WO2018161413A1 - 清醒动物超声神经调控装置 - Google Patents

清醒动物超声神经调控装置 Download PDF

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WO2018161413A1
WO2018161413A1 PCT/CN2017/081381 CN2017081381W WO2018161413A1 WO 2018161413 A1 WO2018161413 A1 WO 2018161413A1 CN 2017081381 W CN2017081381 W CN 2017081381W WO 2018161413 A1 WO2018161413 A1 WO 2018161413A1
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Prior art keywords
module
pulse signal
fixing
animal
ultrasonic transducer
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PCT/CN2017/081381
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English (en)
French (fr)
Inventor
郑海荣
周慧
牛丽丽
郭瑞彪
孟龙
李永川
苏敏
黄继卿
钱明
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中国科学院深圳先进技术研究院
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Priority to EP17900029.4A priority Critical patent/EP3593860A4/en
Priority to US16/492,405 priority patent/US11707635B2/en
Publication of WO2018161413A1 publication Critical patent/WO2018161413A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B06—GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS IN GENERAL
    • B06B—METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, e.g. FOR PERFORMING MECHANICAL WORK IN GENERAL
    • B06B1/00—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency
    • B06B1/02—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy
    • B06B1/0207—Driving circuits
    • B06B1/0215—Driving circuits for generating pulses, e.g. bursts of oscillations, envelopes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B06—GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS IN GENERAL
    • B06B—METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, e.g. FOR PERFORMING MECHANICAL WORK IN GENERAL
    • B06B1/00—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency
    • B06B1/02—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy
    • B06B1/06—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction
    • B06B1/0644—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction using a single piezoelectric element
    • B06B1/0662—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction using a single piezoelectric element with an electrode on the sensitive surface
    • B06B1/067—Methods or apparatus for generating mechanical vibrations of infrasonic, sonic, or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction using a single piezoelectric element with an electrode on the sensitive surface which is used as, or combined with, an impedance matching layer
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K29/00—Other apparatus for animal husbandry
    • A01K29/005—Monitoring or measuring activity, e.g. detecting heat or mating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00017—Electrical control of surgical instruments
    • A61B2017/00137—Details of operation mode
    • A61B2017/00154—Details of operation mode pulsed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0004—Applications of ultrasound therapy
    • A61N2007/0021—Neural system treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0004—Applications of ultrasound therapy
    • A61N2007/0021—Neural system treatment
    • A61N2007/0026—Stimulation of nerve tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0056—Beam shaping elements
    • A61N2007/0065—Concave transducers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B06—GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS IN GENERAL
    • B06B—METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, e.g. FOR PERFORMING MECHANICAL WORK IN GENERAL
    • B06B2201/00—Indexing scheme associated with B06B1/0207 for details covered by B06B1/0207 but not provided for in any of its subgroups
    • B06B2201/70—Specific application
    • B06B2201/76—Medical, dental

