattering caused by the skull but also preserve the brain's physiological environment, allowing for long-term, direct imaging monitoring of the brain and providing a more comprehensive understanding of brain function. Photoacoustic imaging is a non-invasive imaging technique that combines optical and ultrasound imaging. It possesses the high contrast and high resolution of optical imaging with the high penetration of ultrasound imaging. Photoacoustic imaging is based on the fundamental principle that light generates sound. When short-pulse laser light is irradiated onto biological tissue, the tissue absorbs the pulse energy and rapidly expands, generating ultrasound, i.e., a photoacoustic signal. Based on this signal, an image reflecting the structure and function of the biological tissue can be reconstructed. Photoacoustic imaging overcomes some of the shortcomings of traditional imaging methods. For example, compared with optical coherence tomography (OCT), the measurement depth of OCT is limited to the shallow layer on the order of millimeters due to the strong optical scattering of tissues, while photoacoustic imaging technology can reach the order of centimeters. Compared with pure ultrasound imaging, ultrasound imaging has very low contrast in areas where the acoustic impedance is not much different, while photoacoustic imaging uses the absorption differences of different tissues to reconstruct high-contrast images.

[0003] Although the development of cranial windows has significantly enhanced the resolution of optical brain imaging, with the deepening of applied research, high-resolution optical imaging based on cranial windows is limited by the high scattering characteristics of dense brain tissue and the influence of the curvature structure of the skull. Unlike pure optical imaging techniques, in photoacoustic imaging, the cranial window material needs to simultaneously satisfy optical and acoustic transparency. Considering that photoacoustic brain imaging requires the simultaneous reception of photoacoustic signals, piezoelectric materials with optical transparency are the preferred solution for preparing photoacoustic brain imaging devices. The transparent imaging cranial window in this patent, made of transparent indium tin oxide (ITO) electrodes, polyvinylidene fluoride (PVDF) piezoelectric material, epoxy resin backing, and matching layer, not only overcomes the light scattering effect caused by the skull but also preserves the physiological environment of the brain, allowing for long-term, intuitive imaging monitoring of the brain and establishing a more comprehensive understanding of brain function. In research on photoacoustic imaging using transducers made from transparent piezoelectric materials, patent application No. 202110861125.3 discloses a highly sensitive, fully transparent photoacoustic detector and endoscope based on a transparent flexible composite electrode. However, the double-sided polished polarized lithium niobate piezoelectric crystal material used in this design is less flexible than PVDF piezoelectric materials, making it impossible to match the arcuate features of the skull's natural anatomy to create a transducer cranial window. This results in a small effective detection range and an inability to acquire whole-brain photoacoustic imaging. In research on photoacoustic imaging using arcuate transducers, patent application No. 202110925648.X discloses an arcuate transducer array and its fabrication method. However, this method uses a 3D-printed small curved mesh mold, which is inferior to designing a mold matching the skull's curvature based on a three-dimensional skull model. This method cannot match the skull's morphological structure, leading to increased acoustic impedance and failing to improve acoustic detection sensitivity. In flexible substrate curved surface photoacoustic imaging systems, patent application No. 201610743856.7 discloses a flexible substrate MEMS device curved surface array photoacoustic imaging system. The MEMS acoustic transducer array layer, flexible printed circuit board interconnect layer, MEMS micromirror array and fiber optic channel layer used in this design have lower light transmittance than tin-indium oxide (ITO) electrodes, polyvinylidene fluoride (PVDF) piezoelectric materials and epoxy resin backing materials, and cannot achieve a light transmittance greater than 80%, resulting in a weakening of the optical excitation signal and the inability to obtain high-resolution photoacoustic imaging. Summary of the Invention

[0004] The main objective of this invention is to introduce transparent craniotomy technology into photoacoustic brain imaging, overcoming the problem that complex surgical procedures in high-resolution optical imaging can damage the skull and cause dura mater infection, resulting in damage to the rich nerve and immune system on the skull and dura mater. This invention provides a photoacoustic brain imaging system and method based on a PVDF-ITO transparent transducer craniotomy, which enables accurate, long-term, and safe imaging of brain microvessels while ensuring the integrity of the skull and immune system, thus providing technical support for the research of chronic cerebrovascular diseases.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] In a first aspect, the present invention provides a photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window, comprising an arc-shaped transparent transducer, a transparent transducer cranial window, and a photoacoustic brain imaging unit. The arc-shaped transparent transducer is connected to the transparent transducer cranial window, and a pulsed laser is imaged in the photoacoustic brain imaging unit after passing through the transparent transducer cranial window, wherein:

[0007] The arc-shaped transparent transducer is made of a transparent tin-indium oxide (ITO) electrode, polyvinylidene fluoride (PVDF) piezoelectric material, silver wire, epoxy resin backing layer, and arc-shaped matching layer, and is designed according to the arc-shaped structure of the skull. In an inverted stainless steel fixture, the epoxy resin backing layer, the first silver wire, the designed PVDF-ITO piezoelectric film, the second silver wire, and the matching layer are placed in sequence, and a small amount of epoxy resin is applied between each structural layer for fixation. The PVDF-ITO piezoelectric film is an ITO-PVDF-ITO sandwich film structure.

[0008] The transparent transducer cranial window seals the arc-shaped transparent transducer with the scalp tissue through a transducer connecting ring, ensuring the stability of the physiological state of the surgical site and preventing damage to the skull structure during the cranial window preparation process. The transparent transducer cranial window provides an optically transparent imaging window while also receiving photoacoustic signals.

[0009] The photoacoustic brain imaging unit includes an optical excitation scanning module and a signal processing and reconstruction module. The optical excitation scanning module includes, in sequence, a 532nm laser, a first aperture, a first fiber coupler, a first fiber jumper, a first fiber collimator, and a first reflector; in sequence, a 1064nm laser, a second aperture, a second fiber coupler, a second fiber jumper, a second fiber collimator, and a second reflector; a two-dimensional galvanometer scanner and a scanning lens; the first and second reflectors are connected to the two-dimensional galvanometer scanner, which is connected to the scanning lens. The signal processing and reconstruction module includes, in sequence, a pre-amplification and filtering system, a data acquisition system, an image processor, and a display. The signal processing and reconstruction module restores the photoacoustic signal received by the transparent transducer cranial window into a photoacoustic brain image, and after amplification and filtering, reconstructs a high-resolution three-dimensional photoacoustic brain image.

[0010] As a preferred technical solution, the fabrication process of the arc-shaped transparent transducer is as follows:

[0011] Obtain skull parameters of the target imaging animal model, obtain a high-precision backing model, and obtain the epoxy resin backing layer by molding.

[0012] Polishing the upper and lower surfaces of the epoxy resin backing layer increases its optical transmittance.

[0013] Invert the stainless steel jig with release agent and place the epoxy resin backing layer, the first silver wire, the PVDF-ITO piezoelectric film, the second silver wire, and the matching layer in sequence. Apply a small amount of epoxy resin between each structural layer for fixation.

[0014] After a PDMS protective layer is added on top of the matching layer, it is pressed together by a stainless steel fixture and then placed in an insulated box for curing.

[0015] The cured, curved, transparent transducer is fixed to the connecting ring using potting compound.

[0016] As a preferred technical solution, the fabrication process of the transparent transducer cranial window is as follows:

[0017] First, hair removal is performed on the skin according to the target imaging area. Surgical scissors are used to remove the scalp above the skull. The shape and size of the exposed area above the skull are matched with the designed curved transparent transducer.

[0018] The skin was cleaned and treated to stop bleeding and reduce inflammation. Physiological saline solution was applied to the top of the skull to keep it moist.

[0019] Using α-cyanoacrylate, the designed arc-shaped transparent transducer is quickly hemostatically bonded to the surgically removed skin edge to maintain internal homeostasis.

[0020] A fixed structure is used to securely connect the transparent transducer connecting ring to the surrounding skin;

[0021] The electrical signal generated by the PVDF-ITO piezoelectric film after receiving the photoacoustic signal is extracted by connecting a high-frequency coaxial shielded wire to a silver wire in the conductor.

[0022] A PDMS protective layer is added above the curved transparent transducer to protect the surface of the transducer in contact with the outside world and prevent damage to the polished backing surface. This layer is removed during imaging.

