In-situ measurement system and method for ultrasonic sound field in solid medium based on acoustoelectric effect

Abstract

The application relates to the technical field of ultrasonic sound field measurement and biomedical engineering, and discloses a solid medium internal ultrasonic sound field in-situ measurement method and system. The system injects low-frequency alternating current into a solid or semi-solid medium containing movable ions through a multi-contact microelectrode, generates a sound-electric heterodyne modulation signal by using high-frequency ultrasonic sound pressure to modulate local conductivity, carries out differential collection, anti-saturation amplification, frequency domain demodulation and spatial deconvolution based on a lead field kernel function, and reconstructs a three-dimensional ultrasonic sound pressure field distribution in the medium. Therefore, in-situ characterization of a low-intensity sound field in the solid medium can be realized under the condition of reducing mechanical scanning and medium disturbance.

Description

Technical Field

[0001] This application relates to the fields of ultrasonic acoustic field metrology and biomedical engineering technology, and in particular to a technology for in-situ measurement and three-dimensional spatial distribution reconstruction of ultrasonic acoustic pressure field in a solid or semi-solid medium containing mobile ions based on the acoustic-electric effect and multi-contact microelectrodes. Background Technology

[0002] In scenarios such as the development of transcranial ultrasound stimulation devices, calibration of physical phantoms of brain tissue, and acoustic verification of ex vivo skull specimens, it is typically necessary to know the actual sound pressure level, focal point location, and three-dimensional spatial distribution formed inside the skull structure, tissue phantom, or other solid or semi-solid media after the ultrasound waves pass through them. For example, in the preclinical evaluation of low-intensity transcranial ultrasound neuromodulation, it is necessary to confirm whether the target focal point falls within the predetermined area, and to obtain transcranial mechanical index and thermal dose parameters to assess safety. In the testing of solid brain tissue phantoms, it is necessary to calibrate the spatial morphology of the transducer sound beam after passing through the highly heterogeneous skull-phantom interface to verify the accuracy of the numerical simulation model's prediction of focal intensity and distribution volume. In ex vivo skull specimen experiments, it is also necessary to evaluate the influence of the skull structure on the attenuation, refraction, scattering, and focal point shift of the sound field. The common feature of these scenarios is that the tested medium is a solid or semi-solid structure rather than free water, and the ultrasound sound field parameters need to be obtained inside the medium rather than in a liquid outside the medium.

[0003] Existing sound field measurement techniques typically rely on piezoelectric or fiber optic hydrophones scanning in water tanks or liquid environments, or on large imaging systems such as magnetic resonance thermography and magnetic resonance acoustic radiation force imaging for indirect monitoring. However, within solid or semi-solid media, the insertion and movement of traditional hydrophones can easily alter the internal acoustic structure, and the probe itself may introduce impedance mismatch and spatial averaging effects. Magnetic resonance monitoring methods, on the other hand, suffer from problems such as large system size, insufficient sensitivity to low-intensity ultrasonic responses, and limited application flexibility. Therefore, existing methods struggle to simultaneously achieve in-situ measurement within solid media, low-disturbance spatial sampling, extraction of weak sound field responses, and reconstruction of three-dimensional sound pressure distribution. A novel in-situ ultrasonic sound field measurement technique for solid media is urgently needed to address these issues. Summary of the Invention

[0004] The purpose of this application is to provide an in-situ measurement system and method for ultrasonic sound field inside a solid medium based on the acousto-electric effect, so as to solve the problems mentioned in the background art.

