Head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop regulation

Abstract

The invention discloses a head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop regulation and control. The device comprises a nerve-lymph-blood vessel multi-mode imaging monitoring module, a multi-dimensional brain information quantitative analysis module, a closed-loop control module, a light / sound brain regulation and control module and a detachable head-mounted module. The method comprises the following steps: firstly, acquiring brain nerve, lymph and blood vessel information in real time by utilizing a multi-modal imaging monitoring module, then sending data to a multi-dimensional brain information quantitative analysis module, decoding and analyzing multi-dimensional data, extracting key features, performing multi-modal data feature fusion, and establishing an analysis method for quantitatively evaluating the brain microenvironment; therefore, the brain function state is accurately represented. The head-mounted device has the advantages that photoacoustic imaging, fluorescence imaging, optical regulation and control and ultrasonic regulation and control are added into the head-mounted device, closed-loop regulation and control parameters are achieved in a combined mode, and the functions of miniature, wearable and multi-parameter detection of the cerebral vessel-nerve-lymph microenvironment and closed-loop photoacoustic regulation and control are achieved.

Description

Technical Field

[0001] This invention relates to the fields of brain science and neuroscience, specifically a head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop control. It combines optical, photoacoustic, and ultrasonic technologies to achieve coordinated monitoring and closed-loop control of the brain's nerves, blood vessels, and lymphatic systems. This invention aims to overcome the limitations of single-technology or single-system research by comprehensively revealing the complex mechanisms and dynamic regulatory principles of brain function through multi-wavelength optical path design, multimodal signal acquisition, and closed-loop feedback control. Background Art

[0002] Brain function relies on the coordinated action of the lymphatic, neural, and vascular systems. These three systems work together to maintain brain homeostasis, but single-system studies are limited. Brain function and disease often result from the synergistic action of multiple systems, and focusing on a single system alone makes it difficult to fully uncover their complex mechanisms. Single studies often lack the support of multimodal data, failing to provide a systematic and dynamic perspective, making them insufficient for understanding the pathological mechanisms of complex brain diseases and designing precise treatment strategies.

[0003] Traditional single-modality imaging methods, such as functional magnetic resonance imaging (fMRI) and optical imaging techniques, while capable of providing some information about brain function, suffer from significant limitations in spatial and temporal resolution, as well as their ability to fuse multidimensional information. For example, fMRI suffers from low temporal resolution, making it difficult to capture rapid neural activity dynamics; single optical imaging methods have limited penetration into deep tissues and struggle to simultaneously acquire multidimensional information about blood vessels, lymphatics, and neurons. Furthermore, existing brain function regulation technologies are mostly single-modality. For example, optogenetics uses light of specific wavelengths to activate or inhibit neurons, while ultrasound modulation utilizes focused ultrasound to modulate cerebral blood flow or neural activity. However, these methods typically operate independently and lack feedback mechanisms based on real-time brain functional status, making dynamic and precise closed-loop regulation difficult to achieve. Furthermore, these regulatory technologies are often limited in their application by low device integration, poor flexibility, and inadequacy in adapting to freely moving animal experiments.

[0004] In brain function monitoring, photoacoustic imaging and fluorescence imaging, two important multimodal imaging techniques, have attracted widespread attention due to their high spatial resolution, excellent tissue penetration, and ability to visualize specific molecules and cells. Photoacoustic imaging utilizes laser-induced ultrasound signals to achieve high-resolution imaging of vascular and lymphatic structures, while fluorescence imaging can provide dynamic information on neuronal activity by labeling specific molecules. However, a single imaging modality cannot fully characterize the complex brain microenvironment, and the integration and optimization of multimodal imaging technologies is urgently needed. In brain function regulation, optical and ultrasound technologies have become important tools due to their non-invasiveness and high spatiotemporal resolution. Optical regulation modulates neuronal activity and signal transmission by applying lasers of specific wavelengths to brain regions, while ultrasound regulation modulates cerebral blood flow and neural activity through the mechanical and thermal effects of focused acoustic waves. While existing technologies can achieve optical or ultrasound regulation separately, they struggle to achieve closed-loop, precise control based on dynamic feedback and multimodal imaging data. To address these challenges, the development of a head-mounted system that integrates multimodal imaging, quantitative brain function analysis, and closed-loop photoacoustic / acoustic regulation would significantly advance the state of the art in brain science research and neurological disease treatment. This system can achieve synchronous monitoring and regulation of nerves, lymphatics and blood vessels in freely moving animal models, providing important support for exploring the functional mechanisms of complex brain networks and developing new diagnostic and treatment methods. Summary of the Invention

[0005] In order to overcome the shortcomings of the existing technology, the present invention provides a head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop control, aiming to achieve multi-system coordinated monitoring and precise control of brain function and its microenvironment. By combining photoacoustic imaging, fluorescence imaging, optical control and ultrasonic control modules, the system reduces the effects of anesthesia and head fixation on animal brain activity, detects the cerebral vascular-neural-lymphatic microenvironment, and combines it with optical and ultrasonic control to form a closed-loop control. It provides a new multimodal tool for brain science research, which can be widely used in basic research, diagnosis and treatment of brain diseases. The specific technical solutions are as follows:

[0006] A head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop regulation includes a nerve-lymph-vascular multimodal imaging monitoring module, a multi-dimensional brain information quantitative analysis module, a photoacoustic brain regulation module, a closed-loop control module, and a detachable head-mounted module.

