High-channel clinical microelectrode array intelligent brain function localization system and method

Abstract

The application discloses a high-channel clinical microelectrode array intelligent brain function positioning system and method, and belongs to the fields of electronic information and clinical disease diagnosis and treatment technologies. The system comprises a microelectrode array implanted in the brain, a signal processing and transmission unit and a signal identification unit. The microelectrode array adopts a multi-channel design, can synchronously detect neural electrophysiological signals and transmitter chemical signals of different depths and directions, and has a resolution of a single cell level. The signal processing and transmission unit is responsible for signal acquisition, amplification and transmission, and applies electrical stimulation; the signal identification unit performs real-time processing on the signals through a convolutional neural network algorithm, quickly identifies target nuclei, and realizes accurate positioning. The application can realize real-time monitoring of neural cell discharges and transmitter releases at different depths and different directions, and can realize rapid and accurate target positioning with the aid of advanced intelligent algorithms, thereby providing a more reliable basis for DBS surgery.

Description

Technical Field

[0001] The present invention belongs to the fields of electronic information and clinical disease diagnosis and treatment technology, and specifically relates to a high-channel clinical microelectrode array intelligent brain function positioning system and method. Background Art

[0002] Brain disorders, such as Parkinson's disease and epilepsy, significantly impact patients' physical and mental health, placing a heavy burden on patients and their families. Deep brain stimulation (DBS), an effective surgical treatment, involves implanting electrodes in specific target nuclei within the brain and applying electrical stimulation to modulate neural activity, thereby improving symptoms. However, the key to the success of DBS surgery lies in the ability to precisely locate the target nuclei, which is directly related to the surgical efficacy and patient recovery.

[0003] At present, in clinical practice, brain function localization mainly relies on single-channel microelectrode recording technology. This technology usually uses a single-point tungsten wire electrode for functional localization. During the electrode implantation process, it can only record the neuroelectrophysiological signals of a single site, and cannot achieve synchronous detection and identification of nerve cell discharges at different depths and orientations. This results in the need to repeatedly plug and unplug the electrodes during the localization process, which not only increases the operation time and the risk to the patient, but may also cause greater damage to the brain tissue. In addition, when performing target localization, clinicians mainly rely on their own accumulated experience to observe and identify electrophysiological signals. Due to the complexity and diversity of neuroelectrophysiological signals, this requires doctors to have extremely high professional skills and rich clinical experience. However, even experienced doctors find it difficult to guarantee the accuracy and consistency of each positioning, and there is a lack of effective clinical intelligent means of identifying targets.

[0004] With the continuous advancement of science and technology, people have put forward higher requirements for the accuracy and efficiency of brain function localization. In order to overcome the shortcomings of existing technologies, improve the accuracy and reliability of brain function localization, and reduce surgical risks and patient pain, a new type of brain function localization system is urgently needed. Summary of the Invention

[0005] To solve the above technical problems, the present invention provides a high-channel clinical microelectrode array intelligent brain function localization system and method, which can realize multi-channel, high-resolution synchronous detection of neuroelectrophysiological signals and neurotransmitter chemical signals, can monitor the discharge of nerve cells at different depths and different directions in real time, and can use advanced intelligent algorithms to achieve fast and accurate target positioning, providing a more reliable basis for DBS surgery, thereby pushing the treatment technology of brain dysfunction diseases to a new level.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] On the one hand, the present invention provides a high-channel clinical microelectrode array intelligent brain function localization system, comprising a cellular level clinical long brain function localization microelectrode array implanted in the brain, a signal processing and transmission unit and a signal recognition unit, wherein:

[0008] The microelectrode array is used to detect neurophysiological signals and neurotransmitter chemical signals at the cellular level in the brain; the microelectrode array includes multiple detection sites and multiple stimulation sites arranged at different depths in the longitudinal direction and in different transverse directions;

[0009] The signal processing and transmission unit is used to process the neural electrophysiological signals and transmitter chemical signals acquired by the microelectrode array and transmit the processed neural information to the signal recognition unit; and is used to apply the electrical stimulation signal to the microelectrode array;

[0010] The signal recognition unit is used to read and display the processed neural information, extract Spike signal features, and accurately identify and locate deep brain nuclei.

