WO2019041256A1 - Head-mounted ultrasonic transmission apparatus - Google Patents

Head-mounted ultrasonic transmission apparatus Download PDF

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Publication number
WO2019041256A1
WO2019041256A1 PCT/CN2017/099996 CN2017099996W WO2019041256A1 WO 2019041256 A1 WO2019041256 A1 WO 2019041256A1 CN 2017099996 W CN2017099996 W CN 2017099996W WO 2019041256 A1 WO2019041256 A1 WO 2019041256A1
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WO
WIPO (PCT)
Prior art keywords
base
skull
head
top cover
ultrasonic transmission
Prior art date
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PCT/CN2017/099996
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French (fr)
Chinese (zh)
Inventor
郑海荣
邱维宝
黎国锋
苏敏
蔡蕊琳
李永川
Original Assignee
深圳先进技术研究院
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Application filed by 深圳先进技术研究院 filed Critical 深圳先进技术研究院
Priority to PCT/CN2017/099996 priority Critical patent/WO2019041256A1/en
Publication of WO2019041256A1 publication Critical patent/WO2019041256A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00Ultrasound therapy

Definitions

  • the present invention belongs to the technical field of ultrasonic nerve stimulation research, and in particular, to a head-mounted ultrasonic conduction device.
  • Neurostimulation and neuromodulation refers to the use of electrical, electrical, acoustic, thermal, thermal or mechanical stimuli and chemical stimuli, acting on the living nervous system (such as organisms, organs, tissues, cells, etc.) and causing reactions the process of.
  • the effects of stimulation regulation can be divided into excitatory stimuli that cause function display or enhancement and inhibitory stimuli that cause function to disappear or weaken.
  • Stimulation and regulation of neural activity contribute to the study of neurological diseases and mental illnesses. Peer is also the basic means of studying human brain perception, movement and cognitive function.
  • Ultrasound stimulation is an ancient and emerging non-invasive nerve stimulation.
  • High intensity focused ultrasound (HIFU) is often used as an intervention in the central nervous system.
  • HIFU High intensity focused ultrasound
  • Tyler et al. confirmed that ultrasound stimulated hippocampal slices, which stimulated action potentials, pressure-controlled sodium ions, calcium ion transients, and synaptic transmission.
  • the Tyler team first performed positive transcranial ultrasound to stimulate the cranial motor cortex of mice, which induced action potentials and caused action responses of limbs and tails. Since then, the use of ultrasound as a means of nerve stimulation and regulation has attracted widespread attention.
  • the joint system includes: a computer control and data processing unit, a digital to analog/analog to digital conversion unit, a power amplifier, a wearable ultrasonic transducer, an electrode assembly, and a signal amplification unit.
  • the "wearable ultrasonic transducer” mentioned in the above only mentions that the transducer and the subject are fixed by a sealing tape, and the mutual contact faces are to be coupled. Obviously, for conscious animals, their activities are frequent and the scalp is extremely easy to slide relative to the skull. It is difficult to accurately and reliably fix the ultrasound probe to perform ultrasonic stimulation using only a sealing tape. Further, the electrode assembly mentioned in the patent realizes the mounting of the recording electrode by providing a through hole in the ultrasonic transducer, and the above method of fixing the transducer by the sealing tape is difficult to ensure proper mounting of the recording electrode.
  • a wireless wearable ultrasonic nerve stimulation device proposes a wireless wearable ultrasonic nerve stimulation device, comprising: a user control terminal, Control the transmitter chip, ultrasonic transducer and patch housing.
  • the "patch housing” mentioned herein only refers to the filling couplant between the patch housing and the object and is fixed by a sealing tape. Obviously, for awake animals, their activities are frequent and the scalp is very easy to slide relative to the skull. It is difficult to accurately and reliably fix the ultrasound probe with a sealing tape alone; there is no mention of an effective structure to prevent coupling between the ultrasonic transducer and the object. The agent slipped and lost.
  • the patent document "Awakening Animal Ultrasound Neuroregulator" of the application No. 201710138442.6 proposes a conscious animal neuromodulation device, including: a pulse signal generating module, an ultrasonic transducer module and a fixed module.
  • the "fixed modules” mentioned herein only describe in general terms the immobilization of immobilization modules to animal neuromodulation targets by industry-wide methods.
  • how to design a reasonable structure to achieve a reliable connection between the ultrasonic transducer and the skull and ensure that the ultrasound can be effectively transmitted to the inside of the skull is a critical technology for the entire ultrasound stimulation system.
  • the above patent does not propose a feasible solution. .
  • the ultrasonic nerve stimulation technique uses a large-volume, heavy-weight ultrasonic probe to achieve ultrasonic stimulation, and the stimulated animal needs to be anesthetized, and the head needs to be fixed, so the above-mentioned ultrasonic stimulation is not Suitable for animal experiments related to feeling, emotion, cognition and memory.
  • the existing wearable ultrasound stimulation program application number is 201610326489 .0, 201610327257
  • the object of the present invention is to overcome the above deficiencies of the prior art and to provide a head-mounted ultrasonic transmission device.
  • the technical solution of the present invention is: a head-mounted ultrasonic transmission device, comprising: a base that can be placed on a skull of an experimental animal; and a top cover connected to the base, the base has a An inner cavity accommodating a coupling agent, the top cover being coupled with an ultrasonic transducer having a working surface facing the bottom of the inner cavity; the head-mounted ultrasonic conduction device further comprising a base for fixing the base to the skull of the experimental animal
  • the fixing device comprises a skull connector which can be embedded in the skull of the experimental animal, and the base is attached to the skull of the experimental animal and directly connected to the fixing device or connected by an adhesive.
  • a side of the base near the bottom is provided with a convex structure; or / and, a side of the base near the bottom is provided with a groove structure.
  • the skull connector is a threaded connection
  • the adhesive is dental cement
  • the convex structure is an everted convex edge, and the adhesive is connected to the skull connecting piece and the everted convex edge
  • the groove structure is a groove disposed on an outer side surface of the base, and the adhesive is coupled to the skull connecting member and embedded in the groove.
  • the base is disposed on a side of the front side of the skull of the experimental animal with a first protrusion, or/and the base is disposed adjacent to a side of the back side of the skull of the experimental animal. There is a second projection.
  • the bottom of the base is configured as a curved structure, or/and the bottom of the base is provided with a resilient washer.
  • the base has an inverted cone shape that is large and small, or/and the top cover is fixedly or detachably connected to the top of the base.
  • the top cover is connected to the base by a card structure, a snap structure or a threaded structure.
  • the base is provided with at least one L-shaped locking groove, the upper end of the L-shaped locking groove is opened, and the upper end opening of the L-shaped locking groove is located at an upper end surface of the base, the top
  • the cover is provided with a lock block that can be caught in the L-shaped lock groove.
  • a inner side of the top cover is provided with a convex structure for limiting the ultrasonic transducer; or / and, the inner side of the top cover is provided with a wire groove for accommodating the cable.
  • a side of the base is provided with a conduit structure for achieving at least one of ultrasonic stimulation and electrophysiological collection, electrical stimulation, administration, microdialysis, light stimulation, and light imaging, and the catheter structure includes At least one conduit in which at least one of an electrode, a thin tube or an optical fiber is disposed.
  • a head-mounted ultrasonic conduction device provided by an embodiment of the present invention provides an accurate and controllable and reproducible ultrasonic stimulation of a brain of a freely moving experimental animal, and allows The function of intracranial administration, microdialysis, electrical stimulation, light stimulation or electrophysiological acquisition in ultrasound-stimulated peers.
  • FIG. 1 is a front view of a head-mounted ultrasonic conduction device connected to a skull of an experimental animal according to an embodiment of the present invention
  • FIG. 2 is a right side view of a head-mounted ultrasonic conduction device connected to a skull of an experimental animal according to an embodiment of the present invention
  • FIG. 3 is a main body of a head-mounted ultrasonic conduction device connected to a skull of an experimental animal according to an embodiment of the present invention. View.
  • a head-mounted ultrasonic transmission device includes a base 2 that can be placed on a skull 9 of an experimental animal, and a top cover 1 connected to the base 2, the base.
  • the head-mounted ultrasonic transducer further includes a fixing device for fixing the base 2 to the skull 9 of the experimental animal, the fixing device including the front end
  • the skull connector 31 can be embedded in the skull of the experimental animal.
  • the front end of the skull connector 31 can be embedded and connected to the skull of the experimental animal.
  • the skull connector 31 is not easy to loose, and the connection reliability is good.
  • the bottom of the base 2 is attached to the skull of the experimental animal.
  • the base 2 is directly connected to the skull connector 31 or connected by an adhesive 32. That is, the base 2 can be directly fixed by the skull connecting member 31, or the base 2 can also be fixed by connecting the adhesive 32 to the skull connecting member 31.
  • the skull connecting member 31 can be a threaded connecting member (for example, a skull screw), and the front end thereof can be screwed to the skull of the experimental animal without damaging the brain tissue of the experimental animal, and the base 2 can be stably and reliably attached to the skull of the experimental animal.
  • a convex structure for connecting the adhesive 32 or the skull connecting member 31 is disposed on a side of the base 2 near the bottom; or/and, as shown in FIG. 3, the base A groove structure for joining the adhesive 32 or the skull connector 31 is provided on the side near the bottom.
