Implantable positioning stimulation device

Abstract

The invention provides an implantable positioning stimulation device, and relates to the technical field of medical instruments. The implantable positioning stimulation device is used for being implanted into the body of a target object for a long time and comprises at least one electrode, each electrode comprises at least one contact, and each contact is a first contact used for collecting electroencephalogram signals or a second contact used for collecting cerebral blood flow signals; the nerve stimulator is configured to obtain an electroencephalogram signal and / or a cerebral blood flow signal, determine at least one lesion area according to the electroencephalogram signal and / or the cerebral blood flow signal, and determine stimulation information according to the at least one lesion area; and controlling the at least one contact to output a stimulation signal according to the stimulation information so as to perform nerve stimulation on the at least one lesion area. According to the embodiment of the invention, the positioning function of the lesion area can be realized, nerve stimulation can be carried out on the lesion area, the whole operation can be completed through one operation, the operation frequency is reduced, and the injury to a patient is reduced.

Description

Technical Field

[0001] The present application relates to the technical field of medical devices, and in particular, to an implantable positioning stimulation device. Background Art

[0002] Brain diseases often require recording the brain's electrical activity through electrodes placed on the scalp. Once the lesion area is confirmed, another surgery is required to implant the neurostimulator and electrodes into the patient's deep brain and / or subdural cortical area.

[0003] Therefore, the entire process of treating many brain diseases requires a second operation, namely, one to locate the lesion area and one to implant the neurostimulator and electrodes, which causes severe invasive trauma to the patient twice. Summary of the invention

[0004] In view of the shortcomings of the existing methods, the present application proposes an implantable positioning stimulation device to solve the technical problem in the related technology that two operations cause great harm to patients.

[0005] In a first aspect, an embodiment of the present application provides an implantable localization stimulation device for long-term implantation in a target object, comprising: At least one electrode, each electrode comprising at least one contact, each contact being a first contact for collecting an electroencephalogram signal or a second contact for collecting a cerebral blood flow signal; A neurostimulator is electrically connected to both the first contact and the second contact, and is configured to obtain an electroencephalogram signal and / or a cerebral blood flow signal, determine at least one lesion area according to the electroencephalogram signal and / or the cerebral blood flow signal, and determine stimulation information according to the at least one lesion area; and control at least one contact to output a stimulation signal according to the stimulation information to perform neurostimulation on the at least one lesion area; The stimulation information includes stimulation signal information and contact information. The stimulation signal includes at least one of the following: an electrical stimulation signal and an ultrasonic stimulation signal. The stimulation signal information is used to generate the stimulation signal. The contact information is used to indicate the contact for outputting the stimulation signal.

[0006] In one possible implementation, the implantable localized stimulation device is implanted between the scalp and skull of the target subject.

[0007] In one possible implementation, a neurostimulator includes a control module and a stimulation module; The control module is configured to obtain an electroencephalogram signal and / or a cerebral blood flow signal, determine at least one lesion area according to the electroencephalogram signal and / or the cerebral blood flow signal, and determine stimulation information according to the at least one lesion area; control the stimulation module to generate an electrical stimulation signal and / or control the stimulation module to generate an ultrasonic electrical signal according to the stimulation information; the stimulation signal includes at least one of the following: an electrical stimulation signal and an ultrasonic stimulation signal; The stimulation module is configured to output the electrical stimulation signal through at least one first contact; and / or, output the ultrasonic electrical signal to the second contact, so that the second contact outputs the ultrasonic stimulation signal based on the ultrasonic electrical signal.

[0008] In one possible implementation, the stimulation module includes an electrical stimulation unit and an ultrasonic stimulation unit; The electrical stimulation unit is configured to generate an electrical stimulation signal and output the electrical stimulation signal through the first contact; The ultrasound stimulation unit is configured to generate an ultrasound electrical signal and output the ultrasound electrical signal to the second contact, so that the second contact outputs an ultrasound stimulation signal based on the ultrasound electrical signal to change the action potential of neurons in the lesion area based on the direct focused ultrasound technology.

[0009] In a possible implementation, the second contact includes a collection sensor, and the collection sensor includes any one of the following: an ultrasound probe, an imaging sensor, or a near-infrared spectroscopy device.

[0010] In a possible implementation, the acquisition sensor includes an ultrasonic transducer, which is used to generate an ultrasonic detection signal according to an ultrasonic electrical signal, and to generate a cerebral blood flow signal according to an echo signal reflected from the ultrasonic detection signal; the cerebral blood flow signal is used to characterize the velocity of blood flow.

[0011] In a possible implementation, the control module is specifically configured as follows: Determine a neural activity distribution map according to the amount of signal change between the EEG signal and the pre-stored EEG signal, and / or the amount of signal change between the cerebral blood flow signal and the pre-stored cerebral blood flow signal; the neural activity distribution map is used to distinguish between normal neural activity areas and abnormal neural activity areas; According to the signal change amount of each abnormal nerve activity area, the abnormal nerve activity areas are ranked according to the abnormality degree, and a predetermined number of abnormal nerve activity areas with high rankings are selected as at least one lesion area.

[0012] In a possible implementation, the control module is specifically configured as follows: For each lesion area, the stimulation information is determined based on the deep learning algorithm and the signal change amount of the lesion area.

[0013] In a possible implementation, the control module is specifically configured as follows: For each contact point, acquiring an EEG signal and / or a cerebral blood flow signal within a first time period, and determining a first average value of the EEG signal and / or a second average value of the cerebral blood flow signal; If the first average value and / or the second average value is not less than the first threshold value, the neural activity area corresponding to the contact point is determined as a lesion area.

[0014] In a possible implementation, the control module is specifically configured as follows: If the first average value and / or the second average value is not less than the second threshold value and is less than the first threshold value, the neural activity area corresponding to the touch point is taken as a lesion area to be detected; Acquiring an electroencephalogram signal and / or a cerebral blood flow signal within at least one second time period; For each second time period, determining a first average value of the EEG signal and / or a second average value of the cerebral blood flow signal; If the first average value and / or the second average value corresponding to each second time period is not less than the second threshold, the lesion area to be detected is determined as a lesion area.