[0011] In a second aspect, the present invention provides a high-channel clinical microelectrode array intelligent brain function localization method, comprising:

[0012] The microelectrode array detects neurophysiological signals and neurotransmitter chemical signals at the cellular level in the brain. The microelectrode array includes multiple detection sites and multiple stimulation sites arranged at different depths in the longitudinal direction and in different lateral directions.

[0013] The signal processing and transmission unit applies electrical stimulation signals to the microelectrode array, processes the neural electrophysiological signals and transmitter chemical signals acquired by the microelectrode array, and transmits the processed neural information to the signal recognition unit;

[0014] The signal recognition unit reads and displays the processed neural information, extracts the Spike signal features, and accurately identifies and locates the deep brain nuclei.

[0015] In a third aspect, the present invention provides an electronic device comprising: one or more processors; a memory for storing one or more programs; wherein, when the one or more programs are executed by the one or more processors, the one or more processors implement the aforementioned high-channel clinical microelectrode array intelligent brain function localization method.

[0016] In a fourth aspect, the present invention provides a computer-readable storage medium having executable instructions stored thereon, which, when executed by a processor, enables the processor to implement the aforementioned high-channel clinical microelectrode array intelligent brain function localization method.

[0017] The beneficial effects of the present invention are:

[0018] First, the system utilizes a multi-channel microelectrode array to simultaneously detect neuroelectrophysiological and neurotransmitter chemical signals at varying depths and orientations within the brain. This significantly improves the accuracy of brain function localization, even down to the single-cell level, and offers significant advantages over traditional single-channel techniques. Second, the system software incorporates a convolutional neural network algorithm, enabling rapid identification of target nuclei, reducing surgical time, brain tissue damage, and surgical risk. Furthermore, the system features real-time electrical stimulation control, enabling simultaneous evaluation of stimulation efficacy during localization and optimizing treatment parameters. The microelectrode array's small detection sites and high spatial resolution enable it to capture subtle changes in neural activity, providing rich information for clinical diagnosis and research. The system's compact hardware design and user-friendly software reduce reliance on physician experience and enhance surgical reliability and consistency. Furthermore, the system is applicable not only to clinical procedures but also to brain science research, advancing the exploration of neural network activity patterns. By improving surgical precision and efficiency, the system helps reduce postoperative complications, shorten patient recovery periods, and lower healthcare costs, resulting in significant social and economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a schematic diagram of the structure of the high-channel clinical microelectrode array intelligent brain function localization system of the present invention;

[0020] Figure 2 This is a schematic diagram of the preparation of a long microelectrode array for clinical brain function localization at the cellular level implanted into the brain.

[0021] Reference numerals:

[0022] 1-polyimide sleeve; 2-flattened polyimide sleeve; 3-detection electrode site; 4-stimulation electrode site; 5-restored tubular polyimide sleeve; 6-tungsten wire core. DETAILED DESCRIPTION

[0023] The present invention will be further described below with reference to the accompanying drawings and examples.

[0024] like Figure 1 As shown, the present invention provides a high-channel clinical microelectrode array intelligent brain function localization system, which includes a cellular-level clinical long brain function localization microelectrode array implanted in the brain, a signal processing and transmission unit, and a signal recognition unit.

[0025] The long-length clinical brain function positioning microelectrode array implanted in the brain at the cellular level is used to detect high-resolution neuroelectrophysiological signals and transmitter chemical signals at the cellular level in the brain.

[0026] The signal processing and transmission unit is used to implant the microelectrode array into the deep brain nuclei of the patient using a thruster; collect and amplify the weak neurophysiological signals and neurotransmitter chemical signals acquired by the microelectrode array to obtain processed neural information, and transmit the processed neural information to the signal recognition unit on the computer via a USB cable; and is also used to apply electrical stimulation signals to the microelectrode array.

[0027] The signal recognition unit is used to read and display the neural information collected by the signal processing and transmission unit, extract the Spike signal characteristics, apply electrical stimulation control signals and thruster control signals to the signal processing and transmission unit, and accurately identify and locate deep brain nuclei.