Definitions

  • the invention relates to the field of medical instruments, in particular to an ultrasonic nerve regulation device for awake animals.
  • the focal field of the focused ultrasound radiation field is oblong, which makes it easier to stimulate the nervous system with high anatomical accuracy.
  • the invention intends to provide an ultrasonic nerve stimulation system for awake animals, which can eliminate the influence of anesthetic drugs on the nervous activity of animals and achieve neurological regulation of awake animals.
  • the object of the present invention is to provide an ultrasonic nerve regulation device for awake animals, which can perform precise ultrasonic stimulation and regulation on awake normal animals and model animals (Parkinson, epilepsy, etc.) under awake state, and explore and verify ultrasound in the awake state of the nerve for the nerve The role of regulation.
  • awake normal animals and model animals Parkinson, epilepsy, etc.
  • the awake animal nerve regulation device comprises: a pulse signal generating module, an ultrasonic transducer module and a fixed module, wherein the pulse signal generating module is configured to generate a high energy pulse signal;
  • the energy module is configured to convert the pulse signal into ultrasound;
  • the fixing module includes an upper fixing module and a lower fixing module, the upper fixing module is configured to fix the ultrasonic transducer module, and the lower fixing module is used to The animal's neuromodulation target is fixed, and the upper and lower fixation modules are connected by a connecting member.
  • the pulse signal generating module comprises: an independent two-channel signal generator for generating a neuromodulation pulse waveform; a power amplifier for increasing energy of the regulated pulse waveform; and an impedance matching circuit for measuring according to actual conditions
  • the piezoelectric element impedance values are individually designed to achieve impedance matching.
  • the pulse signal generating module further comprises an oscilloscope connected to the independent two-channel signal generator for observing the output waveform.
  • the dual channel signal generator has a fundamental frequency of at least 0.1 MHz to 5 MHz, and can independently generate a sinusoidal signal and a square wave signal, and has a TTL gate trigger output function.
  • the power amplifier has a frequency band of 0.1 MHz to 5 MHz and a power range of 50 W to 150 W.
  • the ultrasonic transducer module includes a lead wire, a piezoelectric array element and a backing, the piezoelectric array element is connected to the lead wire, and the lead wire is connected to an impedance matching circuit of the pulse signal generating module.
  • the backing is an epoxy resin material, and the backing is provided with a water inlet and an air outlet for injecting deionized water.
  • the piezoelectric array element is composed of a single array element, and has an arc structure capable of achieving the depth of the regulation nerve, and is used for focusing the ultrasound generated by the piezoelectric array element on the target point of the animal brain region.
  • the piezoelectric material of the piezoelectric element comprises a piezoelectric ceramic, a composite piezoelectric material, and a crystalline material.
  • the fixing module is a ring structure.
  • the fixing module is a plexiglass material or a plastic.
  • the invention has the beneficial effects: the awake animal ultrasonic nerve regulating device of the awake animal of the invention, the single-array piezoelectric ceramic adopts high-power piezoelectric material, supplemented by the matched ultrasonic electronic system for precise ultrasonic stimulation of the animal cerebral cortex and sub-cortex In order to explore and verify the stimulation effect of ultrasound on animals, the operation is simple and convenient to use.
  • FIG. 1 is a schematic view showing the structure of an ultrasonic nerve regulation device for a conscious animal according to the present invention.
  • FIG. 2 is a schematic view showing the structure of a pulse signal transmitting module of the awake animal ultrasonic nerve regulating device of the present invention.
  • FIG. 3 is a waveform diagram of an ultrasonic neuromodulation pulse emitted by a pulse signal transmitting module.
  • FIG. 4 is a schematic view showing the assembly structure of a transducer module and a fixture module of the awake animal ultrasonic nerve regulation device of the present invention.
  • the invention provides an ultrasonic nerve regulation device for awake animals, as shown in FIG. 1 , which specifically comprises: a pulse signal transmitting module 1 , a transducer module 2 and a fixed module 3 .
  • the pulse signal generation module 1 is used to generate a high energy pulse signal. As shown in FIG. 2, the pulse signal generating module 1 includes: an independent two-channel signal generator 11 for generating a neuromodulation pulse waveform; and a power amplifier 12 connected to the independent two-channel signal generator 11 for increasing the regulation pulse The energy of the waveform; and the impedance matching circuit 13 is connected to the power amplifier 12 for personalization design according to the actually measured piezoelectric element impedance value to achieve impedance matching.
  • the pulse signal generating module 1 further includes an oscilloscope 14 connected to the independent two-channel signal generator 11 for observing the output waveform.
  • the dual channel signal generator 11 is used to generate an ultrasound neuromodulation pulse waveform as shown in FIG.
  • Channel 1 in the dual channel is used to control the pulse repetition frequency PRF, the number of pulses NTB, and the pulse period SD.
