Transcranial ultrasonic stimulation device and control method

Abstract

The invention relates to a transcranial ultrasonic stimulation device and a control method. The transcranial ultrasonic stimulation device comprises a main body and an ultrasonic generation unit. The main body is configured to be suitable for being arranged on the outer side of the head; the ultrasonic generation unit is arranged on the main body, and the ultrasonic generation unit is configured to controllably provide ultrasonic waves to an intracranial target area. Wherein the ultrasonic generating unit is configured to provide ultrasonic waves with the frequency ranging from 1.2 MHz to 3.0 MHz into the skull. According to the scheme, the frequency is increased to 1.2 MHz or above, the spatial resolution is optimized to 0.5 mm-2mm, and the neuron-level regulation and control precision is remarkably improved; moreover, the attenuation characteristic of high-frequency ultrasound is compensated through an array focusing design, it is ensured that ultrasonic waves effectively reach a target area with the depth of 0.5-5 cm such as the cerebral cortex or the hippocampus, and the technical bottleneck that the penetration depth of the high-frequency ultrasound is insufficient is broken through.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of neuromodulation, in particular to a transcranial ultrasound stimulation device and a control method. BACKGROUND

[0002] As a non-invasive neuromodulation technology that has developed rapidly in recent years, transcranial ultrasound stimulation (TUS) has shown unique advantages in the field of neurological disease treatment. Compared with traditional transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), TUS technology can achieve precise regulation of neuronal activity by emitting ultrasound waves to specific target areas in the brain, and has the advantages of non-invasiveness, repeatability, strong penetration, high spatial resolution, etc. At the same time, TUS technology has a dual action mechanism of mechanical vibration and thermal effect, which can regulate neuronal activity through multiple pathways. These technical characteristics make TUS show broad application prospects in the treatment of neurodegenerative diseases and mental illnesses.

[0003] However, the current development of TUS technology still faces technical bottlenecks, and the technical limitations of excessive frequency dependence seriously restrict the application range and treatment effect of TUS technology in clinical practice.

[0004] Therefore, it is necessary to propose a new technical scheme to overcome the deficiencies of the prior art. SUMMARY

[0005] Based on this, the present application provides a transcranial ultrasound stimulation device and a control method, which can be widely applied to the neuromodulation of various diseases while ensuring the safety of application, and provides a new solution for neuroscience research and clinical treatment.

[0006] To this end, the present application adopts the following technical scheme: a transcranial ultrasound stimulation device, comprising:

[0007] a main body configured to be adapted to be placed outside the head; and

[0008] an ultrasound generating unit provided in the main body, the ultrasound generating unit being configured to provide ultrasound waves to a target area in the brain under control;

[0009] wherein the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2 MHz to 3.0 MHz into the brain.

[0010] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2-1.4 MHz to the intracranial.

[0011] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2 or 1.3 MHz to the intracranial.

[0012] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial, which act on the motor function area of the cerebral cortex associated with motor function recovery in stroke rehabilitation.

[0013] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.5-1.8 MHz to the intracranial.

[0014] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.5 or 1.6 or 1.7 MHz to the intracranial.

[0015] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial, which act on the dorsolateral prefrontal cortex associated with the treatment of depression.

[0016] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 2.0-3.0 MHz to the intracranial.

[0017] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 2.4 or 2.5 or 2.6 or 2.7 MHz to the intracranial.

[0018] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial, which act on the trigeminal nucleus-cerebellum region associated with the treatment of migraine.

[0019] In some embodiments, the ultrasound generating unit is configured to generate ultrasound waves that can reach the target region at a depth of 0.5-5 cm in the brain tissue.

[0020] In some embodiments, the ultrasound generating unit is configured to generate ultrasound waves with a spatial resolution of 0.5-2 mm.

[0021] In some embodiments, the ultrasound generating unit is configured to generate ultrasound waves for ultrasound stimulation of the target region in the cerebral cortex or hippocampus.

[0022] In some embodiments, the transcranial ultrasound stimulation device is configured to stimulate a target region in the brain tissue associated with at least one of Alzheimer's disease, Parkinson's disease, depression, obsessive-compulsive disorder, chronic neuropathic pain, migraine, post-stroke motor dysfunction and aphasia, and disorders of consciousness.

[0023] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial region with a spatial peak pulse-averaged intensity in the range of 200 mW / cm 2 to 800 mW / cm 2 .

[0024] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial region with a spatial peak pulse-averaged intensity in the range of 200 mW / cm 2 to 400 mW / cm 2 for pain management.

[0025] Alternatively, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial region with a spatial peak pulse-averaged intensity in the range of 400 mW / cm 2 to 550 mW / cm 2 for depression management.

[0026] Alternatively, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial region with a spatial peak pulse-averaged intensity in the range of 500 mW / cm 2 to 650 mW / cm 2 for neurodegenerative disease management.

[0027] Alternatively, the ultrasound generating unit is configured to provide ultrasound waves to the intracranial region with a spatial peak pulse-averaged intensity in the range of 550 mW / cm 2 to 800 mW / cm 2 for stroke rehabilitation.

[0028] In some embodiments, the ultrasound generating unit comprises a plurality of ultrasound transducers arranged in an array on the main body.