  • the raised structure may be an everted flange 23 to increase the contact surface with the adhesive 32, and the connection reliability is high.
  • the skull connector 31 is provided with one or at least two and is located around the everted flange 23, and the adhesive 32 is attached to the skull connector 31 and the everted flange 23.
  • the skull connector 31 is provided with a plurality of jaws, and the adhesive 32 and the skull connector 31 can be disposed on the left and right sides or/and the front and rear sides.
  • the number and arrangement of the adhesive 32 and the skull connector 31 can also be set according to the actual situation.
  • the valgus protrusion 23 may be in the shape of a ring, or may be in the form of a column, a block or a sheet.
  • the groove structure is a groove 20 disposed on an outer side of the base 2, and the adhesive 32 is coupled to the skull connecting member 31 and embedded in the Included in the recess 20.
  • the groove 20 may be an annular groove or a separate groove (for example, a circular groove or a rectangular groove) circumferentially disposed along the base 2, and a portion of the adhesive 32 (for example, dental cement) is embedded in the groove 20 to form an inverted structure. , the connection is highly stable.
  • the adhesive 32 may be an adhesive having sufficient mechanical strength after solidification, such as dental cement or other type of adhesive 32.
  • the base 2 is provided with a first protrusion 21 on a side close to the front side of the skull 9 of the experimental animal, or / and, the base 2 is provided with a second side on the side of the back side of the skull 9 of the experimental animal.
  • the number and specific structure of the projections 22, the projections can be set according to actual conditions for increasing the fixing strength of the dental cement to the base 2.
  • the bottom of the base 2 (the everted flange 23) is configured as a curved structure that can match the shape of the skull of the skull 9 of the experimental animal.
  • the bottom of the base 2 may have a suitable shape such as a saddle shape.
  • the bottom of the base 2 may be provided with a resilient washer (not shown), the elastic washer may be a silicone gasket, etc., and has good sealing performance and a certain buffering effect.
  • the base 2 has an inverted cone shape that is large and small, and the lower end of the base 2 has a relatively small size to match the size of the head of the laboratory animal.
  • the upper end of the base 2 has a large size, and a large diameter ultrasonic transducer can be installed.
  • the low-frequency, high-intensity ultrasonic waves can be used to stimulate the experimental animals.
  • the piezoelectric material of the ultrasonic transducer in the top cover 1 may adopt a piezoelectric composite material, a piezoelectric ceramic, Piezoelectric single crystal materials and other piezoelectric materials, the thickness of the piezoelectric material can be in the range of 0.01-3 mm; the ultrasonic transducer can be a single-element ultrasound transducer or a multi-element ultrasound transducer, or a focused ultrasound Transducer or planar ultrasound transducer.
  • the ultrasonic transducer in the top cover 1 may be air backed or may be filled with other materials as a backing.
  • the top cover 1 is fixedly or detachably connected to the top of the base 2.
  • the top cover 1 can be detachably connected to the base 2 by a screw card structure, a snap structure or a thread structure, and the top cover 1 can be repeatedly and conveniently removed from the top cover 1 .
  • the top cover 1 can also be fixedly connected to the base 2, or the top cover 1 can be connected to the base 2 body.
  • an anti-slip structure may be disposed outside the top cover 1.
  • the anti-slip structure can be a projection 11 or / and a groove.
  • the base 2 is provided with at least two L-shaped lock grooves 24, and the L-shaped lock grooves 24 penetrate through the side walls of the base 2.
  • the upper end of the L-shaped lock groove 24 is located at the upper end of the base 2, and the top cover 1 is provided with a lock block 14 that can be caught in the L-shaped lock groove 24.
  • the number of the lock block 14 can be It is equal to the number of L-shaped lock grooves 24.
  • the lock block 1 4 may be in the shape of a column or a mushroom.
  • the lock block 14 can be longitudinally engaged from the upper end of the L-shaped lock groove 24, and then the top cover 1 is rotated to make the lock block 14 laterally snap into the L-shaped lock groove 24, which is convenient and reliable.
  • the ultrasonic coupling agent pre-filled into the base 2 can automatically overflow from the L-shaped lock groove 24 after filling the inner cavity space of the base 2, ensuring that the ultrasonic coupling agent is filled with the ultrasonic transducer and Experimental animal between skulls 9.
  • the L-shaped lock groove 2 4 can also adopt the lock groove of other structural shapes, and the number of the L-shaped lock grooves 24 can be set according to actual conditions.
  • an overflow hole may be disposed near the upper end of the base 2, and if the top cover 1 and the base 2 are connected by a thread structure, the top cover 1 and the ultrasonic transducer ⁇ are installed, and the base 2 is pre-filled.
  • the ultrasonic coupling agent can flow out of the overflow hole after filling the inner cavity space of the base 2.
  • the top of the top cover 1 may be provided with a wire through hole and a screw hole to facilitate installation of an ultrasonic transducer or the like.
  • a convex structure (not shown) for limiting the ultrasonic transducer is disposed inside the top cover 1 to facilitate installation and positioning of the ultrasonic transducer.
  • the protruding structure may be a convex ring or a protruding rod integrally formed on the inner side of the top cover 1 or fixedly connected to the inner side of the top cover 1.
  • the inner side of the top cover 1 is provided with a wire groove (not shown) for accommodating the cable, and the cable is connected to the ultrasonic transducer, and the diameter of the ultrasonic transducer can be the same as that of the top cover 1. Inner diameter matching, ultrasonic transducer will not loose It is good for stable ultrasonic stimulation of experimental animals.
  • the side of the base 2 is provided for achieving ultrasonic stimulation and electrophysiological collection, electrical stimulation, administration
  • a catheter structure 4 of at least one of (non-therapeutic purpose), microdialysis, light stimulation, and photo imaging the catheter structure 4 includes at least one catheter, and at least one of an electrode, a thin tube, or an optical fiber is disposed in the catheter, thereby The function of intracranial administration, microdialysis, electrical stimulation, light stimulation or electrophysiological acquisition of ultrasound-stimulated common targets.
  • FIG. 1 shows a schematic view of a head mounted ultrasound transducer mounted on a skull 9 of an experimental animal.
  • the bottommost dotted ellipse represents the sagittal plane of the small animal skull 9, the skull is tightly coupled to the upper head-mounted ultrasound transducer and is secured by the skull connector 31 and dental cement;
  • the upper head-mounted ultrasound transducer includes a cap 1 and the base 2 are two parts;
  • the base 2 and the top cover 1 can be processed by any material such as metal, plastic, plexiglass or the like which is solid at normal temperature after processing.
  • the top cover 1 and the base 2 can be connected by an L-shaped lock groove 24; a circular ultrasonic transducer can be installed inside the top cover 1, and the ultrasonic transducer can include an ultrasonic piezoelectric material, a matching layer and a lead wire (not shown) Out, for generating ultrasonic waves to radiate downward;
  • the top of the top cover 1 has three lock blocks 14 for interlocking connection with the L-shaped lock grooves 24 of the base 2;
  • the top of the top cover 1 has two symmetrical anti-slip protrusions Structure (protrusion 11);
  • the base 2 is in the shape of an inverted hollow cone, including an upper jaw and a lower jaw; the inverted hollow cone shape can reduce the area occupied by the base 2 and allow the ultrasonic transducer to have a higher Large radiation area, thus ensuring that the device can be applied to small animals and has high ultrasonic radiation intensity and low radiation frequency; there are three L-shaped lock grooves 24 around the outlet of the base 2, which can be external to the
  • FIG 2 is a side view of the head-mounted ultrasonic transducer, labeled similar to that shown in Figure 1, in particular, in the right side of the base 2 in Figure 2 (i.e., behind the skull of the experimental animal), the catheter structure 4 is designed.
  • an electrophysiological collection or stimulation electrode, a drug delivery tube, a dialysis tube, an optical fiber and the like may be additionally installed, and the lower end of the tube may extend to different depths of the ultrasound target area to realize electrophysiological signal collection, Site-specific drug delivery, microdialysis, light stimulation and other functions.
  • a head-mounted ultrasonic conduction device is mainly used for performing repetitive operation of ultrasonic stimulation on a awake and freely moving small animal, mainly comprising a top cover 1 and a base 2, and a top cover 1 built-in ultrasonic transducer, the ultrasonic transducer comprises a piezoelectric material and a matching layer, which can generate ultrasonic to achieve ultrasonic stimulation;
  • the base 2 can be in the shape of an inverted hollow cone with upper and lower jaws;
  • An L-shaped lock groove 24 is detachably connected to the top cover 1;
  • the lower jaw has an outer curved outer edge structure having a bottom surface and two outer edge protruding structures on the outer side of the outer edge structure (first convex The upper portion 21 and the second protruding portion 22); the upper and lower jaws are respectively used for connecting the top cover 1 and the experimental animal skull 9; and the top cover 1 can be repeatedly installed and disassembled.
  • a head-mounted ultrasonic transmission device provided by an embodiment of the present invention
  • the bottom surface of the lower exit of the base 2 is curved, and the valgus flange 23 and the protruding portion may also have a curved shape, so that the base 2 can be in close contact with the curved skull of the experimental animal, thereby improving the contact.