[0015] In a possible implementation, the control module is specifically configured as follows: For each lesion area, the contact point information is determined according to the position information of the lesion area and each contact point; the position information includes distance information and orientation information.

[0016] In a possible implementation, the control module is specifically configured as follows: If the distance between the lesion area and each contact point is greater than the first distance threshold, determining the contact point in the contact point information as the second contact point to output an ultrasonic stimulation signal; If the distance between the lesion area and each contact point is within the first predetermined range, the contact point in the contact point information is determined to be the first contact point and / or the second contact point, so as to output an electrical stimulation signal and / or an ultrasonic stimulation signal.

[0017] In a possible implementation, each electrode is provided with at least one first contact and at least one second contact, and the first contacts and the second contacts are alternately distributed at intervals.

[0018] In a possible implementation, one end of each electrode is connected to the neurostimulator, and the other end extends in a direction away from the neurostimulator, and the multiple electrodes are evenly distributed along the circumference of the neurostimulator.

[0019] In a possible implementation, the plurality of electrodes are distributed in a ring shape, and the neurostimulator is located in the middle of the ring.

[0020] The beneficial technical effects brought about by the technical solution provided by the embodiment of the present application include: The implantable positioning stimulation device of the embodiment of the present application includes at least one electrode and a neurostimulator. The entire implantable positioning stimulation device can be implanted in the body of the target object for a long time. The contact of the electrode is a first contact for collecting EEG signals or a second contact for collecting cerebral blood flow signals. At the same time, the neurostimulator can determine the lesion area according to the EEG signal and / or cerebral blood flow signal, and then determine the stimulation information according to the lesion area, and then control at least one contact to output the stimulation signal according to the stimulation information to perform neurostimulation on at least one lesion area. Therefore, the implantable positioning stimulation device of the embodiment of the present application can realize the positioning function of the lesion area and perform neurostimulation on the lesion area. The entire operation can be completed through a single operation, which reduces the number of operations and reduces the harm to the patient.

[0021] At the same time, the implantable positioning stimulation device in the embodiment of the present application can realize long-term brain function detection through contacts. It can not only continuously identify and locate the lesion area, but also perform stimulation treatment when necessary, thereby realizing the triple functions of brain function detection, lesion area positioning and stimulation treatment in one implantation.

[0022] Moreover, the stimulation signal in the embodiment of the present application is an electrical stimulation signal and / or an ultrasonic stimulation signal, and the electrical stimulation and the ultrasonic stimulation can be combined to achieve more precise stimulation.

[0023] Additional aspects and advantages of the present application will be partially given in the following description, which will become apparent from the following description, or will be understood through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which: Figure 1 A schematic diagram of the structure of an implantable localization stimulation device provided in an embodiment of the present application; Figure 2 A schematic diagram of the structure of a neural stimulator provided in an embodiment of the present application; Figure 3 A schematic diagram of the structure of a stimulation module provided in an embodiment of the present application; Figure 4 A schematic diagram of the structure of another implantable positioning stimulation device provided in an embodiment of the present application.

[0025] Reference numerals: 1- Implantable localized stimulation device; 110 - electrode, 111 - first contact, 112 - second contact; 120 - neural stimulator, 121 - control module, 122 - stimulation module, 1221 - electrical stimulation unit, 1222 - ultrasonic stimulation unit. DETAILED DESCRIPTION

[0026] The embodiments of the present application are described below in conjunction with the drawings in the present application. It should be understood that the implementation methods described below in conjunction with the drawings are exemplary descriptions for explaining the technical solutions of the embodiments of the present application and do not constitute a limitation on the technical solutions of the embodiments of the present application.

[0027] It will be understood by those skilled in the art that, unless specifically stated, the "said" and "the" used herein may also include plural forms. It should be further understood that the wording "including" used in the specification of the present application refers to the presence of the features, integers, steps, operations, elements and / or components, but does not exclude the implementation of other features, information, data, steps, operations, elements, components and / or combinations thereof supported by the present technical field. It should be understood that when we say that an element is "connected" or "coupled" to another element, the element may be directly connected or coupled to the other element, or it may refer to the connection relationship between the element and the other element through an intermediate element. In addition, the "connection" or "coupling" used herein may include wireless connection or wireless coupling. The term "and / or" used herein refers to at least one of the items defined by the term, for example, "A and / or B" may be implemented as "A", or as "B", or as "A and B".

[0028] In related technologies, the entire process of treating brain functional diseases generally requires a second operation, such as the treatment of epilepsy, Parkinson's disease, etc.

[0029] Taking epilepsy as an example, epilepsy localization refers to the process of determining the origin of epileptic seizures in clinical practice, which is crucial for the treatment of epilepsy, especially for patients with epilepsy that is difficult to control with drugs. Accurate epilepsy localization can help doctors decide whether epilepsy surgery is suitable and guide the scope of surgical resection of the lesion to achieve the best treatment effect while minimizing the impact on normal brain function.

[0030] The main positioning methods are: 1. Electroencephalogram (EEG): EEG is one of the most commonly used tools for epilepsy localization, recording the brain's electrical activity through electrodes placed on the scalp. Abnormal patterns of electrical activity can help identify the area of ​​origin of epileptic seizures.

[0031] 2. Stereotactic electroencephalogram (SEEG): Electrodes are implanted into deep brain structures through minimally invasive surgery to more accurately record the electrical activity of deep brain areas. It is suitable for cases where scalp EEG cannot clearly locate the location.

[0032] Once the epileptogenic area is confirmed, another surgery is required (because neither EEG nor SEEG can be implanted for a long time) to implant the neurostimulator and electrodes into the patient's deep brain and / or subdural cortical area.

[0033] The whole process requires two surgeries (once to locate the lesion and once to implant the stimulator), which causes serious invasive trauma to the patient. When locating the lesion area, multiple SEEG electrodes need to be implanted. When the stimulator is implanted for treatment, so many SEEG electrodes are not needed, and these electrodes need to be surgically removed. The invasive damage of electrodes implanted deep in the brain and / or in the subdural cortical area is greater, and there is a risk of electrode movement, breakage, and infection.