[0029] In some embodiments, the transcranial ultrasound stimulation device comprises a plurality of ultrasound transducer modules, each of which comprises at least one ultrasound transducer, and the plurality of ultrasound transducer modules form an ultrasound transducer array.

[0030] In some embodiments, each of the ultrasound transducer modules comprises a carrier substrate and at least one ultrasound transducer disposed on the carrier substrate, and the carrier substrates of the plurality of ultrasound transducer modules are spliced to form the main body or are assembled on the main body.

[0031] In some embodiments, the transcranial ultrasound stimulation device comprises at least one ultrasound transducer module, which constitutes an ultrasound transducer array; the ultrasound transducer module comprises a plurality of ultrasound transducers, a plurality of the ultrasound transducers are sequentially electrically connected to form a closed geometric figure, and at least one of the ultrasound transducers is located at the center position of the closed geometric figure.

[0032] In some embodiments, the main body is a flexible sheet body adapted to be deformed to adapt to the contour of the head surface and capable of being attached to the head.

[0033] In some embodiments, the transcranial ultrasound stimulation device is adapted to be attached to at least one of the forehead and the temple of the head.

[0034] In some embodiments, the ultrasound generating unit is configured to have a pulse repetition frequency of the ultrasound waves it sends in a range of 1Hz ~ 5000Hz.

[0035] In some embodiments, the ultrasound generating unit is configured to have a pulse repetition frequency of the ultrasound waves it sends in a range of 50Hz ~ 500Hz.

[0036] The application also adopts the following technical solution: a control method of a transcranial ultrasound stimulation device, the control method comprising: according to the position of a target region, controlling the transcranial ultrasound stimulation device as described in any one of the above embodiments to selectively generate ultrasound waves with a frequency matching the position of the target region, the frequency of the ultrasound waves being at least a part of a range of 1.2MHz to 3.0MHz, to act on the target region.

[0037] The transcranial ultrasound stimulation device and the control method provided by the application stimulate intracranial nerves by ultrasound waves with a working frequency of 1.2MHz ~ 3.0MHz, and one or more frequency bands contained therein are suitable for application in multiple clinical fields including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, mental diseases such as depression and obsessive-compulsive disorder, pain management such as chronic neuropathic pain and migraine, stroke rehabilitation such as motor function recovery and aphasia, and neural regulation and cognitive function improvement of consciousness disorders. The device and method have the advantages of safety and clinical practicability, and are particularly suitable for management of nervous system diseases that require long-term treatment, and provide a new technical solution for neuroscience research and clinical treatment. BRIEF DESCRIPTION OF DRAWINGS

[0038] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the accompanying drawings needed to be used in the embodiments or the prior art description will be briefly introduced as follows. Obviously, the drawings in the following description only represent some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without any creative effort.

[0039] Figure 1 Structure schematic diagram of an embodiment of the transcranial ultrasound stimulation device of the present application.

[0040] Figure 2 Schematic diagram of the transcranial ultrasound stimulation device of the present application for depression treatment.

[0041] Figure 3 Schematic diagram of the transcranial ultrasound stimulation device of the present application for migraine treatment.

[0042] Figure 4 Schematic diagram of the transcranial ultrasound stimulation device of the present application for stroke rehabilitation treatment.

[0043] Figure 5 HDRS value change diagram of an embodiment of the transcranial ultrasound stimulation device of the present application for depression treatment.

[0044] Figure 6 Pain value change diagram of an embodiment of the transcranial ultrasound stimulation device of the present application for migraine treatment.

[0045] Figure 7 WMFT value change diagram of an embodiment of the transcranial ultrasound stimulation device of the present application for stroke rehabilitation treatment.

[0046] The element reference numbers are as follows:

[0047] 1, transcranial ultrasound stimulation device; 11, ultrasound transducer module; 111, ultrasound transducer; 112, bearing substrate. DETAILED DESCRIPTION

[0048] In order to make the above objectives, features and advantages of the present application more apparent and understandable, the specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. In the following description, a lot of specific details are set forth in order to fully understand the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the spirit of the present application, so the present application is not limited to the specific embodiments disclosed below.

[0049] It is to be understood that when an element such as a layer, region or substrate is referred to as being "on" or "connected to" another element, it can be directly on or connected to the other element or intervening elements can be present. In contrast, when an element is referred to as being "directly on" or "directly connected to" another element, there are no intervening elements present. It will be understood that, when a member is referred to as being "on" another member, it can be directly on the other member or intervening members can be present. Relative terms such as "lower", "upper", "horizontal", "vertical", "above", "below", "up", "down", "top" and "bottom" as can be used herein to describe one element's relationship to another element as illustrated in the Figures. Such relative terms are to be construed not as indicating a particular orientation or spatial arrangement, but rather as indicating a relative position as the device is oriented in use.

[0050] In addition, the terms "first", "second", etc. are used herein only to describe various tenninates and do not imply a relative importance or a specific order of the tenninates. Thus, a tenninate having a "first" and a "second" can include at least one of the tenninates, explicitly or implicitly. In the description of the present application, the meaning of "a plurality" is at least two, such as two, three, etc., unless otherwise specifically defined.