  • the base 2 has an inverted hollow cone shape, which not only reduces the area occupied by the base 2, but also allows the ultrasonic transducer to have a larger radiation area, thereby ensuring that the device can be applied to small animals and has Higher ultrasonic radiation intensity and lower radiation frequency;
  • the convex structure and the wire groove structure on the inner side of the top cover 1 enable the ultrasonic sensor (ultrasonic transducer) to operate in the air backing mode to improve the efficiency of ultrasonic radiation;
  • the outer side wall of the base 2 can be installed with a radial catheter, allowing the passage of a drug guiding tube, an electrophysiological electrode or an optical fiber, for performing ultrasound stimulation combined with intracranial administration, microdialysis, electrophysiological collection, electrical stimulation or Experiments such as light stimulation;
  • the entire device is small in size and light in weight, and can be applied to small animals such as mice that are free to move, and perform ultrasonic stimulation.

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  • Engineering & Computer Science (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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Abstract

Provided is a head-mounted ultrasonic transmission apparatus, wherein same falls within the technical field of ultrasonic neural stimulation research, and comprises a base (2) capable of being arranged on a laboratory animal skull (9) and a top cover (1) connected to the base (2), wherein an inner cavity for accommodating a coupling agent is provided in the base (2), and the top cover (1) is connected to an ultrasonic transducer with a working face facing a bottom portion of the inner cavity. The head-mounted ultrasonic transmission apparatus further comprises a fixing device for fixing the base (2) to the laboratory animal skull (9), wherein the fixing device comprises a skull connector (31), with a front end thereof being capable of being embedded into the laboratory animal skull (9), and the base (2) is attached to the laboratory animal skull (9) and is directly connected to the fixing device or is connected to the fixing device via a binder (32). The head-mounted ultrasonic transmission apparatus can implement positionally accurate and controllable and reproducible ultrasonic stimulation on the brain of a free-moving laboratory animal, and is suitable for carrying out animal experiments related to feelings, emotions, cognition and memory.

Description

一种头戴式超声传导装置  Head-mounted ultrasonic conduction device
技术领域 Technical field
[0001] 本发明属于超声神经刺激研究技术领域, 尤其涉及一种头戴式超声传导装置。  [0001] The present invention belongs to the technical field of ultrasonic nerve stimulation research, and in particular, to a head-mounted ultrasonic conduction device.
背景技术  Background technique
[0002] 神经刺激和神经调控是指采用电、 光、 声、 冷热或者机械等物理性刺激以及化 学性刺激, 作用于活体神经系统 (如生物体、 器官、 组织、 细胞等) 并引起反 应的过程。 按刺激调控的效果可分为使功能显示或增强的兴奋性刺激和使功能 消失或减弱的抑制性刺激。 通过刺激, 调控神经活动, 有助于研究神经系统疾 病及精神疾病, 同吋也是研究人脑感受、 动作和认知功能的基本手段。  [0002] Neurostimulation and neuromodulation refers to the use of electrical, electrical, acoustic, thermal, thermal or mechanical stimuli and chemical stimuli, acting on the living nervous system (such as organisms, organs, tissues, cells, etc.) and causing reactions the process of. The effects of stimulation regulation can be divided into excitatory stimuli that cause function display or enhancement and inhibitory stimuli that cause function to disappear or weaken. Stimulation and regulation of neural activity contribute to the study of neurological diseases and mental illnesses. Peer is also the basic means of studying human brain perception, movement and cognitive function.
[0003] 超声刺激属于既古老又新兴的无创神经刺激手段。 早在 1929年, 已经出现超声 对蛙、 龟的神经 (心) 肌肉的有效调控的文献报道。 随后在 1958年, 有文献记 录超声穿透幵颅猫的颅骨, 并能可逆地抑制视网膜的光激发电位。 高强度聚焦 超声 (HIFU) 常用作中枢神经系统的干预手段。 2008年, Tyler等证实超声刺激 海马脑片, 可激发动作电位、 压控钠离子、 钙离子瞬态及突触传递。 2010年, T yler团队首次正面经颅超声刺激小鼠颅脑运动皮层, 可诱发动作电位, 引起肢体 及尾巴的动作响应。 从此, 采用超声作为神经刺激和调控的手段引起人们的广 泛关注。  [0003] Ultrasound stimulation is an ancient and emerging non-invasive nerve stimulation. As early as 1929, there have been reports of ultrasound on the effective regulation of the nerve (heart) muscles of frogs and turtles. Subsequently, in 1958, literature records that the ultrasound penetrated the skull of the scorpion cat and reversibly inhibited the photoexcitation potential of the retina. High intensity focused ultrasound (HIFU) is often used as an intervention in the central nervous system. In 2008, Tyler et al. confirmed that ultrasound stimulated hippocampal slices, which stimulated action potentials, pressure-controlled sodium ions, calcium ion transients, and synaptic transmission. In 2010, the Tyler team first performed positive transcranial ultrasound to stimulate the cranial motor cortex of mice, which induced action potentials and caused action responses of limbs and tails. Since then, the use of ultrasound as a means of nerve stimulation and regulation has attracted widespread attention.
[0004] 然而, 超声刺激的作用机制和应用参数尚未足够明确。 除了幵展基于细胞和离 体组织的研究外, 针对清醒、 可自由活动的啮齿类小动物 (尤其是疾病模型丰 富、 在生物医药领域被广泛使用的小鼠) 幵展与记忆学习认知相关的行为学实 验也非常重要。 但是, 目前针对动物的超声刺激, 通常采用体积庞大的单阵元 聚焦超声换能器来实现。 由于这种换能器体积大, 重量重, 在使用过程中, 探 头必须由相应的定位装置来固定, 而被刺激的动物则需要被麻醉, 其头部也需 要被固定。 上述这些步骤极大限制了行为学实验的幵展。 设计适用于清醒、 自 由活动小动物的超声刺激装置, 将有助于推动超声刺激技术在神经科学的研究 应用。 [0005] 现有技术中, 申请号为 201610326489 .0的专利文献 "可穿戴经颅超声神经刺激 与电生理记录联合系统与方法", 提出了一种可穿戴经颅超声神经刺激与电生理 记录联合系统, 包括: 计算机控制与数据处理单元、 数模 /模数转换单元、 功率 放大器、 可穿戴超声换能器、 电极组件和信号放大单元。 当中提及的"可穿戴超 声换能器"仅提及换能器与实验对象通过密封胶布固定, 相互接触面要耦合处理 。 显然, 对于清醒动物, 其活动频繁且头皮相对颅骨极容易滑动, 仅用密封胶 布是难以准确可靠地固定超声探头来实施超声刺激。 此外, 专利中提及的电极 组件是通过在超声换能器上设置通孔来实现记录电极的安装, 上述的密封胶布 固定换能器的方法难以保证记录电极的合理安装。 [0004] However, the mechanism of action and application parameters of ultrasound stimulation are not sufficiently clear. In addition to the development of cell-based and ex vivo tissue-based studies, conscious, freely active rodent small animals (especially mice with a rich disease model and widely used in biomedical applications) are associated with memory learning cognition. Behavioral experiments are also very important. However, current ultrasound stimulation for animals is typically achieved using a bulky single-element focused ultrasound transducer. Because of the large size and heavy weight of the transducer, the probe must be fixed by the corresponding positioning device during use, while the stimulated animal needs to be anesthetized and its head needs to be fixed. These steps have greatly limited the development of behavioral experiments. Designing an ultrasound stimulating device for awake, free-living small animals will help drive the application of ultrasound stimulation technology in neuroscience. [0005] In the prior art, the patent document "Wearable Transcranial Ultrasound Neural Stimulation and Electrophysiological Recording System and Method" of the application No. 201610326489.0, a wearable transcranial ultrasound nerve stimulation and electrophysiological recording is proposed. The joint system includes: a computer control and data processing unit, a digital to analog/analog to digital conversion unit, a power amplifier, a wearable ultrasonic transducer, an electrode assembly, and a signal amplification unit. The "wearable ultrasonic transducer" mentioned in the above only mentions that the transducer and the subject are fixed by a sealing tape, and the mutual contact faces are to be coupled. Obviously, for conscious animals, their activities are frequent and the scalp is extremely easy to slide relative to the skull. It is difficult to accurately and reliably fix the ultrasound probe to perform ultrasonic stimulation using only a sealing tape. Further, the electrode assembly mentioned in the patent realizes the mounting of the recording electrode by providing a through hole in the ultrasonic transducer, and the above method of fixing the transducer by the sealing tape is difficult to ensure proper mounting of the recording electrode.
[0006] 申请号为申请号为 201610327257 .7的文献"一种无线控制的可穿戴式超声神经 刺激装置", 提出了一种无线可穿戴式的超声神经刺激的装置, 包括: 用户控制 终端、 控制发射芯片、 超声换能器和贴片外壳。 当中提及的"贴片外壳"仅提及 贴片外壳与作用对象间填充耦合剂并通过密封胶布固定。 显然, 对于清醒动物 , 其活动频繁且头皮相对颅骨极容易滑动, 仅用密封胶布是难以准确可靠地固 定超声探头; 而超声换能器与作用对象之间并未提及采用有效结构来防止耦合 剂滑落流失。 [0006] The application No. 201610327257.7, "a wirelessly controlled wearable ultrasonic nerve stimulation device", proposes a wireless wearable ultrasonic nerve stimulation device, comprising: a user control terminal, Control the transmitter chip, ultrasonic transducer and patch housing. The "patch housing" mentioned herein only refers to the filling couplant between the patch housing and the object and is fixed by a sealing tape. Obviously, for awake animals, their activities are frequent and the scalp is very easy to slide relative to the skull. It is difficult to accurately and reliably fix the ultrasound probe with a sealing tape alone; there is no mention of an effective structure to prevent coupling between the ultrasonic transducer and the object. The agent slipped and lost.
