CN115920235A - Wireless nerve regulation and control system and method based on ultrasonic drive piezoelectric material - Google Patents
Wireless nerve regulation and control system and method based on ultrasonic drive piezoelectric material Download PDFInfo
- Publication number
- CN115920235A CN115920235A CN202211711131.1A CN202211711131A CN115920235A CN 115920235 A CN115920235 A CN 115920235A CN 202211711131 A CN202211711131 A CN 202211711131A CN 115920235 A CN115920235 A CN 115920235A
- Authority
- CN
- China
- Prior art keywords
- ultrasonic
- stimulation
- module
- piezoelectric
- piezoelectric material
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Percussion Or Vibration Massage (AREA)
Abstract
The invention discloses a wireless nerve regulation and control system and a method based on an ultrasonic drive piezoelectric material, wherein the system comprises: the ultrasonic module is used for generating ultrasonic signals with adjustable parameters and guiding the stimulation direction and position of the ultrasonic signals; the piezoelectric stimulation module is a micro biocompatible piezoelectric material and is implanted into the central or peripheral nerve region of an object to be tested, the ultrasonic module is arranged outside the object to be tested, and the ultrasonic stimulation generated by the ultrasonic module is directly acted on the piezoelectric stimulation module; a mapping relation between ultrasonic stimulation parameters and the discharge response of the induced piezoelectric material is established between the piezoelectric stimulation module and the ultrasonic module. The invention utilizes the ultrasonic wave with good tissue penetrating power and focusing property, combines the ultrasonic energy source with the piezoelectric effect of the piezoelectric material, and adopts one or more piezoelectric materials in the implanted nerve stimulation area, thereby solving the power supply problem of the implanted nerve stimulation piezoelectric material, the accurate regulation and control of the nerve stimulation area and the equipment portability problem.
Description
Technical Field
The invention belongs to the technical field of nerve regulation and control, and particularly relates to a wireless nerve regulation and control system and method based on an ultrasonic drive piezoelectric material.
Background
The nerve regulation is a biomedical engineering technology which utilizes physical means such as electricity, magnetism, light, ultrasound and the like or chemical means such as adeno-associated viruses, compounds and the like to change signal transmission of a nervous system, regulate neuron and activity of a neural network where the neuron is located and finally cause specific brain function change. With the help of different stimulation means, the neural regulation can not only cause rapid and local function change of the nervous system, but also induce continuous and comprehensive change of the neural network and neural circuit connection, and promote neuron plasticity and neural circuit remodeling. Therefore, the neural regulation and control technology is an important tool for analyzing brain functions and an effective means for treating nervous system diseases.
At present, the neural regulation and control technology is widely applied to the aspects of functional prosthesis, clinical treatment, basic research and the like. The neuromodulation techniques can be classified into invasive and non-invasive depending on the degree of invasiveness of the modulation device into the body.
Common invasive neuromodulation techniques mainly include Deep Brain Stimulation (DBS), spinal cord electrical stimulation (SCS), invasive vagal electrical stimulation (iVNS), sacral nerve electrical stimulation (SNS); non-invasive techniques include mainly Transcranial Magnetic Stimulation (TMS), transcranial direct/alternating current stimulation (tDCS/tACS), transcutaneous vagal stimulation (tVNS), transcutaneous Electrical Nerve Stimulation (TENS), and Transcranial Ultrasound Stimulation (TUS) and light stimulation, among others. In the whole, invasive techniques mainly rely on electrical stimulation means, all belong to active medical instruments relying on electrical energy, and generally comprise three parts, namely a microelectrode, a lead and a pulse emitter (namely a battery); for example, DBS, which is the common treatment for parkinson's disease, requires surgical exposure of the corresponding functional brain area or plexus to implant the electrodes, while the microcurrent stimulation delivered by the electrodes relies on the simultaneously implanted battery and lead; the service life of the battery is limited, and the battery needs to be replaced by an operation in 5-9 years on average; the factors make the invasive technique have complicated operation process, large wound area, high postoperative infection rate, more complications, high treatment cost and limited applicable groups.
Although the non-invasive technique uses more diverse stimulation means and has the advantage of being non-invasive, the spatial resolution of the technique is generally low (centimeter level), and some of the stimulation devices are bulky and not portable; taking electric and magnetic stimulation as an example, the stimulation energy is greatly lost and is difficult to stimulate the subcortical tissues of the brain through skin or skull conduction, the actual action range cannot be accurately judged, and the treatment effect is unstable; even though the recently developed transcranial focused ultrasound regulation and control technology has stronger tissue penetration and higher spatial resolution (about several millimeters), the accuracy of stimulation sites, stimulation parameters, treatment effect, action mechanism and safety of the technology still need to be researched.
To sum up, the current electrical stimulation means is the mainstream nerve regulation and stimulation means, the implanted nerve electrical stimulator has the technical problems of complex structure and lack of reliable energy supply, and the non-implanted nerve stimulation has the technical problems of inaccurate regulation and control position, unstable effect, incapability of being portable and used depending on large-scale wired equipment, and the like.
Disclosure of Invention
In order to solve the technical problems, the invention provides a portable device which is self-powered, has small damage and can realize multi-target stimulation, and therefore, the invention provides a wireless nerve regulation and control system and a wireless nerve regulation and control method based on an ultrasonic drive piezoelectric material.