[0005] This invention provides an in-situ measurement system for ultrasonic sound fields inside solid media based on the acousto-electric effect, comprising: A multi-contact microelectrode module is configured to be placed inside a solid or semi-solid medium containing mobile ions, for injecting low-frequency alternating current into the solid or semi-solid medium through a selected pair of excitation contacts, and for acquiring differential voltage signals through a selected pair of measurement contacts. The dual signal generation and ultrasonic emission module connects the multi-contact microelectrode module and the ultrasonic emission unit. It generates a low-frequency electrical excitation signal to drive the pair of excitation contacts to inject the low-frequency alternating current, and generates a high-frequency ultrasonic signal to drive the ultrasonic emission unit to emit high-frequency ultrasonic waves toward the solid or semi-solid medium. Utilizing the acoustic pressure of the high-frequency ultrasonic waves to modulate the local conductivity of the solid or semi-solid medium at the same frequency, the low-frequency alternating current and the high-frequency ultrasonic waves undergo heterodyne mixing, generating a high-frequency acoustic-electric modulation signal carrying acoustic pressure information on the difference frequency and sum frequency sidebands, which is then extracted by the pair of measurement contacts as the differential voltage signal. The signal conditioning and data acquisition module is connected to the multi-contact microelectrode module and is used to receive the differential voltage signal, sequentially perform low-frequency fundamental wave filtering, anti-saturation differential amplification and digital acquisition on the differential voltage signal, and output the broadband discrete time sequence corresponding to the differential voltage signal. The signal processing and inverse inversion module, connected to the signal conditioning and data acquisition module, is used to receive the broadband discrete-time series, perform heterodyne frequency domain demodulation on the broadband discrete-time series to extract the baseband envelope and generate a three-dimensional voltage envelope voxel matrix; and based on the pre-calibrated spatial lead field kernel function corresponding to the multi-contact microelectrode module, solve the spatial deconvolution or regularization inverse problem of the three-dimensional voltage envelope voxel matrix to reconstruct the three-dimensional ultrasonic sound pressure field distribution map inside the solid or semi-solid medium.

[0006] In a preferred embodiment, the multi-contact microelectrode module is configured to reuse multiple contacts on the same probe: one pair of contacts is configured as the excitation contacts, and another pair of contacts adjacent to, intersecting or nested with them is configured as the measurement contacts, such that the injected current density field coincides and overlaps with the measured spatial conduction field, and a localized spatial sensitivity distribution with exponentially rapid decay is formed in the microscopic range of the contact surface. The center-to-center distance between adjacent contacts of the multi-contact microelectrode module in each axial direction Satisfying the Nyquist sampling theorem ,in The wavelength of the high-frequency ultrasonic wave in the solid or semi-solid medium is given, and the exposure area of ​​a single contact point is between 100 μm. 2 Up to 2500 μm 2 between; The multi-contact microelectrode module is selected from one of the following types: deep brain stimulation electrode, carbon fiber microfilament electrode, microelectromechanical system microelectrode array based on rigid silicon microfilament, or microelectrode array based on flexible polymer substrate; wherein the flexible polymer substrate includes polyimide or parylene.

[0007] In a preferred embodiment, the signal dual generation and ultrasonic transmission module includes a multi-channel arbitrary waveform generator and a voltage-controlled constant current source sharing a common high-precision reference clock; The multi-channel arbitrary waveform generator drives the voltage-controlled constant current source to continuously inject a low-frequency alternating current with a frequency between 10 Hz and 10 kHz and an amplitude between 0.1 mA and 2 mA into the multi-contact microelectrode module. The voltage-controlled constant current source overcomes the distortion of the injected electric field caused by the dynamic fluctuation of the polarization impedance at the interface between the multi-contact microelectrode module and the solid or semi-solid medium with its high impedance output characteristics, and maintains the constant amplitude of the low-frequency alternating current. The multi-channel arbitrary waveform generator drives the ultrasonic transmitting unit to emit high-frequency ultrasonic waves with a frequency between 0.5 MHz and 5 MHz through a high-frequency channel. During spatial scanning, the ultrasonic transmitting unit and the multi-contact microelectrode module remain relatively fixed. The ultrasonic transmitting unit uses a single-element concave-focusing piezoelectric ceramic transducer to form a wide-beam static envelope mode covering the multi-contact microelectrode module, or uses a multi-element ultrasonic phased array to achieve three-dimensional electronic deflection of the focal point by adjusting the phase and delay of the emitted wave, and cooperates with the time-division multiplexing gating in the multi-contact microelectrode module to complete the pure electrical spatial scanning.