[0023] As a preferred technical solution, the polyvinylidene fluoride (PVDF) piezoelectric material can be designed with a large-area transducer window that matches the arc-shaped structure of the skull; the PVDF piezoelectric material can contact and coexist with skin tissue for a long time, establishing a long-term stable imaging window; the PVDF piezoelectric material has a transmittance of more than 80% in both the visible and near-infrared bands.

[0024] As a preferred technical solution, the PVDF-ITO piezoelectric film has a designed thickness of 10μm-50μm; the PVDF-ITO piezoelectric film has strong resistance to deformation and a Young's modulus higher than 2.5GPa; the dielectric constant of the PVDF-ITO piezoelectric film is 10-50.

[0025] As a preferred technical solution, before fabricating the arc-shaped transparent transducer, the three-dimensional morphological parameters of the target skull are first obtained, and then a three-dimensional model of the skull is established using three-dimensional modeling software based on the morphological parameters. A mold matching the curvature of the skull is then designed independently with reference to the three-dimensional model of the skull.

[0026] As a preferred technical solution, in the arc-shaped transparent transducer, the backing layer of the transparent transducer is made of epoxy resin material, and the three-dimensional mold is made into an arc-shaped structure after the epoxy resin is mixed in a certain proportion; the arc-shaped structure ensures the matching of the transducer with the skull structure and space, reduces the gap between the two layers, and improves the acoustic detection sensitivity.

[0027] As a preferred technical solution, the matching layer of the arc-shaped transparent transducer is designed according to the acoustic impedance parameters of the skull of different animal models to reduce the reflection of sound waves from the skull to the transducer.

[0028] As a preferred technical solution, before preparing the transparent transducer cranial window, the skin above the skull is removed using surgical scissors to expose the target imaging brain region. Then, the connecting ring of the arc-shaped transparent transducer and the skin edge are sealed and fixed using a bio-adhesive of α-cyanoacrylate and dental cement to keep the skull moist and the internal environment stable. No manipulation of the skull is required during the cranial window creation process.

[0029] Secondly, the present invention provides an imaging method for a photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window, comprising the following steps:

[0030] The system consists of two excitation optical paths: a 532nm laser and a 1064nm laser. The 532nm laser passes through a first aperture, a first fiber coupler, a first fiber jumper, a first fiber collimator, and a first mirror; the 1064nm laser passes through a second aperture, a second fiber coupler, a second fiber jumper, a second fiber collimator, a second mirror, and a first mirror. After the two optical paths are overlapped, they pass through a two-dimensional galvanometer scanner, which is connected to a scanning lens. The two optical paths are collimated and focused separately to ensure optimal resolution for both wavelengths while adjusting the distance between the two focal points to create an extended depth of focus, increasing the imaging depth. The signal processing and reconstruction module restores the photoacoustic signal received by the transparent transducer cranial window into a photoacoustic brain image. After amplification and filtering, a high-resolution three-dimensional photoacoustic brain image is reconstructed.

[0031] The galvanometer scanning system is driven by a continuous sawtooth wave to perform continuous scanning, thereby achieving non-contact scanning imaging of the transparent cranial window area.

[0032] The input of the signal processing and reconstruction module is connected to the output of the transparent transducer cranial window. The transducer amplifies and filters the photoacoustic signal received by the transparent transducer to reconstruct a three-dimensional photoacoustic brain image of the target area.

[0033] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0034] This invention innovatively proposes the use of flexible PVDF material based on ITO transparent electrodes to develop a transparent transducer cranial window for photoacoustic brain imaging. The established transducer cranial window and photoacoustic brain imaging system have the following characteristics: (a) It has the dual function of providing an optically transparent imaging window and receiving photoacoustic signals; (b) PVDF material has good flexibility, and an imaging cranial window matching the structural features of the skull can be designed according to the arcuate structure of the skull; (c) PVDF material is biocompatible, and a long-term stable imaging window can be established, avoiding the inflammatory response caused by repeated surgical operations required in long-term optical imaging monitoring, and is expected to enable long-term stable longitudinal studies of chronic brain disease models; (d) Combining the transducer cranial window with laser scanning technology enables non-contact, rapid photoacoustic brain imaging, avoiding the configuration of traditional photoacoustic integrated contact imaging probes, and enabling imaging of mice in an awake state; (e) By controlling the two-dimensional galvanometer scanning system, flexible and free switching between large-scale whole-brain imaging and real-time imaging of specific brain regions can be achieved. Attached Figure Description

[0035] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying 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.

