CN116269216A - Photoacoustic brain imaging system and method based on PVDF-ITO transparent transducer cranium window - Google Patents

Abstract

The invention discloses a photoacoustic brain imaging system and imaging method based on a PVDF‑ITO transparent transducer cranial window. The system includes an arc-shaped transparent transducer, a transparent transducer cranial window, and a photoacoustic brain imaging system; The arc-shaped transparent transducer is composed of ITO electrodes, PVDF piezoelectric materials, wire silver wires, epoxy resin backing layer and arc-shaped structure matching layer; the cranial window of the transparent transducer connects the arc-shaped transparent The transducer is connected to the scalp and sealed and fixed; the photoacoustic brain imaging system includes an optical excitation scanning module and a signal processing and reconstruction module; wherein the optical excitation scanning module is driven by a two-dimensional vibrating mirror to drive a dual-wavelength excitation light source in a transparent transduction The surface of the transducer is scanned quickly without contact; the signal processing and reconstruction module restores the photoacoustic signal received by the cranial window of the transducer into a photoacoustic brain image. The advantage of the invention is that the transparent cranial window is transformed into an active sensing device, and the dual functions of the optically transparent imaging window and ultrasonic transducer detection are realized.

Description

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

technical field

The invention relates to the technical field of photoacoustic imaging, in particular to a photoacoustic brain imaging system and imaging method based on a PVDF-ITO transparent transducer cranial window.

Background technique

Cranial windows are widely used in traditional optical imaging fields such as two-photon fluorescence microscopy, optical coherence tomography, and laser speckle contrast imaging. The transparent imaging cranial window can not only overcome the influence of light scattering brought by the skull, but also preserve the physiological environment of the brain, allowing long-term and intuitive imaging monitoring of the brain, and establishing a more comprehensive understanding of brain function. Photoacoustic imaging is a non-invasive imaging technology that combines optical imaging and ultrasound imaging. It has the characteristics of high contrast and high resolution of optical imaging and high penetration of ultrasound imaging. Photoacoustic imaging is based on the basic principle that light produces sound. When a short-pulse laser is irradiated on biological tissue, the biological tissue absorbs the pulse energy and expands rapidly to generate ultrasound, that is, the photoacoustic signal. According to the photoacoustic signal, the structure reflecting the biological tissue can be reconstructed. and images of feature information. Photoacoustic imaging overcomes the shortcomings of some traditional imaging methods. For example, compared with optical coherence tomography (OCT), the measurement depth of OCT is limited to shallow layers on the order of millimeters due to the strong optical scattering of tissues, while photoacoustic imaging The technology can reach the centimeter level; compared with pure ultrasound imaging, the contrast of ultrasound imaging is very low in areas where the acoustic impedance is not much different, while photoacoustic imaging uses the absorption difference of different tissues to reconstruct a high-contrast image.