The specific scheme is as follows:
in one aspect, the present invention provides a wireless neuromodulation system based on an ultrasound-driven piezoelectric material, the system comprising:
the ultrasonic module is used for generating an ultrasonic signal with adjustable parameters and guiding the stimulation direction and position of the ultrasonic signal;
the ultrasonic stimulation module is arranged outside the body of the object to be tested, and the ultrasonic stimulation generated by the ultrasonic stimulation module directly acts on the piezoelectric stimulation module through the transducer; a mapping relation between ultrasonic stimulation parameters and the discharge response of the induced piezoelectric material is established between the piezoelectric stimulation module and the ultrasonic module.
Preferably, the stimulation direction of the ultrasonic wave generated by the ultrasonic module is perpendicular to the piezoelectric module.
Preferably, the ultrasonic module includes an ultrasonic generator, an oscilloscope, a power amplifier and a transducer, the ultrasonic generator is used for generating a parameter-adjustable ultrasonic signal, the oscilloscope is connected with the ultrasonic generator and is used for displaying an ultrasonic waveform, the power amplifier is connected with the ultrasonic generator and is used for amplifying the ultrasonic signal generated by the ultrasonic generator, and the transducer is connected with the power amplifier and is used for guiding the stimulation direction and position of the ultrasonic wave.
Further preferably, the ultrasonic stimulation frequency generated by the ultrasonic generator is less than 0.65MHz, and the sound intensity is less than 500mW/cm 2 And the center frequency of the transducer is 0.5MHz.
The piezoelectric stimulation module comprises one or more micro-sized biocompatible piezoelectric materials, the size of the piezoelectric stimulation module is matched with the size of one or more target nerve stimulation areas to be implanted, and ultrasonic wave stimulation generated by the ultrasonic module acts on the piezoelectric materials in one or more implanted target nerve stimulation areas simultaneously.
Furthermore, the system also comprises a data acquisition module and a processing module, wherein the data acquisition module is an electrophysiological signal acquisition device and is used for extracting the neural electrophysiological signals induced by the piezoelectric stimulation module after regulation and control, and a signal analysis algorithm is embedded in the processing module and is used for automatically monitoring the electrical stimulation characteristics and extracting the neural characteristics.
In another aspect, the present invention further provides a wireless neural regulation method based on an ultrasound-driven piezoelectric material, including:
and 3, adjusting the discharge response of the piezoelectric stimulation module by changing the ultrasonic signal characteristics of the ultrasonic module according to the regulation purpose and the mapping relation established in the step 1.
The method further comprises the following steps:
and step 4, synchronously acquiring electrophysiological signals and body behavior data generated by the target nerve stimulation area, and automatically monitoring electrical stimulation characteristics and extracting nerve characteristics.
After the ultrasonic response test is performed on the bio-compatible piezoelectric material, a mapping relation among the ultrasonic parameters, the distance and the angle between the ultrasonic module and the piezoelectric material to the discharge response of the ultrasonic stimulation-induced piezoelectric material is established in the step 1.
In the step 2, the piezoelectric stimulation module is implanted into one or more target nerve stimulation areas, and the ultrasonic stimulation is performed on one piezoelectric stimulation module or a plurality of piezoelectric stimulation modules synchronously through the ultrasonic module to generate discharge response.
The mapping relation between the ultrasonic stimulation parameters and the discharge response of the induced piezoelectric material conforms to the following formula: v = I × d ij ×t/A；
Where V-the output voltage of the piezoelectric material,
i-the sound intensity of the ultrasonic wave,
d ij piezoelectric constant of piezoelectric material，
t-the thickness of the piezoelectric material,
a-the sectional area of the piezoelectric material,
and on the basis, the interference of factors such as distance and frequency is considered.
The technical scheme of the invention has the following advantages:
A. the invention utilizes an external ultrasonic module to apply ultrasonic stimulation to the piezoelectric material implanted in a nerve stimulation area in vivo, the ultrasonic has good tissue penetrating power and focusing property, the non-contact energy source of the ultrasonic is combined with the piezoelectric effect of the piezoelectric material, and the miniaturized and biocompatible piezoelectric material implanted in the nerve stimulation area is adopted, so that the power supply problem of the implanted nerve stimulation piezoelectric material, the accurate regulation of the nerve stimulation area and the portability problem of equipment can be well solved.
B. On the premise of minimal invasion, the piezoelectric material implanted in a body is driven to discharge by utilizing ultrasonic waves outside the body, and mechanical energy generated by an ultrasonic module is converted into electric energy of the piezoelectric material, so that the piezoelectric material has the self-powered characteristic, and a controllable nerve electrical stimulation signal is generated in a nerve stimulation area; compared with the traditional neural regulation and control mode, the method has high spatial resolution, can not only accurately stimulate and control a single target point, but also synchronously stimulate multiple target points (such as multiple brain areas), realizes accurate and efficient stimulation and control on the neural system, and further gets rid of the limitation of wired regulation and control means, so that the method is more extensive in application population, simple and easy to implement.