[0051] In the present application, unless otherwise specifically defined and limited, the first feature "on", "under", "above" and "over" the second feature can be that the first feature is in direct contact with the second feature, or the first feature is indirectly in contact with the second feature through an intermediate medium. Moreover, the first feature "on", "above" and "over" the second feature can be that the first feature is directly above or obliquely above the second feature, or only indicates that the first feature is higher in horizontal height than the second feature. The first feature "under", "below" and "under" the second feature can be that the first feature is directly below or obliquely below the second feature, or only indicates that the first feature is lower in horizontal height than the second feature.

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The use of the terms "and / or" includes a combination of one or more of the associated listed items.

[0053] Please refer to Figures 1 to 4 As shown in the drawings, the present application provides a transcranial ultrasound stimulation device 1 and a control method. The transcranial ultrasound stimulation device 1 realizes precise regulation of intracranial neural target area through non-invasive ultrasound stimulation technology, while ensuring biological safety, taking into account the penetration depth and treatment accuracy. The technical solutions are described in detail below in combination with the drawings and specific implementation cases.

[0054] First, the overall structure and working principle of an embodiment of the transcranial ultrasound stimulation device 1 provided by the present application are described.

[0055] As Figure 1As shown, the transcranial ultrasound stimulation device 1 comprises a main body and an ultrasound generating unit. The main body is configured to be placed outside the head. The ultrasound generating unit is provided on the main body, and is configured to provide ultrasound waves to a target region in the brain under control. It can be understood that the ultrasound generating unit can be connected to a control unit in a wired or wireless manner, and the control unit controls the generation of ultrasound waves. The control unit can be integrated in the transcranial ultrasound stimulation device 1, or can be a device or equipment independent of the transcranial ultrasound stimulation device 1. The ultrasound generating unit is configured to provide ultrasound waves with a frequency in the range of 1.2 MHz to 3.0 MHz to the target region in the brain.

[0056] Specifically, in some embodiments, the main body is a deformable member, such as a flexible circuit board, or a component that can be combined with a flexible circuit and has a flexible base such as rubber, silicone, braid, hydrogel, etc. Preferably, the main body is a flexible sheet that is adapted to conform to the contour of the head and adhere to the head. In this embodiment, the main body includes a hydrogel layer and a silicone layer, and the hydrogel base design with biological adhesion allows the ultrasound generating unit to well conform to the biological surface of the scalp, and the flexible silicone packaging layer design ensures effective sound 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 stimulation device 1 is tightly adhered to the forehead, temple and other parts as needed, and the flexible main body can form a stable acoustic coupling interface between the ultrasound generating unit and the scalp, effectively reducing the energy loss of the ultrasound wave during transmission.

[0057] In this embodiment, the ultrasound generating unit includes a plurality of ultrasound transducers 111 provided on the main body, and the plurality of ultrasound transducers 111 are arranged in an array on the main body. Each ultrasound transducer 111 is made of piezoelectric ceramic or single crystal material, and has a working frequency range of 1.2 MHz to 3.0 MHz. The ultrasound transducers 111 are connected by flexible lines, so that when the main body is bent, each ultrasound transducer 111 can still maintain stable electrical connection. Further, by electronic phase control technology, the emission phase of each ultrasound transducer 111 is controlled to form a focused ultrasound beam in the brain. In some embodiments, the sound field distribution can be adjusted and optimized according to the anatomical position of the target region.

[0058] In this embodiment, the ultrasound generating unit adopts a modular patch design. Specifically, the transcranial ultrasound stimulation device 1 includes a plurality of ultrasound transducer modules 11, and the plurality of ultrasound transducer modules 11 are configured to be combined in different numbers and positions to form ultrasound transducer arrays of different shapes or sizes. For example, Figure 1As shown, each ultrasonic transducer module 11 is square. Four ultrasonic transducer modules 11 can be assembled into a square, two ultrasonic transducer modules 11 can be assembled into a rectangle, or three ultrasonic transducer modules 11 can be assembled into an L-shape or a straight line, to create different shapes to cover different areas of the skull. Additionally, as... Figure 2 As shown, multiple ultrasound transducer modules 11 can be attached to each other or arranged separately; in some embodiments, the transcranial ultrasound stimulation device 1 may also include only one ultrasound transducer module 11.

[0059] Please continue reading. Figure 1 As shown, in this embodiment, each of the ultrasound transducer modules 11 includes a support substrate 112 and at least one ultrasound transducer 111 disposed on the support substrate 112. In some embodiments, the transcranial ultrasound stimulation device 1 includes at least one ultrasound transducer module 11, which forms an ultrasound transducer array. Each ultrasound transducer module 11 includes a plurality of ultrasound transducers 111, wherein a plurality of ultrasound transducers 111 are electrically connected in sequence, and their sequential connection forms a closed geometric shape, and at least one ultrasound transducer 111 is located at the geometric center of the closed geometric shape. This arrangement allows a plurality of ultrasound transducers 111 to surround the ultrasound transducer 111 located at the center, which is more conducive to ultrasound wave focusing and effectively targeting the target area. For example, in Figure 1 In the illustrated embodiment, each ultrasonic transducer module 11 includes five ultrasonic transducers 111, wherein four ultrasonic transducers 111 are connected sequentially to form a rectangle, and the fifth ultrasonic transducer 111 is located at the center point of the rectangle. It is understood that the number and arrangement of the ultrasonic transducers 111 are not limited to this; for example, as shown... Figure 4 As shown, an ultrasonic transducer module 11 may include nine or other ultrasonic transducers 111. Furthermore, the closed geometric shape formed by the plurality of ultrasonic transducers 111 can be circular, square, rectangular, rhomboid, elliptical, triangular, or other shapes. Further, if the supporting substrates 112 of the plurality of ultrasonic transducer modules 11 are assembled into the main body or mounted on the main body, then the supporting substrate 112 must be made of a flexible material, or a mixture of flexible and rigid materials, so that the main body is a flexible body. That is, in some embodiments, the supporting substrate 112 of each ultrasonic transducer module 11 can itself serve as the main body; in other embodiments, the main body can also be a component independent of the ultrasonic transducer module 11, with each ultrasonic transducer module 11 connected to the main body.