  • Channel 2 is used to control the fundamental frequency f, the number of fundamentals TBD and the input voltage AI.
  • the trigger mode of channel 2 can be selected as an external trigger, and the external trigger source is the TTL signal of channel 2.
  • the signals of channel 2 are connected to oscilloscope 14 and power amplifier 12 via three-way BNC connections, respectively.
  • the oscilloscope 14 is used to observe the output waveform, and the power amplifier 12 increases the energy of the waveform output by the signal generator.
  • the impedance matching circuit 13 is correspondingly set according to the impedance value actually measured by the prepared piezoelectric array element. It is ensured that the power amplifier 12 and the piezoelectric array element 23 can achieve 50 ohm impedance matching, so that the energy of the power amplifier 12 can enter the transducer module 2 without attenuation.
  • the two-channel signal generator 11 has a fundamental frequency of at least 0.1 MHz to 5 MHz, and can independently generate a sinusoidal signal and a square wave signal, and has a TTL gate trigger output function.
  • the utility of the invention can be further enhanced by using different pulse repetition frequencies, pulse durations, fundamental frequency, number of fundamental waves and number of pulses according to the stimulation site and the stimulation effect.
  • the power amplifier 12 has a frequency band of 0.1 MHz to 5 MHz and a power range of 50 W to 150 W.
  • the ultrasonic transducer module 2 is for converting a pulse signal generated by the pulse signal generating module 1 into ultrasound.
  • the transducer module 2 includes a lead 20, a piezoelectric element 23, and a backing 21.
  • the piezoelectric element 23 is connected to the lead 20.
  • the lead 20 may be soldered on the piezoelectric element 23, and the lead 20 may be connected to the impedance matching circuit 13.
  • the piezoelectric element 23 is connected to a cable (not shown) via a lead 20, and the cable is connected to the impedance matching circuit 13 for receiving an electrical signal generated by the pulse signal generating module 1.
  • the cable is selected to be 50 ohms.
  • the piezoelectric array element 23 is composed of a single array element having an arc structure capable of controlling the depth of the nerve for focusing the ultrasound generated by the piezoelectric array element on the target point of the animal brain region. That is, the curved surface of the single-element transducer of the present invention has the feature that the focus axial length and the longitudinal length of the sound field focus due to the bending of the transducer can cover the brain target region. In addition, the piezoelectric array element 23 of the present invention can achieve a depth of focus which is preferably 3-4 mm longer than the target area.
  • the stimulating device thus prepared is small in size and light in weight, and is easy to be fixed in the brain of an animal.
  • the piezoelectric material of the piezoelectric array element includes a piezoelectric ceramic, a composite piezoelectric material, and a crystalline material. Further, when the present invention is used, piezoelectric materials of different areas and different materials can be selected according to the size of the brain stimulation region, thereby further enhancing the practicability of the neuromodulation device of the present invention.
  • the material of the backing 21 is selected from epoxy resin, and is poured into the upper fixing module 26 in a liquid state, and the epoxy resin is solidified to protect the piezoelectric element 23 and the fixed lead 20.
  • the backing 21 material also needs to reserve a water inlet 25 and an air outlet 27 for injecting deionized water. Injecting away from the water inlet 25 In the sub-water, after obscuring the fixed module 3, the water inlet 25 and the air outlet 27 are closed by using a sealing film.
  • deionized water is used in place of the ultrasonic coupling agent to ensure that the ultrasonic wave can enter the brain target region from the piezoelectric element 23 without attenuation.
  • the fixed module 3 includes an upper fixed module 26 and a lower fixed module 22.
  • the upper fixing module 26 is used to fix the ultrasonic transducer module 2.
  • the lower fixation module 22 is used to immobilize an animal's neuromodulation target (animal brain) by dental cement and skull nails. Specifically, the path of the ultrasonic emission in the ultrasound neuromodulation is confirmed, the lower portion 22 of the fixation module is fixed to the surface of the skull through which the path passes, and the upper fixation module 26 is screwed by the screw 24 (connecting member), thereby fixing the piezoelectric element 23 to Animal brain.
  • the upper and lower fixing modules 26, 22 adopt a circular ring, a conical structure, a plastic or plexiglass material, and the ultrasonic transducer system is fixed by an upper ring, and the lower cone is fixed to an animal nerve regulating target. .
  • the fixing module 3 of the invention can be designed to different sizes according to the area of the transducer module 2 and the skull size of the experimental animal, and can satisfy the nerve regulation of different brain regions.
  • the fixing module 2 of the invention has the advantages of small volume and light weight, and the animal can be equipped with an ultrasonic regulating device under the state of waking free movement, thereby realizing the neuromodulation effect of evaluating ultrasound under the state of no anesthetic.
  • the conscious animal ultrasound neuromodulation device can be used for freely moving animals (such as mice), convenient for animals (rats) to wear for a long time, and study the effect of ultrasound on brain diseases, thereby providing preliminary clinical support.