C. The invention can realize the regulation and control of the central nervous system (such as cerebral cortex, deep brain area, spinal cord dorsal horn and the like) and the regulation and control of the peripheral nervous system (such as ganglion, nerve plexus, muscle and the like), and has the advantages of small damage, portable equipment and the like.
Drawings
In order to more clearly illustrate the embodiments of the present invention, the drawings which are needed to be used in the embodiments will be briefly described below, and it is apparent that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained from the drawings without inventive labor to those skilled in the art.
FIG. 1 is a general diagram of a wireless neuromodulation system provided by the present invention;
FIG. 2 is a flow chart of a regulation method provided by the present invention;
FIG. 3 is a flow chart of a method of the present invention for regulating pain in the M1 region of a rat;
FIG. 4 is the original voltage value signal of the ultrasound-driven calcium alginate hydrogel provided in the example;
FIG. 5 shows the piezoelectric effect (differential envelope voltage) of the calcium alginate hydrogel ultrasonically driven in the examples
FIG. 6 is a graphical representation of the modulation of an indicator-delta envelope voltage value by ultrasound stimulation parameters in an embodiment;
fig. 7 shows the piezoelectric effect (difference spectral power value) of the ultrasound-driven calcium alginate hydrogel in the example.
The figures are labeled as follows:
1-an ultrasound module; 11-ultrasonic generator, 12-power amplifier, 13-transducer, 14-oscilloscope; 2-a piezoelectric stimulation module; 3-a data acquisition module; 4-processing module.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it is to be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments of the present invention without making any creative effort, shall fall within the protection scope of the present invention.
As shown in fig. 1, the invention provides a wireless neural regulation and control system based on an ultrasonic-driven piezoelectric material, which comprises an ultrasonic module and a piezoelectric stimulation module, wherein the ultrasonic module is used for generating an ultrasonic signal with adjustable parameters and guiding the stimulation direction and position of the ultrasonic signal; the piezoelectric stimulation module is a micro biocompatible piezoelectric material and is used for being implanted into a central nerve region or a peripheral nerve region of an object to be tested, the ultrasonic module is arranged outside the object to be tested, the stimulation direction of ultrasonic waves generated by the ultrasonic module faces the piezoelectric stimulation module and directly acts on the piezoelectric stimulation module to enable the piezoelectric stimulation module to generate discharge response, a mapping relation between ultrasonic stimulation parameters and discharge response of the induced piezoelectric material is established between the piezoelectric stimulation module and the ultrasonic module, and the output of different discharge voltages of the piezoelectric material can be realized by adjusting the ultrasonic stimulation parameters of the ultrasonic module according to the purpose of regulating and controlling the nerve stimulation region. The direction of the ultrasonic stimulation generated by the ultrasonic module adopted by the invention is preferably perpendicular to the piezoelectric module.
As shown in fig. 1, the ultrasonic module includes an ultrasonic generator for generating a parameter-adjustable ultrasonic signal, an oscilloscope for displaying an ultrasonic waveform generated by the ultrasonic generator, a power amplifier for amplifying the ultrasonic signal generated by the ultrasonic generator, and a transducer connected to the power amplifier for guiding a stimulation direction and a position of the ultrasonic wave, i.e., an ultrasonic action direction. The ultrasonic generator, the oscilloscope, the power amplifier and the transducer which are adopted in the method are all the prior art, and specific product models can be purchased from the market and are not described in detail.
In order to avoid damage to organism tissues, all ultrasonic stimulations generated by the ultrasonic module are controlled to belong to low-frequency and low-intensity ultrasonic stimulations, namely the frequency is less than 0.65MHz, and the sound intensity is less than 500mW/cm 2 (ii) a Meanwhile, the center frequency of the transducer is preferably 0.5MHz. Within the above range, four types of high-frequency pulse waves (frequency =0.5MHz and duration =500 ms), low-frequency pulse waves (frequency =0.25MHz and duration =500 ms), and high-frequency sine waves (frequency =0.5MHz and duration =2 s) and low-frequency sine waves (frequency =0.5MHz and duration =2 s) are preset. The high-frequency pulse wave induces the piezoelectric material to generate short discharge with lower voltage, and the low-frequency pulse wave induces the piezoelectric material to generate short discharge with higher voltage; the high frequency sine wave induces the piezoelectric material to generate continuous discharge with lower voltage, and the low frequency sine wave induces the piezoelectric material to generate continuous discharge with higher voltage. The ultrasound can be used according to different conditionsThe module is adjusted to the desired parameters.
The invention not only realizes the precise regulation and control of a single target point, but also can realize the synchronous ultrasonic stimulation of the same ultrasonic module to multiple target points, namely, the piezoelectric stimulation module in the invention comprises one or more pieces of micro biocompatible piezoelectric materials, the size of the piezoelectric materials is matched with the size of one or more target nerve stimulation areas to be implanted, the piezoelectric materials act on the one or more target nerve stimulation areas through a transducer, the piezoelectric materials generate discharge response under the action of ultrasonic waves and generate stable current with controllable intensity, duration and the like, namely, the conversion from mechanical energy to electric energy is realized, the central nervous system such as cerebral cortex, deep brain area, spinal cord dorsal horn and the like is regulated and controlled, the peripheral nervous system such as ganglion, nerve plexus, muscle and the like can be regulated and controlled, and the ultrasonic stimulation is not limited to the nerve parts given by the examples.
