Implantable ultrasonic stimulation device and method based on electromagnetically induced sound

Abstract

The invention discloses an implantable ultrasonic stimulation device and method based on electromagnetic sound, which can realize a novel transcranial ultrasonic stimulation technology by organically integrating an electromagnetic sound principle and an implantable and controllable high electromagnetic absorption material. The device comprises an electromagnetic wave generation module, a magnetic field generation module, an ultrasonic wave generation module, an ultrasonic signal acquisition module and an image processing and analyzing module. According to the device and the method, the high electromagnetic absorption material implanted into the cranium is excited by using electromagnetic waves to generate ultrasonic waves, so that stimulation on brain tissues in different areas and at different depths is realized, and the stimulation intensity can be adjusted. Compared with traditional transcranial ultrasonic stimulation and transcranial direct current stimulation technologies, the transcranial direct current stimulation system has the advantages of being efficient in stimulation, adjustable in stimulation position, capable of positioning a sound source in real time, adjustable in strength, deep in penetration, capable of achieving long-term stimulation, biocompatible, low in cost and the like, and has large potential application value in the fields of cranial nerve regulation and control, brain medicine precise delivery and the like.

Description

Technical Field

[0001] The present invention belongs to the field of medical equipment and optical and electromagnetic medical imaging, and in particular relates to an implantable ultrasonic stimulation device and method based on electromagnetic sound. Background Art

[0002] Neuromodulation technology is a branch of neuroscience, and it plays a key role in the treatment of neurological diseases. At present, neuromodulation generally uses transcranial ultrasound stimulation technology. This technology transmits ultrasonic energy to the lesion area, and uses the thermal effect, force effect and cavitation effect caused by ultrasound to achieve direct treatment or auxiliary treatment of the lesion area without damaging normal tissue. Transcranial ultrasound stimulation has the advantages of low cost, non-invasiveness, and easy adaptation to closed-loop therapy in the treatment of cranial nerve diseases, and has therefore received widespread attention. However, due to the impedance mismatch between ultrasound in the skull and brain tissue, ultrasound will be severely attenuated and diffused during propagation, making it difficult for ultrasound to accurately stimulate targets deep in the brain after passing through the skull. More importantly, the stimulation target cannot be visualized, making it difficult to dynamically adjust the position of the stimulation target. These factors have greatly limited the application progress of this technology in preclinical and bedside.

[0003] In addition, neuromodulation technologies also include transcranial direct current stimulation and transcranial magnetic stimulation. Transcranial direct current stimulation achieves non-invasive neuromodulation by transmitting electric current to the target area to induce neuronal excitability. However, within the limited depth under the cortex, the current will diffuse throughout the brain, and the technology has a large range of stimulation, so it is difficult to provide ultrasound stimulation to specific areas and depths of the brain. Summary of the invention

[0004] 1. Technical issues to be resolved Traditional transcranial ultrasound stimulation technology has limitations. Since high-frequency ultrasound waves will experience severe attenuation, high reflection, and diffraction effects in the human skull, the efficiency of ultrasound stimulation at the target location is generally low. In addition, traditional transcranial ultrasound stimulation technology is difficult to achieve precise stimulation of different target locations in the skull. Therefore, these factors limit its application in the fields of neural regulation and precise drug delivery. Based on these deficiencies in the prior art, the present invention proposes an implantable ultrasound stimulation device and method based on electromagnetic sound.

[0005] (II) Technical solution In the present invention, the electromagnetic acoustic principle is actually a filling particle with high electromagnetic absorption in a flexible flow channel implanted in the brain. Due to the implant placement, the present invention can greatly avoid the attenuation, high reflection and diffraction effect of the skull on ultrasound. The flexible flow channel is filled with filling liquid and a number of filling particles with high electromagnetic absorption and magnetism are placed, so that the filling particles can move freely under the control of the external magnetic field. By using the strong penetration of low-frequency electromagnetic waves (such as microwave band) and the electromagnetic acoustic principle, the filling particles with high electromagnetic absorption in the flexible flow channel are excited by electromagnetic waves to generate high-frequency ultrasound, and the conversion of electromagnetic energy to mechanical energy is realized in the brain. Subsequently, the ultrasonic signal acquisition module performs A-scan to obtain the time domain ultrasonic signal, and the image processing and analysis module is used to process and analyze the obtained time domain ultrasonic signal to obtain a reconstructed image containing the particle position, which is used to indicate the position of the filling particles in the flow channel. Finally, since the filling particles are magnetic, the magnetic field generated by the magnetic field generation module can be used to guide the filling particles to move to the specified position in the flow channel according to the position of the filling particles in the flow channel in the reconstructed image, so as to realize ultrasonic stimulation in a specific brain area. Since the flexible flow channel is placed inside the skull through implantation technology, the reflection, scattering and absorption loss of ultrasound energy by the skull can be reduced to the greatest extent. In addition, the material of the flexible flow channel is composed of carbon-based or silicon-based polymer materials, which are biocompatible and can minimize the invasive effects of implanted devices on biological tissues.

[0006] In order to solve the technical problem, the present invention provides an implantable ultrasonic stimulation device and method based on electromagnetic sound.

[0007] An implantable ultrasonic stimulation device based on electromagnetic sound is used to achieve electromagnetic wave-induced ultrasonic stimulation at a specific position in intracranial brain tissue. The implantable ultrasonic stimulation device comprises: An electromagnetic wave generating module, used for generating electromagnetic waves; A magnetic field generating module, located outside the skull, for generating a magnetic field; An ultrasonic generating module comprises a flexible flow channel, a filling liquid and filling particles; the flexible flow channel adopts a flat design and has biocompatibility, can be implanted inside the skull and in close contact with brain tissue, and its internal structure is a fluid channel that can traverse most areas of the flexible flow channel; the flexible flow channel can be injected with a filling liquid to fill the entire flow channel, and the filling particles can be placed in the flow channel filled with the filling liquid; the filling particles have high electromagnetic absorption, and are used to absorb the electromagnetic waves generated by the electromagnetic wave generating module and generate high-frequency ultrasonic waves based on the principle of electromagnetic acoustic induction; the filling particles are magnetic and can be manipulated by the magnetic field generated by the magnetic field generating module; An ultrasonic signal acquisition module, used to acquire time-domain ultrasonic signals emitted by the filling particles after absorbing electromagnetic waves; The image processing and analysis module is used to process and analyze the signal obtained by the ultrasonic signal acquisition module to obtain a reconstructed image containing the position of the filling particles. The image can be used to indicate the position of the filling particles in the flow channel.

[0008] Preferably, the electromagnetic wave generating module includes an electromagnetic wave radiation source and an irradiation antenna. The electromagnetic wave radiation source adopts pulse or continuous wave modulation output, and its frequency range covers all frequency bands that can penetrate the skull. Its repetition frequency includes but is not limited to the Hz ~ MHz level.

[0009] Preferably, the magnetic field generating module includes but is not limited to a small magnet or an energized solenoid coil, and is used to generate a magnetic field to manipulate the position movement of the filling particles.

[0010] Preferably, the constituent materials of the flexible flow channel include but are not limited to polydimethylsiloxane PDMS, polyethylene PE and polypropylene PP.

[0011] Preferably, the cross-sectional pattern of the fluid channel of the flexible flow channel includes but is not limited to regular patterns such as square or circle.

[0012] Preferably, the thickness of the flexible flow channel is in the order of magnitude including but not limited to millimeters and sub-millimeters.

[0013] Preferably, the filling liquid includes but is not limited to inorganic or organic solvents such as mineral oil and glycerin.

[0014] Preferably, the position of the electromagnetic wave generating module is adjustable relative to the filling particles.

[0015] The present invention also claims protection for an implantable ultrasonic stimulation method based on electromagnetic sound, which is used to achieve electromagnetic wave-induced ultrasonic stimulation in a specific brain area, and the implantable ultrasonic stimulation method uses the aforementioned implantable ultrasonic stimulation device based on electromagnetic sound to work. The specific steps of the implantable ultrasonic stimulation method are as follows: Step S1, implanting the flexible flow channel filled with filling liquid and loaded with filling particles into the inner side of the skull and making it fit in contact with the brain tissue; Step S2, the electromagnetic wave generating module starts to work, the electromagnetic wave radiation source generates electromagnetic waves and outputs them through the antenna; Step S3, the antenna of the electromagnetic wave generating module forwardly irradiates the flexible flow channel loaded with filling particles, and the filling particles absorb the electromagnetic wave energy to generate ultrasonic waves and stimulate the brain area; the ultrasonic signal acquisition module performs A-scan to obtain time-domain ultrasonic signals, and the image processing and analysis module processes and analyzes the obtained time-domain ultrasonic signals to obtain a reconstructed image containing the positions of the filling particles, and the image is used to indicate the positions of the filling particles in the flow channel; Step S4, adjusting the antenna of the electromagnetic wave generating module to change the distance between the antenna and the filling particles to achieve ultrasonic stimulation of different intensities; Step S5, based on the position of the filling particles in the flow channel in the reconstructed image obtained in step S3, use the magnetic field generated by the magnetic field generating module to guide the filling particles to move to the specified position in the flow channel to achieve adjustment of the ultrasonic stimulation area; after the position movement is completed, repeat steps S3-S4 until ultrasonic stimulation of a specific intensity is achieved in a specific brain area.

[0016] (III) Beneficial effects Compared with the prior art, the present invention has significantly positive technical effects, and its beneficial effects are at least reflected in the following aspects.

[0017] (1) The present invention is based on the principle of electromagnetic acoustic stimulation. By exciting the filling particles with high electromagnetic absorption in the flexible flow channel implanted in the skull with electromagnetic waves, high-intensity ultrasonic stimulation can be achieved. Compared with the traditional transcranial ultrasonic stimulation technology, the present invention avoids the problems of energy dissipation and phase shift caused by ultrasonic waves penetrating the skull, and uses the deep penetration of low-frequency electromagnetic waves to efficiently stimulate ultrasonic waves in the skull.

[0018] (2) The present invention uses filling particles to absorb electromagnetic wave energy to generate ultrasonic waves. The ultrasonic signal acquisition module is used to perform A-scan to obtain time-domain ultrasonic signals, and the obtained time-domain ultrasonic signals are processed and analyzed by the image processing and analysis module to obtain a reconstructed image containing the particle position. The image is used to indicate the position of the filling particles in the flow channel, and the sound source can be located in real time. With this design, the particles can be intuitively guided to move to a specified position using an external magnetic field according to the particle position, and the distance from the antenna to the filling particles can be adjusted to achieve ultrasonic stimulation of a specific area of ​​the brain and a specific intensity. Compared with the traditional transcranial stimulation method of implanting hydrophones to adjust the stimulation position, which requires repeated implantation surgery, the present invention has a simple process for adjusting the stimulation position and intensity, and does not require the implantation of passive devices.

[0019] (3) The flexible flow channel made of one or more materials selected from polydimethylsiloxane (PDMS), polyethylene (PE) and polypropylene (PP) is biocompatible, so this technology can be used for long-term ultrasound brain regulation or treatment. Compared with traditional transcranial ultrasound stimulation technology, this method has low preparation technology requirements and is low in price.

[0020] (4) Compared with traditional transcranial direct current stimulation technology, the present invention can effectively avoid the medical safety issues caused by exciting current in the brain.

[0021] (5) The particles with high electromagnetic absorption in the present invention are abundant in source. Taking electromagnetic waves with a frequency of 3 GHz as an example, the electrolyte solution for preparing particles with high electromagnetic absorption includes but is not limited to: sodium chloride solution, calcium chloride solution, and copper sulfate solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The present invention is a schematic diagram of the device structure.

[0023] Figure 2 Schematic diagram of the structure of the flexible flow channel.

[0024] Figure 3 This is a physical picture of the structure of the flexible flow channel.

[0025] Figure 4 The display shows calcium alginate particles doped with Fe3O4 and immersed in a high concentration sodium chloride solution, including: actual pictures of particles of different particle sizes, photos of individual particles under a microscope, and photos of particles adsorbed by a magnet.

[0026] Figure 5 The time domain signal generated by 4 filling particles with a particle diameter of 2 mm under the irradiation of electromagnetic waves with a pulse width of 0.3 μs and a frequency of 3 GHz is shown.

[0027] Among them, the names of the components shown in the figure are: computer 1-1, electromagnetic wave radiation source 1-2 with selectable repetition rate, frequency and pulse width, antenna or waveguide 1-3, flexible flow channel 1-4 loaded with a number of high-concentration electromagnetic absorption particles, neuron 1-5, skull 1-6, ultrasound probe 1-7, signal amplifier 1-8. DETAILED DESCRIPTION

[0028] In order to solve the technical problem, the present invention provides an implantable ultrasonic stimulation device and method based on electromagnetic sound. The technical solution of the present invention is further described below through specific implementation methods.

[0029] The schematic diagram of the device structure implemented by the present invention is as follows Figure 1 shown.

[0030] Figure 2 It is a schematic diagram of the structure of the flexible flow channel, whose internal structure is a linear fluid channel that can traverse all areas of the flexible flow channel.

[0031] Figure 3 The figure is a physical picture of the structure of the flexible flow channel. The manufacturing steps of the flexible flow channel include: mixing of polymer and hardener, preparing polymer film, thermally curing polymer, preparing flow channel photolithography mold, polymer photolithography, separation and bonding of the flow channel, etc.

[0032] Figure 4 The calcium alginate particles doped with nano-Fe3O4 and immersed in a high concentration of sodium chloride solution are shown: 1. Particles of different sizes can be produced according to demand; 2. The particle size can be measured under a microscope; 3. By doping with Fe3O4, the obtained particles are made magnetic and can be controlled by a magnetic field.

[0033] Figure 5The time domain ultrasonic signals generated by 4 particles with a diameter of 2 mm under the irradiation of pulsed electromagnetic waves with a frequency of 3 GHz and a pulse width of 0.3 μs are shown.

[0034] First, when preparing calcium alginate particles, nano-Fe3O4 (including but not limited to Fe, Co, Ni elements and their alloys) needs to be doped to ensure that they have magnetism. The particles are immersed in a high-concentration sodium chloride solution to fully fill the pores of the particles, thereby obtaining filled particles with magnetism and high electromagnetic absorption. The filled particles are loaded into a flexible flow channel filled with filling liquid, and the flow channel is sealed with glue. The flexible flow channel is implanted into the inside of the skull and is in close contact with the brain tissue.

[0035] The electromagnetic acoustic system is constructed using the simplest traditional single-probe scanning system. This system uses a 3GHz pulsed electromagnetic wave radiation source as the signal excitation source. The pulsed electromagnetic wave generated by it passes through the center of the rotating motor through a coaxial cable and is transmitted to the antenna. Then, the antenna radiates vertically from the top of the skull to the flexible flow channel in the form of linear polarization, circular polarization or elliptical polarization.

[0036] Under the irradiation of pulsed or continuous wave modulated electromagnetic waves, the filling particles in the flexible flow channel will undergo high-efficiency electromagnetic wave-ultrasonic energy conversion. In this process, electromagnetic energy is first converted into thermal energy, and finally converted into mechanical energy through the thermoacoustic effect, which is transmitted to the brain in the form of ultrasound and stimulates neurons.

[0037] In addition, by controlling the distance between the antenna and the filling particles, the ultrasonic sound pressure at the stimulation target can be adjusted.

[0038] Subsequently, the ultrasonic probe is manually operated to perform A-scan and obtain the thermoacoustic signal. This system uses an immersion non-focused ultrasonic probe provided by Olympus to detect the thermoacoustic signal. Its diameter is 15.8mm, the effective response area is 12.7mm, and the center frequency is 2.25MHz. The signal is amplified by the preamplifier and input into the data acquisition card PCI-5122 and stored on the computer. The A-scan signal of the target object is processed by the data processing software on the computer to obtain a reconstructed image containing the particle position, which can be used to indicate the position of the filling particles in the flow channel.

[0039] Finally, according to the reconstructed image containing the particle position, the magnetic field generated by the magnetic field generating module is used to guide the particles in the flow channel to move to the specified position, thereby achieving the adjustment of the ultrasonic stimulation area.

[0040] The implantable ultrasound stimulation transposition based on electromagnetic sound-induced proposed by the present invention can realize ultrasound stimulation of specific intensity to specific brain areas; electromagnetic waves are used to excite the filling particles with high electromagnetic absorption in the flexible flow channel implanted in the skull, which can avoid the problems of energy dissipation and phase shift when ultrasound penetrates the skull, and excite ultrasound in the skull with high efficiency; after the filling particles absorb the electromagnetic wave energy to generate ultrasound, the ultrasound signal acquisition module can perform A-scan to obtain the time domain ultrasound signal, and use the image processing and analysis module to process and analyze it to obtain a reconstructed image containing the particle position. With this design, the external magnetic field can be used to intuitively guide the particles to move to the specified position according to the particle position, so as to realize the adjustable position of ultrasound stimulation; the filling particles of the present invention are magnetic, and the magnetic field generated by the magnetic field generation module is used to guide the filling particles to move to the specified position in the flow channel, and at the same time, by adjusting the distance from the antenna to the filling particles, ultrasound stimulation of specific intensity can be realized in specific areas of the brain; the flexible flow channel of the present invention adopts a flat design and has biocompatibility, is easy to implant in the skull and can exist stably for a long time, so this technology can be used for long-term ultrasound brain regulation or treatment. In traditional transcranial ultrasound stimulation technology, on the one hand, high-frequency ultrasound waves will experience severe attenuation, high reflection, and diffraction effects in the human skull, resulting in generally low efficiency of ultrasound stimulation at the target location; on the other hand, it is difficult for traditional transcranial ultrasound stimulation technology to achieve accurate stimulation of different target locations in the skull. The ultrasound stimulation device proposed in the present invention avoids the problems of high attenuation of ultrasound waves in the skull and difficulty in accurately locating the stimulation target encountered in traditional transcranial ultrasound stimulation technology through a unique design. It has the advantages of high-efficiency excitation, adjustable stimulation position, real-time sound source positioning, adjustable intensity, deep penetration, long-term stimulation, biocompatibility, and low cost, and has great potential application value in the fields of brain regulation and precise delivery of brain drugs.

[0041] The specific implementation cases described in this application are merely examples of the main ideas of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the attached claims.

Claims

1. An implantable ultrasonic stimulation device based on electromagnetic sound, used to achieve electromagnetic wave-induced ultrasonic stimulation at a specific location in intracranial brain tissue, characterized in that: The implantable ultrasound stimulation device comprises: An electromagnetic wave generating module, used for generating electromagnetic waves; A magnetic field generating module, used for generating a magnetic field; An ultrasonic wave generating module includes a flexible flow channel, a filling liquid and filling particles; The flexible flow channel is flat in design and can be injected with filling liquid; the filling particles can be placed in the flow channel filled with the filling liquid; the filling particles have high electromagnetic absorption and are used to absorb electromagnetic waves and generate high-frequency ultrasonic waves; the filling particles are magnetic and can be manipulated by the magnetic field generated by the magnetic field generating module; An ultrasonic signal acquisition module, used to acquire time-domain ultrasonic signals emitted by the filling particles after absorbing electromagnetic waves; The image processing and analysis module is used to process and analyze the signal obtained by the ultrasonic signal acquisition module to obtain a reconstructed image containing the positions of the filling particles.

2. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The electromagnetic wave generating module includes an electromagnetic wave radiation source and an irradiation antenna. The electromagnetic wave radiation source adopts pulse or continuous wave modulation output. Its frequency range includes but is not limited to the electromagnetic wave frequency band that can penetrate the skull, and its repetition frequency includes but is not limited to the Hz ~ MHz level.

3. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The magnetic field generating module includes but is not limited to a small magnet or an energized solenoid coil, and is used to generate a magnetic field to manipulate the position movement of the filling particles.

4. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The flexible flow channel composition materials include but are not limited to polydimethylsiloxane PDMS, polyethylene PE and polypropylene PP.

5. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The cross-sectional pattern of the fluid channel of the flexible flow channel includes but is not limited to regular patterns such as square or circle.

6. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The thickness of the flexible flow channel may be of an order of magnitude including, but not limited to, a sub-millimeter order of magnitude.

7. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The filling liquid includes but is not limited to inorganic or organic solvents such as mineral oil and glycerin.

8. The implantable ultrasonic stimulation device based on electromagnetic sound according to claim 1, characterized in that: The position of the electromagnetic wave generating module is adjustable relative to the filling particles.

9. An implantable ultrasonic stimulation method based on electromagnetic sound, used to achieve electromagnetic wave-induced ultrasonic stimulation of a specific brain area, which is operated by using an implantable ultrasonic stimulation device based on electromagnetic sound as claimed in any one of claims 1 to 8, characterized in that: The specific steps of the implantable ultrasound stimulation method are as follows: Step S1, implanting the flexible flow channel injected with filling liquid and loaded with filling particles into the inner side of the skull and making it fit in contact with the brain tissue; Step S2, the electromagnetic wave generating module starts to work, the electromagnetic wave radiation source generates electromagnetic waves, and irradiates the flexible flow channel through the antenna; Step S3, the antenna of the electromagnetic wave generating module forwardly irradiates the flexible flow channel loaded with filling particles, and the filling particles absorb the electromagnetic wave energy to generate ultrasonic waves and stimulate the brain area; the ultrasonic signal acquisition module performs A-scan to obtain time-domain ultrasonic signals, and the image processing and analysis module processes and analyzes the obtained time-domain ultrasonic signals to obtain a reconstructed image containing the positions of the filling particles, and the image is used to indicate the positions of the filling particles in the flow channel; Step S4, adjusting the antenna of the electromagnetic wave generating module to change the distance between the antenna and the filling particles to achieve ultrasonic stimulation of different intensities; Step S5, based on the position of the filling particles in the flow channel in the reconstructed image obtained in step S3, use the magnetic field generated by the magnetic field generating module to guide the filling particles to move to the specified position in the flow channel to achieve adjustment of the ultrasonic stimulation area; after the position movement is completed, repeat steps S3-S4 until ultrasonic stimulation of a specific intensity is achieved in a specific brain area.

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