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  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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Abstract

本发明提供了一种清醒动物神经调控装置，包括：脉冲信号发生模块、超声换能器模块和固定模块，其中，所述脉冲信号发生模块用于发生高能量脉冲信号；所述超声换能器模块用于将所述脉冲信号转换成超声；所述固定模块包括上部固定模块和下部固定模块，所述上部固定模块用于固定所述超声换能器模块，所述下部固定模块用于固定在动物神经调控靶点，所述上下部固定模块通过连接部件连接。本发明的清醒动物神经调控装置可以对动物大脑皮层和亚皮层进行精准超声刺激，从而探索和验证超声对动物的刺激效果，操作简单，使用方便。

Description

清醒动物超声神经调控装置 技术领域
本发明涉及医疗器械领域，尤其涉及一种清醒动物超声神经调控装置。
背景技术
随着抑郁症、帕金森、癫痫等脑部疾病的患者逐渐增多，脑部功能性疾病的治疗逐渐成为现代医学研究的焦点，研究功能型疾病的关键在于确定病变所在皮层和深部核团的神经传导通路，而超声刺激由于其安全性，无创性和有效性，日渐引起关注，现今世界上有许多实验室正在进行超声动物刺激神经系统的研究。
聚焦超声辐射声场的焦域呈长椭圆形，这种特性使得它更容易对神经系统进行高解剖学精度的刺激。本发明欲提出一种清醒动物超声神经刺激系统，其可以排除麻醉药物对动物神经活动的影响，实现对清醒动物的神经调控。
发明内容
本发明的目的在于提出一种清醒动物超声神经调控装置，能够对清醒正常动物和模型动物(帕金森、癫痫等)进行清醒状态下精准超声刺激和调控，探索和验证动物清醒状态下超声对于神经调控的作用。
为达上述目的，本发明提出的清醒动物神经调控装置包括：脉冲信号发生模块、超声换能器模块和固定模块，其中，所述脉冲信号发生模块用于发生高能量脉冲信号；所述超声换能器模块用于将所述脉冲信号转换成超声；所述固定模块包括上部固定模块和下部固定模块，所述上部固定模块用于固定所述超声换能器模块，所述下部固定模块用于固定在动物神经调控靶点，所述上下部固定模块通过连接部件连接。
优选地，所述脉冲信号发生模块包括：独立双通道信号发生器，用于产生神经调控脉冲波形；功率放大器，用于提高所述调控脉冲波形的能量；和阻抗匹配电路，用于根据实际测量的压电阵元阻抗值进行个性化设计，以实现阻抗匹配。
优选地，所述脉冲信号发生模块还包括与所述独立双通道信号发生器连接的示波器，用于观察输出波形。
优选地，所述双通道信号发生器基波频率至少为0.1MHz-5MHz，可独立产生正弦信号和方波信号，并带有TTL门触发输出功能。
优选地，所述功率放大器频带为0.1MHz-5MHz，功率范围50W-150W。
优选地，所述超声换能器模块包括引线、压电阵元和背衬，所述压电阵元与所述引线连接，所述引线与所述脉冲信号发生模块的阻抗匹配电路连接，所述背衬为环氧树脂材料，所述背衬上设置进水口与出气口，所述进水口用于注入去离子水。
优选地，所述压电阵元为单个阵元构成，具有能达到调控神经深度的弧形结构，用于使所述压电阵元发生的超声聚焦于动物脑区靶点。
优选地，所述压电阵元的压电材料包括压电陶瓷、复合压电材料、晶体材料。
优选地，所述固定模块为环形结构。
优选地，所述固定模块为有机玻璃材料或塑料。
本发明的有益效果：本发明的清醒动物的清醒动物超声神经调控装置，单阵元压电陶瓷采用大功率压电材料，辅以配套的超声电子系统对动物大脑皮层和亚皮层进行精准超声刺激，从而探索和验证超声对动物的刺激效果，操作简单，使用方便。
附图说明
图1为本发明的清醒动物超声神经调控装置的结构示意图。
图2为本发明的清醒动物超声神经调控装置的脉冲信号发射模块的结构示意图。
图3为脉冲信号发射模块发出的超声神经调控脉冲的波形图。
图4为本发明的清醒动物超声神经调控装置的换能器模块、固定装置模块组装结构示意图。
具体实施方式
在下列说明中，为了提供对本发明的彻底了解而提出许多具体细节。本发明可在不具有部分或所有这些具体细节的情况下实施。在其他情况下，为了不对本发明造成不必要的混淆，不详述众所周知的过程操作。虽然本发明将结合具体实施例来进行说明，但应当理解的是，这并非旨在将本发明限制于这些实施例。