When the ultrasonic module performs ultrasonic action on the piezoelectric material, in order to conveniently detect the nerve regulation and control effect, the system is also provided with a data acquisition module and a processing module, wherein the data acquisition module is an electrophysiological signal acquisition device used for extracting the nerve electrophysiological signal induced by the piezoelectric stimulation module after regulation and control, and the device is the prior art. Wherein, a signal analysis algorithm is embedded in the processing module and is used for automatically monitoring the electrical stimulation characteristics and extracting the nerve characteristics.
Wherein, the supersound module can be integrated into little volume integral type equipment, and more portable combines data acquisition module and processing module to use in the laboratory test.
As shown in fig. 2, the invention also provides a wireless neural regulation method based on the ultrasonic drive piezoelectric material, which comprises the following steps:
(S1) changing the attribute of an electric signal generated by the piezoelectric material by using ultrasonic waves, and establishing a mapping relation between ultrasonic wave stimulation parameters between the ultrasonic module and the piezoelectric stimulation module and the discharge response of the induced piezoelectric material;
the mapping relation between the ultrasonic stimulation parameters and the discharge response of the induced piezoelectric material conforms to the following formula: v = I × d ij ×t/A；
Where V-the output voltage of the piezoelectric material,
i-the sound intensity of the ultrasonic wave,
d ij -the piezoelectric constant of the piezoelectric material,
t-the thickness of the piezoelectric material,
a-the sectional area of the piezoelectric material,
meanwhile, the interference of factors such as ultrasonic distance, angle and frequency can be considered on the basis of the formula.
Firstly, testing ultrasonic response of the existing biocompatible piezoelectric material, and determining the distance and angle between ultrasonic wave transmitting and receiving positions and the influence of ultrasonic wave parameters (such as stimulation type, stimulation frequency, stimulation intensity, stimulation duration and the like) on the discharge characteristics of the piezoelectric material induced by ultrasonic wave stimulation; then, a mapping relation between the two is established to ensure that the implanted piezoelectric material can generate safe and controllable nerve electrical stimulation signals under the intermittent stimulation and the continuous stimulation of the ultrasonic wave.
Implanting a piezoelectric stimulation module into a target nerve stimulation area through a minimally invasive surgery, and performing electrical stimulation regulation and control on a nervous system of the target nerve stimulation area by regulating ultrasonic stimulation parameters of an ultrasonic module outside the target nerve stimulation area; taking model animals as an example, embedding a piezoelectric material with definite performance in (S1) into a rat motor cortex M1 area by using an operation, and implanting a brain electric signal recording electrode into the same side M1 for recording; or the piezoelectric material is embedded into the hind limb sciatic nerve of the rat by operation, and the needle-shaped myoelectric recording electrode is embedded into the nearby muscle. The ultrasonic stimulation to the piezoelectric material is executed by controlling the ultrasonic module, so that the nerve stimulation regulation and control of the rat electrode implantation area are realized. Taking the analgesic application as an example, after a nociceptive stimulus (such as thermal pain) is applied to a rat to induce pain behaviors, piezoelectric materials embedded in a pain feeling related area (such as M1) or a pain emotion related area (such as anterior cingulum, ACC) are induced to discharge through ultrasound, so that the pain related emotion is regulated and controlled, and the pain behaviors of the rat are reduced.
And (S3) adjusting the discharge response of the piezoelectric stimulation module by changing the ultrasonic signal characteristics (ultrasonic parameters) of the ultrasonic module according to the regulation purpose and the mapping relation established in the step (S1).
Specifically, an oscilloscope is used for displaying ultrasonic waveforms, a power amplifier is used for amplifying ultrasonic signals, a transducer is used for guiding the stimulation direction and position of ultrasonic waves, and finally the discharge response of the piezoelectric material is regulated and controlled by changing the stimulation of the ultrasonic waves.
Of course, the method can also comprise the step (S4) of recording the discharge condition of the ultrasonic drive piezoelectric material and quantifying the improvement of the body behavior and the change of the electrophysiological signal of the stimulation position so as to clearly regulate and control the effect.
Taking a model animal as an example, the ultrasonic waves are directly guided to the position above the scalp of a target brain area or the position above the outer skin of the hind limb sciatic nerve, electrophysiological signals of the brain, muscles and other parts after receiving electric stimulation are recorded, and video recording of behavioral responses (such as muscle twitching, foot lifting and the like) is synchronously carried out. The collected behavior data and electrophysiological signals are analyzed and counted by using the existing data analysis method to objectively quantify the regulation and control effect of the invention.
In conclusion, the invention adopts the implanted nerve electrical stimulation of the ultrasonic drive piezoelectric material to realize the self-power supply of the piezoelectric material, and the amplitude and the waveform of the electrical stimulation can be adjusted along with the intensity and the frequency of the ultrasonic wave, thereby providing a novel wireless nerve regulation and control solution with accurate action position and various action targets.