[0007] 申请号为 201710138442.6的专利文献"清醒动物超声神经调控装置", 提出了清 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 。 当中提及的 "固定模块"仅笼统地描述通过行业通用的方法把固定模块固定在 动物神经调控靶点。 然而, 如何设计合理的结构来实现超声换能器与颅骨的可 靠连接并保证超声能有效传导至颅骨内部, 对整个超声刺激系统来说是极其关 键的技术, 上述专利并没有对此提出可行方案。  [0007] The patent document "Awakening Animal Ultrasound Neuroregulator" of the application No. 201710138442.6 proposes a conscious animal neuromodulation device, including: a pulse signal generating module, an ultrasonic transducer module and a fixed module. The "fixed modules" mentioned herein only describe in general terms the immobilization of immobilization modules to animal neuromodulation targets by industry-wide methods. However, how to design a reasonable structure to achieve a reliable connection between the ultrasonic transducer and the skull and ensure that the ultrasound can be effectively transmitted to the inside of the skull is a critical technology for the entire ultrasound stimulation system. The above patent does not propose a feasible solution. .
[0008] 现有技术中, 超声神经刺激技术采用体积较大、 重量较重的超声探头来实现超 声刺激, 被刺激的动物则需要被麻醉, 其头部也需要被固定, 因此上述超声刺 激不适合用于幵展与感觉、 情感、 认知和记忆有关的动物实验。 而且, 现有的 可穿戴式超声刺激方案 (申请号为 201610326489 .0、 201610327257 [0008] In the prior art, the ultrasonic nerve stimulation technique uses a large-volume, heavy-weight ultrasonic probe to achieve ultrasonic stimulation, and the stimulated animal needs to be anesthetized, and the head needs to be fixed, so the above-mentioned ultrasonic stimulation is not Suitable for animal experiments related to feeling, emotion, cognition and memory. Moreover, the existing wearable ultrasound stimulation program (application number is 201610326489 .0, 201610327257
.7、 201710138442.6的文献) , 并未明确提出如何把超声换能器可靠固定在头颅 的技术或仅简单提及采用密封胶布的固定方式。 [0009] 综上, 现有技术中, 针对超声神经刺激技术领域中对小动物的刺激装置, 其难 以对清醒、 可自由活动的小动作施以准确可控、 可重复的刺激, 具有实施效果 欠佳等问题。 .7, 201710138442.6 (documents), does not clearly suggest how to securely fix the ultrasonic transducer to the skull or simply mention the fixing method using a sealing tape. [0009] In summary, in the prior art, for a small animal stimulating device in the field of ultrasonic nerve stimulation technology, it is difficult to apply an accurate and controllable and reproducible stimulus to a awake, freely movable small motion, and the implementation effect is insufficient. Good question.
技术问题  technical problem
[0010] 本发明的目的在于克服上述现有技术的不足, 提供了一种头戴式超声传导装置 [0010] The object of the present invention is to overcome the above deficiencies of the prior art and to provide a head-mounted ultrasonic transmission device.
, 其可以在实验动物清醒、 可自由活动的情况对实验动物进行超声神经刺激研 究等, 通过对自由活动的实验动物的大脑实施位置准确可控、 可重复操作的超 声刺激, 适合用于幵展与感觉、 情感、 认知等和记忆有关的动物实验, 实施效 果佳。 It can perform ultrasonic nerve stimulation research on experimental animals in the case of awake, freely movable animals, etc., and implements accurate and controllable and reproducible ultrasonic stimulation on the brain of freely moving experimental animals, which is suitable for use in marginal development. Animal experiments related to feelings, emotions, cognition, etc. and memory are effective.
问题的解决方案  Problem solution
技术解决方案  Technical solution
[0011] 本发明的技术方案是: 一种头戴式超声传导装置, 其特征在于, 包括可置于实 验动物颅骨上的底座和连接于所述底座的顶盖, 所述底座内具有用于容纳耦合 剂的内腔, 所述顶盖连接有工作面朝向于所述内腔底部的超声换能器; 所述头 戴式超声传导装置还包括用于将所述底座固定于实验动物颅骨的固定器件, 所 述固定器件包括前端可嵌入实验动物颅骨的颅骨连接件, 所述底座贴于实验动 物颅骨且与所述固定器件直接连接或通过粘结剂连接。  [0011] The technical solution of the present invention is: a head-mounted ultrasonic transmission device, comprising: a base that can be placed on a skull of an experimental animal; and a top cover connected to the base, the base has a An inner cavity accommodating a coupling agent, the top cover being coupled with an ultrasonic transducer having a working surface facing the bottom of the inner cavity; the head-mounted ultrasonic conduction device further comprising a base for fixing the base to the skull of the experimental animal The fixing device comprises a skull connector which can be embedded in the skull of the experimental animal, and the base is attached to the skull of the experimental animal and directly connected to the fixing device or connected by an adhesive.
[0012] 可选地, 所述底座靠近底部的侧面设置有凸起结构; 或者 /和, 所述底座靠近 底部的侧面设置有凹槽结构。  [0012] Optionally, a side of the base near the bottom is provided with a convex structure; or / and, a side of the base near the bottom is provided with a groove structure.
[0013] 可选地, 所述颅骨连接件为螺纹连接件, 所述粘结剂为牙科水泥;  [0013] Optionally, the skull connector is a threaded connection, the adhesive is dental cement;
[0014] 所述凸起结构为外翻凸沿, 所述粘结剂连接于所述颅骨连接件和所述外翻凸沿  [0014] the convex structure is an everted convex edge, and the adhesive is connected to the skull connecting piece and the everted convex edge
[0015] 或者, 所述凹槽结构为设置于所述底座外侧面的凹槽, 所述粘结剂连接于所述 颅骨连接件且嵌于所述凹槽内。 [0015] Alternatively, the groove structure is a groove disposed on an outer side surface of the base, and the adhesive is coupled to the skull connecting member and embedded in the groove.
[0016] 可选地, 所述底座靠近于所述实验动物颅骨前侧的一侧设置有第一凸出部, 或 者 /和, 所述底座靠近于所述实验动物颅骨后侧的一侧设置有第二凸出部。 [0016] Optionally, the base is disposed on a side of the front side of the skull of the experimental animal with a first protrusion, or/and the base is disposed adjacent to a side of the back side of the skull of the experimental animal. There is a second projection.
[0017] 可选地, 所述底座的底部设置为曲面结构, 或者 /和, 所述底座的底部设置有 弹性垫圈。 [0018] 可选地, 所述底座呈上大下小的倒锥状, 或者 /和, 所述顶盖固定或可拆卸式 连接于所述底座的顶部。 [0017] Optionally, the bottom of the base is configured as a curved structure, or/and the bottom of the base is provided with a resilient washer. [0018] Optionally, the base has an inverted cone shape that is large and small, or/and the top cover is fixedly or detachably connected to the top of the base.
[0019] 可选地, 所述顶盖通过旋卡结构、 卡扣结构或螺纹结构连接于所述底座。 [0019] Optionally, the top cover is connected to the base by a card structure, a snap structure or a threaded structure.
[0020] 可选地, 所述底座设置有至少一个 L形锁槽, 所述 L形锁槽上端幵口, 且所述 L 形锁槽上端幵口位于所述底座的上端面, 所述顶盖设置有可卡于所述 L形锁槽的 锁块。 [0020] Optionally, the base is provided with at least one L-shaped locking groove, the upper end of the L-shaped locking groove is opened, and the upper end opening of the L-shaped locking groove is located at an upper end surface of the base, the top The cover is provided with a lock block that can be caught in the L-shaped lock groove.
[0021] 可选地, 所述顶盖内侧设置有用于对所述超声换能器进行限位的凸起结构; 或 者 /和, 所述顶盖内侧设置有于容纳线缆的导线凹槽。  [0021] Optionally, a inner side of the top cover is provided with a convex structure for limiting the ultrasonic transducer; or / and, the inner side of the top cover is provided with a wire groove for accommodating the cable.
[0022] 可选地, 所述底座的侧面设置有用于实现超声刺激与电生理采集、 电刺激、 给 药、 微透析、 光刺激、 光成像中至少一种的导管结构, 所述导管结构包括至少 一根导管, 所述导管内设置有电极、 细管或光纤中的至少一种。  [0022] Optionally, a side of the base is provided with a conduit structure for achieving at least one of ultrasonic stimulation and electrophysiological collection, electrical stimulation, administration, microdialysis, light stimulation, and light imaging, and the catheter structure includes At least one conduit in which at least one of an electrode, a thin tube or an optical fiber is disposed.