Although the development of cranial windows has significantly enhanced the resolution of optical brain imaging, with the in-depth development of applied research, high-resolution optical imaging based on cranial windows is limited by the high scattering properties of dense brain tissue and the curvature of the skull. Impact. Unlike purely optical imaging techniques, in photoacoustic imaging, cranial window materials need to be both optically transparent and acoustically transparent. Considering that photoacoustic brain imaging needs to receive photoacoustic signals at the same time, piezoelectric materials with optical transparency are the preferred solution for preparing photoacoustic brain imaging. In this patent, the transparent imaging cranial window prepared by transparent tin-indium oxide (ITO) electrodes, polyvinylidene fluoride (PVDF) piezoelectric materials, epoxy resin backing and matching layer can not only overcome the light brought by the skull The effects of scattering, while being able to preserve the physiological environment of the brain, allow for long-term, intuitive imaging monitoring of the brain, building a more comprehensive understanding of brain function. In the research of using transparent piezoelectric materials to prepare transducers for photoacoustic imaging, the patent application with application number 202110861125.3 discloses a highly sensitive fully transparent photoacoustic detector and endoscopic device based on transparent flexible composite electrodes. The design uses The double-sided polished and polarized lithium niobate piezoelectric crystal material is not as flexible as the PVDF piezoelectric material, and cannot match the curved features of the natural anatomy of the skull to make the cranial window of the transducer, resulting in a small effective detection range and unable to obtain the whole brain. Photoacoustic imaging. In the research of photoacoustic imaging using curved transducers, the patent application with application number 202110925648.X discloses a curved transducer array and its preparation method. The design of 3D printed small curved mesh molds by this method is not as good as referring to the three-dimensional skull The model independently designed a mold to match the curvature of the skull, which could not match the morphological structure of the skull, resulting in an increase in acoustic impedance and unable to improve the sensitivity of acoustic detection. In the flexible base curved and surface photoacoustic imaging system, the patent application No. 201610743856.7 discloses a flexible base MEMS device surface array photoacoustic imaging system, and the MEMS acoustic transducer array layer and flexible printed circuit board used in the design are modified. The interconnect layer, MEMS micromirror array and fiber channel layer are not as good as tin-indium oxide (ITO) electrodes, polyvinylidene fluoride (PVDF) piezoelectric materials, and epoxy resin backing materials, and cannot achieve light transmittance If it is greater than 80%, the optical excitation signal will be weakened, and high-resolution photoacoustic imaging cannot be obtained.

Contents of the invention

The main purpose of the present invention is to introduce transparent cranial window technology into photoacoustic brain imaging, to overcome the dura mater infection caused by the destruction of the skull due to complicated surgical operations in high-resolution optical imaging, resulting in abundant nerves and nerves on the skull and dura mater. For the problem of immune system damage, a photoacoustic brain imaging system and imaging method based on a PVDF-ITO transparent transducer cranial window is provided to achieve accurate, long-term and safe imaging research on brain microvessels while ensuring the integrity of the skull’s immune system. Provide technical support for research on chronic cerebrovascular diseases.

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

In the first aspect, the present invention provides 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 shaped transparent transducer is connected with the cranial window of the transparent transducer, and the pulsed laser is imaged in the photoacoustic brain imaging unit after passing through the cranial window of the transparent transducer, wherein:

The curved transparent transducer is prepared from transparent tin-indium oxide ITO electrodes, polyvinylidene fluoride PVDF piezoelectric material, wire silver wire, epoxy resin backing layer and curved structure matching layer, and according to the skull The arc structure is designed; in the stainless steel jig upside down, the epoxy resin backing layer, the first wire silver wire, the designed PVDF-ITO piezoelectric film, the second wire silver wire, and the matching layer are placed in sequence. A small amount of epoxy resin is applied between the structural layers for fixing; the PVDF-ITO piezoelectric film is a sandwich film structure of ITO-PVDF-ITO;

The cranial window of the transparent transducer seals and combines the arc-shaped transparent transducer with the scalp tissue through the transducer connecting ring, ensuring the stability of the physiological state of the surgical site and not damaging the skull structure during the preparation of the cranial window. The transparent transducer The cranial window provides an optically transparent imaging window and is used to receive photoacoustic signals;

The photoacoustic brain imaging unit includes an optical excitation scanning module and a signal processing reconstruction module; wherein the optical excitation scanning module includes a sequentially connected 532nm laser, a first aperture, a first fiber coupler, a first fiber jumper, a first optical fiber Collimator, first mirror, sequentially connected 1064nm laser, second aperture, second fiber coupler, second fiber jumper, second fiber collimator, second mirror, and 2D galvanometer scanning instrument and scanning lens, the first mirror and the second mirror are connected to the two-dimensional vibrating mirror scanner, and the two-dimensional vibrating mirror scanner is connected to the scanning lens; the signal processing and reconstruction module includes sequentially connected Pre-amplification and filtering system, data acquisition system, image processor and display; 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 image after amplification and filtering Photoacoustic Brain Imaging.