The following is a clear and complete description of the method of the present invention, taking the regulation of pain in the M1 region of rat as an example, with reference to FIG. 3, and the specific steps are as follows:
(S01) Sprague-Dawley rats induced by isoflurane anesthesia are placed on a brain stereotaxic apparatus, a skull and an M1 cortex are exposed through brain minimally invasive surgery, a piezoelectric stimulation module is implanted into a left M1 upper limb representative region (bregma: 0.24mm, comparative: 2mm, depth; implanting a neural activity recording electrode (later: 1.8mm, depth: 1mm) in the adjacent area, placing an epidural reference electrode and a grounding electrode at the positions 2mm in front of and 2mm behind an implantation site, recording and comparing the change of brain electrical physiological indexes before and after neural regulation, and finally installing an electrode protection device on the head of a rat.
After the rat recovers 24 hours after the operation, measuring the thermal pain threshold value of the rat by using a hot plate pain measuring instrument, and determining the thermal pain stimulation intensity for inducing pain behaviors; the recording electrode is placed in an electromagnetic shielding behavior box, connected to an amplifier through a signal adapter and a lead and connected to a computer corresponding to the data acquisition module and the analysis module through leads. The sampling rate of the electrophysiological signal is preferably 40000Hz.
(S02) vertically fixing a transducer (with the center frequency of 0.5 Mhz) in an ultrasonic module at the top of the behavior box, and applying ultrasonic stimulation with different parameters for 50 times respectively;
(S03) recording an electric signal of the piezoelectric material during discharging through a computer corresponding to the data acquisition module and the processing module, checking the discharging condition of the piezoelectric material, determining the discharging characteristic of the piezoelectric material, and ensuring that the preset of the ultrasonic module is met.
Behavioral and electrophysiological experiments are performed to investigate the application effects of the neural regulation method proposed by the present invention. Placing the rat on a hot plate pain measuring instrument, recording the paw withdrawal latency of the rat, evaluating behavior change caused by regulation and control, and comparing the difference of the heat pain paw withdrawal latency of the rat after no ultrasonic stimulation and ultrasonic stimulation regulation and control.
Electrophysiological signals of the non-ultrasonic stimulation stage and the ultrasonic stimulation stage are recorded through computers in the data acquisition module and the processing module, and data are stored for off-line analysis so as to evaluate neuron activity changes caused by regulation and control. Taking a common data analysis method as an example, the stored electrophysiological data are used for analysis, including comparison of the spectral power spectral densities of the LFP signals in the non-ultrasound stimulation stage and the ultrasound stimulation stage, and comparison of the population neuron firing rates of Spike signals, and specific data analysis and processing steps may include, but are not limited to, the following:
first, the subsequent data analysis is performed, and the acquired original data is preprocessed, including data splitting (LFP: low pass filtering 300Hz, spike: high pass filtering 300 Hz), LFP down-sampling (1000 Hz), LFP data filtering (LFP: 48-52Hz recess filtering), segmentation (2 s), spike clustering and sorting.
Secondly, analyzing the power spectral density of the LFP signals in the non-ultrasonic stimulation stage and the ultrasonic stimulation stage: converting the preprocessed LFP time domain signal into a frequency domain by using a modified periodogram power spectral density estimation method, and detecting whether the discharge frequency of a piezoelectric material in the ultrasonic stimulation phase signal is within a regulation and control action range determined by a test; then extracting and deducting the extract by using principal component analysis; the spectrum is then divided into 6 bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low frequency gamma (30-50 Hz), high frequency gamma (50-100 Hz), and comparing the power spectral density difference of LFP signals of each frequency band under the conditions of no ultrasonic stimulation and ultrasonic stimulation. In addition, the time-frequency response of the LFP signal is calculated by using a time-frequency analysis algorithm, and the characteristic difference of the time-frequency response under the conditions of no ultrasonic stimulation and ultrasonic stimulation is compared.
And analyzing the discharge rate of the group neurons of the Spike signals in the non-ultrasonic stimulation stage and the ultrasonic stimulation stage again: converting the extracted neuron discharge time sequence into a continuous discharge frequency histogram, converting the continuous discharge frequency histogram into a frequency domain by using a power spectral density estimation method of a modified periodogram, and analyzing and comparing the difference of discharge frequencies under the conditions of no ultrasonic stimulation and ultrasonic stimulation by using frequency point by point; and calculating time-frequency response by using a time-frequency analysis algorithm, and comparing the characteristic difference of the time-frequency response under the conditions of no ultrasonic stimulation and ultrasonic stimulation. In addition, the average firing rate of the neurons in the population is calculated, and the difference of the average firing rate of the neurons under the conditions of no ultrasonic stimulation and ultrasonic stimulation is compared.
This experiment expects that the pain sensitivity of rats is significantly reduced after the piezoelectric material is driven by ultrasonic stimulation to regulate the M1 region, while the pain sensitivity of rats is not significantly changed without ultrasonic stimulation. This decrease in pain sensitivity is characterized behaviorally by a significant increase in the hot paw withdrawal latency of the rat and electrophysiologically by a change in the energy of the cortical region multi-band neurooscillation (mainly an increase in the energy of the alpha and beta band oscillations and a decrease in the energy of the gamma band oscillations). The result can show that the piezoelectric material implanted in the central nervous system is driven by ultrasound, the neuron activity of a specific brain region can be accurately adjusted, the behavior change of an animal is induced, the positive effect of relieving pain is achieved, and the method is a reliable wireless nerve regulation and control method.