[0028] Furthermore, the cellular-level clinical long brain function localization microelectrode array implanted in the brain includes: a tungsten wire core with the tip corroded into a cone, the total length of the tungsten wire core is 150~250mm, and it is implanted into the deep brain nuclei of clinical patients under the push of the microelectrode array propeller module; a polyimide sleeve with multiple neuroelectrophysiological signal detection sites, neurotransmitter chemical signal detection sites and electrical stimulation sites prepared on the outer surface based on MEMS technology, the polyimide sleeve is sleeved on the outside of the tungsten wire core, and is bonded with biocompatible ethylene oxide resin.

[0029] Furthermore, the detection sites and stimulation sites are arranged at different longitudinal depths and transverse directions, which can realize the synchronous detection of neural information of multiple nuclei to achieve rapid and accurate brain function positioning. The detection sites include neuroelectrophysiological signal detection sites and transmitter chemical signal detection sites.

[0030] For example, in the longitudinal direction, the distribution can be gradient, for example, the detection sites are distributed at a certain interval along the axis of the tungsten wire core, covering the input layer (superficial layer), core layer (middle layer), and output layer (deep layer) of the basal nucleus (such as STN), and each layer corresponds to a different functional sub-region (such as the motor / limbic loop). Two detection sites are arranged on both sides of each stimulation site to form a "stimulus-response" unit to ensure that the local field potential and neurotransmitter diffusion can be recorded synchronously after stimulation; and / or in the transverse direction, it can be a radial layout (such as 4 groups of electrodes are evenly distributed circumferentially on the outer surface of the restored polyimide sleeve, each group contains 3 detection sites + 1 stimulation site, and the angle between each group is 90°, which can synchronously monitor the dorsal-ventral / inner-lateral electrical activity heterogeneity of the nucleus), or it can be an inclined implantation layout (such as the tip of the microelectrode array is at a 15° bevel angle, which can avoid blood vessels during advancement, while increasing the contact area with nerve fibers and improving the signal-to-noise ratio).

[0031] Furthermore, the signal processing and transmission unit includes a high-channel digital neural information processing module, a clinical electrical safety power management module and a microelectrode array thruster module, as well as a head-mounted preamplifier module electrically connected to the microelectrode array.

[0032] Further, the head-mounted pre-amplification module electrically connected with the microelectrode array includes a multi-channel weak electrophysiological signal amplification chip, a multi-channel weak neurotransmitter chemical spike signal amplification chip, a programmable electrical stimulation chip, and a power management chip, and the four chips are packaged into an integrated head-mounted pre-amplification module in the form of three-dimensional heterogeneous integration packaging.

[0033] Further, the multi-channel weak electrophysiological signal amplification chip amplifies and converts weak electrophysiological signals of microvolts into digital signals.

[0034] Further, the multi-channel weak neurotransmitter chemical spike signal amplification chip uses a capacitance transimpedance amplifier to realize detection of spike neurotransmitter chemical signals released by vesicles.

[0035] Further, the power management chip is used to provide power supply for each chip of the head-mounted pre-amplification module.

[0036] Further, the high-channel digital neural information processing module is electrically connected with the head-mounted pre-amplification module through an SPI interface; the high-channel digital neural information processing module realizes high-channel neural information processing based on an FPGA chip, including reading and processing neural electrophysiological signals and neurotransmitter chemical signals obtained by the head-mounted pre-amplification module, and transmitting the signals to a signal recognition unit through a USB protocol; and reading an electrical stimulation control signal output by an electrical stimulation signal output module in the signal recognition unit through a USB interface, processing and converting the signal, and transmitting the signal to a programmable electrical stimulation chip of the head-mounted pre-amplification module to control the head-mounted pre-amplification module to output an electrical stimulation signal.

[0037] Further, the clinically electrically safe power management module is used to provide power supply for the remaining modules and ensure safety.

[0038] Further, the microelectrode array pusher module is used to implant a microelectrode array into a deep nuclear group of a brain of a clinical patient.

[0039] Further, the signal recognition unit includes a data reading module, a neural signal filtering module, a Spike signal feature extraction module, a multi-channel neural signal display module, an electrical stimulation signal output module, a microelectrode array pusher control and push depth display module, and an intelligent rapid brain function positioning algorithm module based on a convolutional neural network.