[0034] The implantable localization stimulation device provided by the present application is intended to solve the above technical problems of the related art. To make the purpose, technical solution and advantages of the present application clearer, the implementation mode of the present application will be further described in detail below in conjunction with the accompanying drawings.

[0035] See also Figure 1 As shown, an embodiment of the present application provides a schematic structural diagram of an implantable positioning stimulation device 1. The implantable positioning stimulation device 1 is used to be implanted under the scalp of a target object, and the implantable positioning stimulation device 1 includes: at least one electrode 110 and a neural stimulator 120; Each electrode 110 includes at least one contact, and each contact is a first contact 111 for collecting brain electrical signals or a second contact 112 for collecting cerebral blood flow signals.

[0036] The neurostimulator 120 is electrically connected to both the first contact 111 and the second contact 112, and is configured to obtain an electroencephalogram signal and / or a cerebral blood flow signal, determine at least one lesion area according to the electroencephalogram signal and / or the cerebral blood flow signal, and determine stimulation information according to the at least one lesion area; and control at least one contact to output a stimulation signal according to the stimulation information to perform neurostimulation on the at least one lesion area; The stimulation information includes stimulation signal information and contact information. The stimulation signal includes at least one of the following: an electrical stimulation signal and an ultrasonic stimulation signal. The stimulation signal information is used to generate the stimulation signal. The contact information is used to indicate the contact for outputting the stimulation signal.

[0037] Compared with the prior art, this application has at least the following advantages: 1. Reduce the number of surgeries: The traditional method requires that multiple SEEG electrodes be implanted into the skull to analyze the location of the lesion, then these electrodes are removed, and finally the deep electrodes in the skull are implanted into the lesion for treatment. The implantable localization stimulation device provided by this application can complete the process from lesion localization to treatment in one operation, reducing the number of surgeries and the risks and costs brought by multiple surgeries.

[0038] 2. Improve treatment accuracy: The device can simultaneously collect EEG signals and / or cerebral blood flow signals, and more accurately determine the location of the lesion area by comprehensively analyzing the two signals, thereby improving the accuracy of treatment.

[0039] 3. Flexible stimulation methods: The stimulation signal can be an electrical stimulation signal or an ultrasonic stimulation signal, or even a combination of the two. This allows doctors to choose the most appropriate stimulation method based on the patient's specific situation, thereby improving the treatment effect.

[0040] 4. Wide applicability: For patients with epilepsy who do not have a clear lesion and are difficult to control with drugs, this application provides an effective treatment method, expands the scope of treatment indications, and brings new hope to these patients.

[0041] 5. Real-time monitoring and adjustment: Since the neurostimulator can be directly connected to the contacts on the electrodes, it can not only obtain the patient's EEG signals and / or cerebral blood flow signals in real time, but also adjust the stimulation parameters in real time according to the changes in these signals to ensure the safety and effectiveness of the treatment.

[0042] 6. Minimally invasive: The device is implanted under the scalp. Compared with traditional craniotomy, this method is more minimally invasive, reduces surgical trauma, does not damage the skull, and is beneficial to the patient's postoperative recovery.

[0043] It is worth noting that the implantable positioning stimulation device 1 of the embodiment of the present application includes at least one electrode 110 and a neurostimulator 120. The entire implantable positioning stimulation device 1 can be implanted in the target object for a long time. The contacts of the electrodes are the first contacts 111 for collecting EEG signals or the second contacts 112 for collecting cerebral blood flow signals. At the same time, the neurostimulator 120 can determine the lesion area according to the EEG signals and / or cerebral blood flow signals, and then determine the stimulation information according to the lesion area, and then control at least one contact to output the stimulation signal according to the stimulation information to perform neurostimulation on at least one lesion area. Therefore, the implantable positioning stimulation device 1 of the embodiment of the present application can realize the positioning function of the lesion area and perform neurostimulation on the lesion area. The entire operation can be completed through one operation, which reduces the number of operations and reduces the harm to the patient.

[0044] At the same time, the implantable positioning stimulation device 1 of the embodiment of the present application can realize long-term brain function detection through contacts. It can not only continuously identify and locate the lesion area, but also perform stimulation treatment when necessary, thereby realizing the triple functions of brain function detection, lesion area positioning and stimulation treatment in one implantation.

[0045] Moreover, the stimulation signal of the embodiment of the present application may be an electrical stimulation signal and / or an ultrasonic stimulation signal, and the electrical stimulation and ultrasonic stimulation are combined to achieve more precise stimulation.

[0046] Optionally, all contacts include at least one first contact 111 and at least one second contact 112 , each electrode 110 may be simultaneously provided with at least one first contact 111 and at least one second contact 112 , or some electrodes 110 may be provided with at least one first contact 111 and some electrodes 110 may be provided with at least one second contact 112 .

[0047] Optionally, while some contacts in the embodiment of the present application collect signals, other contacts can output stimulation signals simultaneously.

[0048] Optionally, the information of the lesion area may be the location information of the lesion area, and the stimulation signal information may include electrical parameter information for generating an electrical stimulation signal, such as waveform, pulse, pulse width, frequency, and the stimulation signal information may also include ultrasonic electrical signal information for generating an ultrasonic stimulation signal, and the ultrasonic electrical signal information includes frequency, intensity, pulse width, duty cycle, duration, focal position, etc. The contact information includes information of the selected contact, including the contact type and the number of each contact type, or contact identification information. If the lesion area is located in the shallow layer, the first contact 111 may be preferred, and if the lesion area is located in the deep part of the brain, the second contact 112 may be selected.

[0049] The implantable localization stimulation device 1 of the embodiment of the present application is a SEEG system that can be implanted for a long time, and its working mode can be divided into two types. The first stage is the signal acquisition and lesion area positioning stage, and the second stage is the stimulation output according to the positioning of the lesion area.

[0050] In the prior art, the position of deep intracranial electrodes is fixed after implantation. Even if abnormalities occur in other areas, the stimulation given by the device is still near the electrode position, and the stimulation cannot be given flexibly and accurately. The embodiment of the present application provides precise stimulation based on the lesion area, which has high flexibility.

[0051] In some embodiments, the implantable localized stimulation device 1 is implanted between the scalp and skull of the target subject.