And (S05) according to the data results obtained in the (S03) and the (S04), investigating the effect of the wireless nerve regulation and control technology based on the ultrasonic drive piezoelectric material on behaviors, establishing the association among the discharge characteristic of the ultrasonic piezoelectric material, the nerve regulation and control effect and a brain response signal, and optimizing the regulation and control parameters while investigating the effectiveness of the nerve regulation and control.
Examples
(1) Configuration of ultrasound module
In order to reduce the complexity of the configuration, improve the practicability and guarantee the safety, the ultrasonic device used in the test is a commercially available ultrasonic physiotherapy instrument (brand: contemporary; model: UT 1021) which is licensed by medical instruments; the instrument has two ultrasonic frequencies of 1MHz and 3MHz, output intensity and duty ratio can be adjusted in multiple steps, output mode has pulse mode and continuous mode, and effective radiation area of the therapeutic probe is 5.0cm 2 The highest output sound intensity is 3W/cm 2 The maximum output power is 15W.
The ultrasound stimulation parameters used in the test were as follows:
1. ultrasonic frequency: 1MHz and 3MHz;
2. ultrasonic wave duty ratio: 50% and 100%, i.e. pulsed and continuous waves are generated;
3. the output sound intensity and power are set to maximum output values: the maximum output sound intensity corresponding to 50 percent duty ratio is 3W/cm 2 The highest output power is 15W; the maximum output sound intensity corresponding to 100 percent duty ratio is 2W/cm 2 The highest output power is 10W;
(2) Material selection for piezoelectric stimulation modules
Sodium Alginate (SA) is a by-product obtained by extracting iodine and mannitol from brown algae such as herba Zosterae Marinae or Sargassum, is a natural polysaccharide, has stability, solubility, viscosity and safety required for medicinal adjuvants, and can be used in food industryThe medicine field is widely applied. Calcium chloride (calcium chloride) is a chemical substance consisting of chlorine and calcium elements and has the chemical formula of CaCl 2 Slightly bitter; it is typically an ionic halide that can be absorbed by tissue without damage.
The hydrogel formed by chemically crosslinking the sodium alginate macromolecules and the calcium chloride solution (calcium alginate hydrogel) is a soft and elastic three-dimensional structure, the mechanical strength and the mechanical property of the gel are stable, the gel has biocompatibility and safety, and material tests show that the gel has certain piezoelectric property. Therefore, the current test selects calcium alginate hydrogel as the piezoelectric stimulation module, which can be used as the implant material in the future.
(3) Piezoelectric effect test of ultrasonic-driven calcium alginate hydrogel
Preparing calcium alginate hydrogel by using a calcium alginate solution with the ion concentration of 1% and a 0.5mol/L calcium chloride solution according to the proportion of 3:1; the method comprises the following steps of (1) using a copper sheet with the diameter of 35mm and the thickness of 0.18mm as a carrying and conducting platform, welding two 27mm long leads on the edges of two sides of the copper sheet, and respectively connecting the two leads to the positive and negative electrodes of an oscilloscope probe to carry out testing and voltage signal recording; the oscilloscope was of the common source (Rigol) brand and model DS1000Z-E.
In the test, the vertical distance between a treatment probe of the ultrasonic instrument and a copper sheet is always kept at 1cm, and the test conditions comprise the following five conditions: hydrogel _ baseline condition (ultrasound device turned on, but ultrasound was not excited), hydrogel _50% duty cycle _1MHz, hydrogel _50% duty cycle _3MHz, hydrogel _100% duty cycle _1MHz, hydrogel _100% duty cycle _3MHz.
Two indexes are used in the test to measure the piezoelectric effect of the ultrasonic-driven calcium alginate hydrogel.
The index is the difference envelope voltage value: extracting upper and lower envelope voltage values of the original voltage value signals of each condition, respectively solving absolute values, and then adding to obtain a total envelope voltage value; then, the total envelope voltage values of the four stimulation conditions are subtracted from the total envelope voltage value of the baseline condition to obtain a differential envelope voltage value (mV).
The second index is a difference spectrum power value: and calculating the spectral power values of all conditions through a pwelch function in maltab, and subtracting the spectral power values of the four stimulation conditions from the spectral power values of the baseline condition to obtain a difference spectral power value (dB).
(4) The test results are as follows
1. The oscilloscope records the original voltage value signals of five test conditions, and the original voltage values of all the conditions are in the range of-300 mV to 300mV, which is shown in figure 4.
2. The correlation result of the index one shows that compared with the baseline condition (hydrogel _ baseline condition), ultrasonic stimulation of four parameters (50% duty cycle _1MHz/50% duty cycle _3MHz/100% duty cycle _1MHz/100% duty cycle _3 MHz) can drive the calcium alginate hydrogel to generate the piezoelectric effect, and the measured differential envelope voltage value is in the range of 0-600 mV, as shown in fig. 5.