[0007] First, a multimodal imaging monitoring module acquires real-time information about the brain's nerves, lymphatics, and blood vessels. This data is then sent to a multidimensional brain information quantitative analysis module, which decodes and analyzes the multidimensional data, extracts key features, and fuses multimodal data features to establish an analytical method for quantitatively assessing the brain microenvironment, thereby accurately characterizing brain functional status. This quantified brain function information is then transmitted to a closed-loop control module, which generates optimized control parameters in real time and sends them to the optical / acoustic control module. The multimodal imaging monitoring module and the optical / acoustic brain control module can be combined with a detachable head-mounted module to enable real-time imaging and closed-loop control of freely moving mice.

[0008] Furthermore, the nerve-lymph-vascular multimodal imaging monitoring module includes a multi-wavelength optical path, an optical scanning module, a transparent ultrasonic transducer and a CMOS sensor.

[0009] The laser beam generated by the multi-wavelength optical path is coupled and transmitted through a single-mode fiber. It then passes through an optical scanning module and a transparent ultrasonic transducer and is directed to the imaging area of the animal's head. This generates a photoacoustic signal, which is received by the transparent ultrasonic transducer and converted into an electrical signal for photoacoustic imaging. Simultaneously, the beam illuminates the animal's head and excites a fluorescence signal, which is received by a CMOS sensor and converted into an electrical signal for fluorescence imaging.

[0010] Furthermore, the multi-wavelength optical path of the neuro-lymphatic-vascular multimodal imaging monitoring module includes a nanosecond pulse laser for photoacoustic imaging, a continuous laser for fluorescence imaging, a near-infrared laser for optical brain regulation, and an optical processing component.

[0011] A nanosecond pulsed laser provides 532nm pulses, which are split into three beams by an optical processing component. Two of the 532nm pulses are coupled through a polarization-maintaining fiber and converted to 558nm and 604nm wavelengths, respectively, using the stimulated Raman effect. These are then combined with another 532nm laser beam and coupled into a single-mode fiber. The varying lengths of the polarization-maintaining fiber ensure that the three wavelength pulse sequences are spaced apart. The 532nm and 558nm wavelengths are used for vascular photoacoustic imaging and blood oxygen saturation calculation, while the 604nm wavelength is used for lymphatic photoacoustic imaging excitation.

[0012] The continuous laser provides continuous light with a wavelength of 488nm, which is processed by an optical processing component and used for fluorescence imaging of neurons in target tissues. The nanosecond pulse laser and the continuous laser are combined and coupled to the same single-mode optical fiber to achieve collinear transmission of multi-wavelength light beams.

[0013] The near-infrared laser provides continuous light with a wavelength of 1064nm, which is modulated into a flashing frequency of 10Hz-40Hz and transmitted to the target tissue through multi-mode optical fiber for optical brain regulation; the three lasers use an external trigger control system to synchronously trigger the timing of multi-wavelength lasers, so that the pulse sequences of lasers of different wavelengths maintain a certain interval.

[0014] The optical processing components, including reflectors, filters, polarizers, polarization beam splitters, dichroic mirrors and fiber couplers, are used to process the laser beam and couple the beam into the optical fiber.

[0015] Furthermore, the single-mode optical fiber of the nerve-lymph-vascular multimodal imaging monitoring module transmits the multi-wavelength laser used for imaging to the optical scanning module, which includes a collimating mirror, a first dichroic mirror, a two-dimensional micro-electromechanical scanning galvanometer, a second dichroic mirror and a focusing objective lens. The single-mode optical fiber output laser is collimated by the collimating mirror, then reflected by the two-dimensional micro-electromechanical scanning galvanometer through the first dichroic mirror and passed through the second dichroic mirror to the focusing objective lens to focus on the imaging area of the animal's head.

[0016] Furthermore, the focusing objective lens of the optical scanning module of the nerve-lymph-vascular multimodal imaging monitoring module focuses the laser beam on the imaging area of the animal's head to stimulate the generation of photoacoustic signals. The photoacoustic signals are converted into electrical signals by a transparent ultrasonic transducer, collected by an acquisition card, and then analyzed and processed in a computer. The 532nm and 558nm wavelengths are absorbed by endogenous hemoglobin to achieve vascular imaging, and the 604nm wavelength is injected and drained through the cistern of the occipital magna to achieve lymphatic imaging.

[0017] Furthermore, the optical scanning module of the nerve-lymphatic-vascular multimodal imaging monitoring module also includes a beam preprocessing component and a fluorescence signal preprocessing component. The beam preprocessing component is located in the optical path from the laser to the system to spatially filter and shape the beam.

[0018] The fluorescence signal preprocessing component includes a filter, a pinhole structure and a focusing lens, wherein the fluorescence signal is reflected to the fluorescence signal light path through the first dichroic mirror, filtered by the filter and the pinhole structure, and then focused by the focusing lens and received by the CMOS sensor. After computer processing, fluorescence data of brain neuron activity is obtained.