发明的有益效果  Advantageous effects of the invention
有益效果  Beneficial effect
[0023] 本发明所提供的本发明实施例所提供的一种头戴式超声传导装置, 其可实现对 自由活动的实验动物的大脑实施位置准确可控、 可重复操作的超声刺激, 并且 允许在超声刺激的同吋附加颅内给药、 微透析、 电刺激、 光刺激或者电生理采 集的功能。  [0023] A head-mounted ultrasonic conduction device provided by an embodiment of the present invention provides an accurate and controllable and reproducible ultrasonic stimulation of a brain of a freely moving experimental animal, and allows The function of intracranial administration, microdialysis, electrical stimulation, light stimulation or electrophysiological acquisition in ultrasound-stimulated peers.
对附图的简要说明  Brief description of the drawing
附图说明  DRAWINGS
[0024] 为了更清楚地说明本发明实施例中的技术方案, 下面将对实施例中所需要使用 的附图作简单地介绍, 显而易见地, 下面描述中的附图仅仅是本发明的一些实 施例, 对于本领域普通技术人员来讲, 在不付出创造性劳动的前提下, 还可以 根据这些附图获得其他的附图。  [0024] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings to be used in the embodiments will be briefly described below. Obviously, the drawings in the following description are only some implementations of the present invention. For example, other drawings may be obtained from those of ordinary skill in the art in light of the inventive work.
[0025] 图 1是本发明实施例提供的一种头戴式超声传导装置连接于实验动物颅骨的主 视图;  1 is a front view of a head-mounted ultrasonic conduction device connected to a skull of an experimental animal according to an embodiment of the present invention;
[0026] 图 2是本发明实施例提供的一种头戴式超声传导装置连接于实验动物颅骨的右 视图;  2 is a right side view of a head-mounted ultrasonic conduction device connected to a skull of an experimental animal according to an embodiment of the present invention;
[0027] 图 3是本发明实施例提供的一种头戴式超声传导装置连接于实验动物颅骨的主 视图。 3 is a main body of a head-mounted ultrasonic conduction device connected to a skull of an experimental animal according to an embodiment of the present invention; View.
本发明的实施方式 Embodiments of the invention
[0028] 为了使本发明的目的、 技术方案及优点更加清楚明白, 以下结合附图及实施例 , 对本发明进行进一步详细说明。 应当理解, 此处所描述的具体实施例仅仅用 以解释本发明, 并不用于限定本发明。  The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It is understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
[0029] 需要说明的是, 当元件被称为 "固定于"或"设置于"另一个元件, 它可以直接在 另一个元件上或者可能同吋存在居中元件。 当一个元件被称为是 "连接于"另一个 元件, 它可以是直接连接到另一个元件或者可能同吋存在居中元件。  [0029] It is to be noted that when an element is referred to as being "fixed" or "in" another element, it can be directly on the other element or possibly the same. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or the same element.
[0030] 还需要说明的是, 本发明实施例中的左、 右、 上、 下等方位用语, 仅是互为相 对概念或是以产品的正常使用状态为参考的, 而不应该认为是具有限制性的。  [0030] It should also be noted that the left, right, upper, lower, and the like orientations in the embodiments of the present invention are merely relative concepts or referenced to the normal use state of the product, and should not be considered as having Restrictive.
[0031] 如图 1和图 2所示, 本发明实施例提供的一种头戴式超声传导装置, 包括可置于 实验动物颅骨 9上的底座 2和连接于底座 2的顶盖 1, 底座 2内具有用于容纳耦合剂 的内腔, 底座 2的上下两端幵口, 下端幵口位于实验动物颅骨 9上, 上端幵口用 于连接顶盖 1 ; 顶盖 1连接有工作面朝向于内腔底部 (即实验动物颅骨 9) 的超声 换能器 (图中未示出) , 头戴式超声传导装置还包括用于将底座 2固定于实验动 物颅骨 9的固定器件, 固定器件包括前端可嵌入实验动物颅骨的颅骨连接件 31, 颅骨连接件 31的前端可以嵌入连接于实验动物颅骨 9, 颅骨连接件 31不易松脱, 其连接可靠性佳, 底座 2的底部贴于实验动物颅骨 9, 且底座 2与颅骨连接件 31直 接连接或通过粘结剂 32连接。 即底座 2可以直接由颅骨连接件 31固定, 或者, 底 座 2也可以通过粘结剂 32与颅骨连接件 31连接而固定。 颅骨连接件 31可为螺纹连 接件 (例如颅骨螺钉) , 其前端可以螺纹固定于实验动物颅骨 9而不损伤实验动 物的脑组织, 且可以使底座 2可以稳定、 可靠地贴于实验动物颅骨 9, 从而可以 在实验动物清醒、 可自由活动的情况对实验动物进行超声神经刺激研究等, 通 过对自由活动的实验动物的大脑实施位置准确可控、 可重复操作的超声刺激, 适合用于幵展与感觉、 情感、 认知等和记忆有关的动物实验, 而且, 本实施例 所提供的一种头戴式超声传导装置, 其体积小、 重量轻, 不仅可以适用于兔子 等中小型动物的研究, 还可以适用于小白鼠等小型动物的研究。 [0032] 可选地, 所述底座 2靠近底部的侧面设置有用于连接所述粘结剂 32或所述颅骨 连接件 31的凸起结构; 或者 /和, 如图 3所示, 所述底座 2靠近底部的侧面设置有 用于连接所述粘结剂 32或所述颅骨连接件 31的凹槽结构。 [0031] As shown in FIG. 1 and FIG. 2, a head-mounted ultrasonic transmission device according to an embodiment of the present invention includes a base 2 that can be placed on a skull 9 of an experimental animal, and a top cover 1 connected to the base 2, the base. 2 has a cavity for accommodating the couplant, the upper and lower ends of the base 2 are smashed, the lower end is located on the skull 9 of the experimental animal, and the upper end is used to connect the top cover 1; the top cover 1 is connected with the working surface facing An ultrasonic transducer (not shown) of the bottom of the lumen (ie, the skull of the experimental animal), the head-mounted ultrasonic transducer further includes a fixing device for fixing the base 2 to the skull 9 of the experimental animal, the fixing device including the front end The skull connector 31 can be embedded in the skull of the experimental animal. The front end of the skull connector 31 can be embedded and connected to the skull of the experimental animal. The skull connector 31 is not easy to loose, and the connection reliability is good. The bottom of the base 2 is attached to the skull of the experimental animal. And the base 2 is directly connected to the skull connector 31 or connected by an adhesive 32. That is, the base 2 can be directly fixed by the skull connecting member 31, or the base 2 can also be fixed by connecting the adhesive 32 to the skull connecting member 31. The skull connecting member 31 can be a threaded connecting member (for example, a skull screw), and the front end thereof can be screwed to the skull of the experimental animal without damaging the brain tissue of the experimental animal, and the base 2 can be stably and reliably attached to the skull of the experimental animal. Therefore, it is possible to perform ultrasonic nerve stimulation research on experimental animals in the case of conscious and freely movable animals, and to perform accurate and controllable and reproducible ultrasonic stimulation on the brain of freely moving experimental animals, which is suitable for use in the exhibition. The animal experiment related to feeling, emotion, cognition, etc. and memory, and the head-mounted ultrasonic conduction device provided by the embodiment is small in size and light in weight, and can be applied not only to small and medium-sized animals such as rabbits. It can also be applied to the study of small animals such as mice. [0032] Optionally, a convex structure for connecting the adhesive 32 or the skull connecting member 31 is disposed on a side of the base 2 near the bottom; or/and, as shown in FIG. 3, the base A groove structure for joining the adhesive 32 or the skull connector 31 is provided on the side near the bottom.
[0033] 可选地, 凸起结构可为外翻凸沿 23, 以增加与粘结剂 32的接触面, 连接可靠性 高。 当然, 也可以使颅骨连接件 31直接压于外翻凸沿 23, 或者, 在外翻凸沿 23 设置用于供颅骨连接件 31穿过的孔位。 具体应用中, 颅骨连接件 31设置有一颗 或至少两颗且位于外翻凸沿 23的周围, 粘结剂 32连接于颅骨连接件 31和外翻凸 沿 23。 颅骨连接件 31设置有多个吋, 粘结剂 32和颅骨连接件 31可以分设于左右 两侧或 /和前后两侧。 粘结剂 32和颅骨连接件 31的数量和排布方式也可以根据实 际情况设定。 外翻凸沿 23可呈环状, 也可以呈柱状、 块状或片状等。  [0033] Alternatively, the raised structure may be an everted flange 23 to increase the contact surface with the adhesive 32, and the connection reliability is high. Of course, it is also possible to press the skull connector 31 directly against the everted flange 23, or to provide a hole for the skull connector 31 to pass through at the everted flange 23. In a particular application, the skull connector 31 is provided with one or at least two and is located around the everted flange 23, and the adhesive 32 is attached to the skull connector 31 and the everted flange 23. The skull connector 31 is provided with a plurality of jaws, and the adhesive 32 and the skull connector 31 can be disposed on the left and right sides or/and the front and rear sides. The number and arrangement of the adhesive 32 and the skull connector 31 can also be set according to the actual situation. The valgus protrusion 23 may be in the shape of a ring, or may be in the form of a column, a block or a sheet.
[0034] 可选地, 如图 3所示, 所述凹槽结构为设置于所述底座 2外侧面的凹槽 20, 所述 粘结剂 32连接于所述颅骨连接件 31且嵌于所述凹槽 20内。 凹槽 20可为环形凹槽 或沿底座 2周向设置的独立凹槽 (例如圆形凹槽或矩形凹槽) , 部分粘结剂 32 ( 例如牙科水泥) 嵌入凹槽 20内形成倒扣结构, 连接稳固性高。  [0034] Optionally, as shown in FIG. 3, the groove structure is a groove 20 disposed on an outer side of the base 2, and the adhesive 32 is coupled to the skull connecting member 31 and embedded in the Included in the recess 20. The groove 20 may be an annular groove or a separate groove (for example, a circular groove or a rectangular groove) circumferentially disposed along the base 2, and a portion of the adhesive 32 (for example, dental cement) is embedded in the groove 20 to form an inverted structure. , the connection is highly stable.
[0035] 可选地, 粘结剂 32可为凝固后具有足够机械强度的粘合剂, 例如牙科水泥或其 它类型的粘结剂 32。  [0035] Alternatively, the adhesive 32 may be an adhesive having sufficient mechanical strength after solidification, such as dental cement or other type of adhesive 32.
[0036] 可选地, 底座 2靠近于实验动物颅骨 9前侧的一侧设置有第一凸出部 21, 或者 / 和, 底座 2靠近于实验动物颅骨 9后侧的一侧设置有第二凸出部 22, 凸出部 (第 一凸出部 21和第二凸出部 22) 的数量和具体结构可以根据实际实况设定, 用于 增加牙科水泥对底座 2的固定强度。  [0036] Optionally, the base 2 is provided with a first protrusion 21 on a side close to the front side of the skull 9 of the experimental animal, or / and, the base 2 is provided with a second side on the side of the back side of the skull 9 of the experimental animal. The number and specific structure of the projections 22, the projections (the first projections 21 and the second projections 22) can be set according to actual conditions for increasing the fixing strength of the dental cement to the base 2.
[0037] 可选地, 底座 2的底部 (外翻凸沿 23) 设置为曲面结构, 其可以与实验动物颅 骨 9的颅骨形状匹配, 例如, 底座 2的底部可以呈马鞍形等合适形状。  [0037] Optionally, the bottom of the base 2 (the everted flange 23) is configured as a curved structure that can match the shape of the skull of the skull 9 of the experimental animal. For example, the bottom of the base 2 may have a suitable shape such as a saddle shape.
[0038] 可选地, 底座 2的底部可以设置有弹性垫圈 (图中未示出) , 弹性垫圈可以硅 胶垫圈等, 密封性佳, 且具有一定缓冲的作用。  [0038] Optionally, the bottom of the base 2 may be provided with a resilient washer (not shown), the elastic washer may be a silicone gasket, etc., and has good sealing performance and a certain buffering effect.
[0039] 可选地, 底座 2呈上大下小的倒锥状, 底座 2下端幵口尺寸相对较小, 以与实验 动物的头部大小所匹配。 底座 2上端幵口尺寸较大, 可以安装直径较大的超声换 能器, 可以采用低频、 高强的超声波对实验动物进行刺激。  [0039] Optionally, the base 2 has an inverted cone shape that is large and small, and the lower end of the base 2 has a relatively small size to match the size of the head of the laboratory animal. The upper end of the base 2 has a large size, and a large diameter ultrasonic transducer can be installed. The low-frequency, high-intensity ultrasonic waves can be used to stimulate the experimental animals.
[0040] 可选地, 顶盖 1内超声换能器的压电材料可以采用压电复合材料、 压电陶瓷、 压电单晶材料及其它压电材料, 压电材料的厚度可在 0.01-3mm范围; 超声换能 器可以是单阵元超声换能器或多阵元超声换能器, 也可以是聚焦超声换能器或 平面超声换能器。 顶盖 1内的超声换能器可采用空气背衬, 也可填充其他材料作 为背衬。 [0040] Optionally, the piezoelectric material of the ultrasonic transducer in the top cover 1 may adopt a piezoelectric composite material, a piezoelectric ceramic, Piezoelectric single crystal materials and other piezoelectric materials, the thickness of the piezoelectric material can be in the range of 0.01-3 mm; the ultrasonic transducer can be a single-element ultrasound transducer or a multi-element ultrasound transducer, or a focused ultrasound Transducer or planar ultrasound transducer. The ultrasonic transducer in the top cover 1 may be air backed or may be filled with other materials as a backing.
[0041] 可选地, 顶盖 1固定或可拆卸式连接于底座 2的顶部。 具体应用中, 顶盖 1可以 通过旋卡结构、 卡扣结构或螺纹结构等可拆卸连接于底座 2, 顶盖 1可以方便、 快捷地反复拆顶盖 1装。 当然, 作为替代方案, 顶盖 1也可以固定连接于底座 2, 或者, 顶盖 1与底座 2—体连接。  [0041] Optionally, the top cover 1 is fixedly or detachably connected to the top of the base 2. In a specific application, the top cover 1 can be detachably connected to the base 2 by a screw card structure, a snap structure or a thread structure, and the top cover 1 can be repeatedly and conveniently removed from the top cover 1 . Of course, as an alternative, the top cover 1 can also be fixedly connected to the base 2, or the top cover 1 can be connected to the base 2 body.
[0042] 可选地, 为了更便于拆装顶盖 1, 可以在顶盖 1外侧设置有防滑结构。 防滑结构 可为凸起 11或 /和凹槽。  [0042] Alternatively, in order to facilitate the disassembly and assembly of the top cover 1, an anti-slip structure may be disposed outside the top cover 1. The anti-slip structure can be a projection 11 or / and a groove.
[0043] 本实施例中, 底座 2设置有至少两个 L形锁槽 24, L形锁槽 24贯通于底座 2的侧壁  In this embodiment, the base 2 is provided with at least two L-shaped lock grooves 24, and the L-shaped lock grooves 24 penetrate through the side walls of the base 2.
, L形锁槽 24上端幵口, 且 L形锁槽 24上端幵口位于底座 2的上端面, 顶盖 1设置 有可卡于 L形锁槽 24的锁块 14, 锁块 14的数量可与 L形锁槽 24的数量相等。 锁块 1 4可呈柱状或蘑菇状。 锁块 14可以从 L形锁槽 24上端幵口纵向卡入, 然后旋转顶 盖 1, 使锁块 14横向卡于 L形锁槽 24内, 操作方便且可靠性佳。 安装顶盖 1和超声 换能器吋, 预先灌入底座 2的超声耦合剂能在填满底座 2内腔空间后从 L形锁槽 24 自动溢出, 保证超声耦合剂充满于超声换能器与实验动物颅骨 9之间。 L形锁槽 2 4也可以采用其它结构形状的锁槽, L形锁槽 24的数量可以根据实际情况设定 The upper end of the L-shaped lock groove 24 is located at the upper end of the base 2, and the top cover 1 is provided with a lock block 14 that can be caught in the L-shaped lock groove 24. The number of the lock block 14 can be It is equal to the number of L-shaped lock grooves 24. The lock block 1 4 may be in the shape of a column or a mushroom. The lock block 14 can be longitudinally engaged from the upper end of the L-shaped lock groove 24, and then the top cover 1 is rotated to make the lock block 14 laterally snap into the L-shaped lock groove 24, which is convenient and reliable. After installing the top cover 1 and the ultrasonic transducer 吋, the ultrasonic coupling agent pre-filled into the base 2 can automatically overflow from the L-shaped lock groove 24 after filling the inner cavity space of the base 2, ensuring that the ultrasonic coupling agent is filled with the ultrasonic transducer and Experimental animal between skulls 9. The L-shaped lock groove 2 4 can also adopt the lock groove of other structural shapes, and the number of the L-shaped lock grooves 24 can be set according to actual conditions.
[0044] 可选地, 可以在底座 2靠近上端处设置有溢流孔, 若顶盖 1与底座 2之间通过螺 纹结构连接, 安装顶盖 1和超声换能器吋, 预先灌入底座 2的超声耦合剂能在填 满底座 2内腔空间后从溢流孔流出。 [0044] Optionally, an overflow hole may be disposed near the upper end of the base 2, and if the top cover 1 and the base 2 are connected by a thread structure, the top cover 1 and the ultrasonic transducer 安装 are installed, and the base 2 is pre-filled. The ultrasonic coupling agent can flow out of the overflow hole after filling the inner cavity space of the base 2.
[0045] 可选地, 顶盖 1的顶部可以设置有导线过孔和螺丝孔, 以便于安装超声换能器 等。  [0045] Alternatively, the top of the top cover 1 may be provided with a wire through hole and a screw hole to facilitate installation of an ultrasonic transducer or the like.
[0046] 可选地, 顶盖 1内侧设置有用于对超声换能器进行限位的凸起结构 (图中未示 出) , 以便于超声换能器的安装和定位。 具体应用中, 凸起结构可为一体成型 于顶盖 1内侧或固定连接于顶盖 1内侧的凸环或凸杆等。 [0046] Optionally, a convex structure (not shown) for limiting the ultrasonic transducer is disposed inside the top cover 1 to facilitate installation and positioning of the ultrasonic transducer. In a specific application, the protruding structure may be a convex ring or a protruding rod integrally formed on the inner side of the top cover 1 or fixedly connected to the inner side of the top cover 1.