Furthermore, the results show that this piezoelectric effect is modulated by the ultrasound stimulation parameters, i.e. as the ultrasound duty cycle and frequency increase, the higher the differential envelope voltage value produced (50% duty cycle — 1mhz 209.7mv 50% duty cycle — 3mhz 273.7mv 100% duty cycle — 495.5mv 100% duty cycle — 3mhz; relative to a pulse wave with 50% duty cycle, a continuous wave with 100% duty cycle can induce a higher piezoelectric effect, which is about twice the voltage value of 50% duty cycle, and the difference of the mean value of the maximum values of the continuous wave and the voltage value reaches 272.15mV ([ 495.5+ 532.2)/2- (209.7 + 273.7)/2 ]), as shown in fig. 6.
3. The related result of the index II shows that compared with the baseline condition (hydrogel _ baseline condition), ultrasonic stimulation of four parameters (50% duty ratio _1MHz/50% duty ratio _3MHz/100% duty ratio _1MHz/100% duty ratio _3 MHz) drives the calcium alginate hydrogel to generate piezoelectric effect which is also reflected on the frequency spectrum characteristic; the ultrasound waves induce co-frequency resonance of the hydrogel material near the frequency of the ultrasound stimulus. Similarly, the difference spectral power values are also adjusted by the ultrasound stimulation parameters, i.e. as the ultrasound duty cycle and frequency increase, the higher the difference spectral power values are produced (50% duty cycle — 1mhz 2.436 × 10 -7 dB;50% duty cycle — 3MHz:5.479*10 -8 dB;100% duty cycle — 1mhz -4 dB;100% duty cycle — 3mhz 5.683 × 10 -5 dB). Furthermore, a 100% duty cycle continuous wave can induce higher spectral power values at similar frequencies relative to a 50% duty cycle pulsed wave, as shown in fig. 7.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. This need not be, nor should it be exhaustive of all embodiments. And obvious variations or modifications therefrom are intended to be within the scope of the invention.
Claims (10)
1. A wireless neuromodulation system based on an ultrasonically driven piezoelectric material, the system comprising:
the ultrasonic module is used for generating an ultrasonic signal with adjustable parameters and guiding the stimulation direction and position of the ultrasonic signal;
the ultrasonic stimulation module is arranged outside the body of the object to be tested, and generates ultrasonic stimulation to directly act on the piezoelectric stimulation module;
a mapping relation between ultrasonic stimulation parameters and the discharge response of the induced piezoelectric material is established between the piezoelectric stimulation module and the ultrasonic module.
2. The wireless neuromodulation system as in claim 1, wherein the ultrasound module generates the ultrasound waves with a stimulation direction perpendicular to the piezoelectric module.
3. The wireless nerve regulation and control system based on the ultrasonic drive piezoelectric material of claim 1, wherein the ultrasonic module comprises an ultrasonic generator, an oscilloscope, a power amplifier and a transducer, the ultrasonic generator is used for generating a parameter-adjustable ultrasonic signal, the oscilloscope is connected with the ultrasonic generator and used for displaying an ultrasonic waveform, the power amplifier is connected with the ultrasonic generator and used for amplifying the ultrasonic signal generated by the ultrasonic generator, and the transducer is connected with the power amplifier and used for guiding the stimulation direction and position of the ultrasonic wave.
4. The wireless neuromodulation system as in claim 3, wherein the ultrasound generator generates ultrasound waves having a stimulation frequency of < 0.65MHz and a sound intensity of < 500mW/cm 2 And the center frequency of the transducer is 0.5MHz.
5. The ultrasound-driven piezoelectric material-based wireless neuromodulation system of claim 3, wherein the piezoelectric stimulation module comprises one or more pieces of micro-sized biocompatible piezoelectric material sized to fit one or more target nerve stimulation areas to be implanted, and the ultrasonic stimulation generated by the ultrasound module acts on the piezoelectric material in one or more of the target nerve stimulation areas through the transducer.
6. The wireless nerve regulation and control system based on the ultrasonic drive piezoelectric material according to any one of claims 1 to 5, further comprising a data acquisition module and a processing module, wherein the data acquisition module is an electrophysiological signal acquisition device and is used for extracting the electrophysiological neurosignals induced by the piezoelectric stimulation module after regulation, and the processing module is embedded with a signal analysis algorithm and is used for automatically monitoring electrostimulation characteristics and extracting neurofeatures.
7. A wireless neuromodulation method based on an ultrasound-driven piezoelectric material, the method comprising:
step 1, changing the attribute of an electric signal generated by a piezoelectric material by using ultrasonic waves, and establishing a mapping relation between ultrasonic wave stimulation parameters between an ultrasonic module and a piezoelectric stimulation module and the discharge response of the induced piezoelectric material;
step 2, implanting the piezoelectric stimulation module into a target nerve stimulation area through a minimally invasive surgery, and regulating and controlling a nervous system of the target nerve stimulation area by regulating ultrasonic stimulation parameters of the ultrasonic module outside the target nerve stimulation area;
and 3, adjusting the discharge response of the piezoelectric stimulation module by changing the ultrasonic signal characteristics of the ultrasonic module according to the regulation purpose and the mapping relation established in the step 1.