[0060] For the convenience of wearing and reducing the influence of the device on the user's activities, in the embodiment, the transcranial ultrasound stimulation device 1 is configured as a patch that can be attached to the head or a wearable device that can be worn on the head. The wearable device on the head includes a headband, a cap, a headband, etc. For example, in an embodiment, the transcranial ultrasound stimulation device 1 is arranged on a tight control headband to facilitate long-term and stable wearing by the user. Further, the device is powered by a built-in micro lithium battery, which can work continuously for 8 hours, and is equipped with a low-voltage protection circuit to ensure safety and convenience of use, especially suitable for continuous use by patients in daily life, realizing the portability and practicality of the transcranial ultrasound stimulation device 1.

[0061] In use, the transcranial ultrasound stimulation device 1 can be directly attached to key brain regions such as the temple (temporal window of the head) and the forehead (frontal lobe of the head) for non-invasive neural regulation. The transcranial ultrasound stimulation device 1 uses one or more frequency bands within the frequency range of 1.2MHz-3.0MHz to stimulate intracranial tissues with ultrasound. The frequency band can balance sufficient tissue penetration depth and appropriate spatial resolution. The above frequency range of the transcranial ultrasound stimulation device 1 can cover the ultrasound stimulation of the target region associated with at least one of Alzheimer's disease, Parkinson's disease, depression, obsessive-compulsive disorder, chronic neuropathic pain, migraine, post-stroke motor dysfunction and aphasia, and consciousness disorder. The so-called association means that these target regions play an important role in the pathological mechanism of the above-mentioned diseases, and ultrasound stimulation of these target regions can effectively alleviate or treat the above-mentioned corresponding diseases. Among them, the frequency range of 1.2MHz-3.0MHz includes two end values of 1.2MHz and 3.0MHz, and in some embodiments, the transcranial ultrasound stimulation device 1 generates ultrasound waves with variable frequencies within the above frequency range, and in other embodiments, the transcranial ultrasound stimulation device 1 generates ultrasound waves with fixed frequencies within the above frequency range. Further, within the above frequency range, in cooperation with the spatial peak pulse average acoustic intensity of 550-800mW / cm 2 , the stimulation intensity can cover the treatment of various neural-related diseases. It is suitable for application in multiple clinical fields such as neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, mental illnesses including depression and obsessive-compulsive disorder, pain management including chronic neuropathic pain and migraine, stroke rehabilitation including motor function recovery and aphasia, and neural regulation and cognitive function improvement of consciousness disorders. The device and method have the advantages of safety and clinical practicability, and are particularly suitable for long-term treatment of neurological disease management, providing a new technical solution for neuroscience research and clinical treatment.

[0062] The mechanism of the transcranial ultrasound stimulation device 1 provided in the present application in regulating nerves at a set frequency range in cooperation with different acoustic intensity parameters is described in detail below.

[0063] The ultrasound frequency generated by the ultrasound generating unit of the transcranial ultrasound stimulation device 1 provided in the present application is 1.2 MHz to 3.0 MHz. This frequency range can meet two key requirements at the same time: on the one hand, the present application optimizes the spatial resolution to 0.5 mm~2 mm by increasing the frequency to 1.2 MHz or above, significantly improving the neuron-level regulation accuracy; on the other hand, the attenuation characteristics of high-frequency ultrasound are compensated by array focusing design to ensure that the ultrasound waves can reach the target area at a depth of 0.5 cm~5 cm in the brain tissue, effectively covering the target area such as the cerebral cortex or hippocampus, and breaking through the technical bottleneck of insufficient penetration depth of high-frequency ultrasound.