As a preferred technical solution, the preparation process of the arc-shaped transparent transducer is as follows:

Obtain the skull parameters of the target imaging animal model, obtain a high-precision backing model, and obtain the backing layer of epoxy resin material by turning over the mold;

Polish the upper and lower surfaces of the epoxy resin backing layer to increase its optical transmittance;

Turn the stainless steel jig with the release agent upside down, place the epoxy resin backing layer, the first wire silver wire, the PVDF-ITO piezoelectric film, the second wire silver wire and the matching layer in sequence, between each structural layer Apply a small amount of epoxy resin to fix;

After the PDMS protective layer is added above the matching layer, it is pressed by a stainless steel fixture and placed in an incubator for curing;

Use potting glue to fix the cured curved transparent transducer into the connection ring.

As a preferred technical solution, the preparation process of the transparent transducer cranial window is as follows:

First, the skin is depilated according to the target imaging area, and the scalp above the skull is removed using surgical scissors. The shape and size of the exposed position above the skull match the designed curved transparent transducer;

The skin is hemostatic, anti-inflammatory, and saline is applied on the top of the skull to keep the skull moist;

Use α-cyanoacrylate to quickly hemostatically bond the designed curved transparent transducer to the surgically removed skin edge to maintain a stable internal environment;

Use a fixed structure to fix the connection ring of the transparent transducer with the surrounding skin;

The electrical signal generated by the PVDF-ITO piezoelectric film after receiving the photoacoustic signal is exported by connecting the high-frequency coaxial shielded wire with the silver wire of the wire;

Add a PDMS protective layer above the curved transparent transducer to protect the contact surface between the curved transparent transducer and the outside world, prevent damage to the polished surface of the backing, and remove it during imaging.

As a preferred technical solution, the polyvinylidene fluoride PVDF piezoelectric material can design a large-area transducer cranial window matching it according to the arc structure of the skull; the PVDF piezoelectric material can be in contact with skin tissue and coexist for a long time, establishing Long-term stable imaging window; the light transmittance of the PVDF piezoelectric material in visible light and near-infrared bands is greater than 80%.

As a preferred technical solution, the design thickness of the PVDF-ITO piezoelectric film is 10 μm-50 μm; the PVDF-ITO piezoelectric film has strong resistance to deformation, and its Young’s modulus is higher than 2.5 GPa; the PVDF-ITO piezoelectric film The dielectric constant of the film is 10-50.

As a preferred technical solution, the arc-shaped transparent transducer first obtains the 3D morphological parameters of the target skull before preparation, and then uses 3D modeling software to establish a 3D model of the skull according to the morphological parameters. mold.

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 described after the epoxy resin is mixed in proportion is made into an arc-shaped structure; The structure ensures the matching between the transducer and the skull structure and space, reduces the gap between the two layers of structure, and improves the sensitivity of acoustic detection.

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

As a preferred technical solution, before the cranial window of the transparent transducer is prepared, the skin above the skull is removed with surgical scissors to expose the target imaging brain region, and then the arc is glued using α-cyanoacrylate and dental cement bioglue. The connecting ring of the transparent transducer and the edge of the skin are sealed and fixed to keep the skull moist and the internal environment stable, and there is no need to operate the skull during the establishment of the cranial window.

In a second aspect, the present invention provides an imaging method of a photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranial window, comprising the following steps:

It is divided into two excitation optical paths: 532nm laser and 1064nm laser. The laser emitted by the 532nm laser passes through the first aperture, the first fiber coupler, the first fiber jumper, the first fiber collimator, and the first mirror; the 1064nm laser emits The laser passes through the second aperture, the second fiber coupler, the second fiber jumper, the second fiber collimator, the second mirror, and the first mirror; after the two optical paths overlap and pass through the two-dimensional galvanometer scanner , the two-dimensional galvanometer scanner is connected with the scanning lens, and the two optical paths are collimated and focused separately to ensure that the resolution of the two wavelengths is the best. At the same time, the distance between the two focal points in the depth is adjusted to form an extended focal depth , increase the imaging depth; the signal processing and reconstruction module restores the photoacoustic signal received by the cranial window of the transparent transducer into a photoacoustic brain image, and reconstructs a high-resolution three-dimensional photoacoustic brain image after amplification and filtering;

The galvanometer scanning system is driven by a continuous sawtooth wave to perform continuous scanning to realize non-contact scanning imaging of the transparent cranial window area;

The input end of the signal processing and reconstruction module is connected to the output end of the cranial window of the transparent transducer, and the photoacoustic signal received by the transparent transducer is amplified and filtered to reconstruct a three-dimensional photoacoustic brain image of the target area.

