阅读说明：本技术 用于小动物脑功能区定位刺激的聚焦超声调控装置及方法 (Focused ultrasound regulation and control device and method for positioning stimulation of brain functional region of small animal ) 是由 韩静 张俊敏 尹冠军 任维 郭建中 于 2021-07-29 设计创作，主要内容包括：本发明公开了用于小动物脑功能区定位刺激的聚焦超声调控装置及方法,包括连接在小动物颅骨平面上的头部固定器,头部固定器上依次连接有超声准直器和超声换能器,所述头部固定器、超声准直器和超声换能器同轴设置,且超声准直器和超声换能器之间采用可调连接；还包括能够与头部固定器连接的定位器及保护器,所述定位器用于对小动物颅骨平面进行坐标定位,所述保护器用于在非实验条件下防止小动物颅骨平面接触外界而发生感染。本发明可在小动物清醒自由活动情况下,对小动物脑功能区的不同位置及深度实现不同参数的超声刺激。(The invention discloses a focused ultrasound regulation and control device and a method for positioning stimulation of a functional brain area of a small animal, which comprises a head fixer connected to the skull plane of the small animal, wherein the head fixer is sequentially connected with an ultrasonic collimator and an ultrasonic transducer, the head fixer, the ultrasonic collimator and the ultrasonic transducer are coaxially arranged, and the ultrasonic collimator and the ultrasonic transducer are in adjustable connection; the device also comprises a positioner and a protector, wherein the positioner and the protector can be connected with the head fixator, the positioner is used for carrying out coordinate positioning on the skull plane of the small animal, and the protector is used for preventing the skull plane of the small animal from contacting the outside to cause infection under non-experimental conditions. The invention can realize ultrasonic stimulation of different parameters on different positions and depths of the brain functional area of the small animal under the condition that the small animal is conscious and freely moves.)

1. The focused ultrasound regulation and control device for positioning stimulation of the functional brain area of the small animal is characterized by comprising a head fixator (2) connected to a skull plane (1) of the small animal, wherein the head fixator (2) is sequentially connected with an ultrasound collimator (3) and an ultrasound transducer (4), the head fixator (2), the ultrasound collimator (3) and the ultrasound transducer (4) are coaxially arranged, and the ultrasound collimator (3) and the ultrasound transducer (4) are in adjustable connection; the small animal skull plane positioning device is characterized by further comprising a positioner (5) and a protector (6), wherein the positioner (5) can be connected with the head fixator (2), the positioner (5) is used for carrying out coordinate positioning on the small animal skull plane (1), and the protector (6) is used for preventing the small animal skull plane (1) from contacting the outside to cause infection under non-experimental conditions.

2. The focused ultrasound regulation and control device for small animal brain function region positioning stimulation according to claim 1, characterized in that the ultrasound collimator (3) comprises a cylindrical collimator (32) and a conical convergent tube (31) arranged at the lower side of the cylindrical collimator (32), the cylindrical collimator (32) is a hollow cylindrical structure with internal threads, the conical convergent tube (31) is a hollow circular truncated cone structure with uniform wall thickness, and a plurality of first clamping columns (13) are uniformly arranged at the outer side of the hollow circular truncated cone structure.

3. The focused ultrasound modulation device for small animal brain function region localization stimulation according to claim 2, characterized in that the bottom of the ultrasound transducer (4) is a concave spherical structure for generating focused sound waves, the middle is a first hollow cylindrical structure with external threads for matching and connecting a cylindrical collimator (32), and the top is a second hollow cylindrical structure for wiring.

4. The focused ultrasound modulation device for localized stimulation of functional brain areas of small animals according to claim 3, characterized in that scales are provided on the outside of the ultrasound transducer (4).

5. The focused ultrasound regulation and control device for the small animal brain functional region positioning stimulation according to claim 2, characterized in that the head holder (2) is of a hollow structure as a whole, the lower end of the head holder (2) is of a rounded structure, and the upper end of the head holder is provided with a plurality of clamping grooves (12) which are matched and connected with the first clamping columns (13).