[0047] 可选地, 顶盖 1内侧设置有于容纳线缆的导线凹槽 (图中未示出) , 线缆连接 于超声换能器, 超声换能器的直径可以与顶盖 1的内径匹配, 超声换能器不会松 动, 利于对实验动物进行稳定的超声波刺激。 [0047] Optionally, the inner side of the top cover 1 is provided with a wire groove (not shown) for accommodating the cable, and the cable is connected to the ultrasonic transducer, and the diameter of the ultrasonic transducer can be the same as that of the top cover 1. Inner diameter matching, ultrasonic transducer will not loose It is good for stable ultrasonic stimulation of experimental animals.
[0048] 可选地, 底座 2的侧面设置有用于实现超声刺激与电生理采集、 电刺激、 给药 [0048] Optionally, the side of the base 2 is provided for achieving ultrasonic stimulation and electrophysiological collection, electrical stimulation, administration
(非治疗目的) 、 微透析、 光刺激、 光成像中至少一种的导管结构 4, 导管结构 4包括至少一根导管, 导管内设置有电极、 细管或光纤中的至少一种, 从而可以 实现超声刺激共靶点的颅内给药、 微透析、 电刺激、 光刺激或者电生理采集的 功能。  a catheter structure 4 of at least one of (non-therapeutic purpose), microdialysis, light stimulation, and photo imaging, the catheter structure 4 includes at least one catheter, and at least one of an electrode, a thin tube, or an optical fiber is disposed in the catheter, thereby The function of intracranial administration, microdialysis, electrical stimulation, light stimulation or electrophysiological acquisition of ultrasound-stimulated common targets.
[0049] 图 1展示了安装于实验动物颅骨 9上的头戴式超声传导装置示意图。 最底端的虚 线椭圆表示小动物颅骨 9的矢状面, 颅骨与上方的头戴式超声传导装置紧密结合 , 并由颅骨连接件 31及牙科水泥固定; 上方的头戴式超声传导装置包含顶盖 1和 底座 2两部分; 底座 2和顶盖 1可采用金属、 塑料、 有机玻璃等任何加工后常温下 呈固体状态的材料加工。 顶盖 1与底座 2可通过 L形锁槽 24结构连接; 顶盖 1内部 可安装圆形的超声换能器, 超声换能器可包括超声压电材料、 匹配层及引线 ( 图中未示出) , 用于产生超声波往下方辐射; 顶盖 1外围底部有三个锁块 14, 用 于与底座 2的 L形锁槽 24互扣连接; 顶盖 1外侧顶部有两个对称的防滑凸出结构 ( 凸起 11) ; 底座 2呈倒置空心圆锥体形状, 包含上幵口和下幵口; 倒置空心圆锥 体形状, 既能减少了底座 2占用颅骨的面积, 又允许超声换能器具有较大的辐射 面积, 从而保证该装置能应用于小动物并且具有较高的超声辐射强度和较低的 辐射频率; 底座 2上出口四周有三个 L形锁槽 24, 可与上述顶盖 1外围的三个锁块 14互扣; 底座 2下出口周围有外翻的外沿结构, 外沿结构的底面并非平面, 而是 圆柱面或弧面, 该圆柱面的外翻外沿结构与小动物呈弧面拱起的颅骨表面刚好 吻合, 从而实现底座 2与颅骨的无缝紧贴安装; 上述外翻的外沿结构的前后方分 别有一个凸出结构, 该前后分布的凸出结构, 可在不增加底座 2外沿左右宽度的 前提下增加牙科水泥的接触面积, 防止底座 2绕中心轴转动, 提高安装底座 2的 机械强度。 图 2所示为头戴式超声传导装置侧视图, 标注了类似图 1所示的结构 , 特别地, 在图 2中底座 2的右侧 (即实验动物头颅的后方) , 设计了导管结构 4 ; 通过该导管结构 4, 可附加安装电生理采集或刺激电极、 给药管、 透析管、 光 纤等管道, 这些管道的下端可延伸至超声作用靶点区域的不同深度, 实现电生 理信号采集、 定点药物输送、 微透析、 光刺激等功能。 [0050] 本发明实施例所提供的一种头戴式超声传导装置, 主要应用于对清醒且自由活 动小动物进行可重复操作的超声刺激, 主要包含顶盖 1和底座 2两部分, 顶盖 1内 置超声换能器, 超声换能器包括压电材料和匹配层, 可产生超声实现超声刺激 ; 底座 2可呈倒置空心圆锥体形状, 具有上、 下两幵口; 上幵口周围有若干个 L 形锁槽 24, 便于与顶盖 1可拆卸式连接; 下幵口有底面为弧面的外翻外沿结构以 及位于外沿结构先后侧的两个外沿凸出结构 (第一凸出部 21、 第二凸出部 22) ; 上幵口和下幵口分别用于连接顶盖 1和实验动物颅骨 9; 且顶盖 1可被反复便捷 地安装与拆卸。 本发明实施例所提供的一种头戴式超声传导装置, 其至少具有 以下优点: [0049] FIG. 1 shows a schematic view of a head mounted ultrasound transducer mounted on a skull 9 of an experimental animal. The bottommost dotted ellipse represents the sagittal plane of the small animal skull 9, the skull is tightly coupled to the upper head-mounted ultrasound transducer and is secured by the skull connector 31 and dental cement; the upper head-mounted ultrasound transducer includes a cap 1 and the base 2 are two parts; the base 2 and the top cover 1 can be processed by any material such as metal, plastic, plexiglass or the like which is solid at normal temperature after processing. The top cover 1 and the base 2 can be connected by an L-shaped lock groove 24; a circular ultrasonic transducer can be installed inside the top cover 1, and the ultrasonic transducer can include an ultrasonic piezoelectric material, a matching layer and a lead wire (not shown) Out, for generating ultrasonic waves to radiate downward; the top of the top cover 1 has three lock blocks 14 for interlocking connection with the L-shaped lock grooves 24 of the base 2; the top of the top cover 1 has two symmetrical anti-slip protrusions Structure (protrusion 11); The base 2 is in the shape of an inverted hollow cone, including an upper jaw and a lower jaw; the inverted hollow cone shape can reduce the area occupied by the base 2 and allow the ultrasonic transducer to have a higher Large radiation area, thus ensuring that the device can be applied to small animals and has high ultrasonic radiation intensity and low radiation frequency; there are three L-shaped lock grooves 24 around the outlet of the base 2, which can be external to the top cover 1 The three lock blocks 14 are interlocked; the outer edge of the bottom of the base 2 has an everted outer edge structure, and the bottom surface of the outer edge structure is not a flat surface, but a cylindrical surface or a curved surface, and the outer curved structure of the cylindrical surface is small animal The surface of the skull arched by the curved surface Anastomosis, thereby achieving a seamless close installation of the base 2 and the skull; the outer and outer edges of the outer everted structure respectively have a convex structure, and the front and rear convex structures can be added without increasing the width of the outer edge of the base 2 Under the premise, the contact area of the dental cement is increased to prevent the base 2 from rotating around the central axis, thereby improving the mechanical strength of the mounting base 2. Figure 2 is a side view of the head-mounted ultrasonic transducer, labeled similar to that shown in Figure 1, in particular, in the right side of the base 2 in Figure 2 (i.e., behind the skull of the experimental animal), the catheter structure 4 is designed. Through the catheter structure 4, an electrophysiological collection or stimulation electrode, a drug delivery tube, a dialysis tube, an optical fiber and the like may be additionally installed, and the lower end of the tube may extend to different depths of the ultrasound target area to realize electrophysiological signal collection, Site-specific drug delivery, microdialysis, light stimulation and other functions. [0050] A head-mounted ultrasonic conduction device provided by an embodiment of the present invention is mainly used for performing repetitive operation of ultrasonic stimulation on a awake and freely moving small animal, mainly comprising a top cover 1 and a base 2, and a top cover 1 built-in ultrasonic transducer, the ultrasonic transducer comprises a piezoelectric material and a matching layer, which can generate ultrasonic to achieve ultrasonic stimulation; the base 2 can be in the shape of an inverted hollow cone with upper and lower jaws; An L-shaped lock groove 24 is detachably connected to the top cover 1; the lower jaw has an outer curved outer edge structure having a bottom surface and two outer edge protruding structures on the outer side of the outer edge structure (first convex The upper portion 21 and the second protruding portion 22); the upper and lower jaws are respectively used for connecting the top cover 1 and the experimental animal skull 9; and the top cover 1 can be repeatedly installed and disassembled. A head-mounted ultrasonic transmission device provided by an embodiment of the present invention has at least the following advantages:
[0051] (1) 底座 2的下出口的底面呈曲面状, 外翻凸沿 23及凸出部也可以呈曲面状, 使底座 2能与实验动物弧面状的颅骨紧密可靠接触, 提高了底座 2安装位置的准 确度和装置的使用寿命;  [0051] (1) The bottom surface of the lower exit of the base 2 is curved, and the valgus flange 23 and the protruding portion may also have a curved shape, so that the base 2 can be in close contact with the curved skull of the experimental animal, thereby improving the contact. The accuracy of the mounting position of the base 2 and the service life of the device;
[0052] (2) 底座 2呈倒置空心圆锥体形状, 既减少了底座 2占用颅骨的面积, 又能允许 超声换能器具有较大的辐射面积, 从而保证该装置能应用于小动物并且具有较 高的超声辐射强度和较低的辐射频率;  [0052] (2) The base 2 has an inverted hollow cone shape, which not only reduces the area occupied by the base 2, but also allows the ultrasonic transducer to have a larger radiation area, thereby ensuring that the device can be applied to small animals and has Higher ultrasonic radiation intensity and lower radiation frequency;
[0053] (3) 底座 2和顶盖 1的卡口结构, 保证顶盖 1可被反复安装与拆卸, 便于灵活幵 展需反复超声刺激的实验;  [0053] (3) The bayonet structure of the base 2 and the top cover 1 ensures that the top cover 1 can be repeatedly installed and disassembled, thereby facilitating the flexible experiment of repeated ultrasonic stimulation;
[0054] (4) 底座 2和顶盖 1的卡口结构, 允许安装顶盖 1吋预先灌入的超声耦合剂能在 填满底座 2内腔空间后自动溢出, 保证超声能通过底座 2内腔可靠传导而不增加 底座 2腔内压力;  [0054] (4) The bayonet structure of the base 2 and the top cover 1 allows the ultrasonic coupling agent pre-filled into the top cover 1 to automatically overflow after filling the inner cavity space of the base 2, ensuring that ultrasonic energy can pass through the base 2 The cavity is reliably conducted without increasing the pressure in the cavity of the base 2;
[0055] (5) 顶盖 1内侧的凸起结构和导线凹槽结构, 可使超声传感器 (超声换能器) 工作于空气背衬模式, 提高超声辐射的效率;  [0055] (5) The convex structure and the wire groove structure on the inner side of the top cover 1 enable the ultrasonic sensor (ultrasonic transducer) to operate in the air backing mode to improve the efficiency of ultrasonic radiation;
[0056] (6) 底座 2外侧壁可安装径向导管, 允许导药管、 电生理电极或者光纤通过, 用于幵展超声刺激结合颅内给药、 微透析、 电生理采集、 电刺激或者光刺激等 实验; [0056] (6) The outer side wall of the base 2 can be installed with a radial catheter, allowing the passage of a drug guiding tube, an electrophysiological electrode or an optical fiber, for performing ultrasound stimulation combined with intracranial administration, microdialysis, electrophysiological collection, electrical stimulation or Experiments such as light stimulation;
[0057] (7) 整个装置体积小、 重量轻, 可应用于小鼠等自由活动的小动物, 实施超声 刺激。  [0057] (7) The entire device is small in size and light in weight, and can be applied to small animals such as mice that are free to move, and perform ultrasonic stimulation.