[0008] In a preferred embodiment, the signal conditioning and data acquisition module includes a cascaded anti-saturation analog front-end circuit and a high-speed analog-to-digital converter array; The anti-saturation analog front-end circuit includes a physical high-pass filter and a low-noise differential preamplifier. The cutoff frequency of the physical high-pass filter is configured to be greater than the frequency of the low-frequency alternating current and lower than the frequency of the high-frequency ultrasound, used to isolate the injected fundamental wave and electrochemical DC polarization drift caused by the low-frequency alternating current. The low-noise differential preamplifier is cascaded in the subsequent stage to amplify the filtered signal with high gain. The high-speed analog-to-digital converter array performs oversampling and digital acquisition on the amplified signal to output the broadband discrete-time sequence corresponding to each spatial coordinate. The mixing frequency of the sum and difference frequency sidebands generated by the heterodyne mixer. satisfy: ,in The frequency of the high-frequency ultrasound is [the frequency of the ultrasound]. The frequency of the low-frequency alternating current; the signal processing and inverse inversion module is executed by the host computer workstation, and the heterodyne frequency domain demodulation includes: using a high-order Kaiser window to perform smooth weighting and fast Fourier transform frequency domain shaping on the time domain data of the broadband discrete time series, using stopband attenuation to suppress co-frequency crosstalk spectral leakage, and extracting the frequency located at the mixing frequency. The high-frequency mixing signal at the location is processed by IQ quadrature amplitude demodulation of in-phase and quadrature components, and the harmonic components are filtered out by digital low-pass filter to extract the baseband acoustic-electric envelope signal that is not affected by carrier phase distortion and interface reflection. The three-dimensional voltage envelope voxel matrix is ​​formed by splicing multiple points.

[0009] In a preferred embodiment, the time-domain value of the differential voltage signal It conforms to the following formula for volume integral of the lead field: In the formula, The acoustic-electric interaction constant of the solid or semi-solid medium is given. The initial static resistivity without ultrasonic interference; The measurement volume region is located inside the solid or semi-solid medium. This corresponds to the spatial lead field vector of the measurement contact point in space; The spatial current density field vector formed by the low-frequency alternating current; The transient ultrasonic pressure field to be reconstructed; When the signal processing and inverse inversion module is executed, the three-dimensional voltage envelope voxel matrix is ​​transformed to the three-dimensional spatial frequency domain, and the Wiener deconvolution algorithm is introduced. The inverse problem is solved by combining the spatial lead field kernel function and the system background noise power spectrum. Subsequently, the fuzzy divergence caused by the sensor spatial smoothing integral effect is compensated by the three-dimensional Fourier inverse transform inverse inversion, and the three-dimensional ultrasonic sound pressure field distribution map is restored. Alternatively, the solution of the spatial deconvolution or regularization inverse problem can be replaced by an inverse problem solution algorithm based on Tikhonov regularization or the finite element lumped parameter method.

[0010] In a preferred embodiment, a calibration submodule is further included. The calibration submodule is used to perform physical scanning measurements on the multi-contact microelectrode module in a calibration medium with known acoustic field parameters. By spatially mapping and back-deriving the measured volume integral voltage envelope data with the known acoustic field parameters, a three-dimensional lead field kernel matrix characterizing the microscopic electromagnetic sensitivity of each contact is extracted. This matrix is ​​then used as the spatial lead field kernel function when the signal processing and inverse inversion module performs the spatial deconvolution or regularization inverse problem solution.

[0011] This application provides a method for in-situ measurement of ultrasonic sound field inside a solid medium based on the acousto-electric effect. Using the aforementioned in-situ measurement system for ultrasonic sound field inside a solid medium, the method includes the following time-continuous and coordinated steps: Step S1: A low-frequency electrical excitation signal is sent to a multi-contact microelectrode module placed in a solid or semi-solid medium containing mobile ions through a dual signal generation and ultrasonic emission module, so as to directionally inject low-frequency alternating current into the solid or semi-solid medium, and at the same time drive the ultrasonic emission unit to emit high-frequency ultrasonic waves into the solid or semi-solid medium. Step S2: The acoustic-electric effect of modulating the local conductivity of the solid or semi-solid medium at the same frequency by the sound pressure of the high-frequency ultrasonic wave causes the low-frequency alternating current and the high-frequency ultrasonic wave to undergo nonlinear heterodyne mixing, thereby shifting the sound pressure information and generating a high-frequency acoustic-electric modulation signal carried on the high-frequency difference frequency and sum frequency sidebands. Step S3: The differential voltage signal of the aliased high-frequency acoustic-electric modulation signal is extracted using a pair of measurement contacts selected by the multi-contact microelectrode module; after the signal conditioning and data acquisition module performs physical high-pass fundamental filtering and high-gain differential amplification on the differential voltage signal, it performs oversampling and digital output as the corresponding broadband discrete time series. Step S4: The signal processing and inverse inversion module receives the broadband discrete time series, executes the heterodyne frequency domain demodulation algorithm including Kaiser window weighting and IQ orthogonal amplitude processing, removes electromagnetic crosstalk and phase distortion at the same frequency, extracts acoustic envelope features and reconstructs the three-dimensional voltage envelope voxel matrix. Step S5: The signal processing and inverse inversion module, based on the pre-calibrated spatial lead field kernel function corresponding to the multi-contact microelectrode module within the system, solves the three-dimensional voltage envelope voxel matrix in the three-dimensional spatial frequency domain using spatial deconvolution or regularization inverse problem, inversely eliminating the smoothing and blurring effect caused by the hardware macroscopic aperture, and restoring and resolving the true three-dimensional ultrasonic sound pressure field distribution map inside the solid or semi-solid medium.

[0012] In a preferred embodiment, during the execution of steps S1 to S4, the ultrasonic transmitting unit and the multi-contact microelectrode module remain relatively fixed in physical space; the construction of the three-dimensional voltage envelope voxel matrix in step S4 is achieved by performing millisecond-level high-speed electronic gating switching on the contact pairs at different spatial coordinates in the multi-contact microelectrode module, and repeating steps S1 to S3 in sequence to collect the baseband acoustic-electric envelope signal of each discrete spatial node, thereby completing the pure electrical three-dimensional sound field volume sampling without mechanical displacement; Before introducing the spatial lead field kernel function in step S5 to solve the inverse problem, a pre-calibration step is also included, which is performed independently: the multi-contact microelectrode module is placed in a calibration medium or a degassed conductive aqueous solution with known three-dimensional true focal parameters for physical scanning measurement, and the measured volume integral voltage envelope data of each spatial coordinate is recorded; based on the physical spatial mapping relationship between the measured volume integral voltage envelope data and the known three-dimensional true focal parameters, a back-reasoning algorithm is used to analyze and extract the three-dimensional lead field kernel matrix that characterizes the microscopic electromagnetic sensitivity of different contacts, and it is pre-stored in the system as the spatial lead field kernel function for spatial deconvolution point diffusion inversion correction in step S5.

[0013] In a preferred embodiment, the ultrasonic transmitting unit in step S1 alternatively transmits broadband short-pulse ultrasonic waves or coded excitation ultrasonic waves; in step S4, a broadband bandpass filter is used to extract the high-frequency acoustic-electric signal components in the differential voltage signal, and then the signal envelope is extracted using Hilbert transform or matched filter to form the three-dimensional voltage envelope voxel matrix; or, the multi-contact microelectrode module is alternatively configured as a single-channel microelectrode, and in steps S3 to S4, a high-precision three-dimensional stepper motor is used to perform relative physical translation between the ultrasonic transmitting unit and the single-channel microelectrode, and mechanical tomography scans are performed on different spatial coordinates of the solid or semi-solid medium by repeating steps S1 to S4 in sequence, and the acoustic envelopes of each spatial coordinate obtained together constitute the three-dimensional voltage envelope voxel matrix required in step S5.

[0014] This application provides a focal measurement application of the above-mentioned solid medium internal ultrasound field in-situ measurement system or method in low-intensity transcranial ultrasound stimulation neuromodulation. The physical carrier of the measurement object is limited to ex vivo tissue specimens, ex vivo skull specimens, or solid physical phantoms of brain tissue for non-disease diagnosis and treatment purposes. It is used for in-situ calibration and measurement of real sound wave focal localization, three-dimensional distribution morphology characterization, and target area ultrasound safety dosimetry within the solid object.

[0015] This application organizes a multi-contact microelectrode module 10, a dual signal generation and ultrasound emission module 20, a signal conditioning and data acquisition module 30, and a signal processing and inverse inversion module 40 into a continuous and coordinated measurement link. This allows the ultrasonic sound pressure inside the solid or semi-solid target medium 60 to no longer rely on the macroscopic mechanical deformation of the piezoelectric sensitive film for indirect measurement. Instead, it converts the local conductivity modulation generated by mobile ions inside the medium into a detectable electrical response. Since the multi-contact microelectrode module 10 can remain relatively fixed inside the target medium 60 and complete electrical sampling at different spatial locations by selecting different excitation contact pairs and measurement contact pairs, it helps to reduce the disturbance to the acoustic structure of the medium caused by the movement and scanning of traditional mechanical probes in solid media, while also reducing the reflection and obstruction effects of the probe's own structure on the original sound field. At the same time, since the occurrence of the acousto-electric effect depends on the ionic properties of the medium itself rather than the assistance of external large imaging equipment, this system helps to reduce the dependence on the bulky scanners in magnetic resonance imaging technology, and completes in-situ measurement of low-intensity transcranial ultrasound sound fields on a portable, purely electrical platform.