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

The present invention innovatively proposes to use the flexible PVDF material based on the ITO transparent electrode 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 dual functions of providing an optically transparent imaging window and receiving photoacoustic signals; (b) PVDF material has good flexibility and can be used according to the curved structure of the skull. Design an imaging cranial window that matches the structural features; (c) PVDF material is biocompatible and can establish a long-term stable imaging window, avoiding the inflammatory response caused by repeated surgical operations in long-term optical imaging monitoring, and is expected to treat chronic cerebral palsy. Long-term stable longitudinal study of the disease model; (d) Combined transducer cranial window and laser scanning technology to achieve non-contact, fast photoacoustic brain imaging, avoiding the configuration of traditional photo-acoustic integrated contact imaging probes, and can achieve awake state (e) By controlling the two-dimensional galvanometer scanning system, flexible and free switching between large-scale imaging of the whole brain and real-time imaging of specific brain regions can be realized.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings that need to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application. For those skilled in the art, other drawings can also be obtained based on these drawings without creative effort.

Fig. 1 is the structure schematic diagram of the photoacoustic brain imaging system based on PVDF-ITO transparent transducer cranial window of the present invention;

Figure 2(a), Figure 2(b) and Figure 2(c) are schematic diagrams of the development of the PVDF-ITO transparent transducer in this embodiment.

Fig. 3 is a schematic diagram of establishing the cranial window of the PVDF-ITO transparent transducer in this embodiment.

Fig. 4 is an overall schematic diagram of the cranial window of the PVDF-ITO transparent transducer in this embodiment.

Fig. 5 is a schematic diagram of the photoacoustic brain structure and function imaging system in this embodiment.

Fig. 6 is a schematic diagram of blood vessel imaging in this embodiment.

Description of the serial numbers of the attached drawings: 1 is the pulse laser; 2 is the epoxy resin backing layer; 3 is the ITO electrode; 4 is the PVDF material; 5 is the fixed structure; 6 is the matching layer; 7 is the skin; 8 is the brain structure; 9 10 is a conductive silver wire; 11 is a photoacoustic signal; 12 is a stainless steel fixture; 13 is a PVDF-ITO piezoelectric film; 14 is a first signal line; 15 is a connecting ring; 16 is a transparent arc transducer 17 is epidermal tissue; 18 is brain blood vessel; 19 is the second signal line; 20 is the cranial window of transparent transducer; 21 is scanning lens; 22 is 532nm laser; 23 is 1064nm laser; 24 is aperture; 25 is Fiber coupler; 26 is a fiber jumper; 27 is a fiber collimator; 28 is a mirror; 29 is a two-dimensional galvanometer scanner; 30 is a mouse; 31 is a display; 32 is a graphics processor; system; 34 is a pre-amplification filter system.

Detailed ways

In order to enable those skilled in the art to better understand the solutions of 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. Apparently, the described embodiments are only some of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without making creative efforts belong to the scope of protection of this application.

Example

As shown in Figure 1, this implementation 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 with the cranial window of the transparent transducer, and the pulse laser 1 is imaged in the photoacoustic brain imaging unit after passing through the cranial window of the transparent transducer.

Further, the curved transparent transducer 16 is composed of ITO electrodes 3 (transparent tin-indium oxide), PVDF piezoelectric material 4 (polyvinylidene fluoride), conductive silver wire 10, epoxy resin backing layer 2 and The matching layer 6 is prepared and designed according to the curved structure of the skull 9 .