8. The method for wireless neuromodulation based on an ultrasonically actuated piezoelectric material as claimed in claim 7, further comprising:
and 4, synchronously acquiring electrophysiological signals and body behavior data generated by the target nerve stimulation area, and automatically monitoring electrical stimulation characteristics and extracting nerve characteristics.
9. The wireless nerve regulation and control method based on the ultrasonic drive piezoelectric material according to claim 7, wherein after the ultrasonic response test is performed on the biocompatible piezoelectric material, the mapping relationship among the ultrasonic parameters, the distance and the angle between the ultrasonic module and the piezoelectric material to the discharge response of the ultrasonic stimulation induced piezoelectric material is established in the step 1, and the following formula is satisfied:
V＝I×d ij ×t/A
wherein: v-the output voltage of the piezoelectric material,
i-the sound intensity of the ultrasonic wave,
d ij -the piezoelectric constant of the piezoelectric material,
t-the thickness of the piezoelectric material,
a is the sectional area of the piezoelectric material.
10. The wireless nerve modulation method according to claim 7, wherein in the step 2, the piezoelectric stimulation module is implanted into one or more target nerve stimulation areas, and the ultrasound module performs ultrasonic stimulation on one piezoelectric stimulation module or a plurality of piezoelectric stimulation modules synchronously to generate discharge response.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111645384 | 2021-12-29 | ||
| CN2021116453849 | 2021-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115920235A true CN115920235A (en) | 2023-04-07 |
Family
ID=86555880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211711131.1A Pending CN115920235A (en) | 2021-12-29 | 2022-12-29 | Wireless nerve regulation and control system and method based on ultrasonic drive piezoelectric material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115920235A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116459389A (en) * | 2023-05-04 | 2023-07-21 | 深圳先进技术研究院 | Bionic visual repair material, repair film, preparation method of repair film and repair device |
| CN116492597A (en) * | 2023-06-28 | 2023-07-28 | 南昌大学第一附属医院 | Peripheral-central nerve regulation and control device and storage medium |
-
2022
- 2022-12-29 CN CN202211711131.1A patent/CN115920235A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116459389A (en) * | 2023-05-04 | 2023-07-21 | 深圳先进技术研究院 | Bionic visual repair material, repair film, preparation method of repair film and repair device |
| CN116492597A (en) * | 2023-06-28 | 2023-07-28 | 南昌大学第一附属医院 | Peripheral-central nerve regulation and control device and storage medium |
| CN116492597B (en) * | 2023-06-28 | 2023-11-24 | 南昌大学第一附属医院 | Peripheral-central nerve regulation and control device and storage medium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230309886A1 (en) | Implantable Electrode Positioning | |
| EP3206573B1 (en) | Systems and methods for monitoring muscle rehabilitation | |
| Seo et al. | Wireless recording in the peripheral nervous system with ultrasonic neural dust | |
| King et al. | Effective parameters for ultrasound-induced in vivo neurostimulation | |
| US10849525B2 (en) | Monitoring brain neural activity | |
| CN115920235A (en) | Wireless nerve regulation and control system and method based on ultrasonic drive piezoelectric material | |
| US20150148710A1 (en) | Ultrasound Modulation of the Brain for Treatment of Stroke, Brain Injury, and Other Neurological Disorders | |
| CN113181569B (en) | Closed-loop transcranial brain stimulation system and method | |
| CN105251141A (en) | Closed-loop transcranial magnetoacoustic stimulation device | |
| CN112843477A (en) | Transcranial magnetic acoustic electrical stimulation brain regulation and control device and transcranial magnetic acoustic electrical stimulation brain regulation and control method | |
| CN104922794B (en) | A kind of position apparatus for evaluating of testing stimulus electrode | |
| Lee et al. | An efficient noninvasive neuromodulation modality for overactive bladder using time interfering current method | |
| Seaman et al. | Thresholds of cat cochlear nucleus neurons to microwave pulses | |
| Shannon et al. | Threshold-distance measures from electrical stimulation of human brainstem | |
| CN204864539U (en) | Test stimulating electrode's position evaluation device | |
| WO2021052356A1 (en) | Bone stimulartor and bone stimulation system for bone fracture healing | |
| CN110801223B (en) | Wireless brain deep nerve interface system | |
| Jabban et al. | Pig Ulnar Nerve Recording with Sinusoidal and Temporal Interference Stimulation | |
| Julien et al. | Transcranial focused ultrasonic stimulation to modulate the human primary somatosensory cortex | |
| Krueger et al. | Relationship between peak and mean amplitudes of the stimulating output voltage for functional control of the knee by spinal cord patients and healthy volunteers | |
| Okuno et al. | Effectiveness of intraoperative somatosensory evoked potential monitoring during cervical spinal operations on animals with spinal cord dysfunction | |
| Poljak et al. | Integral equation models in some biomedical applications of electromagnetic fields: Transcranial magnetic stimulation (TMS), nerve fiber stimulation | |
| Ortego-Isasa et al. | First Steps Towards Understanding How Non-Invasive Magnetic Stimulation Affects Neural Firing at Spinal Cord | |
| Hélias et al. | Using Electrochemical Impedance Spectroscopy to Study the in vivo Evolution of the Electrochemical Properties of Neural Implants | |
| Petrova | Focused Ultrasound Neuromodulation on Crayfish |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |