CN113559425B - Focusing ultrasonic regulation and control device and method for small animal brain functional area positioning stimulation - Google Patents
Focusing ultrasonic regulation and control device and method for small animal brain functional area positioning stimulation Download PDFInfo
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- CN113559425B CN113559425B CN202110867011.XA CN202110867011A CN113559425B CN 113559425 B CN113559425 B CN 113559425B CN 202110867011 A CN202110867011 A CN 202110867011A CN 113559425 B CN113559425 B CN 113559425B
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- ultrasonic transducer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N7/00—Ultrasound therapy
- A61N2007/0004—Applications of ultrasound therapy
- A61N2007/0021—Neural system treatment
- A61N2007/0026—Stimulation of nerve tissue
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
- Y02A40/70—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in livestock or poultry
Abstract
The invention discloses a focused ultrasonic regulation and control device and a method for positioning stimulation of brain functional areas of small animals, wherein the device comprises a head fixer connected to the plane of the skull of the small animals, an ultrasonic collimator and an ultrasonic transducer are sequentially connected to the head fixer, the ultrasonic collimator and the ultrasonic transducer are coaxially arranged, and the ultrasonic collimator and the ultrasonic transducer are connected in an adjustable way; the device also comprises a positioner and a protector, wherein the positioner can be connected with the head fixer, the positioner is used for carrying out coordinate positioning on the plane of the skull of the small animal, and the protector is used for preventing the plane of the skull of the small animal from being infected by contacting the outside under non-experimental conditions. The invention can realize ultrasonic stimulation of different parameters for different positions and depths of brain functional areas of small animals under the condition of waking and free movement of the small animals.
Description
Technical Field
The invention belongs to the field of ultrasonic biological application, relates to a device for ultrasonic nerve stimulation, and in particular relates to a focused ultrasonic regulation and control device and method for positioning stimulation of brain functional areas of small animals.
Background
In recent years, low-intensity focused ultrasound has attracted considerable attention as a means of neuromodulation due to the 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 brain region of the small animal is limited. At present, the related technology and device for animal nerve ultrasonic stimulation experiments cannot achieve noninvasive and accurate positioning, and the ultrasonic parameters and the stimulation depth are adjustable. In the related research work of carrying out ultrasonic stimulation of brain areas of awake free moving small animals, the head-mounted device is required 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 the related research under the condition of free activity of waking of small animals; in particular, the existing device can only stimulate a certain position of the brain region of the small animal fixedly, and can not realize different depth stimulation to different brain region positions, so that the effect is limited.
Disclosure of Invention
Aiming at the technical needs of the related research of the brain nerve functional area stimulated by the ultrasound, the invention provides a focused ultrasound control device and a method for positioning and stimulating the brain functional area of a small animal so as to overcome the problems in the prior art.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the focusing ultrasonic regulation and control device for the positioning stimulation of the brain functional area of the small animal comprises a head fixer connected to the plane of the skull of the small animal, wherein an ultrasonic collimator and an ultrasonic transducer are sequentially connected to the head fixer, the ultrasonic collimator and the ultrasonic transducer are coaxially arranged, and the ultrasonic collimator and the ultrasonic transducer are connected in an adjustable way; the device also comprises a positioner and a protector, wherein the positioner can be connected with the head fixer, the positioner is used for carrying out coordinate positioning on the plane of the skull of the small animal, and the protector is used for preventing the plane of the skull of the small animal from being infected by contacting the outside under non-experimental conditions.
Further, the ultrasonic collimator comprises a cylindrical collimator and a conical converging tube arranged on the lower side of the cylindrical collimator, the cylindrical collimator is of a hollow cylindrical structure with internal threads, the conical converging tube is of a hollow round platform structure with uniform wall thickness, and a plurality of first clamping columns are uniformly arranged on the outer side of the hollow round platform structure.
Further, 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, the outer side of the ultrasonic transducer is provided with scales.
Further, the whole hollow structure that is of head fixer, just head fixer lower extreme is the chamfer structure, and the upper end is provided with a plurality of draw-in grooves of being connected with first draw-in column cooperation.
Further, the shape of the locator is consistent with that of the conical converging tube, the middle of the locator is provided with a hollow cylindrical structure for coordinate positioning of the plane of the skull of the small animal by matching with the brain stereotactic instrument, and the outer side of the locator is provided with a plurality of second clamping columns which are matched and connected with the clamping grooves.