It can be understood that ITO is a commonly used transparent electrode material, and its light transmittance is greater than 60% in the range of 450nm-1100nm, which is much higher than that of many other transparent conductors.

PVDF piezoelectric material has the characteristics of wide bandwidth, low acoustic impedance, and high receiving sensitivity, which is very suitable for receiving wide-spectrum photoacoustic signals in photoacoustic imaging, and the mechanical flexibility of PVDF allows custom shapes according to research needs. In terms of optical properties, PVDF has high light transmittance (>80%) in the visible and near-infrared range. Therefore, combining the advantages of PVDF-ITO materials is expected to develop high-performance transparent ultrasonic transducers for photoacoustic imaging.

As shown in Figure 2(a)-Figure 2(c), the preparation process of the curved transparent transducer is as follows:

(1) According to the requirements of acoustic parameters in brain imaging, use COMSOL simulation software and the FieldⅡ toolkit based on MATLAB to simulate and analyze the performance of PVDF-ITO piezoelectric film, and obtain the optimal parameters of piezoelectric material acoustics, optics and electrical impedance untie;

(2) Use SolidWorks to design a backing structure that matches the radian characteristics of the mouse skull, obtain a high-precision backing model through 3D printing, and use the backing model to obtain the epoxy resin backing layer 2 by turning over the mold;

(3) polishing the upper and lower surfaces of the epoxy resin backing layer to increase its optical transmittance;

(4) Invert the stainless steel jig 12 with the release agent, and place the epoxy resin backing layer 2, the first wire silver wire, the designed PVDF-ITO piezoelectric film, the second wire silver wire, For the matching layer, a small amount of epoxy resin is applied between each structural layer to fix it, and then it is pressed by a stainless steel fixture and placed in an incubator for curing.

Further, the PVDF-ITO piezoelectric film is a sandwich film structure of ITO-PVDF-ITO, and the design thickness of the PVDF-ITO piezoelectric film is 10 μm-50 μm; the PVDF-ITO piezoelectric film has strong resistance to deformation, The Young's modulus is higher than 2.5GPa; the dielectric constant of the PVDF-ITO piezoelectric film is 10-50.

In one embodiment of the present application, the cranial window 20 of the transparent transducer seals the arc-shaped transparent transducer with the scalp tissue through the connecting ring 15, ensuring the stability of the physiological state of the surgical site and the preparation of the cranial window. When the skull structure is damaged, the cranial window of the transducer provides an optically transparent imaging window 20 and is used to receive photoacoustic signals, and the photoacoustic signals are transmitted through the first signal line 14 and the second signal line 19 .

Furthermore, the cranial window of the transducer is established by surgical operation, the specific expected effect is shown in Figure 3, and the specific establishment model is shown in Figure 4.

The preparation process of the transparent transducer cranial window is as follows:

(1) First, the epidermal tissue 17 is depilated according to the target imaging area, and 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 curved transparent transducer ; The present embodiment takes mouse 30 as an example to illustrate.

(2) Hemostatic and anti-inflammatory cleaning was performed on the skin 7, physiological saline was applied on the top of the skull to keep the skull moist, and a fixed structure was used to quickly hemostatically bond the designed transparent transducer to the edge of the surgically resected skin to maintain a stable internal environment; Commonly used fixing structures are dental cement and α-cyanoacrylate; (3) Use potting glue to fix the cured curved transparent transducer into the connecting ring;

(4) Use dental cement or bone cement to fix the connection ring of the transparent transducer with the surrounding skin, and connect the high-frequency coaxial shielded wire with the wire silver wire to export the piezoelectric signal generated by PVDF-ITO.

In one embodiment of the present application, an imaging system integrating deep imaging of visible light/near-infrared light and functional imaging based on stimulated Raman scattering effect is shown in Figure 5; high-resolution, large-depth light based on fast galvanometer scanning The principle in the acoustic brain structure and function imaging system is:

Lasers with wavelengths of 532nm and 1064nm are used as excitation sources for photoacoustic imaging, and a dichroic mirror is used to combine beams to obtain a light source with alternate excitation at 532nm/1064nm wavelengths. The vascular information of the cerebral cortex is obtained through 532nm excitation, the blood vessel information of the deep brain is obtained through the excitation of near-infrared light, and the high-resolution and large-depth imaging of brain blood vessels is realized through wavelength complementarity.