[0052] The implantation area of ​​the embodiment of the present application is between the scalp and the skull, and there is no need to implant deep into the brain, and there is no need to damage the skull, dura mater, etc., thus reducing trauma. The electrode 110 and the neurostimulator 120 are both implanted between the scalp and the skull, avoiding the risk of displacement and breakage of the electrode 110, and there is no discomfort caused by scalp EEG electrodes.

[0053] At the same time, the signal acquisition of the embodiment of the present application will not be affected by the secretion of oil and perspiration by the skin, will not affect normal life such as exercise, sleep, and social interaction, and can record changes in EEG activity related to medication, providing a quantitative reference basis for pharmaceutical companies and doctors.

[0054] After suturing, the embodiment of the present application is completely located under the scalp, with no wounds on the surface, and is not prone to infection. The signal-to-noise ratio of the signal under the scalp is better than that of the scalp EEG signal. The embodiment of the present application implements EEG detection, lesion localization and stimulation through one implantation, without the need to first perform SEEG localization and then implant the neurostimulator 120.

[0055] See also Figure 2 As shown, the present application embodiment provides a structural schematic diagram of a neural stimulator 120. Figure 2 As shown, the neurostimulator 120 includes a control module 121 and a stimulation module 122 .

[0056] The control module 121 is configured to obtain an electroencephalogram signal and / or a cerebral blood flow signal, determine at least one lesion area according to the electroencephalogram signal and / or the cerebral blood flow signal, and determine stimulation information according to the at least one lesion area; control the stimulation module 122 to generate an electrical stimulation signal and / or control the stimulation module 122 to generate an ultrasonic electrical signal according to the stimulation information; the stimulation signal includes at least one of the following: an electrical stimulation signal, an ultrasonic stimulation signal; The stimulation module 122 is configured to output the electrical stimulation signal through at least one first contact 111; and / or output the ultrasonic electrical signal to the second contact 112, so that the second contact 112 outputs the ultrasonic stimulation signal based on the ultrasonic electrical signal.

[0057] The control module 121 may be a CPU (Central Processing Unit), a general processor, a DSP (Digital Signal Processor), an ASIC (Application Specific Integrated Circuit), an FPGA (Field-Programmable Gate Array) or other programmable logic devices, transistor logic devices, hardware components or any combination thereof. It may implement or execute various exemplary logic blocks, modules and circuits described in conjunction with the disclosure of this application. The processor 2001 may also be a combination that implements computing functions, such as a combination of one or more microprocessors, a combination of a DSP and a microprocessor, etc.

[0058] The implantable localization stimulation device 1 of the embodiment of the present application can combine EEG signals and cerebral blood flow signals to locate the lesion area, thereby realizing the location of the lesion area. The lesion localization of the embodiment of the present application combines ultrasound technology to solve the problem of accurate detection of deep brain signals, and the combination of EEG signals and cerebral blood flow signals can accurately locate the lesion area.

[0059] The control module 121 of the embodiment of the present application has the function of monitoring and positioning, and is used to receive the signal collected by the electrode 110, analyze it, identify and locate the lesion area through analysis, and send instructions to the stimulation module 122 for stimulation when there is an abnormality in the lesion area.

[0060] See also Figure 3 As shown, the present embodiment provides a schematic diagram of the structure of a stimulation module 122. Figure 3 As shown, the stimulation module 122 includes an electrical stimulation unit 1221 and an ultrasonic stimulation unit 1222 .

[0061] The electrical stimulation unit 1221 is configured to generate an electrical stimulation signal and output the electrical stimulation signal through the first contact 111; the ultrasonic stimulation unit 1222 is configured to generate an ultrasonic electrical signal and output the ultrasonic electrical signal to the second contact 112, so that the second contact 112 outputs an ultrasonic stimulation signal based on the ultrasonic electrical signal to change the action potential of neurons in the lesion area based on the direct focused ultrasound technology.

[0062] The implantable localized stimulation device 1 of the embodiment of the present application can realize a new method of long-term monitoring of EEG signals. In comparison, SEEG can only monitor intracranial EEG for up to 30 days, and long-term monitoring of scalp EEG may cause discomfort or allergies. The method of implanting it outside the skull under the scalp can monitor EEG for a long time without causing excessive damage.

[0063] The embodiment of the present application is based on functional ultrasound imaging (FUSI) technology, which monitors neural activity in the brain area by measuring local blood flow changes through the Doppler effect, and changes the action potential of neurons based on direct focused ultrasound (FUSI) technology to achieve stimulation of the lesion area.

[0064] The contacts in the embodiment of the present application are preferably arranged in all directions to ensure that signals in all directions can be received.

[0065] In some embodiments, the second contact 112 includes an acquisition sensor, and the acquisition sensor includes any one of the following: an ultrasound probe, an imaging sensor, or a near infrared spectroscopy device.

[0066] In some embodiments, the acquisition sensor includes an ultrasonic transducer, which is used to generate an ultrasonic detection signal based on an ultrasonic electrical signal, and to generate a cerebral blood flow signal based on an echo signal reflected from the ultrasonic detection signal; the cerebral blood flow signal is used to characterize the velocity of blood flow.

[0067] Specifically, the second contact 112 is an ultrasonic contact and may be a miniature ultrasonic transducer. The cerebral blood flow signal is based on functional ultrasound imaging (FUSI) technology, which measures local blood flow changes through the Doppler effect to monitor neural activity in the brain region.

[0068] The control module 121 can monitor and analyze the state of neural activity in real time, and flexibly adjust the frequency, intensity and other parameters of the ultrasound according to needs to achieve precise control of neural activity.

[0069] The second contact 112 is used to generate ultrasound waves, and based on the technology of functional ultrasound imaging (FUSI), the ultrasound waves are used to stimulate the neural activities in a specific area of ​​the brain.

[0070] Among them, like all cells, neurons need blood to function, and the increase in neuron "activity" means that the brain needs an increase in blood flow. FUSI technology uses ultrasound to detect tiny changes in brain blood flow to infer the activity level of neurons.

