Transcranial ultrasonic nerve regulation and control device and control method

Abstract

The invention relates to a transcranial ultrasonic nerve regulation and control device and a control method. The transcranial ultrasonic nerve regulation and control device comprises an ultrasonic generation unit, ultrasonic waves are controllably provided to an intracranial target area, and the ultrasonic generation unit is configured to provide the ultrasonic waves with the frequency ranging from 3.0 MHz to 8.0 MHz to the intracranial target area. According to the transcranial ultrasonic nerve regulation device and the control method, the intracranial nerves are stimulated through the high-frequency ultrasonic waves with the working frequency of 3.0-8.0 MHz, the transcranial ultrasonic nerve regulation device and the control method have remarkable advantages in cortex regulation, energy is more easily absorbed by superficial tissue, the stimulated area covers the cerebral cortex and superficial white matter, and interference of a non-targeted deep structure is avoided. Meanwhile, the spatial resolution of the ultrasound of the frequency band can reach the submillimeter level, the ultrasound can be accurately focused on a tiny functional subregion, and the ultrasound is particularly suitable for nerve regulation scenes needing accurate positioning intervention and is suitable for nerve regulation of focal epilepsy, chronic pain syndromes, visual and auditory cortex dysfunction and mental and psychological disorders.

Description

Technical Field

[0001] This application relates to the field of neuromodulation technology, and in particular to a transcranial ultrasound neuromodulation device and control method. Background Technology

[0002] In recent years, transcranial ultrasound neurostimulation (TUS) technology has shown broad application prospects in neuroscience research and clinical treatment due to its non-invasive, highly penetrating, and precise positioning characteristics. This technology utilizes the mechanical and cavitation effects of ultrasound waves to achieve targeted neuromodulation of specific brain regions, providing a new technical approach for the intervention and treatment of various neurological diseases.

[0003] Traditional transcranial ultrasound stimulation devices generally employ neuromodulation techniques, which have limited spatial resolution (typically >5mm), making it difficult to meet the requirements for precise control of functional areas of the cerebral cortex. In practical applications, especially when treating functional areas requiring precise intervention, such as the motor cortex and visual cortex, this low spatial resolution often leads to an excessively wide stimulation range, affecting treatment efficacy and potentially causing unnecessary side effects.

[0004] Although some studies have attempted to improve resolution by increasing ultrasound frequency, they face the challenge of significant attenuation of high-frequency ultrasound when penetrating the skull, which has prevented the full exploration of the application potential of high-frequency ultrasound in the field of neuromodulation.

[0005] Therefore, it is necessary to propose a new technical solution to overcome the shortcomings of existing technologies. Summary of the Invention

[0006] Based on this, this application provides a transcranial ultrasound neuromodulation device and control method, which has high focusing accuracy and can accurately focus on small functional subregions to achieve high-precision neuromodulation.

[0007] Therefore, this application adopts the following technical solution: a transcranial ultrasound neuromodulation device, comprising:

[0008] An ultrasound generating unit that delivers ultrasound waves to the target area within the skull in a controlled manner;

[0009] The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 3.0 MHz to 8.0 MHz into the cranium.

[0010] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves at a frequency of 3.5 MHz to 3.8 MHz into the intracranial cavity.

[0011] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves at a frequency of 3.7 MHz into the cranium.

[0012] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves into the cranium to target the prefrontal cortex region associated with post-traumatic stress disorder.

[0013] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 4.5 MHz to 5.5 MHz into the cranium.

[0014] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves at a frequency of 5.0 MHz into the cranium.

[0015] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves into the cranium to the right temporal lobe target area associated with focal epilepsy.

[0016] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 6.2 MHz to 6.5 MHz into the cranium.

[0017] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves at a frequency of 6.3 MHz into the cranium.

[0018] In some embodiments, the ultrasound generating unit is configured to deliver ultrasound waves into the cranium to target primary somatosensory cortical areas associated with chronic pain.

[0019] In some embodiments, the ultrasound generating unit is configured such that the ultrasound waves it generates can reach a target area in brain tissue at a depth of no more than 3 cm.

[0020] In some embodiments, the ultrasonic generating unit is configured to generate ultrasonic waves with sub-millimeter spatial resolution.

[0021] In some embodiments, the ultrasound generating unit is configured to generate ultrasound waves for ultrasound stimulation of the primary somatosensory cortex, temporal neocortex, anterior cingulate cortex, orbitofrontal cortex, amygdala surface projection area, and prefrontal cortex target area located in the cerebral cortex or superficial white matter layer.

[0022] In some embodiments, the transcranial ultrasound neuromodulation device is configured to perform ultrasound stimulation on a target area in brain tissue associated with at least one of the following conditions: focal epilepsy, chronic pain syndrome, visual and auditory cortical dysfunction, and mental disorders including obsessive-compulsive disorder and post-traumatic stress disorder.

[0023] In some embodiments, the ultrasound generating unit is configured to provide a spatial peak pulse with a mean acoustic intensity of 0.5 W / cm² into the intracranial space. 2 Up to 10W / cm 2 Ultrasound.

[0024] In some embodiments, the ultrasonic generating unit includes a plurality of ultrasonic transducers arranged in an array.

[0025] In some embodiments, the number of ultrasonic transducers is 5 to 256, and the spacing between two adjacent ultrasonic transducers is no greater than 0.8 mm.

[0026] In some embodiments, the transcranial ultrasound neuromodulation device includes at least one ultrasound transducer module, the at least one ultrasound transducer module forming an ultrasound transducer array; the ultrasound transducer module includes a plurality of ultrasound transducers, a plurality of the plurality of ultrasound transducers being electrically connected in sequence to form a closed geometric shape, and at least one of the plurality of ultrasound transducers being located at the center of the closed geometric shape.

[0027] In some embodiments, each of the ultrasonic transducers is independently controlled by a phase control system so that the focal diameter formed by the ultrasonic generating unit in the target area can be controlled to be less than 0.5 mm.

[0028] In some embodiments, the transcranial ultrasound neuromodulation device is configured as a flexible patch that can be attached to the head, or as a wearable device that can be worn on the head.

[0029] In some embodiments, the transcranial ultrasound neuromodulation device is adapted to conform to the contours of the skull surface and fits at least one location in the forehead and temples.

[0030] In some embodiments, the ultrasound generating unit is configured to transmit ultrasound waves with a pulse repetition frequency of 1 Hz to 5000 Hz.

[0031] In some embodiments, the ultrasound generating unit is configured to transmit ultrasound waves with a pulse repetition frequency of 50 Hz to 500 Hz.

[0032] This application also adopts the following technical solution: a control method for a transcranial ultrasound neuromodulation device, the control method comprising: according to the location of the target area, controlling the transcranial ultrasound neuromodulation device as described above to selectively generate ultrasound waves with a frequency matching the location of the target area, wherein the frequency of the ultrasound waves is at least a portion within the range of 3.0MHz to 8.0MHz, to act on the target area in the cranium.

[0033] The transcranial ultrasound neuromodulation device and control method provided in this application stimulate intracranial nerves with high-frequency ultrasound waves operating at a frequency of 3.0MHz to 8.0MHz. One or more frequency bands included in this method have significant advantages in cortical modulation, with energy more easily absorbed by superficial tissues. The stimulation area covers the cerebral cortex and superficial white matter, avoiding interference from non-targeted deep structures. Furthermore, compared to ultrasound in traditional frequency bands, the spatial resolution of this frequency band can reach sub-millimeter levels, enabling more precise target localization and focusing on small functional subregions. This is particularly suitable for neuromodulation scenarios requiring precise localization intervention. This application's solution can be used for neuromodulation of focal epilepsy, chronic pain syndromes, visual and auditory cortical dysfunction, and mental and psychological disorders including obsessive-compulsive disorder and post-traumatic stress disorder, providing a new technical solution for neuroscience research and clinical treatment. Attached Figure Description

[0034] To more clearly illustrate the technical solutions in the embodiments of this application or the conventional technology, the drawings used in the description of the embodiments or the conventional technology will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0035] Figure 1 This is a schematic diagram of the structure of an embodiment of the transcranial ultrasound neuromodulation device of this application.

[0036] Figure 2 This is a schematic diagram of another embodiment of the transcranial ultrasound neuromodulation device of this application.

[0037] Figure 3 This is a schematic diagram of the transcranial ultrasound neuromodulation device used in the treatment of epilepsy.

[0038] Figure 4 This is a schematic diagram of the transcranial ultrasound neuromodulation device used in the treatment of chronic pain.

[0039] Figure 5 This is a schematic diagram of the transcranial ultrasound neuromodulation device used in the treatment of obsessive-compulsive disorder.

[0040] Figure 6 This is a graph showing the change in score values ​​in an embodiment of the transcranial ultrasound neuromodulation device used for the treatment of focal epilepsy according to this application.

[0041] Figure 7 This is a graph showing the change in pain values ​​in an embodiment of the transcranial ultrasound neuromodulation device used for chronic pain treatment according to this application.

[0042] Figure 8This is a graph showing the changes in MASQ values ​​in an embodiment of the transcranial ultrasound neuromodulation device used for the treatment of anxiety disorder according to this application.

[0043] The component labels are as follows:

[0044] 1. Transcranial ultrasound neuromodulation device; 11. Main body; 12. Ultrasonic transducer. Detailed Implementation

[0045] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0046] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on the other component or there may be an intermediate component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intermediate component present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this application's specification are for illustrative purposes only and do not represent the only possible implementation.

[0047] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0048] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature and the second feature are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0049] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used in this application includes any and all combinations of one or more of the associated listed items.

[0050] Please see Figures 1 to 5 As shown, this application provides a transcranial ultrasound neuromodulation device 1 and its control method. The transcranial ultrasound neuromodulation device 1 achieves precise modulation of the intracranial target area through non-invasive ultrasound stimulation technology. The technical solution is described in detail below with reference to the accompanying drawings and specific implementation examples.

[0051] First, the overall structure and working principle of an embodiment of the transcranial ultrasound neuromodulation device 1 provided in this application will be briefly described.

[0052] like Figure 1 As shown, the transcranial ultrasound neuromodulation device 1 includes a main body 11 and an ultrasound generating unit. The main body 11 is configured to be placed on the lateral side of the skull. The ultrasound generating unit is disposed on the main body 11 and is configured to controllably deliver ultrasound waves to a target area within the skull. It is understood that the ultrasound generating unit can be connected to a control unit via a wired or wireless connection, and the control unit can control the generation of ultrasound waves. The control unit can be integrated within the transcranial ultrasound neuromodulation device 1 or can be a device or equipment independent of the transcranial ultrasound neuromodulation device 1. The ultrasound generating unit is configured to deliver ultrasound waves with a frequency of 3.0 MHz to 8.0 MHz into the skull to act on the target area within the skull.

[0053] Specifically, in some embodiments, the main body 11 is a deformable component, such as a flexible circuit board, or a component with a flexible substrate such as silicone, woven fabric, or hydrogel that can be combined with flexible circuitry. Preferably, the main body 11 is a flexible sheet to adapt to the contours of the skull surface and fit snugly against the skull. In this embodiment, the main body 11 includes a hydrogel layer and a silicone layer. The bio-adhesive hydrogel substrate design allows the ultrasound generating unit to fit well against the biological surface of the scalp. Combined with the flexible silicone encapsulation layer design, it achieves effective acoustic energy transmission without the need for traditional gel operation, avoiding the inconvenience caused by the use of acoustic impedance matching gel in traditional ultrasound stimulation devices. In use, the transcranial ultrasound neuromodulation device 1 is tightly fitted to the forehead, temples, or other areas as needed. The flexible main body 11 allows a stable acoustic coupling interface to be formed between the ultrasound generating unit and the scalp, effectively reducing energy loss of ultrasound waves during propagation.

[0054] In this embodiment, the ultrasonic generating unit includes a plurality of ultrasonic transducers 12 disposed on the main body 11, and the plurality of ultrasonic transducers 12 are arranged in an array on the main body 11. Each ultrasonic transducer 12 may be made of piezoelectric ceramic or single crystal material, and its operating frequency range is between 3.0MHz and 8.0MHz. The ultrasonic transducers 12 are connected by flexible wires, so that when the main body 11 is bent, each ultrasonic transducer 12 can still maintain a stable electrical connection. In some embodiments, the number of ultrasonic transducers 12 is 5 to 256, and the spacing between two adjacent ultrasonic transducers is no greater than 0.8mm. Further, the ultrasonic transducers are made of PZT-5H piezoelectric material. When the number of ultrasonic transducers 12 is large, the spacing between two adjacent ultrasonic transducers and the diameter of each ultrasonic transducer can be reduced accordingly. The densely arranged miniaturized transducers form a focusing array, which has excellent electromechanical coupling characteristics in the high frequency range of 3.0MHz to 8.0MHz.

[0055] In some embodiments, such as Figure 2 As shown, the transcranial ultrasound neuromodulation device 1 includes at least one ultrasound transducer module, which comprises a plurality of ultrasound transducers 12. Multiple ultrasound transducers 12 are sequentially electrically connected, forming a closed geometric shape. At least one ultrasound transducer 12 is located at the geometric center of this closed geometric shape. This arrangement allows multiple ultrasound transducers 12 to surround the centrally located transducer 12, which is more conducive to ultrasound wave focusing and effective targeting of the target area. For example, in... Figure 2 and Figure 3 In the illustrated embodiment, each ultrasonic transducer module includes five ultrasonic transducers 12, wherein four ultrasonic transducers 12 are connected in sequence to form a rectangle, and the fifth ultrasonic transducer 12 is located at the center point of the rectangle; it is understood that the number and layout of ultrasonic transducers 12 are not limited thereto.

[0056] Furthermore, through electronic phase control technology, the emission phase of each ultrasound transducer 12 is independently controlled to form a focused ultrasound beam within the cranium. In some embodiments, the sound field distribution can be adjusted and optimized according to the anatomical location of the target area. Specifically, each ultrasound transducer 12 is equipped with an independent phase control system, which can precisely adjust the emission waveform, enabling the system to achieve precise control of the sound field in three-dimensional space through beamforming technology. The acoustic focusing scheme adopts a calculation method based on spherical wave superposition, and through optimization algorithms, precisely controls the excitation timing and phase of each transducer unit, so that the focal diameter formed in the target area can be controlled to be less than 0.5 mm. This device achieves sub-millimeter-level tissue stimulation accuracy through innovative multi-element transducer structure and acoustic beam focusing technology, and its performance indicators are significantly better than traditional ultrasound neuromodulation therapy devices.

[0057] To facilitate wearing and minimize the impact of the device on the user's activities, in this embodiment, the transcranial ultrasound neuromodulation device 1 is configured as a patch that can be attached to the head, or as a wearable device that can be worn on the head. Wearable devices that can be worn on the head specifically include headbands, caps, headbands, etc. For example, in one embodiment, the transcranial ultrasound neuromodulation device 1 is mounted on a headband with adjustable tightness to facilitate long-term and stable wear by the user. Furthermore, the device is powered by a built-in micro lithium battery, allowing for continuous operation for 8 hours, and features a built-in low-voltage protection circuit, ensuring safety and convenience of use. It is particularly suitable for continuous daily use by patients, realizing the portability and practicality of the transcranial ultrasound neuromodulation device 1.

[0058] In use, the transcranial ultrasound neuromodulation device 1 can be directly attached to key brain regions such as the temples (temporal window of the head) and forehead (frontal lobe of the head) for non-invasive neuromodulation. This transcranial ultrasound neuromodulation device 1 uses ultrasound waves in the frequency range of 3.0MHz to 8.0MHz to stimulate intracranial tissues, offering significant advantages in cortical modulation. The energy is more easily absorbed by superficial tissues, and the stimulation area covers the cerebral cortex and superficial white matter, avoiding interference from non-targeted deep structures. Simultaneously, the spatial resolution of ultrasound in this frequency band can reach sub-millimeter level, enabling precise focusing on small functional subregions, making it particularly suitable for neuromodulation scenarios requiring precise localization intervention. This proposed solution can be used for neuromodulation of focal epilepsy, chronic pain syndromes, visual and auditory cortical dysfunction, and mental and psychological disorders including obsessive-compulsive disorder and post-traumatic stress disorder, providing a new technical solution for neuroscience research and clinical treatment.

[0059] The mechanism by which the transcranial ultrasound neuromodulation device 1 provided in this application modulates nerves in combination with different sound intensity parameters at a set operating frequency band is described in detail below.

[0060] The transcranial ultrasound neuromodulation device provided in this application generates ultrasound waves with a frequency range of 3.0 MHz to 8.0 MHz; preferably, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 3.5 MHz to 6.5 MHz into the cranium. Compared with traditional ultrasound stimulation methods, the high-frequency ultrasound provided in this application has a spatial resolution of sub-millimeter level (<1 mm) in brain tissue, and can accurately focus on functional subregions such as the primary somatosensory cortex and the temporal lobe neocortex; in addition, through the synergistic focusing of the arrayed transducers, the attenuation of high-frequency ultrasound in the skull can be compensated, ensuring that the ultrasound waves effectively reach the superficial white matter target area with a depth not exceeding 3 cm, such as the deep white matter junction areas such as the anterior cingulate cortex and the orbitofrontal cortex.

[0061] Specifically, ultrasound in the 3.0MHz–8.0MHz frequency range has significant advantages in cortical modulation. Its shorter wavelength allows for easier energy absorption by superficial tissues, and its penetration depth is typically limited to less than 3 cm, precisely covering the cerebral cortex and superficial white matter, avoiding interference from non-targeted deep structures. Simultaneously, high-frequency ultrasound boasts sub-millimeter spatial resolution, enabling precise focusing on minute functional subregions, such as specific finger representation areas in the primary somatosensory cortex or functional columns in the visual cortex. This high spatial selectivity makes it particularly suitable for neuromodulation scenarios requiring precise localization. Furthermore, the significant energy attenuation of high-frequency ultrasound as it passes through the skull reduces non-specific effects on deep nuclei, further enhancing the specificity of the intervention.

[0062] To achieve targeted regulation of different conditions, the spatial peak pulse mean acoustic intensity (ISPPA) of the ultrasound generator is selected within the range of 0.5 W / cm² to 10 W / cm². For example, for the regulation of the lesion area in focal epilepsy, a high-intensity mode of 5-8 W / cm² is used to inhibit the synchronous firing of abnormal neurons through strong mechanical effects; for the regulation of pain conduction pathways in chronic pain syndromes, a medium-intensity mode of 2 W / cm² to 5 W / cm² is selected to modulate abnormal oscillations in the thalamus-cortex circuit; while for the treatment of mental and psychological disorders, such as obsessive-compulsive disorder and post-traumatic stress disorder, a low-intensity mode of 0.5 W / cm² to 2 W / cm² is used to gently regulate the connectivity activity of the prefrontal cortex-amygdala pathway.

[0063] In the treatment of focal epilepsy, high-frequency ultrasound (3.0 MHz to 8.0 MHz) can directly target the epileptogenic focus in the cortex. Animal experiments have shown that 3.5 MHz to 5.0 MHz ultrasound interferes with the synchronized firing of neurons through mechanical pressure waves, reducing abnormal spike activity. The mechanism may involve inhibiting synaptic transmission or enhancing the activity of local GABAergic inhibitory interneurons. Compared to traditional deep brain stimulation (DBS) or craniotomy, high-frequency ultrasound stimulation provides a non-invasive and reversible intervention, particularly suitable for drug-resistant but focal epilepsy types, such as temporal lobe neocortical epilepsy or gray matter heterotopia-related epilepsy.

[0064] In some embodiments of chronic neuropathic pain treatment, high-frequency ultrasound at 4.0 MHz was used to reverse pain-related cortical plasticity abnormalities by modulating the excitability of the primary somatosensory cortex (S1). Studies have shown that stimulation of the S1 area can reduce local blood flow signals and decrease the intensity of pain perception. Simultaneously, high-frequency intervention targeting the anterior cingulate cortex (ACC) can modulate the emotional component of pain by inhibiting the functional connection between the ACC and the insula, thus alleviating anxiety and depressive symptoms associated with pain. This dual regulatory mechanism provides a novel intervention strategy for chronic pain.

[0065] In one embodiment of visual and auditory system modulation, targeting the V1 / V2 region of the occipital lobe with 5.0 MHz high-frequency ultrasound can transiently enhance visual contrast sensitivity, potentially applicable to adjunctive treatment of visual dysfunction. For the auditory system, high-frequency stimulation of the transverse temporal gyrus can intervene in abnormal neural oscillations, showing the potential to reset abnormal cortical activity in tinnitus animal models. These applications are based on ultrasound's ability to precisely modulate local cortical field potentials and synchronize neural clusters.

[0066] In the treatment of mental illnesses, high-frequency ultrasound is being used to focus on the neuromodulation of cortical-limbic circuits. For example, in some embodiments, for obsessive-compulsive disorder (OCD), targeting the dorsolateral subregion of the orbitofrontal cortex (OFC) with 3.5 MHz ultrasound can weaken its overconnection to the striatum, reducing compulsive behaviors. In post-traumatic stress disorder (PTSD), high-frequency ultrasound intervention in superficial projection areas of the amygdala (such as the basolateral nucleus) can inhibit the reconsolidation process of fear memories. Animal studies have confirmed that this intervention can block the expression of conditioned fear responses, providing a new direction for the intervention of traumatic memories.

[0067] Regarding the control method, the transcranial ultrasound neuromodulation device generates ultrasound waves with a frequency between 3.0 MHz and 8.0 MHz to act on the target area within the cranium. Depending on the application scenario, the pulse repetition frequency (PRF) of the ultrasound generating unit is controlled within the range of 1 Hz to 5000 Hz, and the duty cycle is controlled within the range of 1% to 90%. Preferably, the parameters are set as follows: PRF within the range of 50 Hz to 500 Hz, and duty cycle within the range of 5% to 20%. This setting balances two technical effects: lower PRF and duty cycle reduce the risk of tissue heat accumulation, meeting the safety standards of non-invasive treatment, ensuring treatment efficiency while avoiding tissue thermal damage; simultaneously, intermittent neuromodulation is achieved through pulsed ultrasound emission, simulating physiological neural oscillation rhythms and improving treatment biocompatibility.

[0068] The clinical application process of this device is as follows: First, the coordinates of the target area are located using functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). Then, preset sound intensity and frequency parameters are selected according to the type of disease. Next, a flexible patch is attached to the corresponding area on the patient's head. Finally, the control system is activated to emit ultrasound waves. During treatment, the transducer array converts electrical energy into high-frequency mechanical vibrations, which are transmitted to the skull through the acoustic coupling layer. After penetration, the vibrations are focused on the target brain region, regulating neuronal membrane potential, synaptic plasticity, and brain network connectivity through cavitation effects and mechanical stress.

[0069] This application also provides a control method for a transcranial ultrasound neuromodulation device 1. The transcranial ultrasound neuromodulation device 1 is the transcranial ultrasound neuromodulation device 1 described in the above embodiments. The control method includes: controlling the ultrasound generating unit to selectively generate ultrasound waves with frequencies matching the location of the target area, based on the location of the target area. The frequency of the ultrasound waves includes at least a portion of the range from 3.0 MHz to 8.0 MHz, to act on the target area. In some embodiments, the transcranial ultrasound neuromodulation device 1 generates ultrasound waves selectable in all or part of the aforementioned frequency range. In other embodiments, the transcranial ultrasound neuromodulation device 1 generates ultrasound waves at one or more fixed frequencies within the aforementioned frequency range.

[0070] It should be noted that the control method can be executed by the control unit inside the transcranial ultrasound neuromodulation device 1, specifically, for example, a main control chip. Furthermore, control commands can be sent to the control unit by operating an external controller or terminal APP. These control commands can specifically include the frequency of the generated ultrasound waves, stimulation duration, stimulation period, stimulation duty cycle, and sound intensity. In some embodiments, specific parameter combinations can be pre-set, allowing for one-click initiation of ultrasound stimulation based on these specific parameter combinations. For example, a parameter combination suitable for anxiety treatment can be set via the APP and named "Epilepsy Treatment" or similar names. When epilepsy treatment is needed, the transcranial ultrasound neuromodulation device 1 is attached to a suitable position on the head, and the treatment program can be started with one click on the APP.

[0071] The following examples illustrate the application of the transcranial ultrasound neuromodulation device 1 provided in this application in neuromodulation.

[0072] Example 1: Intervention for focal epilepsy

[0073] In some embodiments, the ultrasound generating unit provides ultrasound waves with a frequency of 4.5MHz to 5.5MHz into the cranium, for example, in one specific embodiment, it provides ultrasound waves with a frequency of 5.0MHz. Ultrasound waves in this frequency band can act on the right temporal lobe target area associated with focal epilepsy, thereby achieving a therapeutic effect on focal epilepsy. The term "associated" refers to the fact that the target area plays an important role in the pathological mechanism of the aforementioned condition; ultrasound stimulation of this target area can effectively alleviate or treat the corresponding condition. Specifically, this embodiment is a clinical application of the transcranial ultrasound neuromodulation device 1 of this application in the intervention of focal epilepsy. The subject was a 35-year-old male who was clinically diagnosed and confirmed by MRI to have a right temporal lobe epileptic focus with a depth of approximately 25mm, and conventional drug treatment was ineffective. Before treatment, the coordinates of the target brain region were accurately located using 3.0T MRI imaging, and the coordinate information was transmitted to the navigation system of this device.

[0074] like Figure 3 As shown, during treatment, the transcranial ultrasound neuromodulation device 1 is set to generate a fixed operating frequency of 5.0 MHz to ensure matching of penetration depth and spatial resolution. Stimulation parameters are set as follows: pulse repetition frequency range of 1 Hz to 5000 Hz, preferably 50 Hz; duty cycle range of 1 to 90%, preferably 30%; and spatial peak pulse mean acoustic intensity (Isppa) maintained within a safe range of 5 W / cm². The patient is seated, and the device is fixed to the corresponding position on the scalp, temporal bone, or temple, ensuring good coupling between the ultrasound transducer and the scalp. Each treatment lasts 10 minutes, and the entire procedure is non-invasive.

[0075] Following the above treatment, the efficacy and safety were assessed using multiple methods. Electrocorticometry (ECoG) monitoring during treatment showed a 65% reduction in epileptiform abnormal discharge activity, confirming the effectiveness of neuromodulation. A follow-up T2-weighted MRI within 24 hours showed no significant signal abnormalities, ensuring the absence of adverse reactions such as cerebral hemorrhage or edema. Furthermore, the patient reported no subjective symptoms such as headache or dizziness, and clinical neurological function examinations revealed no abnormalities. Figure 6 As shown, this is the epilepsy score of a subject with focal epilepsy after treatment with this device. From Figure 6 As can be seen, the epilepsy score decreased significantly after one month of treatment. In the subsequent two to four months of treatment, the epilepsy score remained at a relatively low level compared to the sham treatment group, indicating that it has an effective inhibitory effect on epilepsy.

[0076] Example 2: Relief of chronic low back pain

[0077] In some embodiments, the ultrasound generating unit provides ultrasound waves with a frequency of 6.2MHz to 6.5MHz into the cranium, for example, in one specific embodiment, it provides ultrasound waves with a frequency of 6.3MHz. Ultrasound waves in this frequency band can act on the primary somatosensory cortex target area associated with chronic pain, thereby achieving a therapeutic effect on focal epilepsy. The term "associated" refers to the target area playing an important role in the pathological mechanism of the aforementioned conditions; ultrasound stimulation of this target area can effectively alleviate or treat the corresponding conditions. Specifically, this embodiment is a clinical application of the transcranial ultrasound neuromodulation device 1 of this application in chronic low back pain. The subject was a 45-year-old male who suffered from low back pain caused by lumbar disc herniation for a long time. Before treatment, the anatomical location of the primary somatosensory cortex (S1 area) was confirmed by imaging examination, and the target area coordinates were determined to be the left S1 area, with a subcortical depth of 15mm, using a neuronavigation system. Intervention was performed using a continuous wave mode with a fixed frequency of 6.3MHz and a sound intensity of 3W / cm² (Isppa).

[0078] like Figure 4 As shown, during the operation, the flexible ultrasonic transducer patch provided with the device is precisely attached to the patient's forehead (frontal cortex) at the corresponding S1 zone projection position, ensuring stable acoustic coupling between the transducer and the scalp. The treatment is set to a single stimulation duration of 8 minutes. The entire process requires no additional anesthesia or sedation; the patient remains conscious and can adjust their sitting posture independently. To ensure treatment safety, the system's built-in real-time temperature monitoring module records the local temperature rise throughout the entire process, keeping it below 0.5℃.

[0079] Post-treatment efficacy assessment showed a significant decrease in patients' VAS scores and an approximately three-fold increase in pain threshold. No adverse reactions such as headache or dizziness were observed during the efficacy assessment period, and physiological monitoring showed that blood pressure and heart rate fluctuated within the normal range. Follow-up MRI showed no abnormal signal changes, confirming the safety of the treatment. A 48-hour follow-up assessment showed that the pain relief effect remained at a low level post-treatment, confirming the sustained and stable efficacy of the device of this invention in chronic pain management. Figure 7 As shown, this figure represents the change in pain levels in a patient with chronic low back pain after treatment with this device. The data for the Sham group corresponds to sham stimulation, while the data for the dACC group corresponds to real stimulation. An asterisk indicates a p-value less than 0.05, meaning the result is significant at the 0.05 level. The p-value is a commonly used statistical expression, representing the probability of observing the current experimental data or more extreme data given the null hypothesis. The null hypothesis is a default, conservative assumption, typically indicating "no effect," "no difference," or "ineffectiveness." The smaller the p-value, the less likely it is that the observed data would occur given the null hypothesis, thus providing stronger evidence to reject the null hypothesis. In this example, ultrasound stimulation has a significant effect. As can be seen from the figure, the pain level decreased after real stimulation by the device described in this application.

[0080] Example 3: Adjunctive Treatment for Post-Traumatic Stress Disorder

[0081] In some embodiments, the ultrasound generating unit provides ultrasound waves with a frequency of 3.5MHz to 3.8MHz into the cranium, for example, in one specific embodiment, it provides ultrasound waves with a frequency of 3.7MHz. Ultrasound waves in this frequency band can act on the prefrontal cortex target area associated with post-traumatic stress disorder (PTSD) to treat focal epilepsy. The term "associated" refers to the target area playing an important role in the pathological mechanism of the aforementioned conditions; ultrasound stimulation of this target area can effectively alleviate or treat the corresponding conditions. Specifically, this embodiment describes the application of the transcranial ultrasound neuromodulation device 1 of this application in post-traumatic stress disorder (PTSD). The subject was a 38-year-old male clinically diagnosed with moderate PTSD (PCL-5 score of 48), who had poor response to conventional drug treatment and significant tolerance issues. Before treatment, the prefrontal cortex target area was precisely located using functional magnetic resonance imaging (fMRI), and the neural networks related to emotion processing were targeted and modulated.

[0082] like Figure 5 As shown, this device is used for non-invasive neuromodulation during treatment. Specific parameters are set to a fixed operating frequency of 3.7MHz, a 5Hz theta rhythm pulse envelope modulation mode, and a sound intensity (Isppa) controlled at 4W / cm². 2Within safe limits. The flexible ultrasound transducer patch forms a stable coupling with the patient's forehead skin via medical-grade adhesive hydrogel, eliminating the need for additional skull drilling or invasive procedures. Each treatment session lasts 20 minutes, with a total treatment cycle of 4 weeks, administered 3 times per week. Efficacy was assessed using the internationally recognized PCL-5 scale as the primary indicator, combined with patient subjective symptom reports and clinician evaluations. Results showed that after 12 interventions, patients' PCL-5 scores significantly decreased to 28 points, an improvement rate of 41%, with particularly noticeable improvements in sleep disturbances and flashback symptoms. Regarding safety monitoring, no adverse reactions such as headaches or skin allergies were reported during treatment, and continuous EEG monitoring revealed no abnormal electrical activity.

[0083] like Figure 8 The figure shows the change in a subject's Mood and Anxiety Symptom Questionnaire-General Distress (MASQ-GD) score before and after transcranial ultrasound nerve stimulation. The MASQ score is widely used to test theoretical models of mood disorders, analyze symptom structure, and assess the impact of treatment interventions on different symptoms; a lower score indicates milder symptoms. As can be seen from the figure, the MASQ score significantly decreased after nerve stimulation using this device.

[0084] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of protection of this application. Therefore, the patent protection scope of this application should be determined by the appended claims.

Claims

1. A transcranial ultrasound neuromodulation device, characterized in that, The transcranial ultrasound neuromodulation device includes: An ultrasound generating unit that delivers ultrasound waves to the target area within the skull in a controlled manner; The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 3.0 MHz to 8.0 MHz into the cranium.

2. The transcranial ultrasound neuromodulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 3.5MHz to 3.8MHz into the cranium.

3. The transcranial ultrasound neuromodulation device according to claim 2, characterized in that, The ultrasound generating unit is configured to deliver ultrasound waves at a frequency of 3.7 MHz into the cranium.

4. The transcranial ultrasound neuromodulation device according to claim 2, characterized in that, The ultrasound generating unit is configured such that the ultrasound waves it provides to the intracranial cavity act on the prefrontal cortex target area associated with post-traumatic stress disorder.

5. The transcranial ultrasound neuromodulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 4.5MHz to 5.5MHz into the cranium.

6. The transcranial ultrasound neuromodulation device according to claim 5, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves at a frequency of 5.0 MHz into the cranium.

7. The transcranial ultrasound neuromodulation device according to claim 5, characterized in that, The ultrasound generating unit is configured such that the ultrasound waves it provides to the intracranial cavity act on the right temporal lobe target area associated with focal epilepsy.

8. The transcranial ultrasound neuromodulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 6.2MHz to 6.5MHz into the cranium.

9. The transcranial ultrasound neuromodulation device according to claim 8, characterized in that, The ultrasound generating unit is configured to deliver ultrasound waves at a frequency of 6.3 MHz into the cranium.

10. The transcranial ultrasound neuromodulation device according to claim 8, characterized in that, The ultrasound generating unit is configured such that the ultrasound waves it delivers into the cranium act on the primary somatosensory cortex target area associated with chronic pain.

11. The transcranial ultrasound neuromodulation device according to claim 1, characterized in that, The ultrasound generating unit is configured such that the ultrasound waves it generates can reach the target area of ​​brain tissue at a depth of no more than 3 cm.

12. The transcranial ultrasound neuromodulation device according to claim 1 or 11, characterized in that, The ultrasound generating unit is configured to generate ultrasound waves for ultrasound stimulation of the primary somatosensory cortex, temporal neocortex, anterior cingulate cortex, orbitofrontal cortex, amygdala surface projection area, and prefrontal cortex target area located in the cerebral cortex or superficial white matter layer.

13. The transcranial ultrasound neuromodulation device according to claim 1 or 11, characterized in that, The transcranial ultrasound neuromodulation device is configured to provide ultrasound stimulation to target areas in brain tissue associated with at least one of the following conditions: focal epilepsy, chronic pain syndrome, visual and auditory cortical dysfunction, and mental disorders including obsessive-compulsive disorder and post-traumatic stress disorder.

14. The transcranial ultrasound neuromodulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide a spatial peak pulse with a mean sound intensity of 0.5 W / cm² into the intracranial cavity. 2 Up to 10W / cm 2 Ultrasound.

15. The transcranial ultrasound neuromodulation device according to any one of claims 1 to 11, characterized in that, The ultrasonic generating unit is configured such that the ultrasonic waves it generates have sub-millimeter spatial resolution.

16. The transcranial ultrasound neuromodulation device according to claim 1, characterized in that, The ultrasonic generating unit includes multiple ultrasonic transducers arranged in an array.

17. The transcranial ultrasound neuromodulation device according to claim 16, characterized in that, The number of ultrasonic transducers is 5 to 256, and the distance between two adjacent ultrasonic transducers is no greater than 0.8 mm.

18. The transcranial ultrasound neuromodulation device according to claim 16 or 17, characterized in that, Each of the ultrasonic transducers is independently controlled by a phase control system so that the focal diameter formed by the ultrasonic generating unit in the target area can be controlled to be less than 0.5 mm.

19. The transcranial ultrasound neuromodulation device according to claim 16, characterized in that, The transcranial ultrasound neuromodulation device includes at least one ultrasound transducer module, which forms an ultrasound transducer array. Each ultrasound transducer module includes a plurality of ultrasound transducers, which are electrically connected in sequence to form a closed geometric shape, and at least one of the ultrasound transducers is located at the center of the closed geometric shape.

20. The transcranial ultrasound neuromodulation device according to any one of claims 1 to 11, characterized in that, The transcranial ultrasound neuromodulation device is configured as a flexible patch that can be attached to the head, or as a wearable device that can be worn on the head.

21. The transcranial ultrasound neuromodulation device according to any one of claims 1 to 11, characterized in that, The transcranial ultrasound neuromodulation device is adapted to the contours of the skull and fits at least one location on the forehead and temples of the skull.

22. The transcranial ultrasound neuromodulation device according to any one of claims 1 to 11, characterized in that, The ultrasonic generating unit is configured to transmit ultrasonic waves with a pulse repetition frequency of 1Hz to 5000Hz.

23. The transcranial ultrasound neuromodulation device according to any one of claims 1 to 11, characterized in that, The ultrasonic generating unit is configured to transmit ultrasonic waves with a pulse repetition frequency of 50Hz to 500Hz.

24. A control method for a transcranial ultrasound neuromodulation device, characterized in that, The control method includes: according to the location of the target area, controlling the transcranial ultrasound neuromodulation device as described in any one of claims 1 to 23 to selectively generate ultrasound waves with a frequency matching the location of the target area, wherein the frequency of the ultrasound waves is at least a portion within the range of 3.0 MHz to 8.0 MHz, to act on the intracranial target area.

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