Further, the photoacoustic brain imaging unit includes an optical excitation scanning module and a signal processing reconstruction module; wherein the optical excitation scanning module includes a 532nm laser 22, a 1064nm laser 23, an aperture 24, a fiber coupler 25, an optical fiber jumper 26, an optical fiber Collimator 27, reflector 28, two-dimensional vibrating mirror scanner 29 and scanning lens 21; Described optical excitation scanning module comprises two optical paths, and the first optical path comprises: the 532nm laser device that connects in sequence, the first diaphragm, the first Fiber coupler, first fiber jumper, first fiber collimator, first mirror; the second optical path includes: sequentially connected 1064nm laser, second aperture, second fiber coupler, second fiber jumper , the second fiber collimator, the second reflector; after the first reflector and the second reflector are connected, they are connected to the two-dimensional vibrating mirror scanner, and the two-dimensional vibrating mirror scanner is connected to the scanning lens; the described The signal processing and reconstruction module includes a sequentially connected preamplification and filtering system, a data acquisition system, an image processor, and a display; the signal processing and reconstruction module restores the photoacoustic signal 11 received by the cranial window of the transparent transducer into a photoacoustic brain image. After amplification and filtering, a high-resolution three-dimensional photoacoustic brain image is reconstructed; the signal processing and reconstruction module includes a sequentially connected preamplification filter system 34, a data acquisition system 33, an image processor 32 and a display 31; the signal processing and reconstruction module will be transparent The photoacoustic signal received by the cranial window of the transducer is restored to a photoacoustic brain image, and after amplification and filtering, a high-resolution three-dimensional photoacoustic brain image is reconstructed.

In another embodiment of the present application, the imaging method of the photoacoustic brain imaging system based on the PVDF-ITO transparent transducer cranial window comprises the following steps:

The FPGA timing control system realizes the laser excitation of near-infrared light and visible light, and controls the galvanometer scanning system to perform continuous scanning with continuous sawtooth wave drive.

The energy of the excitation light pulse is monitored by the photodiode, and the functional imaging is corrected and compensated.

Programs for scanning control, data acquisition and imaging were written through LabVIEW software.

Accelerate signal processing, multi-wavelength signal reconstruction, image registration, and real-time display through GPU.

In this embodiment, the photoacoustic brain imaging method based on the PVDF-ITO transparent transducer cranial window and the image formed by the system thereof are shown in Figure 6, as can be seen from Figure 6, the distribution of the entire brain blood vessel 18 network , to achieve high-resolution deep imaging of the cerebral cortex and deep cerebral blood vessels.

In the present invention, unless otherwise clearly specified and limited, terms such as "installation", "connection", "connection" and "fixation" should be understood in a broad sense, for example, it can be a fixed connection or a detachable connection , or integrated; it may be mechanically connected or electrically connected; it may be directly connected or indirectly connected through an intermediary, and it may be the internal communication of two components or the interaction relationship between two components, unless otherwise specified limit. Those of ordinary skill in the art can understand the specific meanings of the above terms in the present invention according to specific situations.

In the description of this specification, descriptions referring to the terms "one embodiment", "some embodiments", "example", "specific examples", or "some examples" mean that specific features described in connection with the embodiment or example , structure, material or characteristic is included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the described specific features, structures, materials or characteristics may be combined in any suitable manner in any one or more embodiments or examples. In addition, those skilled in the art can combine and combine different embodiments or examples and features of different embodiments or examples described in this specification without conflicting with each other.

Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present invention, those skilled in the art can make the above-mentioned The embodiments are subject to changes, modifications, substitutions and variations.

Claims (10)

1. The photoacoustic brain imaging system based on PVDF-ITO transparent energy converter cranium window is characterized by comprising an arc transparent energy converter, a transparent energy converter cranium window and a photoacoustic brain imaging unit, wherein the arc transparent energy converter is connected with the transparent energy converter cranium window, and pulse laser is imaged in the photoacoustic brain imaging unit after passing through the transparent energy converter cranium window, wherein:

the arc-shaped transparent transducer is prepared from a transparent tin-indium oxide ITO electrode, a polyvinylidene fluoride PVDF piezoelectric material, a wire silver wire, an epoxy resin backing layer and an arc-shaped structure matching layer, and is designed according to the arc-shaped structure of the skull; in the inversion of the stainless steel jig, an epoxy resin backing layer, a first lead silver wire, a designed PVDF-ITO piezoelectric film, a second lead silver wire and a matching layer are sequentially placed, and a small amount of epoxy resin is smeared between all the structural layers for fixing; the PVDF-ITO piezoelectric film is of an ITO-PVDF-ITO sandwich film structure;

the transparent transducer cranium window is used for sealing and combining the arc transparent transducer and scalp tissues through the transducer connecting ring, so that the physiological state stability of an operation part is ensured, the skull structure is not damaged in the cranium window preparation process, and the transparent transducer cranium window is used for receiving photoacoustic signals while providing an optical transparent imaging window;

the photoacoustic brain imaging unit comprises an optical excitation scanning module and a signal processing reconstruction module; the optical excitation scanning module comprises a 532nm laser, a first diaphragm, a first optical fiber coupler, a first optical fiber jumper, a first optical fiber collimator and a first reflecting mirror which are sequentially connected, a 1064nm laser, a second diaphragm, a second optical fiber coupler, a second optical fiber jumper, a second optical fiber collimator, a second reflecting mirror, a two-dimensional galvanometer scanner and a scanning lens which are sequentially connected, wherein the first reflecting mirror and the second reflecting mirror are connected and then are connected with the two-dimensional galvanometer scanner, and the two-dimensional galvanometer scanner is connected with the scanning lens; the signal processing reconstruction module comprises a pre-amplifying filter system, a data acquisition system, an image processor and a display which are sequentially connected; the signal processing reconstruction module restores the photoacoustic signal received by the transparent transducer cranium window into a photoacoustic brain image, and reconstructs a high-resolution three-dimensional photoacoustic brain image after amplification and filtering.

2. The photoacoustic brain imaging system of claim 1 based on PVDF-ITO transparent transducer cranium window, wherein the arc transparent transducer is prepared by the process of:

acquiring skull parameters of a target imaging animal model, acquiring a high-precision backing model, and acquiring a backing layer of an epoxy resin material by a turnover method;

polishing the upper and lower surfaces of the epoxy resin backing layer to increase the optical transmittance thereof;

inverting the stainless steel jig with the release agent, sequentially placing an epoxy resin backing layer, a first lead silver wire, a PVDF-ITO piezoelectric film, a second lead silver wire and a matching layer in sequence, and smearing a small amount of epoxy resin between each structural layer for fixing;

adding a PDMS protective layer above the matching layer, compacting by a stainless steel jig, and then placing into an incubator for curing;

the cured arc transparent transducer is secured into the attachment ring using a potting adhesive.

3. The photoacoustic brain imaging system of claim 1 based on PVDF-ITO transparent transducer craniotomy, wherein the transparent transducer craniotomy is prepared by the process of:

firstly, dehairing the skin according to a target imaging area, removing the scalp above the skull by using surgical scissors, and matching the shape and the size of an exposed position above the skull with a designed arc transparent transducer;

the skin is subjected to hemostasis, anti-inflammation and cleaning, and physiological saline is smeared above the skull to keep the wettability of the skull;

the designed arc transparent transducer is quickly bonded with the edge of the skin after surgical excision by using alpha-cyanoacrylate, so that the homeostasis of the internal environment is maintained;

fixedly connecting the transparent transducer connecting ring part with the peripheral skin by using a fixing structure;

the PVDF-ITO piezoelectric film receives the photoacoustic signal and then generates an electric signal to be led out through the connection of the high-frequency coaxial shielding wire and the lead silver wire;

and a PDMS protective layer is added above the arc-shaped transparent transducer to protect the contact surface of the arc-shaped transparent transducer and the outside, so that the polished surface of the backing is prevented from being damaged, and the polished surface is removed during imaging.