[0071] The specific method is to transmit ultrasound to a certain area of ​​the brain and then detect the "echo" (reflected wave affected by blood flow). Because blood will cause the "Doppler effect" when it moves, it will slightly affect the vibration frequency of the echo. Therefore, by analyzing the changes in the echo frequency, the FUSI system can determine the changes in blood flow velocity and then infer the neural activity there.

[0072] In some embodiments, the control module 121 is specifically configured to: determine a neural activity distribution map according to the signal change amount between the EEG signal and the pre-stored EEG signal, and / or the signal change amount between the cerebral blood flow signal and the pre-stored cerebral blood flow signal; the neural activity distribution map is used to distinguish between normal neural activity areas and abnormal neural activity areas; According to the signal change amount of each abnormal nerve activity area, the abnormal nerve activity areas are ranked according to the abnormality degree, and a predetermined number of abnormal nerve activity areas with high rankings are selected as at least one lesion area.

[0073] Optionally, the signal change amount between the EEG signal and the pre-stored EEG signal and the signal change amount between the cerebral blood flow signal and the pre-stored cerebral blood flow signal are used to determine the neural activity distribution map. The abnormal neural activity areas obtained by using the signal change amount between the EEG signal and the pre-stored EEG signal and the abnormal areas obtained by using the signal change amount between the cerebral blood flow signal and the pre-stored cerebral blood flow signal can all be regarded as abnormal neural activity areas, or weighted processing can be performed according to predetermined weights of the two signal changes to obtain a comprehensive weight to determine the abnormal neural activity areas, etc.

[0074] In some embodiments, the control module 121 is specifically configured to: for each lesion area, determine the stimulation information according to the deep learning algorithm and the signal change amount of the lesion area.

[0075] As an example, the embodiment of the present application compares the collected EEG signals and cerebral blood flow signals with the EEG signals and cerebral blood flow signals in a resting state (the resting state refers to a state in which there is no external brain stimulation or brain activity itself that can cause brain activity), and then identifies areas where the EEG signals and cerebral blood flow signals change significantly, and then forms a neural activity distribution map to distinguish between abnormal neural activity areas and / or normal neural activity areas (coarse screening process).

[0076] Then, the control module 121 further analyzes the data of the abnormal neural activity area (discarding the data of the normal neural activity area and not analyzing it to reduce the power consumption and storage space of the device), such as ranking the abnormal neural activity area according to the signal change amount of the abnormal neural activity area, and finally locating the lesion area that needs stimulation intervention (fine screening process). Then, a deep learning algorithm can be used to output stimulation information according to the signal change amount. The stimulation information includes the type / number of contacts (if the target area is located in the shallow layer, electrical stimulation can be preferred, and if the lesion area is located in the deep brain, ultrasonic stimulation can be selected), waveform, pulse, pulse width, frequency, etc.

[0077] Optionally, the embodiments of the present application can determine the stimulation information through a neural network model. For example, a preset initial model is trained using multiple sample data to obtain a trained target model, and the signal change amount is input into the target model to obtain the stimulation information. The sample data includes the sample signal change amount and the sample stimulation information corresponding to each sample signal change amount. The sample data can be collected in actual medical tests or obtained through medical model simulation tests.

[0078] Optionally, if the embodiment of the present application determines that the signal change amount used in the lesion area is an electroencephalogram signal, then the target model is obtained by training with sample data corresponding to the signal change amount of the electroencephalogram signal; if the embodiment of the present application determines that the signal change amount used in the lesion area is a cerebral blood flow signal, then the target model is obtained by training with sample data of the signal change amount of the cerebral blood flow signal.

[0079] If the signal variation of the embodiment of the present application includes the signal variation of the EEG signal and the signal variation of the cerebral blood flow signal, the sample data of the lesion area includes the signal variation of the EEG signal and the signal variation of the cerebral blood flow signal, as well as the sample stimulation information, to obtain the target model. In actual processing, the signal variation of the EEG signal and the signal variation of the cerebral blood flow signal can also be weighted according to the corresponding predetermined weights to obtain a comprehensive signal variation, and the sample data corresponding to the comprehensive signal variation is used to train the target model.

[0080] In some embodiments, the control module 121 is specifically configured to: for each contact point, obtain an EEG signal and / or a cerebral blood flow signal within a first time period, and determine a first average value of the EEG signal and / or a second average value of the cerebral blood flow signal; If the first average value and / or the second average value is not less than the first threshold value, the neural activity area corresponding to the contact point is determined as a lesion area.

[0081] In some embodiments, the control module 121 is specifically configured to: if the first average value and / or the second average value is not less than the second threshold value and less than the first threshold value, then the neural activity area corresponding to the contact point is used as a lesion area to be detected; Acquiring an electroencephalogram signal and / or a cerebral blood flow signal within at least one second time period; For each second time period, determining a first average value of the EEG signal and / or a second average value of the cerebral blood flow signal; If the first average value and / or the second average value corresponding to each second time period is not less than the second threshold, the lesion area to be detected is determined as a lesion area.

[0082] Optionally, the duration of the second time period can be set according to the EEG signals and cerebral blood flow signals to be detected. For example, the second time period can be set to obtain a predetermined number of EEG signals and cerebral blood flow signals. At least one second time period can be 3 or 5. The specific duration and quantity can be adaptively adjusted in actual limitations.

[0083] The implementation method of the embodiment of the present application for locating the diseased area requiring stimulation intervention is as follows: an analysis time period is selected, the average value of the EEG signal and / or the cerebral blood flow signal within the time period is obtained, at least one threshold is set (threshold A corresponds to data abnormality but the patient has no symptoms, threshold B corresponds to data abnormality and the patient has symptoms... Of course, more thresholds can be set, and examples can be given in the instruction manual), and the threshold range in which the average value falls is analyzed to determine whether a certain area requires stimulation intervention. For example, if the average value is ≤ threshold A, it is not the target area, and if the average value is ≥ threshold B, the first target area is selected, and if the average value is between AB, it is selected as the second target area, and stimulation intervention is preferentially performed on the first target area.

[0084] Furthermore, because the second target area is a secondary area, the patient may not need stimulation at this time, and his or her nerve signals will recover in a short time. If stimulation is applied, it will cause damage. In order to more accurately locate the target area that requires stimulation intervention, the following analysis can also be performed: calculate multiple signal energy values ​​within a certain analysis time period. When the energy value exceeds a certain number (such as 3 or 5) continuously within a continuous time period, it is divided into the first target area.

[0085] Therefore, the embodiments of the present application realize full-process monitoring and intervention with low trauma, precise positioning, and precise stimulation. Compared with the existing DBS technology, the selection of stimulation parameters is more flexible, especially suitable for situations where the lesions are unclear and not suitable for deep electrode implantation. In order to further improve the treatment effect in this application, the present application gives priority to precise stimulation of the first target area that is highly related to the disease. In this way, effective measures can be taken on the main lesions of the disease in the shortest time. At the same time, for areas with a low correlation with the disease, further in-depth monitoring and analysis are carried out. Only when the abnormal activity or energy value of these secondary areas reaches or exceeds a certain number (for example, 3 or 5) will the corresponding stimulation intervention be initiated. This method aims to avoid overtreatment and ensure that each stimulation is necessary and effective, thereby improving the safety and efficiency of the overall treatment.

[0086] In some embodiments, the control module 121 is specifically configured to: for each lesion area, determine the contact information according to the position information of the lesion area and each contact; the position information includes distance information and orientation information.

[0087] In some embodiments, the control module 121 is specifically configured as follows: if the distance between the lesion area and each contact is greater than a first distance threshold, then the contact in the contact information is determined to be the second contact 112 to output an ultrasonic stimulation signal; if the distance between the lesion area and each contact is within a first predetermined range, then the contact in the contact information is determined to be the first contact 111 and / or the second contact 112 to output an electrical stimulation signal and / or an ultrasonic stimulation signal.

[0088] The embodiment of the present application can flexibly select between which two contacts the stimulation signal is outputted based on the positional relationship between the implanted position of the contact and the position of the lesion area. At the same time, when providing stimulation, the embodiment of the present application can determine whether the stimulation signal is sent by the first contact 111 and / or the second contact 112 based on information such as the distance and / or orientation between the lesion area and the contact.

[0089] Optionally, the distance between the lesion area and each contact point is greater than a first distance threshold, which indicates that the lesion area is deep in the brain; the distance between the lesion area and each contact point is within a first predetermined range, which indicates that the lesion area is on the surface of the brain.

[0090] The embodiment of the present application can realize that when the lesion area is deep in the brain, ultrasound stimulation is mainly used; when the lesion area is on the surface of the brain, electrical stimulation and / or ultrasound stimulation can be used according to actual conditions.

[0091] The embodiment of the present application can achieve the same stimulation effect as the deep intracranial electrode through ultrasonic stimulation; at the same time, the embodiment of the present application combines ultrasonic stimulation with electrical stimulation to achieve more precise stimulation, and with the help of ultrasonic technology, the location and distance information of the lesion area can be obtained, thereby providing precise stimulation.

[0092] In the embodiment of the present application, at least one lesion area is determined according to the EEG signal and / or the cerebral blood flow signal, and the implementation method may also be as follows: 1. Spatial changes of brain changes (coarse screening process): A neural activity distribution map is formed based on cerebral blood flow signals to distinguish normal neural activity areas and / or abnormal neural activity areas.

[0093] 2. Changes in brain changes over time (fine screening process): According to the neural activity distribution map, the abnormal neural activity area is divided into the shallow area and the deep area (Note: the shallow area is the farthest area that the electrical stimulation signal can reach, and the deep area is the farthest area that the ultrasound stimulation signal can reach). The ranking of the shallow / deep areas can be achieved by: Shallow area: EEG signals are used for analysis first. If the first average value of the EEG signals is not less than the first threshold, the neural activity area corresponding to the contact point is determined as a lesion area. If the first average value is not less than the second threshold and is less than the first threshold, the neural activity area corresponding to the contact point is determined as a lesion area to be detected; then, in each second time period, if the first average value of the EEG signals is determined to be not less than the second threshold, the lesion area to be detected is determined as a lesion area.

[0094] Deep area: cerebral blood flow signals are used for analysis first. If the second average value of the cerebral blood flow signal is not less than the first threshold, the neural activity area corresponding to the touch point is determined as a lesion area. If the second average value is not less than the second threshold and less than the first threshold, the neural activity area corresponding to the touch point is determined as a lesion area to be detected; then, in each second time period, if the second average value of the EEG signal is determined to be not less than the second threshold, the lesion area to be detected is determined as a lesion area.

[0095] Determining the lesion region to be detected as a lesion region is the same as above and will not be described in detail here.

[0096] Through the above embodiments, the embodiments of the present application have the following technical advantages: Improve positioning accuracy: Multimodal data fusion combining EEG signals and cerebral blood flow signals can more comprehensively reflect changes in brain activity, thereby improving the accuracy of positioning the lesion area.

[0097] Enhanced resolution: Through coarse screening in space and fine screening in time, it is possible to more finely distinguish between areas of normal neural activity and areas of abnormal neural activity, reducing misjudgment.

[0098] Optimize stimulation strategy: According to the division of shallow and deep areas, different stimulation strategies can be adopted for lesion areas of different depths to improve the treatment effect.

[0099] The control module 121 of the embodiment of the present application is also used to analyze and determine the distance and / or orientation information between the lesion source and the electrode 110 according to the positioning result of the monitoring positioning, so as to determine whether the sender of the stimulation signal is the first contact 111 and / or the second contact 112 according to the distance and / or orientation information. Generally speaking, the lesions deep in the brain can be emitted by the second contact 112 (ultrasound has strong penetrating power).

[0100] See also Figure 4 As shown, the present application embodiment provides a structural schematic diagram of another implantable localization stimulation device 1. Figure 4 As shown, each electrode 110 is provided with at least one first contact 111 and at least one second contact 112, and the first contacts 111 and the second contacts 112 are alternately distributed at intervals.

[0101] See also Figure 4 As shown, one end of each electrode 110 is connected to the neurostimulator 120 , and the other end extends in a direction away from the neurostimulator 120 , and the multiple electrodes 110 are evenly distributed along the circumference of the neurostimulator 120 .