本发明提供了清醒动物超声神经调控装置，如图1所示，具体包括：脉冲信号发射模块1、换能器模块2和固定模块3。
下面具体介绍上述各模块及其连接关系。脉冲信号发生模块1用于发生高能量脉冲信号。如图2所示，脉冲信号发生模块1包括：独立双通道信号发生器11，用于产生神经调控脉冲波形；功率放大器12，与独立双通道信号发生器11连接，用于提高所述调控脉冲波形的能量；和阻抗匹配电路13，与功率放大器12连接，用于根据实际测量的压电阵元阻抗值进行个性化设计，以实现阻抗匹配。脉冲信号发生模块1还包括与独立双通道信号发生器11连接的示波器14，用于观察输出波形。
双通道信号发生器11用于产生超声神经调控脉冲波形，如图3所示。双通道中的通道1用于控制脉冲重复频率PRF、脉冲个数NTB和脉冲周期SD。通道2用于控制基波频率f，基波个数TBD和输入电压AI。通道2的触发方式可选择外部触发，其外部触发来源是通道2的TTL信号。通道2的信号通过三通BNC接线分别连接至示波器14和功率放大器12。示波器14用于观察输出波形，功率放大器12提高信号发生器所输出波形的能量。
阻抗匹配电路13根据所制备的压电阵元实际测量的阻抗值进行相应设 计，保证功率放大器12和压电阵元23能实现50欧姆阻抗匹配，实现功率放大器12的能量能够无衰减的进入换能器模块2。
本发明中，双通道信号发生器11的基波频率至少为0.1MHz-5MHz，可独立产生正弦信号和方波信号，并带有TTL门触发输出功能。本发明在使用时，可根据刺激部位和刺激效果，采用不同脉冲重复频率、脉冲持续时间、基波频率、基波个数和脉冲个数，进一步增强该发明的实用性。功率放大器12的频带为0.1MHz-5MHz，功率范围50W-150W。
下面根据图4详细介绍超声换能器模块2与固定模块3的结构和功能。
超声换能器模块2用于将脉冲信号发生模块1发生的脉冲信号转换成超声。如图4所示，换能器模块2包含引线20、压电阵元23和背衬21。压电阵元23与引线20连接。具体地，可以在压电阵元23上焊接引线20，再将引线20与阻抗匹配电路13相连。更具体地，压电阵元23通过引线20与电缆线(未图示)连接，电缆线与阻抗匹配电路13连接，用于接收由脉冲信号发生模块1产生的电信号。较佳地，电缆线均选择50欧姆。
较佳地，压电阵元23为单个阵元构成，具有能达到调控神经深度的弧形结构，用于使压电阵元发生的超声聚焦于动物脑区靶点。也即，本发明的单阵元换能器的弧面具有如下特征：换能器弯曲所致声场焦点的聚焦轴向长度和纵向长度能够覆盖脑部靶区。此外，本发明涉及的压电阵元23可实现的聚焦深度应比作用靶区长3-4mm范围为最佳，这样制备的刺激装置体积小、重量轻，便于固定在动物脑部。本发明中，压电阵元的压电材料包括压电陶瓷、复合压电材料、晶体材料。进一步地，本发明在使用时，可根据脑刺激区域的大小，选择不同面积、不同材料的压电材料，进一步增强本发明神经调控装置的实用性。
背衬21材料选择环氧树脂，在液体状态下灌入上部固定模块26，待环氧树脂凝固可起到保护压电阵元23和固定引线20的作用。背衬21材料上还需要预留进水口25及出气口27，用于注入去离子水。向进水口25注入去离 子水，观察固定模块3中无气泡后使用封口膜封闭进水口25和出气口27。本发明中用去离子水取代超声耦合剂使用，保证超声能够无衰减地从压电阵元23进入脑靶区。
如图4所示，固定模块3包括上部固定模块26和下部固定模块22。上部固定模块26用于固定超声换能器模块2。下部固定模块22用于通过牙科水泥和颅骨钉固定在动物神经调控靶点(动物脑部)。具体地，确认超声神经调控中超声发射的路径，将固定模块下部22固定于发生路径经过的颅骨表面，通过螺纹24(连接部件)拧上上部固定模块26，从而将压电阵元23固定于动物脑部。本发明中，较佳地，上下部固定模块26，22采用圆环、圆锥结构，塑料或有机玻璃材料，通过上圆环固定所述超声换能器系统，下圆锥固定于动物神经调控靶点。
本发明的固定模块3，可根据换能器模块2的面积和实验动物的颅骨大小设计成不同尺寸，满足不同脑区域的神经调控。另外，本发明的固定模块2体积小、重量轻，可以实现动物在清醒自由活动状态下佩戴超声调控装置，实现无麻药状态下评估超声的神经调控作用。以此，使得清醒动物超声神经调控装置可用于自由活动动物(例如老鼠)，方便动物(老鼠)长期佩戴，研究超声对脑部疾病的疗效，从而提供前期临床支持。

Claims (10)

  1. 一种清醒动物神经调控装置，其特征在于，包括：脉冲信号发生模块、超声换能器模块和固定模块，其中，
    所述脉冲信号发生模块用于发生高能量脉冲信号；
    所述超声换能器模块用于将所述脉冲信号转换成超声；
    所述固定模块包括上部固定模块和下部固定模块，所述上部固定模块用于固定所述超声换能器模块，所述下部固定模块用于固定在动物神经调控靶点，所述上下部固定模块通过连接部件连接。
  2. 根据权利要求1所述的装置，其中，所述脉冲信号发生模块包括：
    独立双通道信号发生器，用于产生神经调控脉冲波形；
    功率放大器，用于提高所述调控脉冲波形的能量；和
    阻抗匹配电路，用于根据实际测量的压电阵元阻抗值进行个性化设计，以实现阻抗匹配。
  3. 根据权利要求2所述的装置，其中，所述脉冲信号发生模块还包括与所述独立双通道信号发生器连接的示波器，用于观察输出波形。
  4. 根据权利要求2所述的装置，其中，所述双通道信号发生器基波频率至少为0.1MHz-5MHz，可独立产生正弦信号和方波信号，并带有TTL门触发输出功能。
  5. 根据权利要求2所述的装置，其中，所述功率放大器频带为0.1MHz-5MHz，功率范围50W-150W。
  6. 根据权利要求2所述的装置，其中，所述超声换能器模块包括引线、压电阵元和背衬，所述压电阵元与所述引线连接，所述引线与所述脉冲信号发生模块的阻抗匹配电路连接，所述背衬为环氧树脂材料，所述背衬上设置进水口与出气口，所述进水口用于注入去离子水。
  7. 根据权利要求6所述的装置，其中，所述压电阵元为由单个阵元构成，具有能达到调控神经深度的弧形结构，用于使所述压电阵元发生的超声聚焦于动物脑区靶点。
  8. 根据权利要求6所述的装置，其中，所述压电阵元的压电材料包括压电陶瓷、复合压电材料、晶体材料。
  9. 根据权利要求1所述的装置，其中，所述固定模块为环形结构。
  10. 根据权利要求1所述的装置，其中，所述固定模块为有机玻璃材料或塑料。
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Families Citing this family (7)