[0064] The determination of the frequency range of 1.2 MHz~3.0 MHz provided in the present application is derived from the comprehensive analysis of the treatment needs of various indications. In the treatment of neurodegenerative diseases (such as Alzheimer's disease), ultrasound waves of 1.2 MHz~3.0 MHz can penetrate brain tissue to a depth of about 5 cm, effectively covering key target points such as the cortex and hippocampus, while maintaining a spatial resolution of 0.5 mm~2 mm to achieve precise stimulation; in the treatment of Parkinson's disease, ultrasound waves at this frequency range can precisely act on the basal ganglia region, and improve motor symptoms by adjusting neuronal electrical activity; in the field of mental illness, depression treatment requires both extensive regulation of the prefrontal cortex and fine stimulation of specific functional subareas, and the working frequency of 1.2 MHz~3.0 MHz provides an ideal parameter window for this purpose; for chronic pain management and stroke rehabilitation applications, this frequency range ensures effective stimulation of deep pain transmission pathways (such as the trigeminal spinal nucleus) and the motor cortex, while avoiding excessive energy attenuation caused by high-frequency ultrasound. In terms of cognitive function regulation, the working frequency of 1.2 MHz~3.0 MHz can achieve selective activation of working memory-related neural networks. In specific applications, the ultrasound generating unit can generate ultrasound waves at fixed frequencies of 1.2 MHz, 1.3 MHz, 1.4 MHz, 1.5 MHz, 1.6 MHz, 1.7 MHz, 1.8 MHz, 1.9 MHz, 2.0 MHz, 2.1 MHz, 2.2 MHz, 2.3 MHz, 2.4 MHz, 2.5 Hz, 2.6 MHz, 2.7 MHz, 2.8 MHz, 2.9 MHz, 3.0 MHz, or ultrasound waves with variable frequencies within the range of any two of the above frequency points.

[0065] In terms of acoustic intensity parameter design, in the present embodiment, the ultrasound generating unit is configured to provide a spatial peak pulse average acoustic intensity of 200 mW / cm 2 to 800 mW / cm 2ultrasound waves in the range of 200mW / cm 2 ~400mW / cm 2 ultrasound waves in the range of 400mW / cm 2 ~550mW / cm 2 ultrasound waves in the range of 500mW / cm 2 ~650mW / cm 2 ultrasound waves in the range of 550mW / cm 2 ~800mW / cm 2 ultrasound waves in the range of 550mW / cm

[0066] Specifically, pain management adopts a low-intensity mode of 200mW / cm 2 ~400mW / cm², inhibits abnormal firing of pain sensory neurons through mild mechanical vibration; depression treatment selects a medium-intensity mode of 400mW / cm 2 ~550mW / cm², adjusts prefrontal cortex neural circuit activity, and optimizes mechanical sensitivity activation of neuronal calcium channels; neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease) adopt a medium-high intensity mode of 500mW / cm 2 ~650mW / cm², which can effectively promote secretion of neurotrophic factors and clearance of abnormal protein aggregation without causing tissue thermal damage; stroke rehabilitation adopts a high-intensity mode of 550mW / cm 2 ~800mW / cm², promotes neural plasticity remodeling through stronger mechanical effects. The above parameter classification is based on a large number of animal experiments and preclinical research data to ensure treatment safety and effectiveness.

[0067] In terms of control methods, parameter adjustment is realized through a matching control unit. According to different application scenarios, the pulse repetition frequency (PRF) of the ultrasound generating unit is controlled in the range of 1Hz~5000Hz. Preferably, the parameter setting is PRF in the range of 50Hz~500Hz. This setting can take into account two technical effects: lower PRF can reduce the risk of tissue heat accumulation, meeting the safety standards of non-invasive treatment; at the same time, intermittent neural regulation is realized through pulsed ultrasound emission, simulating physiological neural oscillation rhythm, and improving treatment biocompatibility.

[0068] The clinical application process of the device is as follows: first, locate the target target area coordinates through medical imaging (such as MRI, etc.), then select the preset sound intensity parameters according to the type of the disease, then fit the flexible main body to the patient's head, and finally start the control unit to control the ultrasonic generating unit to emit ultrasonic waves. During treatment, the ultrasonic transducer 111 array converts electrical energy into mechanical vibration, which is coupled to the skull through the hydrogel layer, penetrates the bone structure, and focuses on the target brain area, and stimulates and regulates the target brain area through the dual mechanisms of mechanical stress and thermal effect.

[0069] The application also provides a control method of the transcranial ultrasound stimulation device 1. The transcranial ultrasound stimulation device 1 is the transcranial ultrasound stimulation device 1 described in the above embodiments, and the control method comprises: according to the position of the target target area, controlling the ultrasonic generating unit to selectively generate ultrasonic waves with a frequency matched with the position of the target target area, and the frequency of the ultrasonic waves at least includes at least a part of 1.3 MHz to 3.0 MHz, so as to act on the target target area. In some embodiments, the transcranial ultrasound stimulation device 1 generates ultrasonic waves with all or part of the frequency bands in the above frequency range, and in other embodiments, the transcranial ultrasound stimulation device 1 generates ultrasonic waves with one or more fixed frequencies in the above frequency range.

[0070] It should be noted that the control method can be executed by a control unit inside the transcranial ultrasound stimulation device 1, and the control unit is specifically, for example, a master control chip or the like. Further, the control instruction can be sent to the control unit by operating the external controller or terminal APP and the like. The control instruction can specifically include the frequency of the generated ultrasonic wave, the stimulation time, the stimulation cycle, the stimulation duty cycle, the sound intensity, etc. In some embodiments, a specific parameter combination can also be preset, and a one-key start ultrasonic stimulation based on the specific parameter combination. For example, the parameters suitable for migraine treatment can be set through the APP and named "migraine treatment" or the like, and when migraine treatment is needed, the transcranial ultrasound stimulation device 1 is attached to the appropriate position of the head, and the treatment program can be started on the APP.

[0071] The following is an example of the application of the transcranial ultrasound stimulation device 1 provided by the application in the field of neural regulation.

[0072] Example 1: Depression treatment

[0073] In the present embodiment, the transcranial ultrasound stimulation device 1 is used for the treatment of depression. The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.5-1.8 MHz to the intracranial to act on the dorsolateral prefrontal cortex associated with the treatment of depression. For example, ultrasound waves with a frequency of 1.5 MHz, 1.6 MHz or 1.7 MHz are provided to the intracranial. Specifically, as shown in Figure 2 In the present embodiment, 10 groups of ultrasound transducer modules 11 are used to generate ultrasound waves with a frequency of 1.5 MHz. These ultrasound transducer modules 11 are accurately arranged on the inner side of the elastic headband with biocompatibility according to the standard of neuroanatomy, forming a symmetrical bilateral stimulation array, which is consistent with the projection area of the cerebral prefrontal cortex (DLPFC) on the skull surface. Since the main body of the transcranial ultrasound stimulation device 1 is flexible and deformable to adapt to the contour of the skull, the two form a curved surface fit, ensuring that the device forms a stable anatomic adaptive contact with the prefrontal region of the human body.

[0074] In terms of technical parameter design, the pulse repetition frequency (PRF) in the present embodiment is taken from the range of 1-5000 Hz, and is preferably stably maintained at 100 Hz. The spatial peak time-averaged intensity is accurately adjusted to 500 mW / cm². All the above parameters meet the international ultrasound safety standards. A single 20-minute treatment cycle per day is adopted, and this length is set based on the balance point obtained from clinical research, which can ensure the treatment effect and avoid possible side effects.

[0075] The present embodiment achieves therapeutic effect through the mechanical pressure effect of 1.5 MHz ultrasound waves. When the ultrasound waves penetrate the skull and act on the DLPFC target area, the periodic mechanical vibration can specifically activate the mechanically sensitive ion channels (especially Piezo1 / 2 channels) on the neuron membrane, thereby regulating the excitability of local neurons. This precise neural regulation can effectively inhibit the overactive state of the default mode network (DMN) of patients with depression and improve the core symptoms such as rumination and emotional regulation disorder.

[0076] Clinical data shows that after following the treatment scheme of the present embodiment for 4 weeks, the subjects' scores on the standard Hamilton Depression Scale (HAMD-17) showed significant improvement, with an average decrease of 40±5%, and no significant adverse reactions were reported during the treatment. As shown in Figure 5 As shown in the figure, after 1-2 weeks of ultrasound stimulation treatment, the HDRS value is significantly reduced, and the treatment effect of depression is obvious.

[0077] Example 2: Migraine relief

[0078] In this embodiment, the transcranial ultrasound stimulation device 1 is used for the relief of migraine. The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 2.0-3.0 MHz to the intracranial to act on the trigeminal nucleus spinal tract region associated with migraine treatment. For example, ultrasound waves with a frequency of 2.4 MHz or 2.5 MHz or 2.6 MHz or 2.7 MHz are provided to the intracranial. Specifically, as shown in FIG. 2, the transcranial ultrasound stimulation device 1 of this embodiment adopts a patch design, integrating an ultrasound transducer module 11 capable of generating 2.5 MHz frequency ultrasound on a biocompatible patch substrate, which is fixed to the temple (temporal window of the head) during use and precisely positioned to the extracranial projection area of the trigeminal nucleus spinal tract. The trigeminal vascular system plays a key role in the pathogenesis of migraine, and the pain signal transmission pathway can be adjusted by ultrasound stimulation. Figure 3

[0079] In terms of technical parameter design, the pulse repetition frequency (PRF) in this embodiment is taken from the range of 1-5000 Hz, and is preferably stably maintained at 80 Hz. The spatial peak time-averaged intensity is accurately adjusted to 300 mW / cm2. This combination of parameters can ensure effective stimulation within the safety threshold. In this embodiment, the device can adopt an instant start mode, which is automatically started immediately according to the automatic sensing of the patient's prodromal symptoms of migraine or when the pain occurs.

[0080] This embodiment achieves analgesic effect through the mechanical pressure effect of 2.5 MHz ultrasound waves. When the ultrasound waves penetrate the skull and act on the trigeminal nucleus spinal tract region, the periodic mechanical vibration can inhibit the pain signal transmission of C fibers, while adjusting the abnormal electrical activity of local neurons. This targeted neural regulation can effectively block the cascade amplification of pain signals and relieve the pathological processes of migraine such as abnormal vascular dilation and neurogenic inflammation.

[0081] Clinical studies show that patients using the scheme of this embodiment have an average reduction of 3.2±0.8 points in visual analogue scale (VAS) within 15-30 minutes of treatment, and 82% of patients report a significant reduction in pain. As shown in FIG. 3, it is a plot of the pain value of a migraine test patient over time after treatment with the device. As can be seen from the figure, after about 30 minutes of treatment, the pain value is significantly reduced, and as the treatment time reaches 75 minutes, the pain value is further reduced. Figure 6

[0082] Example 3: Stroke rehabilitation

[0083] ​​In the present embodiment, the transcranial ultrasound stimulation device 1 is used for stroke rehabilitation. The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2 MHz to 1.4 MHz to the intracranial to act on the motor function area of the cerebral cortex associated with the recovery of motor function in stroke rehabilitation. For example, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2 MHz or 1.3 MHz to the intracranial. Specifically, as shown in Figure 3 The transcranial ultrasound stimulation device 1 of the present embodiment adopts a patch design and contains 9 ultrasound transducers 111 capable of generating 1.2 MHz ultrasound, forming a 3X3 array to accurately cover the cranial surface projection area of the motor cortex of the affected side of the patient. The diameter of each ultrasound transducer 111 is designed to be 5 mm, and the ultrasound transducer 111 array is arranged on a flexible main body with an arc-shaped curved surface design to ensure close fit with the scalp contour and cooperate with a medical-grade adhesive layer to achieve stable fixation on the forehead (frontal lobe of the head), without the need for additional use of acoustic impedance matching gel.

[0084] In terms of technical parameter design, the control unit adopts a fixed output mode, sets the pulse repetition frequency (PRF) range to 1 to 5000 Hz, preferably 120 Hz, and accurately adjusts the spatial peak time-averaged acoustic intensity to 600 mW / cm². This parameter combination has undergone strict in vitro skull penetration tests and animal experiments and can achieve effective stimulation under the premise of safety. The device is activated at the same time as the patient performs active rehabilitation training, and the recommended use time is not more than 60 minutes each time.

[0085] The present embodiment promotes synaptic plasticity changes of neurons in the target area through the mechanical vibration effect of 1.2 MHz ultrasound waves. Specifically, the periodic mechanical stress generated by 1.2 MHz ultrasound waves after penetrating the skull can activate the mechanically sensitive ion channels on the motor cortex neurons, enhance the synchronization of neuronal electrical activity, and promote the release of neurotrophic factors. This targeted neuroregulation effect produces a synergistic effect with rehabilitation training, which can significantly promote the reconstruction of neural pathways and functional reorganization after stroke. Clinical observation data show that the upper limb Fugl-Meyer score improvement speed of patients using the present scheme combined with conventional rehabilitation training is about 30% higher than that of the control group, and no significant adverse reactions have been observed. The device adopts an integrated wireless design and is equipped with a high-energy-density battery to support long-term continuous operation. Its light and thin flexible structure characteristics make the patient feel almost no additional burden during training.

[0086] As shown in Figure 7 Fig. 2 is a graph showing the change of the Wolf Motor Function Test (WMFT) of the motor function scale of a stroke rehabilitation test patient after treatment with the device over time. WMFT is a standardized and quantitative behavioral assessment method specifically for assessing the motor function of the upper limbs, especially the hands and arms. From Figure 7As can be seen, compared with the sham treatment, the WMFT time of the patient is significantly shortened after the ultrasonic stimulation treatment by the device, indicating that the movement efficiency of the upper limbs of the patient is improved, and the rehabilitation effect is good.

[0087] As can be seen from the above description of the specific embodiments, the transcranial ultrasonic stimulation device 1 provided in the application has an ultrasonic generating unit that generates ultrasonic waves with a frequency of 1.2 MHz to 3.0 MHz. This frequency range can meet two key requirements at the same time: on the one hand, the scheme improves the frequency to more than 1.2 MHz, optimizes the spatial resolution to 0.5 mm~2 mm, and significantly improves the neuron-level regulation accuracy; on the other hand, the array focusing design compensates for the attenuation characteristics of high-frequency ultrasonic waves, ensuring that the ultrasonic waves effectively reach the target region of the cerebral cortex or hippocampus with a depth of 0.5 cm~5 cm, breaking through the technical bottleneck of insufficient penetration depth of high-frequency ultrasonic waves. In addition, the transcranial ultrasonic stimulation device 1 provided in the application adopts a combination of a flexible main body and an ultrasonic transducer 111 array, which is comfortable to wear and can be attached to the human head to maintain excellent acoustic coupling performance, suitable for home use. Importantly, the transcranial ultrasonic stimulation device 1 provided in the embodiments of the application uses the temple or the forehead as an incident window, or a combination of the temple and the forehead as an incident window, which can effectively improve the penetration of ultrasonic waves, and the ultrasonic frequency used can effectively act on the brain tissue on the path and then reach the target region, making the regulation more sufficient. At the same time, under the international ultrasonic safety requirements, the focal spot obtained by the incident in other parts is more accurate and effective. For the requirement of long-term continuous wearing, the influence of the patient's hair and skull undulations is reduced, and the incident from the temple or the forehead is more convenient for the patient to wear. The embodiments of the application solve the key problems of insufficient penetration depth, poor targeting, and safety concerns in the field of non-invasive neural regulation through technical innovation, and provide a new solution for the treatment of nervous system diseases.

[0088] The above-described embodiments only express several implementation manners of the application, and the description is more specific and detailed, but it should not be understood as a limitation on the patent scope of the application. It should be noted that, for ordinary skilled persons in the art, without departing from the concept of the application, a number of modifications and improvements can be made, which are all within the protection scope of the application. Therefore, the patent protection scope of the application should be subject to the appended claims.