[0036] Figure 1 This is a schematic diagram of the photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to the present invention;

[0037] Figure 2 (a) Figure 2 (b) and Figure 2 (c) is a schematic diagram of the development of the PVDF-ITO transparent transducer in this embodiment.

[0038] Figure 3 This is a schematic diagram of the establishment of the PVDF-ITO transparent transducer cranial window in this embodiment.

[0039] Figure 4 This is an overall schematic diagram of the PVDF-ITO transparent transducer cranial window in this embodiment.

[0040] Figure 5This is a schematic diagram of the photoacoustic brain structure and function imaging system in this embodiment.

[0041] Figure 6 This is a schematic diagram of blood vessel imaging in this embodiment.

[0042] Figure numbering explanations: 1. Pulsed laser; 2. Epoxy resin backing layer; 3. ITO electrode; 4. PVDF material; 5. Fixation structure; 6. Matching layer; 7. Skin; 8. Brain structure; 9. Skull; 10. Conductive silver wire; 11. Photoacoustic signal; 12. Stainless steel fixture; 13. PVDF-ITO piezoelectric film; 14. First signal line; 15. Connecting ring; 16. Transparent arc transducer; 17. Epidermal tissue; 18. Cerebral blood vessels; 19. Second signal line; 20. Transparent transducer cranial window; 21. Scanning lens; 22. 532nm laser; 23. 1064nm laser; 24. Aperture; 25. Fiber optic coupler; 26. Fiber optic jumper; 27. Fiber optic collimator; 28. Mirror; 29. ​​Two-dimensional galvanometer scanner; 30. Mouse; 31. Display; 32. Graphics processor; 33. Data acquisition system; 34. Preamplifier and filter system. Detailed Implementation

[0043] 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 with reference to the accompanying drawings. Obviously, the described embodiments are merely some embodiments of the present application, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present application without creative effort are within the scope of protection of the present application.

[0044] Example

[0045] like Figure 1 As shown, this embodiment discloses a photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window, including an arc-shaped transparent transducer, a transparent transducer cranial window, and a photoacoustic brain imaging unit. The arc-shaped transparent transducer is connected to the transparent transducer cranial window, and the pulsed laser 1 is imaged in the photoacoustic brain imaging unit after passing through the transparent transducer cranial window.

[0046] Furthermore, the arc-shaped transparent transducer 16 is made of ITO electrode 3 (transparent tin-indium oxide), PVDF piezoelectric material 4 (polyvinylidene fluoride), conductive silver wire 10, epoxy resin backing layer 2 and matching layer 6, and is designed according to the arc-shaped structure of the skull 9.

[0047] Understandably, ITO is a commonly used transparent electrode material with a transmittance of over 60% in the 450nm-1100nm range, which is far higher than many other transparent conductors.

[0048] PVDF piezoelectric materials possess wide bandwidth, low acoustic impedance, and high receiver sensitivity, making them ideal for receiving broadband photoacoustic signals in photoacoustic imaging. Furthermore, the mechanical flexibility of PVDF allows for customized shapes to meet specific research needs. In terms of optical performance, PVDF exhibits high transmittance (>80%) in the visible and near-infrared bands. Therefore, combining the advantages of PVDF-ITO materials holds promise for developing high-performance transparent ultrasonic transducers for photoacoustic imaging.

[0049] like Figure 2 (a)- Figure 2 As shown in (c), the fabrication process of the arc-shaped transparent transducer is as follows:

[0050] (1) Based on the requirements of acoustic parameters in brain imaging, COMSOL simulation software and Field II toolkit in MATLAB were used to simulate and analyze the performance of PVDF-ITO piezoelectric film to obtain the optimal solution of acoustic, optical and electrical impedance parameters of piezoelectric material;

[0051] (2) A backing structure matching the curvature of the mouse skull was designed using SolidWorks. A high-precision backing model was obtained by 3D printing. The epoxy resin backing layer 2 was obtained by using the backing model through a molding process.

[0052] (3) Polish the upper and lower surfaces of the epoxy resin backing layer to increase its optical transmittance.

[0053] (4) Invert the stainless steel fixture 12 with release agent, and place the epoxy resin backing layer 2, the first conductor silver wire, the designed PVDF-ITO piezoelectric film, the second conductor silver wire, and the matching layer in sequence. Apply a small amount of epoxy resin between each structural layer for fixation, press it with the stainless steel fixture, and then put it into the heat preservation box for curing.

[0054] Furthermore, the PVDF-ITO piezoelectric film has an ITO-PVDF-ITO sandwich film structure, and the designed thickness of the PVDF-ITO piezoelectric film is 10μm-50μm; the PVDF-ITO piezoelectric film has strong resistance to deformation and a Young's modulus higher than 2.5GPa; the dielectric constant of the PVDF-ITO piezoelectric film is 10-50.

[0055] In one embodiment of this application, the transparent transducer cranial window 20 is sealed to the scalp tissue via a connecting ring 15, ensuring the stability of the physiological state of the surgical site and preventing damage to the skull structure during the preparation of the cranial window. The transducer cranial window provides an optically transparent imaging window 20 while also receiving photoacoustic signals, which are transmitted via a first signal line 14 and a second signal line 19.

[0056] Furthermore, a transducer cranial window can be created surgically, with the specific expected results as follows: Figure 3 As shown, the specific model is established as follows: Figure 4 As shown.

[0057] The fabrication process of the transparent transducer cranial window is as follows:

[0058] (1) First, the epidermal tissue 17 is treated with hair removal according to the target imaging area. The scalp above the skull 9 in the brain structure 8 is removed using surgical scissors. The shape and size of the exposed position above the skull match the designed arc-shaped transparent transducer. This embodiment uses a mouse 30 as an example for illustration.

[0059] (2) Clean and disinfect the skin 7 to stop bleeding and reduce inflammation. Apply saline solution to the top of the skull to keep the skull moist. Use a fixation structure to quickly stop bleeding and bond the designed transparent transducer to the edge of the surgically removed skin to maintain the homeostasis of the internal environment. Commonly used fixation structures are dental cement and α-cyanoacrylate. (3) Use potting compound to fix the cured arc-shaped transparent transducer to the connecting ring.

[0060] (4) Use dental cement or bone cement to fix the transparent transducer connecting ring to the surrounding skin, and export the piezoelectric signal generated by PVDF-ITO by connecting it to the silver wire of the conductor through a high-frequency coaxial shielded wire.

[0061] In one embodiment of this application, an imaging system integrating visible / near-infrared deep imaging and functional imaging based on stimulated Raman scattering is described as follows: Figure 5 As shown; the principle of a high-resolution, deep-depth photoacoustic brain structure and function imaging system based on rapid galvanometer scanning is as follows:

[0062] Lasers with wavelengths of 532nm and 1064nm are used as excitation sources for photoacoustic imaging. A dichroic mirror is used to combine the beams to obtain a light source that is excited by alternating wavelengths of 532nm and 1064nm. Vascular information of the cerebral cortex is obtained by excitation with 532nm light, while vascular information of the deep brain is obtained by excitation with near-infrared light. High-resolution, deep-depth imaging of brain blood vessels is achieved through wavelength complementarity.

[0063] Furthermore, the photoacoustic brain imaging unit includes an optical excitation scanning module and a signal processing and reconstruction module; wherein the optical excitation scanning module includes a 532nm laser 22, a 1064nm laser 23, an aperture 24, an optical fiber coupler 25, an optical fiber jumper 26, an optical fiber collimator 27, a reflector 28, a two-dimensional galvanometer scanner 29, and a scanning lens 21; the optical excitation scanning module includes two optical paths, the first optical path including: a 532nm laser, a first aperture, a first optical fiber coupler, a first optical fiber jumper, a first optical fiber collimator, and a first reflector connected in sequence; the second optical path including: a 1064nm laser, a second aperture, a second optical fiber coupler, a second optical fiber jumper, a second optical fiber collimator, and a second reflector connected in sequence; The first and second reflecting mirrors are connected to a two-dimensional galvanometer scanner, which is connected to a scanning lens. The signal processing and reconstruction module includes a pre-amplification and filtering system, a data acquisition system, an image processor, and a display connected in sequence. The signal processing and reconstruction module restores the photoacoustic signal 11 received by the transparent transducer cranial window into a photoacoustic brain image, and reconstructs a high-resolution three-dimensional photoacoustic brain image after amplification and filtering. The signal processing and reconstruction module includes a pre-amplification and filtering system 34, a data acquisition system 33, an image processor 32, and a display 31 connected in sequence. The signal processing and reconstruction module restores the photoacoustic signal received by the transparent transducer cranial window into a photoacoustic brain image, and reconstructs a high-resolution three-dimensional photoacoustic brain image after amplification and filtering.