[0019] Furthermore, the multi-dimensional brain information quantitative analysis module performs comprehensive processing on the monitored neural-lymphatic-vascular signals. First, the acquired multimodal data is denoised and corrected to ensure the clarity of the signal and the temporal and spatial synchronization of the multimodal data. Subsequently, advanced algorithms are used to extract features such as blood oxygen saturation and blood flow velocity from the photoacoustic signal, and to capture the dynamic changes of neuronal activity from the fluorescence signal, decoding its time series and spatial distribution characteristics. By deeply integrating the photoacoustic and fluorescence features, a multidimensional feature matrix is constructed based on the spatial alignment and time series consistency of the multimodal data. Through the deep learning algorithm, the fused feature matrix is decoded and analyzed, and the core features closely related to the state of the brain microenvironment are extracted. The functional associations between blood vessels, lymphatic vessels and neurons are analyzed to construct a unified feature space. Finally, based on the extracted multimodal features, a quantitative evaluation model is established to accurately characterize the state of brain function.

[0020] Furthermore, the light / acoustic brain control module includes an optical control module and an ultrasonic control module.

[0021] The optical control module comprises a near-infrared light source and a digital micromirror. The near-infrared light source is a modulated near-infrared laser generated by a multi-wavelength optical path. This laser is coupled into a multimode optical fiber and serves as the near-infrared light source for the optical control module. The near-infrared laser passes through a programmable digital micromirror, is reflected by a second dichroic mirror, and then illuminates a specific brain region for optical control. The optical control module adjusts the frequency and intensity of light stimulation based on the real-time brain function state to achieve precise activation or inhibition of brain regions.

[0022] The ultrasonic control module, composed of piezoelectric ceramics and an impedance matching circuit, generates effective controllable sound pressure through a power amplifier. This sound pressure is focused and precisely applied to the target brain area, forming an ultrasonic control field. By controlling the frequency, intensity, and pulse pattern of the sound waves, the ultrasonic control module can non-invasively stimulate specific areas within the brain, modulating neural activity or promoting lymphatic clearance.

[0023] Furthermore, the closed-loop control module implements closed-loop regulation through the following steps: It receives quantitative brain function information, analyzes brain function status in real time, and generates optimized light / acoustic control parameters based on this information. Using intelligent algorithms, the closed-loop control module transforms characteristics such as neural activity, vascular function, and lymphatic circulation into a control strategy, dynamically adjusting the intensity and frequency of light stimulation and the power and pulse width of acoustic stimulation. During the control process, the module monitors changes in brain function status in real time, assesses whether the control effect is achieving the desired goal, and automatically optimizes the control parameters based on the feedback to ensure accurate and efficient stimulation.

[0024] Furthermore, the detachable head-mounted module uses a lightweight design and integrates a multimodal imaging monitoring module and a light / acoustic brain control module to achieve real-time imaging and closed-loop control of freely moving mice, ensuring wearing stability and minimal interference with mouse behavior.

[0025] The detachable head-mounted module includes a housing and a base plate. An optical scanning module, CMOS sensor, and optical control module are built into the housing. The housing is compact and lightweight, enabling head-mounted photoacoustic-fluorescent multi-parameter monitoring and photoacoustic / acoustic control on freely moving animals. A transparent ultrasonic transducer and ultrasonic control module are affixed to the base plate. The animal's scalp is removed, and a portion of the skull is peeled off and secured to the base plate with dental cement. This is then connected to the housing via magnets.

[0026] Furthermore, an imaging method of a head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop control comprises the following specific steps:

[0027] S1. Use a multi-wavelength laser light source to generate laser beams of different wavelengths.

[0028] A pulsed laser provides 532nm pulsed light, which is split into three beams by an optical processing component. Two of the 532nm pulses are coupled through a polarization-maintaining fiber and converted to 558nm and 604nm wavelengths, respectively, using the stimulated Raman effect. These are then combined with another 532nm laser beam and coupled into a single-mode fiber. The varying lengths of the polarization-maintaining fiber ensure that the pulse sequences of the three wavelengths are spaced apart. The 532nm and 558nm wavelengths are used for vascular photoacoustic imaging and blood oxygen saturation calculation, while the 604nm wavelength is used for lymphatic photoacoustic imaging excitation.

[0029] The continuous laser provides continuous light with a wavelength of 488nm for fluorescence imaging of neurons in target tissues; the pulsed laser and the continuous laser are coupled to the same single-mode optical fiber through an optical processing component to achieve collinear transmission of multi-wavelength light beams.

[0030] A near-infrared laser provides continuous light at a wavelength of 1064 nm, modulated to a flash frequency of 10 Hz to 40 Hz, and transmitted to the target tissue via a multimode optical fiber for optical brain control. An external trigger control system synchronizes the timing of the three lasers, ensuring that the pulse sequences of the different wavelengths are kept at a constant interval.

[0031] S2. The generated laser beam is transmitted via a single-mode fiber coupling, passing through an optical scanning unit and an ultrasonic transducer to the imaging area of the animal's head. This generates a photoacoustic signal, which is received by the ultrasonic transducer and converted into an electrical signal for photoacoustic imaging. Simultaneously, a fluorescence signal is generated, which is received by a fluorescence sensor and converted into an electrical signal for fluorescence imaging.

[0032] S3. Send the acquired multimodal imaging data to the multidimensional brain information quantitative analysis module, decode and analyze the multidimensional data, extract key features, perform multimodal data feature fusion, establish an analysis method for quantitatively evaluating the brain microenvironment, and accurately characterize the brain functional state.

[0033] S4. Quantified brain function information is transmitted to the closed-loop control module, which generates optimized control parameters in real time and sends them to the optical and ultrasonic control unit. The optical and ultrasonic control unit adjusts the near-infrared laser, digital micromirror, and focused ultrasonic transducer based on the optimized parameters to achieve precise control of brain function.

[0034] S5. The neural-lymphatic-vascular multimodal imaging monitoring module, optical control unit, and ultrasonic control unit are combined with a detachable head-mounted module to achieve real-time imaging and closed-loop control of freely moving mice.

[0035] The head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop control of the present invention provides an important tool for the coordinated study of the brain's nerves, blood vessels, and lymphatic systems, and can play an important role in the fields of neurodegenerative diseases, stroke, brain trauma, etc. At the same time, the system also provides new technical support for basic research in brain science, filling the gap in existing technologies in the coordinated monitoring and control of multiple systems. The advantages of the embodiments of the present invention are mainly reflected in the following aspects:

[0036] First, this invention overcomes the limitations of traditional single-modality imaging by integrating photoacoustic and fluorescence imaging technologies. It can simultaneously acquire multidimensional information about brain blood vessels, lymph nodes, and neurons, enabling a comprehensive characterization of the brain microenvironment. Compared to existing technologies, this system combines the high resolution of photoacoustic imaging with the molecular specificity of fluorescence imaging, improving both spatial and temporal resolution while significantly enhancing the ability to fuse multimodal data. This provides powerful technical support for studying the functional mechanisms of complex brain networks.

[0037] Second, this invention innovatively combines multimodal imaging with closed-loop control technology, enabling real-time acquisition of brain function data and generation of precise optical / acoustic control parameters, thereby achieving closed-loop control with dynamic feedback. Compared with traditional stand-alone control technologies, this system significantly improves control flexibility and precision through intelligent control and highly integrated hardware design. It also overcomes the limitations of low device integration and a lack of feedback mechanisms, providing a novel solution for the precise diagnosis and treatment of brain diseases.

[0038] Third, the present invention has designed a detachable head-mounted device suitable for studying freely moving animal models. This device is lightweight and flexible, enabling multimodal imaging and precise control while the animal is freely moving, significantly expanding the system's application scenarios and experimental conditions. This design not only enhances the ecological validity of brain science research but also provides important support for exploring the dynamic mechanisms of complex brain diseases and developing novel treatments. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following briefly introduces the drawings required for use in the embodiments. The drawings herein are incorporated into and constitute a part of the specification. These drawings illustrate embodiments consistent with the present disclosure and, together with the specification, are used to illustrate the technical solutions of the present disclosure. It should be understood that the following drawings only illustrate certain embodiments of the present disclosure and should not be regarded as limiting the scope. For those of ordinary skill in the art, other relevant drawings can be obtained based on these drawings without creative effort.

[0040] Figure 1 Schematic diagram of a multi-wavelength optical path in an embodiment of the present invention.

[0041] Figure 2 It is a structural diagram of the system module in an embodiment of the present invention.

[0042] Figure 3 4 is a flow chart of the closed-loop regulation process in an embodiment of the present invention.

[0043] Figure 4 2 is a schematic structural diagram of a fixing assembly in an embodiment of the present invention.

[0044] Figure 5 It is a schematic diagram of the three-dimensional structure of the fixing component fixed to the head of an animal in an embodiment of the present invention.

[0045] Figure 6 Schematic diagram of the base plate installation of the fixed component in an embodiment of the present invention.

[0046] Reference numerals: 101, nano-pulse laser; 102, continuous laser; 103, near-infrared laser; 111-117, half-wave plate; 121-122, polarization beam splitter; 131-133, dichroic mirror; 141-142, narrow bandpass filter; 151, 7 m polarization-maintaining fiber; 152, 30 m polarization-maintaining fiber; 1601-1613, reflector; 171-174, collimator; 201, CMOS sensor; 202, objective lens; 203, filter; 204, single-mode fiber output end; 205, collimating lens; 206, two-dimensional micro-electromechanical system galvanometer; 207. Reflector; 208. Multimode fiber output end; 209. First dichroic mirror; 210. Second dichroic mirror; 211. Digital micromirror; 212. Focusing objective lens; 213. Transparent transducer; 214. Ultrasonic control module; 215. Mouse brain; 216. Pinhole structure; 401. Magnet; 402. Ultrasonic control module; 403. Transparent transducer; 404. Base plate; 501. CMOS sensor; 502. Light source assembly; 503. Optical control module; 504. Base plate; 505. Transparent transducer; 601. Skull; 602. Open skull; 603. Base plate. DETAILED DESCRIPTION

[0047] The accompanying drawings are for illustrative purposes only and are not to be construed as limiting the scope of this patent. To better illustrate the embodiments, some components in the accompanying drawings may be omitted, enlarged, or reduced in size, and do not represent the dimensions of actual products. It is understandable to those skilled in the art that some well-known structures and their descriptions may be omitted from the accompanying drawings. The present invention will be further described in detail below in conjunction with the embodiments and accompanying drawings, but the embodiments of the present invention are not limited thereto.

[0048] Combine Figures 1 to 6 As shown, an embodiment of the present invention provides a head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop regulation, including a neural-lymphatic-vascular multimodal imaging monitoring module, a multi-dimensional brain information quantitative analysis module, a photoacoustic brain regulation module, a closed-loop control module, and a detachable head-mounted module.

[0049] This example uses a fixed assembly to secure the imaging device to the animal's head. Combined with a monitoring module and a control module, it enables closed-loop monitoring and regulation of the animal's cerebral vasculature, lymph nodes, and nerves in awake, freely moving mice. Closed-loop regulation is achieved by dynamically adjusting the parameters of optical control and ultrasonic stimulation in real time based on the photoacoustic and fluorescent signals. Therefore, embodiments of the present invention can be used to conduct experimental studies on the brains of freely moving animals.

[0050] Figure 1The schematic diagram of the multi-wavelength optical path in the embodiment of the present invention is characterized in that the timing of the continuous laser (102) and the nanosecond pulse laser (101) is synchronously triggered by an external trigger control system for the excitation laser, and a time delay is introduced by the external trigger signal to achieve a precise interval between the output pulses of the two lasers. In addition, the nanosecond pulse laser (101) realizes the stimulated Raman effect through the different lengths of the polarization-maintaining optical fiber to generate light beams of 558nm and 604nm wavelengths, and introduces a time delay of the pulse sequence by the difference in optical fiber length. Based on the optical absorption characteristics of hemoglobin, 532nm and 558nm dual-wavelength light is selected as the excitation light for vascular photoacoustic imaging; based on the absorption characteristics of lymphatic imaging dye, 604nm wavelength light is selected as the excitation light for lymphatic photoacoustic imaging; based on the absorption wavelength of the fluorescent dye, 488nm continuous light is selected as the excitation light for the fluorescent signal. Finally, the four wavelengths of laser light are combined by an optical fiber coupling device, coupled into the first end of the single-mode optical fiber, and emitted through the second end of the single-mode optical fiber to form a multi-wavelength beam.

[0051] Refer again Figure 1 A nanosecond pulse laser (101) is used to provide pulsed light with a wavelength of 532 nm, which is divided into three beams of 532-nm pulsed light after passing through half-wave plates (111, 112) and polarization beam splitters (121, 122). One beam is reflected by a set of reflective mirror frames (1603, 1604). The angle of the reflective mirror frames is adjusted to couple the laser into a single-mode optical fiber through a first dichroic mirror (131), a second dichroic mirror (132), and a third dichroic mirror (133). The other two beams of 532-nm pulsed light are respectively coupled into polarization-maintaining optical fibers (151, 152) and pass through corresponding narrow bandpass filters (141, 142) to pass through stimulated Raman spectroscopy. The light beams are converted to generate light beams with wavelengths of 558 nm and 604 nm, which are then combined with other light beams of wavelengths through a first dichroic mirror (131), a second dichroic mirror (132), and a third dichroic mirror (133) and then coupled into a single-mode optical fiber; a continuous laser (102) is used to provide continuous light with a wavelength of 488 nm, which is combined with other light beams of wavelengths through a set of reflective mirror frames (1611, 1612) and through a third dichroic mirror (133) and then coupled into the same single-mode optical fiber; a near-infrared laser (103) is used to provide continuous light with a wavelength of 1064 nm, which is coupled into a multimode optical fiber through a coupler (172) and transmitted to a target tissue for optical regulation;

[0052] Figure 2The structure diagram of the system module in the example of the present invention is shown. The system module diagram mainly includes an optical scanning module, a transparent ultrasonic transducer (213), a CMOS sensor (201), and a control module. The focusing objective lens of the embodiment of the present invention focuses the laser beam on the imaging area of the animal's head to stimulate the generation of ultrasonic signals and fluorescent signals. The ultrasonic signal is converted into an electrical signal by the transparent ultrasonic transducer, and the fluorescent signal is converted into an electrical signal by the CMOS sensor and collected by the acquisition card. The material used in the transparent ultrasonic transducer (213) allows the light beam to pass through to simplify the overall structure of the system. The CMOS sensor (201) has low power consumption and high integration, and can quickly and stably convert the fluorescent signal into an electrical signal, and transmit the data to the acquisition card for storage and processing.

[0053] In the present invention, the optical scanning module may include a collimator mirror (205), a first dichroic mirror (209), a scanning mirror (206), a second dichroic mirror (210), and an objective lens (212). A laser generates an incident light beam, which passes through an output end (204), is collimated by the collimator mirror (205), and then passes through the first dichroic mirror (209). After being reflected by the scanning mirror (206), the light beam passes through the second dichroic mirror (210), and is focused by the objective lens (212) before being incident on the animal's head (215). The scanning action of the scanning mirror performs raster scanning imaging on different positions of the imaging area of the animal's head, i.e., two-dimensional imaging is performed.

[0054] In one embodiment, the optical scanning module further includes a beam pre-processing component and a fluorescence signal pre-processing component. The beam pre-processing component is located in the optical path from the laser to the system to spatially filter and shape the beam.

[0055] The fluorescence signal preprocessing component includes a filter (203), a pinhole structure (216) and a focusing lens (202), wherein the fluorescence signal is reflected to the fluorescence signal optical path via a first dichroic mirror (209), filtered by the filter (203) and the pinhole structure, and then focused by the focusing lens (202) and received by the CMOS sensor (201).

[0056] In one embodiment, the regulation module includes an optical regulation module and an ultrasonic regulation module. The optical regulation module is used to optically stimulate or inhibit the target tissue through light of a specific wavelength, and the ultrasonic regulation module is used to ultrasonically stimulate the target tissue. The control module combines optical signals, photoacoustic signals and neural signals to generate collaborative regulation parameters to achieve closed-loop control of optical regulation and ultrasonic regulation.

[0057] Refer again Figure 2The optical control system comprises a near-infrared light source and a digital micromirror (211). The near-infrared light source emits a near-infrared laser beam which is reflected by the output end (208) via the reflector (207) to the programmable optical modulation component (211), and then reflected by the second dichroic mirror (210) to the focusing objective lens (212) for focusing and irradiating a specific brain area for optical control.

[0058] A digital micromirror is a miniature matrix array consisting of thousands of tiny, controllable mirrors, each of which can be independently tilted to reflect light to form an image. Each micromirror represents a pixel of the image and is typically controlled by programmable electrical signals to illuminate specific brain areas for optical manipulation.

[0059] Figure 3 It is a flow chart of the closed-loop regulation process in an embodiment of the present invention. The photoacoustic imaging probe acquires the photoacoustic signal, the fluorescence imaging probe acquires the fluorescence signal, and the EEG signal acquired by the neural signal acquisition module is sent to the computer for signal analysis. The onset of the disease is detected online by calculating the average photoacoustic signal intensity, analyzing the blood oxygen saturation, and calculating the fluorescence signal amplitude, time dynamic characteristics, spatial distribution, spectral characteristics and fluorescence signal amplitude, frequency and other parameters. According to the detection results, the computer dynamically plans reasonable control parameters and sends them to the FPGA through the serial port, triggering the FPGA to send the corresponding optical control parameters and ultrasonic trigger signals. The optical control parameters are sent to the fourth laser to trigger the corresponding laser, and sent to the digital micromirror to generate a mask for activation control of a specific brain area. The ultrasonic trigger signal is sent to the power amplifier, and the amplifier drives the ultrasonic transducer to emit ultrasonic waves for ultrasonic stimulation.

[0060] Furthermore, the method influences and regulates animal brain function by controlling the intensity, phase, and frequency of the near-infrared light source. After regulating the neural activity information corresponding to a specific brain region of the animal to control the brain activity level of the target subject, the method further includes: observing the effects of the regulation in real time and determining the degree of regulation of the target subject's brain activity level based on the results.

[0061] In addition, the specific implementation methods of the multi-dimensional brain information quantitative analysis module and the closed-loop control module are as follows:

[0062] First, the collected photoacoustic and fluorescence signals are processed using a signal denoising algorithm to eliminate environmental noise and equipment interference, ensuring signal clarity and accuracy. Simultaneously, time correction and spatial registration methods are used to synchronize the multimodal data, ensuring consistency in the temporal sequence and spatial distribution of the different signals.

[0063] Physics-based modeling and machine learning algorithms are used to extract key features related to blood vessels and lymph, including blood oxygen saturation, blood flow velocity, vascular morphology, and lymphatic flow characteristics. Spatiotemporal decoding techniques are used to capture the dynamic changes in neuronal activity in fluorescence signals, analyzing their time series characteristics and spatial distribution patterns to extract information such as neuronal activity intensity, synchronization, and network connectivity.

[0064] The extracted photoacoustic and fluorescence signal features are deeply integrated, and a multidimensional feature matrix is constructed through spatial alignment and time series consistency correction. The feature matrix contains multimodal data features of blood vessels, lymphatics, and neurons, which can comprehensively characterize the dynamic changes in the brain microenvironment.

[0065] A deep learning algorithm is used to decode and analyze the fused feature matrix. By training a neural network model, core features closely related to the brain microenvironment are extracted, focusing on analyzing the functional connections between blood vessels, lymph nodes, and neurons, revealing the laws of multi-system synergy and constructing a unified feature space.

[0066] Based on the extracted multimodal features, a quantitative assessment model is constructed to accurately characterize brain functional status. The model output includes multidimensional indicators of the brain microenvironment, such as hemodynamic parameters, neuronal activity characteristics, and lymphatic circulation status, enabling a comprehensive assessment of brain functional status and providing a reliable basis for subsequent closed-loop regulation.

[0067] The closed-loop control module receives brain function information from the multidimensional brain information quantitative analysis module, including characteristic parameters of neural activity, vascular function, and lymphatic circulation. Using intelligent algorithms based on machine learning, it analyzes brain function in real time, identifying abnormal patterns or target areas requiring regulation. The analysis results include dynamic trends in brain function and the specific needs of the target regulation areas.

[0068] Based on the analyzed brain function state, the closed-loop control module generates optimized light / acoustic control parameters. It adjusts the intensity, wavelength, and frequency of light stimulation to achieve precise optical control of the target brain area. It also adjusts the power, pulse width, and frequency of ultrasound stimulation to ensure safe and efficient control of blood vessels and nerves. Based on changes in brain function state, the module uses algorithms to optimize control strategies and dynamically generate the optimal stimulation plan.

[0069] The optimized light stimulation parameters are transmitted to the optical control module, which controls the output intensity and frequency of the near-infrared laser and precisely projects it onto the target brain area via a digital micromirror system. The acoustic stimulation parameters are then transmitted to the ultrasonic control module, which drives the piezoelectric ceramics to generate focused sound waves, regulating cerebral blood flow or neural activity. The optical and ultrasonic control modules work together, using a time synchronization mechanism to ensure the precision and consistency of multimodal control.

[0070] During the stimulation process, the closed-loop control module monitors changes in brain function in real time, assessing whether the desired effects are being achieved. Based on these real-time monitoring results, the module automatically adjusts the light / sound stimulation parameters to optimize the desired effect. If the desired effects are not achieved, the module recalculates the stimulation parameters through an iterative algorithm to ensure accurate and efficient stimulation.

[0071] When brain function returns to the desired state or meets the set control criteria, the module stops controlling and records key parameters and data. The multimodal data collected during the control process is stored in a database, providing data support for subsequent experiments and model optimization. Furthermore, reinforcement learning algorithms are used to further enhance the intelligence of closed-loop control.

[0072] Figure 4 The diagram is a structural diagram of the bottom plate of the fixed component in an embodiment of the present invention. The ultrasonic control module (402) and the photoacoustic imaging probe (403) are integrated in the bottom plate (404) of the fixed component.

[0073] Figure 5 The present invention is a schematic diagram of a three-dimensional structure in which a fixed assembly is fixed to an animal's head, wherein the fixed assembly includes a housing (501-505) and a base plate (504). A light source assembly (502), a fluorescence imaging probe (501), and an optical control module (503) are built into the housing. Photoacoustic signals are collected by a transparent transducer (505). The housing is small in size and light in weight, enabling head-mounted photoacoustic-fluorescence multi-parameter monitoring and control on freely moving animals.

[0074] Figure 6 FIG. 1 is a schematic diagram of the base plate installation of the fixed component in an embodiment of the present invention. Figure 6 As shown, the mouse scalp is peeled off to expose the skull (601), and the skull is opened for the imaging area (602). The base plate (603) of the fixing assembly is fixed to the skull by dental cement.

[0075] This embodiment of the present invention integrates photoacoustic imaging, fluorescence imaging, optical control, and ultrasonic control, making it suitable for research on the brain's nerves, blood vessels, and lymphatic systems. By combining imaging monitoring with control, this technology enables real-time closed-loop monitoring and precise control of multimodal data.

[0076] In an embodiment of the present invention, the FPGA timing control system realizes laser excitation of the laser, controls the two-dimensional micro-electromechanical system galvanometer to perform continuous scanning using continuous sawtooth wave drive, realizes the acquisition timing of the acquisition card, and provides serial port communication to accept computer-generated control parameters and generate corresponding waveforms for optical and ultrasonic control.

[0077] Embodiments of the present invention also include monitoring the excitation light pulse energy through a photodiode to perform correction and compensation for functional imaging. Scanning control, data acquisition, and imaging programs are written using LabVIEW software. A GPU is used to accelerate signal processing, multi-wavelength signal reconstruction, image registration, and real-time display. A computer processes multimodal data, analyzes the signals, and generates control parameters based on actual needs, which are then sent to an FPGA.

[0078] In the present invention, unless otherwise specified or limited, the terms "installed," "connected," "connected," "fixed," etc. should be understood in a broad sense. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on specific circumstances.

[0079] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0080] 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 considered as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. A head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop control, characterized in that: include: The neural-lymphatic-vascular multimodal imaging monitoring module is used to obtain brain neural, lymphatic and vascular information in real time; A multi-dimensional brain information quantitative analysis module is used to decode, extract features and fuse the data acquired by the neural-lymphatic-vascular multimodal imaging monitoring module to establish a quantitative assessment model for brain function status; A closed-loop control module, configured to generate optimized light / acoustic control parameters according to the quantitative evaluation model; A light / acoustic brain regulation module, comprising an optical regulation unit and an ultrasonic regulation unit, for implementing light stimulation and ultrasonic stimulation on the target brain area according to the regulation parameters; The detachable head-mounted module integrates the neural-lymphatic-vascular multimodal imaging monitoring module and the optical / acoustic brain control module, and is adapted to the head of a freely moving animal to achieve real-time imaging and closed-loop control.

2. The device according to claim 1, characterized in that The neuro-lymphatic-vascular multimodal imaging monitoring module includes: Multi-wavelength laser light source, used to generate excitation light of different wavelengths; an optical scanning unit, configured to transmit and focus the excitation light onto a target brain area; an ultrasonic transducer, for receiving photoacoustic signals and converting them into electrical signals; Fluorescence sensor, used to receive fluorescence signals and convert them into electrical signals.

3. The device according to claim 2, characterized in that The multi-wavelength laser light source comprises: pulsed lasers to generate excitation light for vascular and lymphatic imaging; A continuous laser for generating excitation light for neuronal fluorescence imaging; Near-infrared lasers for generating optically regulated excitation light; Optical processing components used to couple lasers of different wavelengths into the same transmission path.

4. The device according to claim 3, characterized in that The laser light output by the pulsed laser is converted into light of at least two different wavelengths through the stimulated Raman effect, wherein the first wavelength retains the original wavelength for vascular structure imaging, the second wavelength is used for lymphatic imaging, and the third wavelength is used together with the first wavelength for vascular blood oxygen saturation calculation; the wavelength of the continuous laser is adapted to the absorption characteristics of the fluorescent marker dye.

5. The device according to claim 2, characterized in that The optical scanning unit comprises: Collimating lens, used to collimate the laser beam; A two-dimensional scanning galvanometer, used to control the scanning path of the light beam; A focusing objective lens is used to focus the light beam onto the target brain area; Beam splitting component, used to separate the excitation light and the fluorescence signal.

6. The device according to claim 1, characterized in that The multi-dimensional brain information quantitative analysis module includes: Signal preprocessing unit, used for denoising, temporal synchronization and spatial registration of multimodal data; A feature extraction unit, used to extract hemodynamic parameters from photoacoustic signals and spatiotemporal features of neuronal activity from fluorescence signals; The multimodal fusion unit integrates vascular, lymphatic and neural features based on deep learning algorithms to construct a quantitative assessment model for brain functional status.

7. The device according to claim 1, characterized in that The optical control unit includes a near-infrared laser and a programmable digital micromirror array, which are used to dynamically adjust the irradiation area, intensity and frequency of light stimulation; the ultrasonic control unit includes a focused ultrasonic transducer, which is used to generate an acoustic pressure field with adjustable parameters to regulate neural activity or lymphatic circulation.

8. The device according to claim 1, characterized in that The closed-loop control module implements regulation through the following steps: receiving output data of the quantitative evaluation model in real time; Analyze brain functional status and generate regulatory strategies; Dynamically adjust light stimulation parameters and ultrasound stimulation parameters; Optimize control parameters based on feedback data to achieve closed-loop control.

9. The device according to claim 1, characterized in that The detachable head-mounted module comprises: A lightweight housing integrating the optical scanning unit and the fluorescence sensor; a bottom plate, fixed to the animal's skull and magnetically connected to the housing, the ultrasonic transducer and the ultrasonic control unit being arranged on the bottom plate; The base plate is fixed to the animal's skull through surgery, and the outer shell is detachable to accommodate the needs of free movement; The fixing method of the base plate to the animal skull includes: removing part of the scalp and skull, bonding the base plate to the skull with a biocompatible adhesive, and detachably connecting the base plate to the shell through a magnetic structure.

10. An imaging method for a head-mounted photoacoustic device for multi-parameter brain function monitoring and closed-loop control, characterized in that: S1. Use a multi-wavelength laser light source to generate laser beams of different wavelengths. A pulsed laser provides 532nm pulsed light, which is split into three beams by an optical processing component. Two of the 532nm pulses are coupled through a polarization-maintaining fiber and converted to 558nm and 604nm wavelengths, respectively, using the stimulated Raman effect. These are then combined with another 532nm laser beam and coupled into a single-mode fiber. The varying lengths of the polarization-maintaining fiber ensure that the pulse sequences of the three wavelengths are spaced apart. The 532nm and 558nm wavelengths are used for vascular photoacoustic imaging and blood oxygen saturation calculation, while the 604nm wavelength is used for lymphatic photoacoustic imaging excitation. The continuous laser provides continuous light with a wavelength of 488nm for fluorescence imaging of neurons in target tissues; the pulsed laser and the continuous laser are coupled to the same single-mode optical fiber through an optical processing component to achieve collinear transmission of multi-wavelength light beams. A near-infrared laser provides continuous light at a wavelength of 1064nm, modulated to a flash frequency of 10Hz-40Hz, and transmitted to the target tissue via multimode optical fiber for optical brain control. An external trigger control system synchronizes the timing of the three lasers, ensuring that the pulse sequences of the different wavelengths are kept at a constant interval. S2. The generated laser beam is transmitted via a single-mode fiber coupling, passing through an optical scanning unit and an ultrasonic transducer to the imaging area of the animal's head. This generates a photoacoustic signal, which is received by the ultrasonic transducer and converted into an electrical signal for photoacoustic imaging. Simultaneously, a fluorescence signal is generated, which is received by a fluorescence sensor and converted into an electrical signal for fluorescence imaging. S3. Send the acquired multimodal imaging data to the multidimensional brain information quantitative analysis module, decode and analyze the multidimensional data, extract key features, perform multimodal data feature fusion, establish an analysis method for quantitatively evaluating the brain microenvironment, and accurately characterize the brain functional state. S4. Quantified brain function information is transmitted to the closed-loop control module, which generates optimized control parameters in real time and sends them to the optical and ultrasonic control unit. The optical and ultrasonic control unit adjusts the near-infrared laser, digital micromirror, and focused ultrasonic transducer based on the optimized parameters to achieve precise control of brain function. S5. The neural-lymphatic-vascular multimodal imaging monitoring module, optical control unit, and ultrasonic control unit are combined with a detachable head-mounted module to achieve real-time imaging and closed-loop control of freely moving mice.

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