Claims

1. A transcranial ultrasound stimulation device, characterized in that, The transcranial ultrasound stimulation device includes: The main body, which is configured to be placed on the outside of the skull; and An ultrasound generating unit is disposed in the main body, the ultrasound generating unit being configured to controllably deliver ultrasound waves to a target area within the cranium; The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2 MHz to 3.0 MHz into the cranium.

2. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2MHz to 1.4MHz into the cranium.

3. The transcranial ultrasound stimulation device according to claim 2, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.2 MHz or 1.3 MHz into the cranium.

4. The transcranial ultrasound stimulation 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 motor function areas of the cerebral cortex associated with the recovery of motor function in stroke rehabilitation.

5. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.5MHz to 1.8MHz into the cranium.

6. The transcranial ultrasound stimulation device according to claim 4, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 1.5 MHz, 1.6 MHz, or 1.7 MHz into the cranium.

7. The transcranial ultrasound stimulation 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 dorsolateral prefrontal cortex associated with the treatment of depression.

8. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 2.0MHz to 3.0MHz into the cranium.

9. The transcranial ultrasound stimulation device according to claim 8, characterized in that, The ultrasound generating unit is configured to provide ultrasound waves with a frequency of 2.4 MHz, 2.5 MHz, 2.6 MHz, or 2.7 MHz into the cranium.

10. The transcranial ultrasound stimulation device according to claim 8, characterized in that, The ultrasound generating unit is configured such that the ultrasound waves it provides to the intracranial cavity act on the trigeminal spinal tract nucleus region associated with migraine treatment.

11. The transcranial ultrasound stimulation 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 at a depth of 0.5cm to 5cm in brain tissue.

12. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The ultrasonic generating unit is configured such that the ultrasonic waves it generates have a spatial resolution of 0.5 mm to 2 mm.

13. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to generate ultrasound waves for ultrasound stimulation of a target area located in the cerebral cortex or hippocampus.

14. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The transcranial ultrasound stimulation device is configured to perform ultrasound stimulation on target areas in brain tissue associated with at least one of the following conditions: Alzheimer's disease, Parkinson's disease, depression, obsessive-compulsive disorder, chronic neuropathic pain, migraine, post-stroke motor dysfunction and aphasia, and impaired consciousness.

15. The transcranial ultrasound stimulation device according to claim 1, characterized in that, The ultrasound generating unit is configured to provide a spatial peak pulse with an average sound intensity of 200 mW / cm² into the intracranial cavity. 2 Up to 800mW / cm 2 Ultrasound within the range.

16. The transcranial ultrasound stimulation device according to claim 15, characterized in that, The ultrasound generating unit is configured to provide a spatial peak pulse with an average sound intensity of 200 mW / cm² into the intracranial cavity. 2 ~400mW / cm 2 Ultrasound within a certain range for modulation in pain management; Alternatively, the ultrasound generating unit is configured to provide a spatial peak pulse with an average sound intensity of 400 mW / cm² into the intracranial cavity. 2 ~550mW / cm 2 Ultrasound within a certain range can be used to regulate depression. Alternatively, the ultrasound generating unit is configured to provide a spatial peak pulse with a mean acoustic intensity of 500 mW / cm² into the intracranial cavity. 2 ~650mW / cm 2 Ultrasound within a certain range for the modulation of neurodegenerative diseases; Alternatively, the ultrasound generating unit is configured to provide a spatial peak pulse with a mean acoustic intensity of 550 mW / cm² into the intracranial cavity. 2 ~800mW / cm 2 Ultrasound within a certain range is used for modulation in stroke rehabilitation.

17. The transcranial ultrasound stimulation device according to any one of claims 1 to 16, characterized in that, The ultrasonic generating unit includes multiple ultrasonic transducers arranged in an array on the main body.

18. The transcranial ultrasound stimulation device according to claim 17, characterized in that, The transcranial ultrasound stimulation device includes at least one ultrasound transducer module, and the at least one ultrasound transducer module forms an ultrasound transducer array; the ultrasound transducer module includes a plurality of ultrasound transducers, and a plurality of the plurality of ultrasound transducers are electrically connected in sequence to form a closed geometric shape, and at least one of the plurality of ultrasound transducers is located at the center of the closed geometric shape.

19. The transcranial ultrasound stimulation device according to claim 18, characterized in that, Each of the ultrasonic transducer modules includes a support substrate and at least one ultrasonic transducer disposed on the support substrate. The support substrates of multiple ultrasonic transducer modules are spliced ​​together to form the main body or assembled on the main body.

20. The transcranial ultrasound stimulation device according to any one of claims 1 to 16, characterized in that, The main body is a flexible sheet that is adaptable to deform to fit the contours of the skull surface and can conform to the skull.

21. The transcranial ultrasound stimulation device according to any one of claims 1 to 16, characterized in that, The transcranial ultrasound stimulation device is adapted to be applied to at least one location on the forehead and temple of the head.

22. The transcranial ultrasound stimulation device according to claim 1, 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 stimulation device according to claim 22, 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 stimulation device, characterized in that, The control method includes: according to the location of the target area, controlling the transcranial ultrasound stimulation 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 in the range of 1.2 MHz to 3.0 MHz, to act on the target area.

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