4. The photoacoustic brain imaging system of claim 1, wherein the polyvinylidene fluoride PVDF piezoelectric material can design a large area transducer cranium window matching it according to the skull arc structure; the PVDF piezoelectric material can be in contact with skin tissues and coexist for a long time, and a long-term stable imaging window is established; the transmittance of the PVDF piezoelectric material in visible light and near infrared bands is more than 80%.

5. The photoacoustic brain imaging system of claim 1 based on PVDF-ITO transparent transducer cranium window, wherein the PVDF-ITO piezoelectric film design thickness is 10 μm-50 μm; the PVDF-ITO piezoelectric film has strong deformation resistance and Young modulus higher than 2.5GPa; the dielectric constant of the PVDF-ITO piezoelectric film is 10-50.

6. The photoacoustic brain imaging system of claim 1, wherein the arc-shaped transparent transducer first acquires three-dimensional morphological parameters of the target skull before preparation, then builds a skull three-dimensional model according to the morphological parameters using three-dimensional modeling software, and autonomously designs a mold matching the radian of the skull with reference to the skull three-dimensional model.

7. The photoacoustic brain imaging system based on PVDF-ITO transparent energy converter cranium window according to claim 1, wherein in the arc-shaped transparent energy converter, the back lining layer of the transparent energy converter is made of epoxy resin material, and the three-dimensional mould is made into an arc-shaped structure after the epoxy resin is mixed according to proportion; the arc structure ensures the matching between the transducer and the skull structure and the space, reduces the gap between the two layers of structures, and improves the acoustic detection sensitivity.

8. The PVDF-ITO transparent transducer cranium window based photoacoustic brain imaging system of claim 1, wherein the matching layers of the curved transparent transducers are designed according to the cranium acoustic impedance parameters of different animal models, reducing reflections of sound waves from the cranium to the transducers.

9. The photoacoustic brain imaging system of claim 1, wherein the transparent transducer skull window is prepared by removing the skin above the skull bone with surgical scissors to expose the target imaging brain region, and then sealing and fixing the connecting ring of the arc transparent transducer and the skin edge with alpha-cyanoacrylate and biological glue of dental cement to keep the skull bone moist and stable in environment, and the skull window is not required to be operated during the establishment process.

10. A method of imaging a photoacoustic brain imaging system based on a PVDF-ITO transparent transducer cranium window according to any one of the claims 1 to 9, characterized by the following steps:

the laser beam emitted by the 532nm laser passes through a first diaphragm, a first optical fiber coupler, a first optical fiber jumper, a first optical fiber collimator and a first reflecting mirror; laser emitted by the 1064nm laser passes through a second diaphragm, a second optical fiber coupler, a second optical fiber jumper, a second optical fiber collimator, a second reflecting mirror and a first reflecting mirror; the two paths are overlapped and then are connected with a scanning lens through a two-dimensional galvanometer scanner, the two paths are respectively collimated and focused, the optimal resolution of two wavelengths is ensured, and the distance between the two focuses at depth is adjusted to form an extended focal depth and increase the imaging depth; the signal processing reconstruction module restores the photoacoustic signal received by the transparent transducer cranium window into a photoacoustic brain image, and reconstructs a high-resolution three-dimensional photoacoustic brain image after amplification and filtering;

the galvanometer scanning system is driven by continuous sawtooth waves to perform continuous scanning, so that non-contact scanning imaging of a transparent cranium window area is realized;

and the input end of the signal processing reconstruction module is connected with the output end of the transparent transducer cranium window, and the photoacoustic signal received by the transparent transducer is amplified and filtered to reconstruct a three-dimensional photoacoustic brain image of the target area.

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