[0102] In some embodiments, the plurality of electrodes 110 are distributed in a ring shape, and the neurostimulator 120 is located in the middle of the ring.

[0103] As an example, Figure 4 As shown, the pattern of the electrodes 110 can be a cross-shaped distribution. In practical applications, they can also be annularly distributed to cover a larger skull area. The first contact 111 and the second contact 112 are spaced apart, and the neurostimulator 120 can be located at the center of all the electrodes 110, or at one end of all the electrodes 110, or in between the two.

[0104] The implantable localization stimulation device 1 of the embodiment of the present application may be battery-powered or battery-free, and may be wirelessly charged by an external device. The implantable localization stimulation device 1 may be partially made of flexible material to facilitate implantation between the scalp and the skull.

[0105] Different central nervous system diseases in the embodiments of the present application have their corresponding biomarker signals. Taking epilepsy as an example, when a patient's symptoms appear, the EEG amplitude of a specific brain area will become abnormal. By analyzing the amplitude characteristics of the EEG signals and / or cerebral blood flow signals collected by each contact in real time, it is possible to know which contacts have abnormal EEG amplitudes, and then know which brain areas near which contacts may have epileptic seizures.

[0106] Therefore, the brain area where the disease occurs can be located by analyzing the biomarker signals of EEG. When a specific brain area is affected, it is usually accompanied by abnormal cerebral blood flow signals. After analyzing the abnormal EEG signals, the abnormal brain area can be further identified in combination with the abnormal cerebral blood flow signals of ultrasound, so as to finally locate the target area. After the target area is confirmed, electrical stimulation can be applied to the optimal electrode configuration according to the location of the electrode configuration to complete the treatment.

[0107] The application of the embodiments of the present application can at least achieve the following technical effects: (1) The implantable positioning stimulation device 1 of the embodiment of the present application can realize nerve stimulation of the lesion area, and the entire operation can be completed through a single operation, which reduces the number of operations and reduces the harm to the patient. Moreover, the implantable positioning stimulation device 1 of the embodiment of the present application can realize long-term brain function detection through the contacts, which can not only continuously identify and locate the lesion area, but also stimulate and treat it when necessary, so that a single implantation can realize the triple functions of brain function detection, lesion area positioning and stimulation treatment.

[0108] (2) The implantation area of ​​the embodiment of the present application is between the scalp and the skull, and there is no need to damage the skull, dura mater, etc., thus reducing trauma. The electrode 110 and the neurostimulator 120 are both implanted between the scalp and the skull, avoiding the risk of displacement and breakage of the electrode 110, and there is no discomfort caused by the scalp EEG electrode.

[0109] (3) The signal acquisition of the embodiment of the present application will not be affected by the secretion of oil and perspiration by the skin, and will not affect normal life such as exercise, sleep, and social interaction. It can record changes in EEG activity related to medication, and provide a quantitative reference basis for pharmaceutical companies and doctors.

[0110] (4) After suturing, the embodiment of the present application is completely located under the scalp, with no wounds on the surface, and is not prone to infection. The signal-to-noise ratio of the signal under the scalp is better than that of the scalp EEG signal. The embodiment of the present application is a one-time implant to achieve EEG detection, lesion localization and stimulation, without the need to perform SEEG localization first and then implant the neurostimulator 120.

[0111] (5) The implantable localization stimulation device 1 of the embodiment of the present application combines EEG signals and cerebral blood flow signals to locate the lesion area, thereby realizing the location of the lesion area. The lesion localization of the embodiment of the present application combines ultrasound technology to solve the problem of accurate detection of deep brain signals. The combination of EEG signals and cerebral blood flow signals can accurately locate the lesion area.

[0112] (6) The implantable localized stimulation device 1 of the embodiment of the present application can realize a new method of long-term monitoring of EEG signals. In comparison, SEEG can only monitor intracranial EEG for up to 30 days. Long-term monitoring of scalp EEG may cause discomfort or allergies. The method of implanting it outside the skull under the scalp can monitor EEG for a long time without causing excessive damage.

[0113] (7) The embodiments of the present application are based on functional ultrasound imaging (fUSI) technology, which monitors neural activity in the brain area by measuring local blood flow changes through the Doppler effect, and changes the action potential of neurons based on direct focused ultrasound (FUS) technology to achieve stimulation of the lesion area.

[0114] (8) The embodiment of the present application can flexibly select between which two contacts the stimulation signal is outputted based on the positional relationship between the implanted position of the contact and the position of the lesion area. At the same time, when providing stimulation, the embodiment of the present application can determine whether the stimulation signal is emitted by the first contact 111 and / or the second contact 112 based on information such as the distance and / or orientation between the lesion area and the contact.

[0115] (9) The stimulation signal of the embodiment of the present application may be an electrical stimulation signal and / or an ultrasonic stimulation signal. According to the location of the lesion area, the contact for outputting the stimulation signal may be flexibly selected to output the electrical stimulation signal and / or the ultrasonic stimulation signal, thereby combining electrical stimulation and ultrasonic stimulation to achieve more precise stimulation.

[0116] Those skilled in the art will appreciate that the various operations, methods, steps, measures, and schemes in the processes discussed in this application may be alternated, changed, combined, or deleted. Furthermore, other steps, measures, and schemes in the various operations, methods, and processes discussed in this application may also be alternated, changed, rearranged, decomposed, combined, or deleted. Furthermore, steps, measures, and schemes in the related art that are similar to those disclosed in this application may also be alternated, changed, rearranged, decomposed, combined, or deleted.

[0117] In the description of the present application, the directions or positional relationships indicated by words such as "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" are based on the exemplary directions or positional relationships shown in the accompanying drawings. They are for the convenience of describing or simplifying the description of the embodiments of the present application, and do not indicate or imply that the referred device or component must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be understood as limitations on the present application.

[0118] The terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise specified, "plurality" means two or more.

[0119] In the description of this application, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0120] In the description of this specification, specific features, structures, materials or characteristics may be combined in an appropriate manner in any one or more embodiments or examples.

[0121] The above is only a partial implementation method of the present application. It should be pointed out that for ordinary technicians in this technical field, without departing from the technical concept of the scheme of the present application, other similar implementation methods based on the technical ideas of the present application are also within the protection scope of the embodiments of the present application.

Claims

1. An implantable localization stimulation device, characterized in that: For long-term implantation in the target subject, including: At least one electrode, each of the electrodes comprises at least one contact, and each of the contact is a first contact for collecting an electroencephalogram signal or a second contact for collecting a cerebral blood flow signal; A neurostimulator, electrically connected to both the first contact and the second contact, configured to obtain the EEG signal and / or the cerebral blood flow signal, determine at least one lesion area according to the EEG signal and / or the cerebral blood flow signal, and determine stimulation information according to at least one lesion area; and control at least one of the contacts to output a stimulation signal according to the stimulation information to perform neurostimulation on at least one lesion area; The stimulation information includes stimulation signal information and contact information, the stimulation signal includes at least one of the following: an electrical stimulation signal, an ultrasonic stimulation signal, the stimulation signal information is used to generate a stimulation signal, and the contact information is used to indicate a contact for outputting a stimulation signal.

2. The implantable localization stimulation device according to claim 1, characterized in that: The implantable localization stimulation device is implanted between the scalp and skull of the target subject.

3. The implantable localization stimulation device according to claim 1, characterized in that: The neural stimulator comprises a control module and a stimulation module; The control module is configured to obtain the EEG signal and / or the cerebral blood flow signal, determine at least one lesion area according to the EEG signal and / or the cerebral blood flow signal, and determine stimulation information according to at least one lesion area; control the stimulation module to generate an electrical stimulation signal and / or control the stimulation module to generate an ultrasonic electrical signal according to the stimulation information; The stimulation module is configured to output the electrical stimulation signal through at least one of the first contacts; and / or output the ultrasonic electrical signal to the second contact, so that the second contact outputs the ultrasonic stimulation signal based on the ultrasonic electrical signal.

4. The implantable localization stimulation device according to claim 3, characterized in that: The stimulation module includes an electrical stimulation unit and an ultrasonic stimulation unit; The electrical stimulation unit is configured to generate the electrical stimulation signal and output the electrical stimulation signal through the first contact; The ultrasound stimulation unit is configured to generate the ultrasound electrical signal and output the ultrasound electrical signal to the second contact, so that the second contact outputs an ultrasound stimulation signal based on the ultrasound electrical signal to change the action potential of neurons in the lesion area based on direct focused ultrasound technology.

5. The implantable localization stimulation device according to claim 3, characterized in that: The second contact point includes a collection sensor, and the collection sensor includes any one of the following: an ultrasound probe, an imaging sensor, or a near-infrared spectroscopy device.

6. The implantable localization stimulation device according to claim 5, characterized in that: The acquisition sensor includes an ultrasonic transducer, which is used to generate an ultrasonic detection signal according to the ultrasonic electrical signal, and to generate the cerebral blood flow signal according to the echo signal reflected by the ultrasonic detection signal; the cerebral blood flow signal is used to characterize the velocity of blood flow.

7. The implantable localization stimulation device according to claim 3, characterized in that: The control module is specifically configured as follows: Determine a neural activity distribution map according to the signal change amount between the EEG signal and the pre-stored EEG signal, and / or the signal change amount between the cerebral blood flow signal and the pre-stored cerebral blood flow signal; the neural activity distribution map is used to distinguish between normal neural activity areas and abnormal neural activity areas; According to the signal change amount of each abnormal nerve activity area, the abnormal nerve activity areas are ranked according to the abnormality degree, and a predetermined number of abnormal nerve activity areas with high rankings are selected as at least one of the lesion areas.

8. The implantable localization stimulation device according to claim 7, characterized in that: The control module is specifically configured as follows: For each of the lesion areas, the stimulation information is determined based on a deep learning algorithm and a signal change amount of the lesion area.

9. The implantable localization stimulation device according to claim 3, characterized in that: The control module is specifically configured as follows: For each of the touch points, acquiring the EEG signal and / or the cerebral blood flow signal within a first time period, and determining a first average value of the EEG signal and / or a second average value of the cerebral blood flow signal; If the first average value and / or the second average value is not less than a first threshold value, the neural activity area corresponding to the contact point is determined as a lesion area.

10. The implantable localization stimulation device according to claim 9, characterized in that: The control module is specifically configured as follows: If the first average value and / or the second average value is not less than the second threshold value and is less than the first threshold value, the nerve activity area corresponding to the contact point is taken as a lesion area to be detected; Acquiring the EEG signal and / or the cerebral blood flow signal within at least one second time period; For each second time period, determining a first average value of the EEG signal and / or a second average value of the cerebral blood flow signal; If the first average value and / or the second average value corresponding to each of the second time periods are not less than a second threshold, the lesion region to be detected is determined as a lesion region.

11. The implantable localization stimulation device according to claim 3, characterized in that: The control module is specifically configured as follows: For each of the lesion areas, the contact point information is determined according to the position information of the lesion area and each of the contact points; the position information includes distance information and orientation information.

12. The implantable localization stimulation device according to claim 11, characterized in that: The control module is specifically configured as follows: If the distance between the lesion area and each of the touch points is greater than a first distance threshold, determining the touch point in the touch point information as a second touch point to output an ultrasonic stimulation signal; If the distance between the lesion area and each of the contact points is within a first predetermined range, the contact point in the contact point information is determined to be a first contact point and / or a second contact point, so as to output an electrical stimulation signal and / or an ultrasonic stimulation signal.

13. The implantable localization stimulation device according to claim 1, characterized in that: Each of the electrodes is provided with at least one first contact point and at least one second contact point, and the first contact points and the second contact points are alternately distributed at intervals.

14. The implantable localization stimulation device according to claim 1, characterized in that: One end of each electrode is connected to the neural stimulator, and the other end extends in a direction away from the neural stimulator. The plurality of electrodes are evenly distributed along the circumference of the neural stimulator.

15. The implantable localization stimulation device according to claim 1, characterized in that: The plurality of electrodes are distributed in a ring shape, and the neurostimulator is located in the middle of the ring.

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