Further, the shape of the protector is consistent with that of the conical converging tube, the protector is of a solid structure, a plurality of third clamping columns which are connected with the clamping grooves in a matched mode are arranged on the outer side of the protector, and a plurality of grooves used for locking the protector and the head fixing device are formed in the top of the protector.
Further, the lower end of the head fixer is fixed on the surface of the skull of the small animal through an ion water portal; 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 toy on the base, articulates on the montant has the horizontal pole, 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.
The method comprises the steps of disinfecting the surfaces of the cranium of the small animals, a head fixer, an ultrasonic collimator, an ultrasonic transducer, a positioner and a protector, fixing the head fixer on the surfaces of the cranium of the small animals with the aid of the positioner, connecting the ultrasonic collimator to the head fixer after the small animals are adapted, connecting the ultrasonic transducer to the ultrasonic collimator, and carrying out experiments by adjusting the ultrasonic transducer to the required ultrasonic intensity to observe the neuron activation state of the stimulated region of the brain of the small animals.
Compared with the prior art, the invention has the following beneficial technical effects:
the device of the invention can improve the coordinate accuracy by matching and positioning the head fixer and the positioner; compared with the prior ultrasonic experiment head fixing assembly, the device has the advantages that the device is provided with the fixing device and the protector which are daily wearing parts, the ultrasonic collimator and the ultrasonic transducer are only worn in the experiment process, the weight and the volume are reduced, and the purpose of not affecting the free movement of small animals is achieved.
Furthermore, the device can realize the stimulation depth of brain regions by fine adjustment through threaded fit between the ultrasonic collimator and the ultrasonic transducer, and the stimulation depth of brain regions is coarsely adjusted by adjusting the radius of the joint of the cylindrical collimator and the conical converging tube and the height of the conical converging tube.
Furthermore, the device can be matched with ultrasonic transducers with different parameters according to requirements, is simple to replace and operate, does not influence the shape and energy transmission of an ultrasonic field, and can realize the comparison of the stimulation effects of ultrasonic waves with different parameters of the same animal.
Further, the device is sequentially and coaxially connected with the ultrasonic collimator and the head fixator through the clamping columns and the clamping grooves to perform ultrasonic action, and is connected with the ultrasonic collimator and the ultrasonic transducer through threads, so that the device is convenient and quick to connect, and has small stress degree on small animals.
Furthermore, the whole set of device is made of transparent biocompatible photosensitive resin materials, so that the compression and infection of the device to the brain area exposed by the small animals are reduced, the defects of overlarge ultrasonic transducer, high brain tissue exposure infection rate and the like in the brain area of the small animals under the ultrasonic action are overcome, and the repeated operation requirement of ultrasonic stimulation is met.
Further, the device adopts the test bed to cooperate with each other, and through using the extremely fine lead wire and cooperating with the test bed provided with the universal rotating wheel, the load on the head of the small animal during the ultrasonic work is greatly reduced, and in addition, the lead wire winding can be avoided by the universal rotating wheel.
Drawings
The accompanying drawings, which 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.
FIG. 1 is an overall view of the device of the present invention;
FIG. 2 is a block diagram of an ultrasound collimator of the present invention, wherein (a) is a perspective view and (b) is a cross-sectional view;
FIG. 3 is a block diagram of a positioner according to the present invention, wherein (a) is a perspective view and (b) is a cross-sectional view;
FIG. 4 is a block diagram of the protector of the present invention, wherein (a) is a perspective view and (b) is a sectional view;
fig. 5 is a schematic illustration of an experiment of the apparatus of the present invention.
Wherein, 1, the plane of the skull of the small animal, 2, a head fixer, 3, an ultrasonic collimator, 4, an ultrasonic transducer, 5, a positioner, 6, a protector, 12, clamping grooves, 13, a first clamping column, 31, a conical converging tube, 32, a cylindrical collimator, 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 terms such as "upper", "lower", "left", "right", "front", "rear", "center", "vertical", "horizontal", "top", "bottom", "inner", "outer", "two sides", "one side", "inner side", "outer side", etc. indicate azimuth or positional relationship, are based on azimuth or positional relationship shown in the drawings, and are not actually specific positions, and thus should not be construed as limiting the present invention, and embodiments of the present invention will be described in detail with reference to the accompanying drawings:
referring to fig. 1 to 5, a focused ultrasound control device for positioning stimulation of brain functional areas of small animals comprises a head fixer 2, an ultrasound collimator 3 and an ultrasound transducer 4 which are coaxially connected to the surface 1 of the small animal skull in sequence, and further comprises a positioner 5 and a protector 6 which can be connected with the head fixer 2, wherein the positioner 5 is used for positioning coordinates of the small animal skull plane 1, and the protector 6 is used for preventing the small animal skull plane 1 from being infected by contacting the outside under non-experimental conditions.