[0040] Firstly, the obtained neural information is read by a data reading module; then the detected neural electrophysiological signals are sent to a neural signal filtering module for processing, including obtaining action potential signals by high-pass filtering and obtaining field potential signals by low-pass filtering; the action potential signals are extracted by a Spike signal feature extraction module through threshold extraction for Spike signal feature extraction; a multi-channel neural information display module can synchronously display multi-channel neural electrophysiological signals, action potential signals and field potential signals, neurotransmitter chemical spike signals, and extracted Spike signals. According to the firing rate, waveform, firing index and interval, normalized root mean square and power spectral density, and neurotransmitter chemical spike signal parameters of the multi-channel neural electrophysiological signals acquired in real time, an intelligent rapid brain function positioning algorithm module is constructed based on a convolutional neural network, and the intelligent rapid brain function positioning algorithm is embedded into a signal recognition unit. When the signal recognition unit reads the deep brain nuclear group neural electrophysiological and neurotransmitter chemical spike signals detected by the microelectrode array in real time, the nuclear group reached by the microelectrode array is quickly identified through the intelligent rapid brain function positioning algorithm, so as to realize intelligent rapid function positioning.

[0041] Further, the intelligent rapid brain function positioning algorithm based on the convolutional neural network extracts features of the neural electrophysiological signals and neurotransmitter chemical signals of each deep brain nuclear group read, trains by using the convolutional neural network, establishes a dual-mode neural information intelligent rapid brain function positioning algorithm, and realizes rapid intelligent positioning of target nuclear groups in deep brain electrical stimulation.

[0042] When the microelectrode array reaches the target nuclear group, electrical stimulation needs to be applied to the nuclear group and the effect of the electrical stimulation needs to be evaluated. The electrical stimulation mode (voltage stimulation, current stimulation), electrical stimulation waveform (which can be edited), electrical stimulation duration and other parameters are set by an electrical stimulation signal output module of the signal recognition unit, transmitted to the high-channel digital neural information processing module through the USB interface for format conversion processing, and then transmitted to the programmable electrical stimulation chip of the head-mounted preamplifier module through the SPI interface. The programmable electrical stimulation chip will output the stimulation waveform according to the software settings, apply it to the neural cells of the deep brain nuclear group through the electrical stimulation site of the microelectrode array, and realize deep brain electrical stimulation regulation. Then, the neural electrophysiological signals and neurotransmitter chemical spike signals under the electrical stimulation regulation are detected to evaluate the stimulation effect.

[0043] As Figure 2The figure shows a schematic diagram of the preparation of a long, clinical brain function localization microelectrode array implanted in the brain at the cellular level. A 200-micron diameter polyimide tube 1 is flattened to obtain a flattened polyimide tube 2. Microelectrode arrays are then fabricated on the upper and lower surfaces of the flattened polyimide tube 2 using a MEMS process, forming multiple detection electrode sites 3 and stimulation electrode sites 4. The detection electrode sites 3 are circular with a diameter of 10 microns, and the stimulation electrode sites 4 are rectangular. The detection electrode sites 3 are modified with different nanocomposite functional materials to detect neuroelectrophysiological signals and transmitter chemical spike signals, respectively. The flattened polyimide sleeve 2 with the prepared electrode sites is then restored to a hollow cylinder, that is, the tubular polyimide sleeve 5 is restored. Then, a tungsten wire core 6 with one tip etched into a cone and the other side remaining cylindrical is inserted into the restored tubular polyimide sleeve 5 and bonded with a biocompatible ethylene oxide resin to form a cellular-level clinical long brain function positioning microelectrode array implanted in the brain, wherein the length of the tungsten wire core 6 is greater than that of the restored tubular polyimide sleeve 5, and both ends thereof extend beyond the two end faces of the restored tubular polyimide sleeve 5.

[0044] Furthermore, in addition to its supporting function, the exposed tip of the tungsten wire core 6 can be used as an additional recording point for calibrating the electrode position (analyzing the brain-tissue interface state through impedance spectroscopy).

[0045] In a second aspect, the present invention provides an electronic device comprising: one or more processors; a memory for storing one or more programs; wherein, when the one or more programs are executed by the one or more processors, the one or more processors implement the aforementioned high-channel clinical microelectrode array intelligent brain function localization method.

[0046] In a third aspect, the present invention provides a computer-readable storage medium having executable instructions stored thereon, which, when executed by a processor, enables the processor to implement the aforementioned high-channel clinical microelectrode array intelligent brain function localization method.

[0047] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A high-channel clinical microelectrode array intelligent brain function localization system, characterized in that: It includes a cellular level clinical long brain function positioning microelectrode array implanted in the brain, a signal processing and transmission unit and a signal recognition unit, among which, The microelectrode array is used to detect neuroelectrophysiological signals and transmitter chemical signals at the cellular level in the brain. The microelectrode array includes multiple detection sites and multiple stimulation sites arranged at different depths in the longitudinal direction and in different transverse directions. In the longitudinal direction, the detection sites are distributed at preset intervals along the axial direction of the tungsten wire core, and two detection sites are arranged on both sides of each stimulation electrode site to form a "stimulus-response" unit. In the transverse direction, the detection sites and stimulation electrode sites are arranged in a radial pattern. The signal processing and transmission unit is used to process the neural electrophysiological signals and transmitter chemical signals acquired by the microelectrode array and transmit the processed neural information to the signal recognition unit; and is used to apply the electrical stimulation signal to the microelectrode array; The signal recognition unit is used to read and display the processed neural information, extract Spike signal features, and accurately identify and locate deep brain nuclei based on convolutional neural networks; wherein, the signal recognition unit includes a data reading module connected to the signal processing and transmission unit, a neural signal filtering module, a Spike signal feature extraction module, and an intelligent and rapid brain function localization algorithm module based on convolutional neural networks; the obtained neural information is read by the data reading module; then the detected neural electrophysiological signal is sent to the neural signal filtering module for processing, including obtaining action potential signals through high-pass filtering and obtaining field potential signals through low-pass filtering; wherein, for the action potential signal, the Spike signal feature extraction module uses a threshold extraction method to extract the Spike signal features; based on the firing rate, waveform, firing index and interval, normalized root mean square and power spectral density of the multi-channel neural electrophysiological signal acquired in real time, and the chemical spike signal parameters of the neurotransmitter, an intelligent and rapid brain function localization algorithm module is constructed based on the convolutional neural network to quickly identify the nuclei reached by the microelectrode array, thereby achieving intelligent and rapid function localization.

2. A high-channel clinical microelectrode array intelligent brain function localization system according to claim 1, characterized in that: The microelectrode array is located on the outer surface of the restored tubular polyimide sleeve, and the inside is a tungsten wire core with a tip corroded into a cone. The outer surface is prepared with multiple neural electrophysiological signal detection sites, multiple neurotransmitter chemical signal detection sites, and multiple stimulation electrode sites.

3. A high-channel clinical microelectrode array intelligent brain function localization system according to claim 2, characterized in that: The multiple detection sites are circular with a diameter of 10 microns, and the stimulation electrode sites are rectangular.

4. A high-channel clinical microelectrode array intelligent brain function localization system according to claim 2, characterized in that: The tip of one side of the tungsten wire core is etched into a cone, and the other side remains cylindrical and is inserted into the restored tubular polyimide sleeve and bonded with biocompatible ethylene oxide resin. The length of the tungsten wire core is greater than the restored tubular polyimide sleeve, and both ends of the tungsten wire core exceed the two end surfaces of the restored tubular polyimide sleeve.

5. The high-channel clinical microelectrode array intelligent brain function localization system according to claim 1, characterized in that: The signal processing and transmission unit includes a high-channel digital neural information processing module and a head-mounted preamplifier module electrically connected to the microelectrode array. The high-channel digital neural information processing module and the head-mounted preamplifier module are electrically connected via an SPI interface, read and process the neural electrophysiological signals and neurotransmitter chemical signals acquired by the head-mounted preamplifier module, and transmit them to the signal recognition unit via a USB protocol; and read the electrical stimulation control signal emitted by the electrical stimulation signal output module in the signal recognition unit via the USB interface, and process and convert it and transmit it to the programmable electrical stimulation chip of the head-mounted preamplifier module to control the head-mounted preamplifier module to output the electrical stimulation signal.

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