[0064] In another embodiment of this application, the imaging method of the photoacoustic brain imaging system based on the PVDF-ITO transparent transducer cranial window includes the following steps:

[0065] The FPGA timing control system enables laser excitation and control of near-infrared and visible light, and the galvanometer scanning system uses continuous sawtooth wave drive for continuous scanning.

[0066] The energy of the excitation light pulse is monitored using a photodiode, which is then used to correct and compensate for the functional imaging.

[0067] Write scanning control, data acquisition, and imaging programs using LabVIEW software.

[0068] GPU-accelerated signal processing, multi-wavelength signal reconstruction, image registration, and real-time display.

[0069] In this embodiment, the photoacoustic brain imaging method and system based on a PVDF-ITO transparent transducer cranial window produce images such as... Figure 6 As shown, from Figure 6 The distribution of the entire cerebral vascular network can be seen, enabling high-resolution deep imaging of the cerebral cortex and deep cerebral blood vessels.

[0070] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise explicitly limited. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0071] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0072] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window, characterized in that, The system includes an arc-shaped transparent transducer, a transparent transducer cranial window, and a photoacoustic brain imaging unit. The arc-shaped transparent transducer is connected to the transparent transducer cranial window. Pulsed laser light passes through the transparent transducer cranial window and is imaged in the photoacoustic brain imaging unit. The arc-shaped transparent transducer is made of a transparent tin-indium oxide (ITO) electrode, polyvinylidene fluoride (PVDF) piezoelectric material, silver wire, epoxy resin backing layer, and arc-shaped matching layer, and is designed according to the arc-shaped structure of the skull. In an inverted stainless steel fixture, the epoxy resin backing layer, the first silver wire, the designed PVDF-ITO piezoelectric film, the second silver wire, and the matching layer are placed in sequence, and a small amount of epoxy resin is applied between each structural layer for fixation. The PVDF-ITO piezoelectric film is an ITO-PVDF-ITO sandwich film structure. The transparent transducer cranial window seals the arc-shaped transparent transducer with the scalp tissue through a transducer connecting ring, ensuring the stability of the physiological state of the surgical site and preventing damage to the skull structure during the cranial window preparation process. The transparent transducer cranial window provides an optically transparent imaging window while also receiving photoacoustic signals. The photoacoustic brain imaging unit includes an optical excitation scanning module and a signal processing and reconstruction module. The optical excitation scanning module includes, in sequence, a 532nm laser, a first aperture, a first fiber coupler, a first fiber jumper, a first fiber collimator, and a first reflector; in sequence, a 1064nm laser, a second aperture, a second fiber coupler, a second fiber jumper, a second fiber collimator, and a second reflector; a two-dimensional galvanometer scanner and a scanning lens; the first and second reflectors are connected to the two-dimensional galvanometer scanner, which is connected to the scanning lens. The signal processing and reconstruction module includes, in sequence, a pre-amplification and filtering system, a data acquisition system, an image processor, and a display. The signal processing and reconstruction module restores the photoacoustic signal received by the transparent transducer cranial window into a photoacoustic brain image, and after amplification and filtering, reconstructs a high-resolution three-dimensional photoacoustic brain image.

2. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, The fabrication process of the arc-shaped transparent transducer is as follows: Obtain skull parameters of the target imaging animal model, obtain a high-precision backing model, and obtain the epoxy resin backing layer by molding. Polishing the upper and lower surfaces of the epoxy resin backing layer increases its optical transmittance. Invert the stainless steel jig with release agent and place the epoxy resin backing layer, the first conductor silver wire, the PVDF-ITO piezoelectric film, the second conductor silver wire and the matching layer in sequence. Apply a small amount of epoxy resin between each structural layer for fixation. After a PDMS protective layer is added on top of the matching layer, it is pressed together by a stainless steel fixture and then placed in an insulated box for curing. The cured, curved, transparent transducer is fixed to the connecting ring using potting compound.

3. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, The fabrication process of the transparent transducer cranial window is as follows: First, hair removal is performed on the skin according to the target imaging area. Surgical scissors are used to remove the scalp above the skull. The shape and size of the exposed area above the skull are matched with the designed curved transparent transducer. The skin was cleaned and treated to stop bleeding and reduce inflammation. Physiological saline solution was applied to the top of the skull to keep it moist. use α - Cyanoacrylate allows for rapid hemostasis and adhesion between the designed arc-shaped transparent transducer and the surgically removed skin edge, maintaining homeostasis of the internal environment; A fixed structure is used to securely connect the transparent transducer connecting ring to the surrounding skin; The electrical signal generated by the PVDF-ITO piezoelectric film after receiving the photoacoustic signal is extracted by connecting a high-frequency coaxial shielded wire to a silver wire in the conductor. A PDMS protective layer is added above the curved transparent transducer to protect the surface of the transducer in contact with the outside world and prevent damage to the polished backing surface. This layer is removed during imaging.

4. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, The polyvinylidene fluoride (PVDF) piezoelectric material can be designed with a large-area transducer window that matches the arc-shaped structure of the skull; the PVDF piezoelectric material can contact and coexist with skin tissue for a long time, establishing a long-term stable imaging window; the PVDF piezoelectric material has a transmittance of more than 80% in both the visible and near-infrared bands.

5. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, The PVDF-ITO piezoelectric film has a designed thickness of 10 μm-50 μm; the PVDF-ITO piezoelectric film has strong resistance to deformation and a Young's modulus higher than 2.5 GPa; the dielectric constant of the PVDF-ITO piezoelectric film is 10-50.

6. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, Before fabricating the arc-shaped transparent transducer, the three-dimensional morphological parameters of the target skull are first obtained. Then, a three-dimensional model of the skull is established using three-dimensional modeling software based on the morphological parameters. A mold matching the curvature of the skull is designed independently with reference to the three-dimensional model of the skull.

7. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 6, characterized in that, In the aforementioned arc-shaped transparent transducer, the backing layer of the transparent transducer is made of epoxy resin material. The epoxy resin is mixed in a certain proportion and then molded into an arc-shaped structure using a three-dimensional mold. The arc-shaped structure ensures the matching of the transducer with the skull structure and space, reduces the gap between the two layers, and improves the acoustic detection sensitivity.

8. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, The matching layer of the arc-shaped transparent transducer is designed according to the acoustic impedance parameters of the skull of different animal models to reduce the reflection of sound waves from the skull to the transducer.

9. The photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to claim 1, characterized in that, Before preparing the transparent transducer cranial window, the skin above the skull is removed using surgical scissors to expose the target imaging brain region. Then, a bio-adhesive of α-cyanoacrylate and dental cement is used to seal and fix the connecting ring of the arc-shaped transparent transducer to the skin edge, keeping the skull moist and the internal environment stable. No manipulation of the skull is required during the cranial window creation process.

10. The imaging method of the photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window according to any one of claims 1-9, characterized in that, Includes the following steps: The system consists of two excitation optical paths: a 532nm laser and a 1064nm laser. The 532nm laser passes through a first aperture, a first fiber coupler, a first fiber jumper, a first fiber collimator, and a first mirror; the 1064nm laser passes through a second aperture, a second fiber coupler, a second fiber jumper, a second fiber collimator, a second mirror, and a first mirror. After the two optical paths are overlapped, they pass through a two-dimensional galvanometer scanner, which is connected to a scanning lens. The two optical paths are collimated and focused separately to ensure optimal resolution for both wavelengths while adjusting the distance between the two focal points to create an extended depth of focus, increasing the imaging depth. The signal processing and reconstruction module restores the photoacoustic signal received by the transparent transducer cranial window into a photoacoustic brain image. After amplification and filtering, a high-resolution three-dimensional photoacoustic brain image is reconstructed. The galvanometer scanning system is driven by a continuous sawtooth wave to perform continuous scanning, enabling non-contact scanning imaging of the transparent cranial window area; The input of the signal processing and reconstruction module is connected to the output of the transparent transducer cranial window. The transducer amplifies and filters the photoacoustic signal received by the transparent transducer to reconstruct a three-dimensional photoacoustic brain image of the target area.

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