The ultrasonic collimator 3 comprises a conical beam converging tube 31 and a cylindrical collimator tube 32, and a thread structure is arranged inside the cylindrical collimator tube 32; the conical converging tube 31 is used for restraining ultrasonic waves, and the cylindrical collimator tube 32 is used for forming plane waves and outputting the plane waves; the thread matching positions of the ultrasonic transducer 4 and the ultrasonic collimator 3 are adjusted by roughly adjusting the radius of the connection position of the conical converging tube 31 and the cylindrical collimator 32 and the height of the conical converging tube 31, so that the ultrasonic can be controlled to act on brain regions with different depths of small animals.
The head fixer 2 is of a hollow structure as a whole; the lower end is of a rounded structure, and the upper end is provided with a clamping groove 12; the lower end of the artificial bone is adhered to the skull plane 1 of the small animal through an ion water portal; 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 of a concave spherical structure and is used for emitting focused ultrasound; the top is of a hollow cylindrical structure and is used for wiring; the middle part is a hollow cylindrical structure with threads, and is fixed with the cylindrical collimator 32 through threaded connection.
The shape of the locator 5 is the same as that of the conical converging tube 31, but the middle part is of a hollow cylinder structure, and the locator is positioned under the assistance of a brain stereotactic instrument after being connected with the head fixer 2.
The shape of the protector 6 is the same as that of the locator 5, but the whole protector is of a solid structure, and the top of the protector is of a groove structure; when no experiment is carried out, the protector 6 can be connected and locked with the head fixer 2 through the cooperation of forceps and the groove structure, so that the small animal skull plane 1 is prevented from being infected by contacting the outside.
The head fixer 2, the ultrasonic collimator 3, the ultrasonic transducer 4, the locator 5 and the protector 6 are made of transparent photosensitive resin materials, so that the compression and infection risk of the device to the exposed brain area of the small animal is reduced.
When the ultrasonic testing device is used, the ultrasonic testing device further comprises a test bed 7, wherein the test bed 7 comprises a base 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, 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 ultrasonic transducer 4 through a wire.
The following specific embodiments of the present invention are provided, and it should be noted that the present invention is not limited to the following specific embodiments, and all equivalent changes made on the basis of the technical solutions of the present application fall within the protection scope of the present invention.
The present example uses mice as subjects.
Specific example 1:
before the first experiment, the surface 1 of the skull 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 sterilized; secondly, carrying out operation treatment on the target small animal skull plane 1, fixing the head fixer 2 on the small animal skull plane 1 through an ion water portal with the assistance of the locator 5, and carrying out experiments after the mice are adapted.
In the first experiment, the ultrasound is adjusted to the intensity of the ultrasound required by the experiment, an ultrasound collimator 3 consisting of a conical beam-converging tube 31 with the height of 2mm and a cylindrical collimator tube 32 with the diameter of 6.2mm is selected and connected together through threads, and then the ultrasound collimator 3 is connected to the head fixer 2 through a first clamping column 13 and a clamping groove 12, so that the experiment is performed, and the neuron in the stimulated region of the brain region 111 of the small animal is observed to be activated.
After the first experiment, the ultrasonic collimator 3 and the ultrasonic transducer 4 are sequentially taken down, the protector 6 is connected to the head fixer 2 through the third clamping column and the clamping groove 12, and all experimental equipment is collected in a tidying way by utilizing tweezers and locked through a groove structure on the protector 6.
Preferably, in the implementation process of the invention, the test can be carried out by the test bed 7, and the weight of the device for the head of the mouse is reduced by the vertical rod, the transverse rod, the matched weights and the outward rotating wheel, so that the mouse can freely move in the cage on the base without winding wires, and the upper part of the cage is provided with an opening.
Specific example 2:
and for secondary and multiple experiments, only the protector 6 is taken down by forceps, then the ultrasound is regulated to target parameters, the ultrasound collimator 3 with proper size is selected, the ultrasound transducer 4 and the ultrasound collimator 3 are connected together through threads, and then the ultrasound collimator 3 is connected to the head fixer 2 through the first clamping column 13 and the clamping groove 12 for experiments. After the experiment is completed, the ultrasonic collimator 3 and the ultrasonic transducer 4 are sequentially removed, the protector 6 is connected to the head fixer 2 through the third clamping column and the clamping groove 12, and all experimental equipment is tidied and contained by utilizing tweezers and locking through grooves on the protector 6.