[0058] 以上仅为本发明的较佳实施例而已, 并不用以限制本发明, 凡在本发明的精神 和原则之内所作的任何修改、 等同替换或改进等, 均应包含在本发明的保护范 围之内。 The above are only the preferred embodiments of the present invention, and are not intended to limit the present invention, and are in the spirit of the present invention. Any modifications, equivalent substitutions or improvements made within the principles and principles are intended to be included within the scope of the invention.

Claims

权利要求书 Claim
一种头戴式超声传导装置, 其特征在于, 包括可置于实验动物颅骨上 的底座和连接于所述底座的顶盖, 所述底座内具有用于容纳耦合剂的 内腔, 所述顶盖连接有工作面朝向于所述内腔底部的超声换能器; 所 述头戴式超声传导装置还包括用于将所述底座固定于实验动物颅骨的 固定器件, 所述固定器件包括前端可嵌入实验动物颅骨的颅骨连接件 , 所述底座贴于实验动物颅骨且与所述固定器件直接连接或通过粘结 剂连接。 A head-mounted ultrasonic transmission device, comprising: a base that can be placed on a skull of an experimental animal; and a top cover connected to the base, the base having a cavity for receiving a coupling agent, the top The cover is coupled with an ultrasonic transducer having a working surface facing the bottom of the inner cavity; the head-mounted ultrasonic transmission device further includes a fixing device for fixing the base to the skull of the experimental animal, the fixing device including the front end A skull connector embedded in the skull of the experimental animal, the base being attached to the skull of the experimental animal and directly connected to the fixation device or connected by an adhesive.
如权利要求 1所述的一种头戴式超声传导装置, 其特征在于, 所述底 座靠近底部的侧面设置有凸起结构; 或者 /和, 所述底座靠近底部的 侧面设置有凹槽结构。 A head-mounted ultrasonic transmission device according to claim 1, wherein a side of the base near the bottom is provided with a convex structure; or / and a side of the base near the bottom is provided with a groove structure.
如权利要求 2所述的一种头戴式超声传导装置, 其特征在于, 所述颅 骨连接件为螺纹连接件, 所述粘结剂为牙科水泥; The head-mounted ultrasonic transmission device according to claim 2, wherein the cranial connector is a threaded connection, and the adhesive is dental cement;
所述凸起结构为外翻凸沿, 所述粘结剂连接于所述颅骨连接件和所述 外翻凸沿; The convex structure is an everted convex edge, and the adhesive is connected to the skull connecting member and the everted convex edge;
或者, 所述凹槽结构为设置于所述底座外侧面的凹槽, 所述粘结剂连 接于所述颅骨连接件且嵌于所述凹槽内。 Alternatively, the groove structure is a groove disposed on an outer side surface of the base, and the adhesive is coupled to the skull connector and embedded in the groove.
如权利要求 1所述的一种头戴式超声传导装置, 其特征在于, 所述底 座靠近于所述实验动物颅骨前侧的一侧设置有第一凸出部, 或者 /和 , 所述底座靠近于所述实验动物颅骨后侧的一侧设置有第二凸出部。 如权利要求 1至 4中任一项所述的一种头戴式超声传导装置, 其特征在 于, 所述底座的底部设置为曲面结构, 或者 /和, 所述底座的底部设 置有弹性垫圈。 The head-mounted ultrasonic transmission device according to claim 1, wherein the base is provided with a first protrusion on a side close to a front side of the skull of the experimental animal, or/and the base A second protrusion is provided on a side close to the back side of the skull of the experimental animal. A head-mounted ultrasonic transmission device according to any one of claims 1 to 4, characterized in that the bottom of the base is provided in a curved structure, or / and the bottom of the base is provided with a resilient washer.
如权利要求 1至 4中任一项所述的一种头戴式超声传导装置, 其特征在 于, 所述底座呈上大下小的倒锥状, 或者 /和, 所述顶盖固定或可拆 卸式连接于所述底座的顶部。 The head-mounted ultrasonic transmission device according to any one of claims 1 to 4, wherein the base has an inverted cone shape that is large and small, or/and the top cover is fixed or A detachable connection to the top of the base.
如权利要求 1至 4中任一项所述的一种头戴式超声传导装置, 其特征在 于, 所述顶盖通过旋卡结构、 卡扣结构或螺纹结构连接于所述底座。 [权利要求 8] 如权利要求 1至 4中任一项所述的一种头戴式超声传导装置, 其特征在 于, 所述底座设置有至少一个 L形锁槽, 所述 L形锁槽上端幵口, 且 所述 L形锁槽上端幵口位于所述底座的上端面, 所述顶盖设置有可卡 于所述 L形锁槽的锁块。 A head-mounted ultrasonic transmission device according to any one of claims 1 to 4, wherein the top cover is coupled to the base by a screw card structure, a snap structure or a threaded structure. [Claim 8] A head-mounted ultrasonic transmission device according to any one of claims 1 to 4, wherein the base is provided with at least one L-shaped lock groove, and the upper end of the L-shaped lock groove a mouthpiece, and the upper end of the L-shaped lock groove is located at an upper end surface of the base, and the top cover is provided with a lock block that can be caught in the L-shaped lock groove.
[权利要求 9] 如权利要求 1至 4中任一项所述的一种头戴式超声传导装置, 其特征在 于, 所述顶盖内侧设置有用于对所述超声换能器进行限位的凸起结构 ; 或者 /和, 所述顶盖内侧设置有于容纳线缆的导线凹槽。  [Claim 9] A head-mounted ultrasonic transmission device according to any one of claims 1 to 4, wherein a side of the top cover is provided for limiting the ultrasonic transducer a raised structure; or/and, the inside of the top cover is provided with a wire groove for accommodating the cable.
[权利要求 10] 如权利要求 1至 4中任一项所述的一种头戴式超声传导装置, 其特征在 于, 所述底座的侧面设置有用于实现超声刺激与电生理采集、 电刺激 、 给药、 微透析、 光刺激、 光成像中至少一种的导管结构, 所述导管 结构包括至少一根导管, 所述导管内设置有电极、 细管或光纤中的至 少一种。  [Claim 10] A head-mounted ultrasonic transmission device according to any one of claims 1 to 4, wherein a side surface of the base is provided for achieving ultrasonic stimulation and electrophysiological collection, electrical stimulation, A catheter structure of at least one of administration, microdialysis, light stimulation, and photo imaging, the catheter structure comprising at least one catheter, the catheter being provided with at least one of an electrode, a capillary tube, or an optical fiber.
PCT/CN2017/099996 2017-08-31 2017-08-31 Head-mounted ultrasonic transmission apparatus WO2019041256A1 (en)

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