6. The focused ultrasound regulation and control device for small animal brain function region positioning stimulation according to claim 5, characterized in that the shape of the positioner (5) is consistent with that of the conical convergent tube (31), the middle part of the positioner (5) is provided with a hollow cylinder structure for matching with a brain stereotaxic apparatus to perform coordinate positioning on the skull plane (1) of the small animal, and the outer side of the positioner (5) is provided with a plurality of second clamping columns which are matched and connected with the clamping grooves (12).

7. The focused ultrasound regulation and control device for small animal brain function region positioning stimulation according to claim 2, characterized in that the shape of the protector (6) is consistent with that of the conical convergent tube (31), the protector (6) is of a solid structure, a plurality of third clamping columns which are matched and connected with the clamping grooves (12) are arranged on the outer side of the protector (6), and a plurality of grooves for locking the protector (6) and the head holder (1) are arranged on the top of the protector (6).

8. The focused ultrasound regulation and control device for small animal brain functional area positioning stimulation according to claim 1, characterized in that the lower end of the head fixator (2) is fixed on the surface (1) of the small animal skull through an ion watergate; the head fixator (2), the ultrasonic collimator (3), the ultrasonic transducer (4), the positioner (5) and the protector (6) are all made of transparent photosensitive resin materials.

9. The focused ultrasound regulation and control device for the small animal brain functional area positioning stimulation according to claim 1, characterized by further comprising a test bench (7) when in use, wherein the test bench (7) comprises a base for providing a movable platform for the small animal, a vertical rod is arranged on the base, a cross rod is hinged on the vertical rod, one end of the cross rod is provided with a weight, the other end of the cross rod is provided with a universal rotating wheel, and the lower part of the universal rotating wheel is connected with the ultrasound transducer (4) through a wire.

10. A focused ultrasound control method for small animal brain functional region positioning stimulation, based on the focused ultrasound control device for small animal brain functional region positioning stimulation of any one of claims 1-9, it is characterized in that the skull surface (1), the head fixer (2), the ultrasonic collimator (3), the ultrasonic transducer (4), the locator (5) and the protector (6) of the small animal are sterilized, then the head fixator (2) is fixed on the skull surface (1) of the small animal with the help of the positioner (5), after the small animal is adapted, the ultrasonic collimator (3) is connected to the head fixator (2), then, an ultrasonic transducer (4) is connected to an ultrasonic collimator (3), and the neuron activation state of the stimulated region of the brain region of the small animal is observed by adjusting the ultrasonic transducer (4) to the required ultrasonic intensity to carry out experiments.

Technical Field

The invention belongs to the field of ultrasound biological application, relates to a device for ultrasonic nerve stimulation, and particularly relates to a focused ultrasound regulation and control device and method for positioning stimulation of a functional brain area of a small animal.

Background

In recent years, low-intensity focused ultrasound has attracted much attention as a neuromodulation means due to its advantages of non-invasiveness, high spatial resolution, and high penetration depth. However, the small animal brain is small in size and the skull is thin and fragile, so that the stimulation of the existing ultrasonic equipment to the small animal brain area is limited. At present, related technologies and devices for animal nerve ultrasonic stimulation experiments cannot give consideration to non-wound, accurate positioning and adjustable ultrasonic parameters and stimulation depth. In the related research work of the ultrasonic stimulation of the brain area of the conscious freely moving small animal, the head-mounted device needs to be small enough in weight, high in biocompatibility and accurate enough in stimulation action position. The ultrasonic equipment adopted in the prior art has larger weight and volume, so that the ultrasonic equipment is not beneficial to relevant research under the condition that small animals are conscious and freely move; particularly, the existing device can only stimulate a certain position of the brain area of the small animal fixedly, and can not stimulate different depths of different brain area positions, so that the effect is limited.

Disclosure of Invention

The invention provides a focused ultrasound regulation and control device and a focused ultrasound regulation and control method for positioning stimulation of a brain functional area of a small animal aiming at technical needs of related researches on the brain functional area stimulated by ultrasound, so as to overcome the problems in the prior art.

In order to achieve the purpose, the invention adopts the following technical scheme:

the focused ultrasound regulation and control device for the positioning stimulation of the brain functional area of the small animal comprises a head fixator connected to the skull plane of the small animal, wherein an ultrasound collimator and an ultrasound transducer are sequentially connected to the head fixator; the device also comprises a positioner and a protector, wherein the positioner and the protector can be connected with the head fixator, the positioner is used for carrying out coordinate positioning on the skull plane of the small animal, and the protector is used for preventing the skull plane of the small animal from contacting the outside to cause infection under non-experimental conditions.

Further, the ultrasonic collimator comprises a cylindrical collimator and a cone converging tube arranged on the lower side of the cylindrical collimator, the cylindrical collimator is of a hollow cylindrical structure with internal threads, the cone converging tube is of a hollow round table structure with uniform wall thickness, and a plurality of first clamping columns are uniformly arranged on the outer side of the hollow round table structure.

Furthermore, the bottom of the ultrasonic transducer is a concave spherical structure for generating focused sound waves, the middle of the ultrasonic transducer is a first hollow cylindrical structure with external threads for being matched and connected with a cylindrical collimator, and the top of the ultrasonic transducer is a second hollow cylindrical structure for wiring.

Further, scales are arranged on the outer side of the ultrasonic transducer.

Furthermore, the head fixer is of a hollow structure integrally, the lower end of the head fixer is of a fillet structure, and a plurality of clamping grooves connected with the first clamping columns in a matched mode are formed in the upper end of the head fixer.

Furthermore, the shape of the positioner is consistent with that of the conical convergent tube, the middle of the positioner is provided with a hollow cylindrical structure used for being matched with a brain stereotaxic apparatus to perform coordinate positioning on the plane of the skull of the small animal, and the outer side of the positioner is provided with a plurality of second clamping columns which are matched and connected with the clamping grooves.

Further, the shape of protector is unanimous with the circular cone beam-closing pipe, just the protector is solid construction, and the outside of protector is provided with a plurality of third card posts of being connected with the draw-in groove cooperation, the top of protector is provided with a plurality of recesses that are used for locking protector and head fixer.

Further, the lower end of the head fixator is fixed on the surface of the skull of the small animal through the ion water cement; the head fixer, the ultrasonic collimator, the ultrasonic transducer, the positioner and the protector are all made of transparent photosensitive resin materials.

Further, when using, still include the test bench, the test bench is provided with the montant including being used for providing movable platform's base for the toy on the base, and it has the horizontal pole to articulate on the montant, and the one end of horizontal pole is provided with the weight, and the other end is provided with universal runner, and universal runner lower part passes through the wire and is connected with ultrasonic transducer.

A focused ultrasound regulation and control method for positioning stimulation of a brain functional area of a small animal is characterized in that the surface of a skull of the small animal, a head fixator, an ultrasound collimator, an ultrasound transducer, a positioner and a protector are disinfected, then the head fixator is fixed on the surface of the skull of the small animal under the assistance of the positioner, after the small animal is adapted, the ultrasound collimator is connected to the head fixator, then the ultrasound transducer is connected to the ultrasound collimator, an experiment is carried out by adjusting the ultrasound transducer to required ultrasound intensity, and the neuron activation state of a stimulated area of the brain area of the small animal is observed.

Compared with the prior art, the invention has the following beneficial technical effects:

the device can improve the coordinate accuracy by matching and positioning the head fixer and the positioner; compared with the previous head fixing component for the ultrasonic experiment, the device fixer and the protector are daily worn parts, and the ultrasonic collimator and the ultrasonic transducer are worn only in the experiment process, so that the weight and the volume are reduced, and the purpose of not influencing the free movement of small animals is achieved.

Further, this device supersound collimater passes through the amazing degree of depth that screw-thread fit can realize fine regulation brain district with ultrasonic transducer, and the amazing degree of depth that highly carries out coarse adjustment brain district through the radius of adjusting cylinder collimation pipe and the pipe junction of conical beam narrowing and conical beam narrowing, compares than amazing device in the past, and the repeated amazing demand in the different degree of depth brain district of same animal in this device can satisfy the experiment.

Furthermore, the device can be matched with ultrasonic transducers with different parameters according to requirements, the replacement operation is simple, the shape and the energy transmission of an ultrasonic sound field are not influenced, and the stimulation effect comparison of ultrasonic waves with different parameters of the same animal can be realized.

Further, this device carries out the ultrasonic action through card post and draw-in groove coaxial coupling supersound collimater and head fixer in proper order, through threaded connection supersound collimater and ultrasonic transducer, connects conveniently, and is little to the toy stress degree.

Furthermore, the whole device is made of transparent photosensitive resin with biocompatibility, so that the compression and infection of the device to the brain exposure area of the small animal are reduced, the defects of overlarge ultrasonic transducer, high brain tissue exposure infection rate and the like in the brain area of the small animal under the ultrasonic action are overcome, and the repeated operation requirement of ultrasonic stimulation is met.

Furthermore, the device adopts the test bed to be matched for use, and the superfine wire is matched with the test bed provided with the universal rotating wheel for use, so that the head load of the small animal during ultrasonic work is greatly reduced, and the universal rotating wheel can also avoid the wire winding.

Drawings

The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 is an overall view of the apparatus of the present invention;

FIG. 2 is a structural view of an ultrasonic collimator of the present invention, wherein (a) is a perspective view and (b) is a sectional view;

FIG. 3 is a view showing the construction of a positioner according to the present invention, wherein (a) is a perspective view and (b) is a sectional view;

FIG. 4 is a structural view of a protector of the present invention, wherein (a) is a perspective view and (b) is a sectional view;

FIG. 5 is an experimental schematic of the apparatus of the present invention.

The device comprises a small animal skull plane 1, a head fixer 2, an ultrasonic collimator 3, an ultrasonic transducer 4, an ultrasonic transducer 5, a positioner 6, a protector 12, a clamping groove 13, a first clamping column 31, a conical convergent tube 32, a cylindrical collimator tube 111, a small animal brain area 7 and a test bed.

Detailed Description

In the description of the present invention, it should be understood that the terms "upper", "lower", "left", "right", "front", "back", "center", "vertical", "horizontal", "top", "bottom", "inner", "outer", "both sides", "one side", "inner side", "outer side", etc. indicating the orientation or positional relationship are based on the orientation or positional relationship shown in the drawings, not the actual specific position, and therefore, should not be construed as limiting the present invention, and the following detailed description of the embodiments of the present invention is made with reference to the drawings:

referring to fig. 1 to 5, the focused ultrasound regulation and control device for positioning and stimulating the brain functional region of the small animal comprises a head fixator 2, an ultrasound collimator 3 and an ultrasound transducer 4 which are coaxially connected on the skull surface 1 of the small animal in sequence, and further comprises a positioner 5 and a protector 6 which can be connected with the head fixator 2, wherein the positioner 5 is used for performing coordinate positioning on the skull plane 1 of the small animal, and the protector 6 is used for preventing the skull plane 1 of the small animal from contacting the outside to cause infection under the non-experimental condition.

The ultrasonic collimator 3 comprises a conical convergent tube 31 and a cylindrical collimator tube 32, and the inside of the cylindrical collimator tube 32 is of a threaded structure; the conical convergent tube 31 is used for restraining ultrasonic waves, and the cylindrical collimator tube 32 is used for forming and outputting plane waves; the radius of the connecting position of the conical convergent tube 31 and the cylindrical collimator tube 32 and the height of the conical convergent tube 31 are roughly adjusted, and the thread matching position of the ultrasonic transducer 4 and the ultrasonic collimator 3 is finely adjusted, so that the ultrasonic action on different depth brain areas of the small animal can be controlled.

The head fixer 2 is of a hollow structure as a whole; the lower end is in a rounded structure, and the upper end is provided with a clamping groove 12; the lower end of the small animal skull is bonded on the small animal skull plane 1 through the ion water heater; the clamping groove 12 at the upper end can be respectively connected with the ultrasonic collimator 3, the positioner 5 and the protector 6 through a first clamping column 13, a second clamping column and a third clamping column.

The ultrasonic transducer 4 is provided with scales for adjusting the spiral depth; the bottom is a concave spherical structure and is used for transmitting focused ultrasound; the top part is of a hollow cylindrical structure and is used for wiring; the middle part is a hollow cylinder structure with screw threads and is fixedly connected with the cylindrical collimator 32 through screw threads.

The shape of the locator 5 is the same as that of the cone convergent tube 31, but the middle part of the locator is of a hollow cylindrical structure, and the locator is located under the assistance of a brain stereotaxic apparatus after being connected with the head fixator 2.

The protector 6 has the same shape as the locator 5, but the whole protector is of a solid structure, and the top of the protector is of a groove structure; when not in experiment, the protector 6 can be connected and locked with the head fixer 2 through the matching of the tweezers and the groove structure, so that the infection caused by the contact of the skull plane 1 of the small animal with the outside can be prevented.

The head fixator 2, the ultrasonic collimator 3, the ultrasonic transducer 4, the positioner 5 and the protector 6 are all made of transparent photosensitive resin materials, so that the compression and infection risks of the device on the exposed brain area of the small animal are reduced.

When the test bed is used, the test bed 7 comprises a base used for providing a movable platform for small animals, a vertical rod is arranged on the base, a cross rod is hinged to the vertical rod, a weight is arranged at one end of the cross rod, a universal rotating wheel is arranged at the other end of the cross rod, and the lower portion of the universal rotating wheel is connected with an ultrasonic transducer 4 through a wire.

The following embodiments of the present invention are provided, and it should be noted that the present invention is not limited to the following embodiments, and all equivalent changes based on the technical solutions of the present invention are within the protection scope of the present invention.

The present example used mice as the subjects.

Specific example 1:

before the first experiment, firstly, the skull surface 1 of the small animal and an ultrasonic action device comprising a head fixer 2, an ultrasonic collimator 3, an ultrasonic transducer 4, a positioner 5 and a protector 6 are disinfected; secondly, performing surgical treatment on the skull plane 1 of the target small animal, fixing the head fixator 2 on the skull surface 1 of the small animal through the ionostome with the assistance of the positioner 5, and performing an experiment after the mouse adapts.

During the first experiment, adjust the required ultrasonic intensity of experiment with the supersound, select for use the cone convergent tube 31 that highly is 2mm and the supersound collimater 3 that the diameter is 6.2mm cylinder collimator 32 constitutes, through threaded connection together, be connected to head fixer 2 through first card post 13 and draw-in groove 12 with supersound collimater 3 again on, experiment, the experiment is observed the neuron that little animal brain region 111 receives the stimulation region and is activated.

After the experiment for the first time, take off ultrasonic collimator 3 and ultrasonic transducer 4 in proper order to be connected to head fixer 2 with protector 6 through third card post 13 and draw-in groove 12 on, and utilize tweezers to pass through groove structure locking on protector 6, all experimental facilities are accomodate in the arrangement.

Preferably, in the implementation process of the invention, the test can be carried out through the test bed 7, the weight of the device at the head of the mouse is reduced through the vertical rods, the transverse rods, the matched weights and the outward rotating wheels, so that the mouse can freely move in the cage on the base, the lead cannot be wound, and the upper part of the cage is provided with an opening.

Specific example 2:

the secondary and many times of experiments only need take off protector 5 with tweezers, then adjust the target parameter with the supersound, choose for use the supersound collimater 3 of suitable size, link together ultrasonic transducer 4 and supersound collimater 3 through the screw thread, again with supersound collimater 3 through first card post 13 and draw-in groove 12 be connected to head fixer 2 on, experiment. After the experiment was accomplished, take off ultrasonic collimator 3 and ultrasonic transducer 4 in proper order to be connected to head fixer 2 with protector 6 through third card post and draw-in groove 12 on, and utilize tweezers to pass through the recess locking on the protector 6, all experimental facilities are accomodate in the arrangement.

Preferably, the test stand 7 can also be used for auxiliary operations.

The above-mentioned contents are only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited thereby, and any modification made on the basis of the technical idea of the present invention falls within the protection scope of the claims of the present invention.