Preferably, the test stand 7 may be used for the auxiliary operation.
The above is only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited by this, and any modification made on the basis of the technical scheme according to the technical idea of the present invention falls within the protection scope of the claims of the present invention.
Claims (7)
1. The focusing ultrasonic regulation and control device for the positioning stimulation of the brain functional area of the small animal is characterized by comprising a head fixer (2) connected to the skull plane (1) of the small animal, wherein the head fixer (2) is sequentially connected with an ultrasonic collimator (3) and an ultrasonic transducer (4), the head fixer (2), the ultrasonic collimator (3) and the ultrasonic transducer (4) are coaxially arranged, and the ultrasonic collimator (3) and the ultrasonic transducer (4) are connected in an adjustable way; the device also comprises a locator (5) and a protector (6) which can be connected with the head fixer (2), wherein the locator (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 being infected when contacting the outside under the non-experimental condition;
the ultrasonic collimator (3) comprises a cylindrical collimator tube (32) and a conical converging tube (31) arranged at the lower side of the cylindrical collimator tube (32), wherein the conical converging tube (31) is used for restraining ultrasonic waves, the cylindrical collimator tube (32) is of a hollow cylindrical structure with internal threads, and the cylindrical collimator tube (32) is used for forming plane waves and outputting the plane waves;
the bottom of the ultrasonic transducer (4) is of a concave spherical structure for emitting focused ultrasonic, the middle of the ultrasonic transducer is of a first hollow cylindrical structure with external threads for being matched and connected with a cylindrical collimator (32), and the top of the ultrasonic transducer is of a second hollow cylindrical structure for wiring;
the outer side of the ultrasonic transducer (4) is provided with scales for spiral depth adjustment;
the thread matching positions of the ultrasonic transducer (4) and the ultrasonic collimator (3) are finely adjusted through coarse adjustment of the radius of the connection position of the conical converging tube (31) and the cylindrical collimator (32) and the height of the conical converging tube (31), so that the ultrasonic can be controlled to act on brain areas with different depths of small animals.
2. The focused ultrasound control device for positioning stimulation of brain functional areas of small animals according to claim 1, wherein the conical converging tube (31) is of a hollow round platform structure with uniform wall thickness, and a plurality of first clamping columns (13) are uniformly arranged on the outer side of the hollow round platform structure.
3. The focused ultrasound control device for positioning stimulation of brain functional areas of small animals according to claim 2, wherein 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 a plurality of clamping grooves (12) which are connected with the first clamping columns (13) in a matching way are arranged at the upper end of the head holder.
4. The focused ultrasound control device for positioning stimulation of brain functional areas of small animals according to claim 3, wherein the shape of the positioner (5) is consistent with that of the conical converging tube (31), a hollow cylindrical structure for coordinate positioning of the plane (1) of the skull of the small animals by matching with a brain stereotactic instrument is arranged in the middle of the positioner (5), and a plurality of second clamping columns matched and connected with the clamping grooves (12) are arranged on the outer side of the positioner (5).
5. The focused ultrasound control device for positioning stimulation of brain functional areas of small animals according to claim 2, wherein the shape of the protector (6) is consistent with that of a conical converging tube (31), the protector (6) is of a solid structure, a plurality of third clamping columns which are matched and connected with 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 fixator (2) are formed in the top of the protector (6).
6. The focused ultrasound control device for small animal brain functional area positioning stimulation according to claim 1, characterized in that the lower end of the head fixer (2) is fixed on the small animal skull surface (1) through an ion water portal; the head fixer (2), the ultrasonic collimator (3), the ultrasonic transducer (4), the locator (5) and the protector (6) are made of transparent photosensitive resin materials.
7. The focused ultrasound control device for positioning stimulation of brain functional areas of small animals according to claim 1, further comprising a test bed (7) when in use, wherein the test bed (7) comprises a base for providing a movable platform for the small animals, 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 an ultrasound transducer (4) through a wire.
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| CN114432604B (en) * | 2022-02-18 | 2023-04-07 | 天津大学 | Angle-adjustable wearable double-channel conduction device and ultrasonic regulation and control system |
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