Double-frequency ultrasonic noninvasive targeted sound genetic regulation method and system

Through dual-frequency ultrasound non-invasive targeted acoustic genetic regulation method, microbubble and sound field simulation technology are used to solve the problem of mismatch in the acoustic impedance of skull and brain tissue in ultrasound neural regulation technology, and high-precision and safe neural network manipulation are achieved to meet the needs of the high-precision and safe neural network manipulation. The need for clinical application.

CN119236334APending Publication Date: 2025-01-03BEIJING INST OF TECH
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Patent Information

Application Number
CN202411567509.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-05
Publication Date
2025-01-03

AI Technical Summary

Technical Problem

The existing ultrasound neuroregulatory technology has caused low regulation accuracy in the problem of mismatch in the acoustic impedance of skull and brain tissues, and there are biosafety and medical ethical challenges in clinical applications.

Method used

Dual-frequency ultrasound non-invasive targeted acoustic genetic regulation method is used to determine the optimal ultrasound stimulation parameters through microbubble parameters and ultrasound parameter frequency. Combined with sound field simulation and robotic arm module, the transducer position and angle are accurately adjusted, and targeted injection acoustic genetics are targeted. Virus, realizes non-invasive precise neural network manipulation.

Benefits of technology

It improves the accuracy and safety of ultrasound neural regulation, realizes non-invasive targeted acoustic genetic regulation, and meets the needs of high temporal and spatial resolution and precise stimulation in deep brain areas.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to a double-frequency ultrasonic noninvasive targeted sound genetic regulation method and system, and the method comprises the steps: determining an optimal ultrasonic stimulation parameter based on a microbubble parameter and an ultrasonic parameter frequency; based on the optimal ultrasonic stimulation parameters, performing sound field simulation on the transducer, and obtaining a target position and included angle information of the transducer; moving a transducer based on the target position and the included angle information, and injecting the mixed microbubble and acoustic genetic virus into the target body; after the ultrasonic stimulation parameters are injected into a target body, the transducer is moved to a designated position and an included angle according to simulation information based on the optimal ultrasonic stimulation parameters, and ultrasonic non-invasive targeted sound genetic regulation and control are carried out.
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Description

Technical Field

[0001] The present invention relates to the technical field of ultrasonic nerve regulation, and in particular to a method and system for dual-frequency ultrasonic non-invasive targeted acoustic genetic regulation. Background Art

[0002] Neuromodulation refers to regulating the activity of the nervous system through physical, chemical or biological methods to achieve the purpose of treating diseases or improving certain physiological functions. Neuromodulation technology is widely used in medical treatment and research, especially in the treatment of neurological diseases such as chronic pain, Parkinson's disease, epilepsy and depression. At present, non-invasive neuromodulation technologies such as transcranial magnetic stimulation, transcranial alternating current stimulation, and transcranial direct current stimulation have been widely used in the treatment of neuropsychiatric diseases. However, spatial resolution and penetration depth limit the application of these technologies. Transcranial focused ultrasound transmits a form of mechanical energy that can non-invasively target deep brain areas with a millimeter-sized focus through the skull. It has been widely used in medicine for its advantages such as high resolution, controllability and non-invasiveness.

[0003] Sonogenetics refers to the non-invasive and selective control of neural activity using genetically encoded ultrasound-responsive media. It induces cell-type-specific neuromodulation by genetically inserting exogenous mediators, making targeted neurons sensitive to ultrasound. Sonogenetics is a promising tool for studying neural circuits. The concept of "sonogenetics" was proposed in 2015. Simply put, it is to use genetic manipulation technology to express mechanosensitive receptors on neurons, giving cells sensitivity to ultrasound stimulation, and ultrasound stimulation also has specificity for cells or tissues. Through cell-type-specific gene expression, targeted expression of intracellular mechanosensitive mechanisms (such as ion channels) and precise delivery of ultrasound can be combined to achieve precise neural network manipulation with whole-brain resolution, with high spatiotemporal resolution and accurate deep brain targeting of non-invasive stimulation.

[0004] Although ultrasonic neuromodulation and sonogenetics have developed rapidly in recent years, the following problems still exist. Ultrasonic transcranial therapy will have problems with the acoustic impedance mismatch between the skull and brain tissue, making it difficult to achieve higher precision regulation. Ultrasonic neuromodulation will eventually be applied to the clinical treatment of human nervous system diseases, but in the current experimental research stage, precise neuromodulation mediated by mechanosensitive channels uses AAV viruses as vectors to overexpress target genes on neurons (sonogenetics). The existing technology faces huge challenges in terms of regulation accuracy, biosafety, and medical ethics, and the development and application of this technology are accompanied by huge challenges. Summary of the invention

[0005] The purpose of the present invention is to provide a method and system for dual-frequency ultrasound non-invasive targeted acoustic genetic regulation to solve the problems existing in the above-mentioned prior art.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] A method for non-invasive targeted acoustic genetic regulation using dual-frequency ultrasound, comprising:

[0008] Determining optimal ultrasound stimulation parameters based on microbubble parameters and ultrasound parameter frequency, wherein the microbubble parameters include: microbubble diameter and microbubble envelope material;

[0009] Based on the optimal ultrasonic stimulation parameters, a sound field simulation is performed on the transducer to obtain target position and angle information of the transducer;

[0010] The microbubbles and the sonogenetic virus are mixed evenly and injected into the target body, so that the mixture circulates in the blood;

[0011] After injection into the target body, the transducer is moved to a specified position and angle based on the optimal ultrasound stimulation parameters and according to the simulation information to perform ultrasound non-invasive targeted acoustic genetic regulation.

[0012] Optionally, determining the optimal ultrasound stimulation parameters includes:

[0013] The dynamic model of microbubble envelope was constructed by coupling the dynamic model of single microbubble under ultrasound excitation with the microbubble envelope model.

[0014] Construct a nonlinear sound field model through nonlinear sound field equations;

[0015] Combining the enveloped microbubble dynamics model with the nonlinear acoustic field model, constructing an enveloped microbubble dynamics model under a nonlinear acoustic field;

[0016] Based on the envelope microbubble dynamics model under the nonlinear acoustic field, the change of cavitation threshold under different sound pressures, different amplitudes and different phase combinations of dual-frequency ultrasound is analyzed, and the optimal ultrasonic stimulation parameters are determined in combination with the ultrasonic frequency information.

[0017] Optionally, obtaining the target position and angle information of the transducer includes: placing the focus of the transducer at the stimulation target position, and obtaining the angle and position information when the focus is minimum and the intensity is maximum by changing the angle of the transducer.

[0018] Optionally, performing ultrasound non-invasive targeted sonogenetic regulation includes:

[0019] Targeted control of microbubble cavitation releases the sonogenetic virus, allowing the sonogenetic virus to be expressed in the target area.

[0020] A dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system is used to implement the dual-frequency ultrasound non-invasive targeted acoustic genetic regulation method, the system comprising: a microbubble dynamics calculation module, an acoustic field simulation module, a mechanical arm module, an intravenous injection module, and an acoustic emission module;

[0021] The microbubble dynamics calculation module is used to determine the optimal ultrasound stimulation parameters based on microbubble parameters and ultrasound parameter frequency, wherein the microbubble parameters include: microbubble diameter and microbubble envelope material;

[0022] The sound field simulation module is used to perform sound field simulation on the transducer based on the optimal ultrasonic stimulation parameters to obtain the target position and angle information of the transducer;

[0023] The mechanical arm module is used to move the transducer based on the target position and angle information;

[0024] The intravenous injection module is used to inject the mixed microbubbles and sonogenetic virus into the target body;

[0025] The acoustic emission module is used to move the transducer to a specified position and angle based on the optimal ultrasonic stimulation parameters and according to the simulation information after being injected into the target body, so as to perform ultrasonic non-invasive targeted acoustic genetic regulation.

[0026] Optionally, the microbubble dynamics calculation module includes: a first construction unit, a second construction unit, a third construction unit and an analysis unit;

[0027] The first construction unit is used to construct an envelope microbubble dynamics model by coupling a dynamics model of a single microbubble under ultrasonic excitation with a microbubble envelope model;

[0028] The second construction unit is used to construct a nonlinear sound field model through a nonlinear sound field equation;

[0029] The third construction unit is used to combine the envelope microbubble dynamics model and the nonlinear acoustic field model to construct the envelope microbubble dynamics model under the nonlinear acoustic field;

[0030] The analysis unit is used to analyze the change of cavitation threshold under different sound pressures, different amplitudes, and different phase combinations of dual-frequency ultrasound based on the envelope microbubble dynamics model under the nonlinear sound field, and determine the optimal ultrasound stimulation parameters in combination with the ultrasound frequency information.

[0031] Optionally, obtaining the target position and angle information of the transducer in the sound field simulation module includes:

[0032] The transducer focus is placed at the stimulation target position, and the angle and position information when the focus is minimum and the intensity is maximum are obtained by changing the angle of the transducer.

[0033] Optionally, in the acoustic emission module, based on the loaded optimal ultrasonic stimulation parameters, the cavitation of microbubbles is targeted and controlled to release the acoustic genetic virus so that the acoustic genetic virus is expressed in the target area.

[0034] The beneficial effects of the present invention are:

[0035] The present invention proposes a dual-frequency ultrasound non-invasive targeted acoustic genetic regulation method and system. After the ultrasound parameter frequency and microbubble parameters are input into the microbubble dynamics calculation module, the minimum sound pressure required for microbubble transient cavitation is calculated, and the sound field simulation module is used to determine the angle between the two transducers to obtain the minimum focus. According to the calculated angle, the dual mechanical arm module is used to adjust the transducer angle and position so that the focus is located on the stimulation target. Finally, the microbubbles and acoustic genetic viruses are injected into the target body through the intravenous injection module, and the dual-frequency ultrasound system is used to target and control the cavitation of the microbubbles, release the acoustic genetic viruses, and express the viruses in the target area, thereby realizing non-invasive targeted acoustic genetic regulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0037] Figure 1 This is a schematic diagram of the overall control process of an embodiment of the present invention;

[0038] Figure 2 This is a workflow diagram of a microbubble dynamics calculation module according to an embodiment of the present invention;

[0039] Figure 3 A flowchart of a sound field simulation module according to an embodiment of the present invention;

[0040] Figure 4 This is a working diagram of a robot arm module according to an embodiment of the present invention;

[0041] Figure 5 This is a workflow diagram of an intravenous injection module according to an embodiment of the present invention;

[0042] Figure 6 This is a working diagram of the acoustic emission module according to an embodiment of the present invention;

[0043] Figure 7 The figure is an overall workflow diagram of an embodiment of the present invention. DETAILED DESCRIPTION

[0044] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0046] This embodiment provides a method for non-invasive targeted acoustic genetic regulation using dual-frequency ultrasound, including:

[0047] Determining optimal ultrasound stimulation parameters based on microbubble parameters and ultrasound parameter frequency, wherein the microbubble parameters include: microbubble diameter and microbubble envelope material;

[0048] Based on the optimal ultrasonic stimulation parameters, the acoustic field of the transducer is simulated to obtain the target position and angle information of the transducer;

[0049] The microbubbles and the acoustic genetic virus are mixed evenly, and the transducer is moved based on the target position and angle information to inject the mixed microbubbles and the acoustic genetic virus into the target body;

[0050] After injection into the target body, the transducer is moved to a specified position and angle based on the optimal ultrasound stimulation parameters and according to the simulation information to perform ultrasound non-invasive targeted acoustic genetic regulation.

[0051] Further, determining the optimal ultrasound stimulation parameters includes:

[0052] By coupling the dynamics model of a single microbubble under ultrasonic excitation (Gilmore-Akulichev-Zener) with the microbubble envelope model, an envelope microbubble dynamics model (a dynamics model describing the envelope microbubble under ultrasonic action) is constructed:

[0053] Through the nonlinear sound field equation (KZK equation): construct a nonlinear sound field model (when the sound wave amplitude reaches a certain level, a series of nonlinear phenomena such as waveform distortion, acoustic saturation, and nonlinear interaction between sound waves will occur during the sound wave propagation);

[0054] Combining the envelope microbubble dynamics model and the nonlinear acoustic field model, a envelope microbubble dynamics model under nonlinear acoustic field (acoustic cavitation dynamics transient physical process model of envelope microbubbles in tissues under ultrasound) is constructed;

[0055] Based on the envelope microbubble dynamics model, the changes in cavitation threshold under different sound pressures, amplitudes, and phase combinations of dual-frequency ultrasound were analyzed. At the same time, the optimal ultrasound stimulation parameters were determined in combination with the ultrasound frequency information.

[0056] Furthermore, obtaining the target position and angle information of the transducer includes: placing the focus of the transducer at the stimulation target position, and obtaining the angle and position information when the focus is minimum and the intensity is maximum by changing the angle of the transducer.

[0057] Furthermore, ultrasound non-invasive targeted acoustic genetic regulation includes:

[0058] Targeted control of microbubble cavitation releases the sonogenetic virus, allowing the sonogenetic virus to be expressed in the target area.

[0059] Specifically, in this embodiment, a method for dual-frequency ultrasound non-invasive targeted acoustic genetic regulation includes the following steps:

[0060] S1: Obtain the particle size, coating material, use environment and dual-frequency ultrasound frequency data of microbubbles, build a microbubble dynamics model, determine the relationship between the cavitation threshold of microbubbles and the change of ultrasound parameters, and determine the optimal ultrasound parameters based on the numerical calculation results;

[0061] S2: According to the ultrasonic parameters, the acoustic field simulation of the ultrasonic transducer is performed to determine the angle of the transducer so that the acoustic field focus generated by the two crossed transducers is minimized;

[0062] S3: Determine the transducer position according to the transducer focal length and angle, and use the robotic arm system to move the two transducers to the specified angle and position;

[0063] S4: Mix the microbubbles with the sonogenetic virus using an intravenous injection module and inject it into the target body through the vein to circulate in the blood;

[0064] S5: After intravenous injection, the position of the ultrasonic transducer is adjusted so that the focus is placed on the stimulation target, and the ultrasonic parameters are given in the numerical calculation to achieve ultrasonic non-invasive targeted acoustic genetic regulation.

[0065] Wherein, in step S1, the envelope microbubble dynamics model is constructed by coupling the Gilmore-Akulichev-Zener model with the microbubble envelope model; and the nonlinear acoustic field model is constructed by the KZK equation.

[0066] Specifically, in step S1, the envelope microbubble dynamics model and the acoustic field model are combined to construct an envelope microbubble dynamics model under a nonlinear acoustic field.

[0067] In step S1, the optimal ultrasound parameters are determined by the microbubble cavitation threshold. The optimal ultrasound stimulation parameters are determined by using the changes in the cavitation threshold under different sound pressures, different amplitudes, and different phase combinations, and combining the ultrasound frequency information.

[0068] In step S2, the transducer sound field simulation uses COMSOL software to perform ultrasonic simulation according to actual acoustic emission conditions. During the simulation, the foci of the two transducers are superimposed.

[0069] In step S5, microbubbles and sonogenetic viruses are injected into the target body, and the dual-frequency ultrasound system is used to control the cavitation of the microbubbles in a targeted manner to release the sonogenetic viruses so that the viruses are expressed in the target area.

[0070] This embodiment also proposes a dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system, the system comprising: a microbubble dynamics calculation module, an acoustic field simulation module, a robotic arm module, an intravenous injection module, and an acoustic emission module;

[0071] A microbubble dynamics calculation module, used to determine optimal ultrasound stimulation parameters based on microbubble parameters and ultrasound parameter frequency;

[0072] The sound field simulation module is used to simulate the sound field of the transducer based on the optimal ultrasonic stimulation parameters to obtain the target position and angle information of the transducer;

[0073] A robotic arm module for moving the transducer based on target position and angle information;

[0074] An intravenous injection module is used to inject the mixed microbubbles and sonogenetic virus into the target body;

[0075] The acoustic emission module is used to move the transducer to a specified position and angle based on the optimal ultrasonic stimulation parameters and simulation information after being injected into the target body, so as to perform ultrasonic non-invasive targeted acoustic genetic regulation.

[0076] Further, the microbubble dynamics calculation module includes: a first construction unit, a second construction unit, a third construction unit and an analysis unit;

[0077] The first construction unit is used to construct an envelope microbubble dynamics model by coupling the Gilmore-Akulichev-Zener model with the microbubble envelope model;

[0078] The second construction unit is used to construct a nonlinear sound field model through the KZK equation;

[0079] The third construction unit is used to combine the envelope microbubble dynamics model and the nonlinear acoustic field model to construct the envelope microbubble dynamics model under the nonlinear acoustic field;

[0080] The analysis unit is used to analyze the changes in cavitation threshold of dual-frequency ultrasound under different sound pressures, different amplitudes, and different phase combinations based on the envelope microbubble dynamics model, and to determine the optimal ultrasound stimulation parameters in combination with ultrasound frequency information.

[0081] Furthermore, obtaining the target position and angle information of the transducer in the sound field simulation module includes:

[0082] The transducer focus is placed at the stimulation target position, and the angle and position information when the focus is minimum and the intensity is maximum are obtained by changing the angle of the transducer.

[0083] Furthermore, in the acoustic emission module, based on the loaded optimal ultrasonic stimulation parameters, the cavitation of microbubbles is targeted and controlled to release the acoustic genetic virus, so that the acoustic genetic virus is expressed in the target area.

[0084] Specifically, a dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system proposed in this embodiment realizes accurate and non-invasive ultrasound neural regulation, and includes a microbubble dynamics calculation module, an acoustic field simulation module, a robotic arm module, an intravenous injection module, and an acoustic emission module;

[0085] The microbubble dynamics calculation module establishes the microbubble dynamics calculation model under this state through microbubble parameters and environmental condition information, combines the ultrasonic frequency information to determine the microbubble cavitation threshold, and calculates the optimal acoustic emission conditions at the same time;

[0086] The sound field simulation module simulates the sound field of two cross transducers and finds the angle and transducer position information when the focus is minimum and the intensity is maximum by changing the angle between the two transducers.

[0087] The robot module analyzes the angle and position information obtained by the simulation module and moves the two transducers to the specified positions respectively;

[0088] The intravenous injection module mixes the microbubbles with the sonogenetic virus and injects them into the target body through the vein so that they circulate in the blood.

[0089] The acoustic emission module loads the acoustic emission conditions for microbubble movement onto the acoustic emission module. The stimulation time is 1 minute, which causes microbubble cavitation, opens the blood-brain barrier, and allows the acoustic genetic virus to be expressed at the target site, thus achieving non-invasive acoustic genetic regulation.

[0090] like Figure 1As shown, the overall process of this embodiment is obtained by combining the microbubble dynamics calculation module with the ultrasonic frequency information to obtain the acoustic cavitation threshold information, and then calculate the minimum sound pressure parameters required for the transient cavitation of the microbubble; the sound field simulation module performs simulation according to the sound pressure parameters output by the microbubble dynamics calculation module, and during the simulation process, the angle and position of the two transducers are changed to make the focus of the transducer sound field minimum and the energy highest; after the sound field simulation is completed, the robotic arm module will adjust the transducer according to the position and angle information of the two transducers in the simulation, and make the focus located on the stimulation target; after determining the transducer position, the microbubble and the acoustic genetic virus are injected into the body through the intravenous injection module so that they circulate in the blood; after the intravenous injection is completed, the ultrasonic emission module is used to target and control the cavitation of the microbubble, release the acoustic genetic virus, and express the virus in the target area, thereby realizing non-invasive targeted acoustic genetic regulation.

[0091] like Figure 2 As shown in the figure, the microbubble dynamics calculation module constructs the microbubble dynamics model by coupling the Gilmore-Akulichev-Zener model with the microbubble envelope model; and constructs the nonlinear acoustic field model through the KZK equation. Combining the microbubble dynamics model with the acoustic field model, the cavitation threshold changes of dual-frequency ultrasound under different sound pressures, different amplitudes, and different phase combinations are analyzed, and the optimal ultrasonic stimulation parameters are determined by combining the ultrasonic frequency information.

[0092] like Figure 3 As shown in the figure, the acoustic field simulation module is mainly used to determine the position and angle information of the transducer during regulation. The acoustic field of the two cross transducers is simulated, and the optimal ultrasonic stimulation parameters calculated by microbubble dynamics are used. By changing the angle and position information of the two transducers, the transducer focus is placed at the stimulation target position, and the angle and transducer position information when the focus is minimum and the intensity is maximum are found.

[0093] like Figure 4 As shown, the robot module is composed of 1 moving axis, 2 rotating axes and 4 stepper motors. The angle and position information obtained by the simulation module are analyzed, and the two transducers are moved to the specified positions respectively by the robot module so that the focus position is located at the stimulation target.

[0094] like Figure 5 As shown, the intravenous injection module is mainly used to inject microbubbles and sonogenetic viruses into the body, and use the dual-frequency ultrasound system to target and control the cavitation of microbubbles, release the sonogenetic viruses, and make the viruses expressed in the target area.

[0095] like Figure 6 As shown, the ultrasonic transmitting module includes a signal generator module, a power amplifier module, and a transducer module, which mainly analyzes the sound pressure information obtained by the microbubble dynamics simulation module and controls the output of ultrasonic energy, thereby achieving precise ultrasonic nerve regulation.

[0096] Figure 7 The specific process for the implementation of the present invention is as follows: after the ultrasound parameter frequency and the microbubble parameter are input into the microbubble dynamics calculation module, the minimum sound pressure required for the transient cavitation of the microbubble is calculated, and at the same time, the angle between the two transducers is determined by the sound field simulation module to obtain the minimum focus. According to the calculated angle, the transducer angle and position are adjusted by the mechanical arm module so that the focus is located on the stimulation target. Finally, the microbubbles and the acoustic genetic virus are injected into the body through the intravenous injection module, and the dual-frequency ultrasound system is used to target and control the cavitation of the microbubbles, release the acoustic genetic virus, and express the virus in the target area to achieve non-invasive targeted acoustic genetic regulation.

[0097] like Figure 7 As shown, the present invention includes a microbubble dynamics calculation module, an acoustic field simulation module, a robotic arm module, an intravenous injection module, and an ultrasonic emission module, which can realize precise and non-invasive acoustic genetic regulation and meet the needs of precise regulation.

[0098] The embodiments described above are only descriptions of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A method for non-invasive targeted acoustic genetic regulation using dual-frequency ultrasound, characterized in that: include: Determining optimal ultrasound stimulation parameters based on microbubble parameters and ultrasound parameter frequency, wherein the microbubble parameters include: microbubble diameter and microbubble envelope material; Based on the optimal ultrasonic stimulation parameters, a sound field simulation is performed on the transducer to obtain target position and angle information of the transducer; The microbubbles and the sonogenetic virus are mixed evenly and injected into the target body, so that the mixture circulates in the blood; After injection into the target body, the transducer is moved to a specified position and angle based on the optimal ultrasound stimulation parameters and according to the simulation information to perform ultrasound non-invasive targeted acoustic genetic regulation.

2. The method of non-invasive targeted acoustic genetic regulation by dual-frequency ultrasound according to claim 1, characterized in that: Determining the optimal ultrasound stimulation parameters includes: The dynamic model of microbubble envelope was constructed by coupling the dynamic model of single microbubble under ultrasound excitation with the microbubble envelope model. Construct a nonlinear sound field model through nonlinear sound field equations; Combining the enveloped microbubble dynamics model with the nonlinear acoustic field model, constructing an enveloped microbubble dynamics model under a nonlinear acoustic field; Based on the envelope microbubble dynamics model under the nonlinear acoustic field, the change of cavitation threshold under different sound pressures, different amplitudes and different phase combinations of dual-frequency ultrasound is analyzed, and the optimal ultrasonic stimulation parameters are determined in combination with the ultrasonic frequency information.

3. The method of non-invasive targeted acoustic genetic regulation by dual-frequency ultrasound according to claim 1, characterized in that: Acquiring the target position and angle information of the transducer includes: placing the focus of the transducer at the stimulation target position, and acquiring the angle and position information when the focus is minimum and the intensity is maximum by changing the angle of the transducer.

4. The method of non-invasive targeted acoustic genetic regulation by dual-frequency ultrasound according to claim 1, characterized in that: Ultrasound non-invasive targeted sonogenetic regulation includes: Ultrasonic radiation force is used to control the cavitation of microbubbles in a targeted manner, release the sonogenetic virus, and allow the sonogenetic virus to be expressed in the target area.

5. A dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system, characterized in that: A method for implementing the dual-frequency ultrasound non-invasive targeted acoustic genetic regulation as described in any one of claims 1 to 4, wherein the system comprises: a microbubble dynamics calculation module, an acoustic field simulation module, a robotic arm module, an intravenous injection module, and an acoustic emission module; The microbubble dynamics calculation module is used to determine the optimal ultrasound stimulation parameters based on microbubble parameters and ultrasound parameter frequency, wherein the microbubble parameters include: microbubble diameter and microbubble envelope material; The sound field simulation module is used to perform sound field simulation on the transducer based on the optimal ultrasonic stimulation parameters to obtain the target position and angle information of the transducer; The mechanical arm module is used to move the transducer based on the target position and angle information; The intravenous injection module is used to evenly mix the microbubbles and the sonogenetic virus and inject them into the target body so that the mixture circulates in the blood; The acoustic emission module is used to move the transducer to a specified position and angle based on the optimal ultrasonic stimulation parameters and according to the simulation information after being injected into the target body, so as to perform ultrasonic non-invasive targeted acoustic genetic regulation.

6. The dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system according to claim 5, characterized in that: The microbubble dynamics calculation module includes: a first construction unit, a second construction unit, a third construction unit and an analysis unit; The first construction unit is used to construct an envelope microbubble dynamics model by coupling a dynamics model of a single microbubble under ultrasonic excitation with a microbubble envelope model; The second construction unit is used to construct a nonlinear sound field model through a nonlinear sound field equation; The third construction unit is used to combine the envelope microbubble dynamics model and the nonlinear acoustic field model to construct the envelope microbubble dynamics model under the nonlinear acoustic field; The analysis unit is used to analyze the change of cavitation threshold under different sound pressures, different amplitudes, and different phase combinations of dual-frequency ultrasound based on the envelope microbubble dynamics model under the nonlinear sound field, and determine the optimal ultrasound stimulation parameters in combination with the ultrasound frequency information.

7. The dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system according to claim 5, characterized in that: Acquiring the target position and angle information of the transducer in the sound field simulation module includes: The transducer focus is placed at the stimulation target position, and the angle and position information when the focus is minimum and the intensity is maximum are obtained by changing the angle of the transducer.

8. The dual-frequency ultrasound non-invasive targeted acoustic genetic regulation system according to claim 5, characterized in that: In the acoustic emission module, based on the loaded optimal ultrasonic stimulation parameters, the cavitation of microbubbles is targeted and controlled to release the acoustic genetic virus, so that the acoustic genetic virus is expressed in the target area.