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Publication number Priority date Publication date Assignee Title
CN107551412A (zh) * 2017-07-31 2018-01-09 深圳先进技术研究院 一种自动收线的超声神经调控装置
WO2019041256A1 (zh) * 2017-08-31 2019-03-07 深圳先进技术研究院 一种头戴式超声传导装置
CN107670183B (zh) * 2017-11-08 2024-02-20 深圳市普罗医学股份有限公司 一种自聚焦超声换能器
CN109011228B (zh) * 2018-09-06 2019-08-16 西安交通大学 一种高空间分辨率超声神经调控方法及系统
CN109044307B (zh) * 2018-09-17 2020-07-21 西安交通大学 一种基于超声神经刺激的无创血压调控系统
WO2021087960A1 (zh) * 2019-11-08 2021-05-14 中国科学院深圳先进技术研究院 一种闭环超声神经调控系统及方法
CN112774048A (zh) * 2019-11-08 2021-05-11 中国科学院深圳先进技术研究院 一种闭环超声神经调控系统及方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101698121A (zh) * 2009-10-23 2010-04-28 西安交通大学 促进药物透过血脑屏障的适型超声系统
CN102232856A (zh) * 2010-05-06 2011-11-09 高春平 双频超声多维聚焦脑血管溶栓系统
CN104826243A (zh) * 2015-05-15 2015-08-12 深圳先进技术研究院 一种超声刺激神经组织的装置
CN105344023A (zh) * 2015-12-01 2016-02-24 中国医学科学院生物医学工程研究所 一种结合磁场和超声产生矢量性无创聚焦电刺激的装置

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102791332A (zh) * 2009-11-04 2012-11-21 代理并代表亚利桑那州立大学的亚利桑那董事会 调节大脑活动的设备和方法
US20130281890A1 (en) * 2009-11-11 2013-10-24 David J. Mishelevich Neuromodulation devices and methods
RU2620867C2 (ru) * 2012-03-20 2017-05-30 Конинклейке Филипс Н.В. Ультразвуковой матричный зонд с рассеивающим тепло кабелем и теплообменом через опорный блок
US10252085B2 (en) * 2012-05-22 2019-04-09 Arizona Board Of Regents On Behalf Of Arizona State University Apparatus, system and method for neurostimulation by high frequency ultrasound
CN103028202A (zh) * 2012-12-26 2013-04-10 上海交通大学 经颅超声刺激修复脑神经功能的装置及方法
US20160038770A1 (en) * 2013-04-26 2016-02-11 Thync, Inc. Focused transcranial ultrasound systems and methods for using them
US9867999B2 (en) * 2014-05-15 2018-01-16 The Regents Of The University Of Michigan Pulse amplifier for driving ultrasound transducers
CN105944245A (zh) * 2016-05-31 2016-09-21 深圳先进技术研究院 头戴式超声换能器

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101698121A (zh) * 2009-10-23 2010-04-28 西安交通大学 促进药物透过血脑屏障的适型超声系统
CN102232856A (zh) * 2010-05-06 2011-11-09 高春平 双频超声多维聚焦脑血管溶栓系统
CN104826243A (zh) * 2015-05-15 2015-08-12 深圳先进技术研究院 一种超声刺激神经组织的装置
CN105344023A (zh) * 2015-12-01 2016-02-24 中国医学科学院生物医学工程研究所 一种结合磁场和超声产生矢量性无创聚焦电刺激的装置

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3593860A4 *

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