[0016] Furthermore, when the multi-contact microelectrode module 10 configures one pair of contacts as excitation contacts and another pair of adjacent contacts as measurement contacts on the same probe, the injected current density field Spatial guiding field of measurement The two contacts overlap and superimpose significantly in a localized space, and the spatial sensitivity matrix formed by their dot product exhibits an exponentially rapid decay within the microscopic range of the contact surface. This highly localized spatial sensitivity distribution transforms the macroscopic mean surface integral into a three-dimensional soft-weighted integral with extremely high central weights. This helps to mitigate the spatial averaging effect caused by phase cancellation at different positions within the macroscopic effective aperture in traditional piezoelectric hydrophones during high-frequency focusing sound fields, from a hardware physics perspective. In conjunction with this, the center-to-center distance between adjacent contacts satisfies the Nyquist sampling theorem. The spatial sampling criteria are beneficial for preventing signal aliasing in the spatial frequency domain. The multi-contact microelectrode module 10 can be configured with deep brain stimulation electrodes, carbon fiber microfilament electrodes, microelectromechanical system microelectrode arrays based on rigid silicon microfilaments, or microelectrode arrays based on flexible polymer substrates, which provides flexibility for the system to adapt to different solid media environments and different mechanical compliance requirements.

[0017] During the combined action of low-frequency alternating current and high-frequency ultrasound, sound pressure information is modulated onto the difference frequency and sum frequency sidebands. This allows the effective signal to be distinguished in the frequency domain from the low-frequency fundamental wave, DC polarization drift, and potential crosstalk from the ultrasonic transmitting unit 50. Therefore, the signal conditioning and data acquisition module 30 employs a cascaded approach of first filtering out the low-frequency fundamental wave, then performing differential amplification and digital acquisition. This reduces the risk of saturation or truncation in the subsequent amplification circuit under conditions where weak acoustic signals and strong background injection signals coexist, and provides a processable broadband discrete-time sequence for subsequent heterodyne frequency domain demodulation. The dual signal generation and ultrasonic transmission module 20 uses a high-precision reference clock shared by the multi-channel arbitrary waveform generator and the voltage-controlled constant current source. This design helps reduce the impact of inherent clock drift between independent devices on the phase demodulation accuracy of weak acoustic and electrical signals. The voltage-controlled constant current source overcomes the dynamic fluctuations of polarization impedance at the interface between the microelectrode and the medium with its high impedance output characteristics, which helps maintain the amplitude constantness of the background current density field. The two acoustic coverage modes provided by this module—wide-beam static envelope mode and phased array electronic deflection mode—combined with the time-division multiplexing electronic gating of the contact array in the multi-contact microelectrode module 10, facilitates the completion of purely electrical volumetric sampling of the deep three-dimensional sound field of solid media while keeping both the ultrasonic transducer and the microelectrode module physically fixed.

[0018] The signal processing and inverse inversion module 40 extracts signals located in the frequency domain through Kaiser window shaping. The mixed signal at the location, and through the in-phase component Orthogonal components The orthogonal demodulation of the baseband acoustic envelope helps to reduce the impact of carrier phase drift, interface reflection, and spectral leakage on sound pressure information extraction. After the baseband acoustic envelopes at multiple spatial locations are formed into a three-dimensional voltage envelope voxel matrix according to the physical coordinates of the contact points, the spatial deconvolution or regularized inverse problem is solved by combining the pre-calibrated spatial lead field kernel function. This can transform the volume-weighted response caused by the microelectrode lead field into a three-dimensional sound pressure field result that is closer to the real spatial distribution, thereby improving the focal morphology blurring problem caused by the spatial averaging effect of traditional hydrophones. In addition to Wiener deconvolution, the system can also alternatively use inverse problem solving algorithms based on Tikhonov regularization or finite element lumped parameter method, providing flexibility for engineering implementation under different computational resource constraints and boundary conditions. The acquisition of the lead field kernel function depends on an independent pre-calibration process: the multi-contact microelectrode module 10 is physically scanned and measured in a calibration medium with known sound field parameters, and the three-dimensional lead field kernel matrix is ​​obtained by back-reasoning. This kernel matrix is ​​pre-stored in the system as a prerequisite for Wiener deconvolution inversion.

[0019] When the multi-contact microelectrode module 10 is configured as a three-dimensional multi-contact microelectrode array and combined with an on-chip front-end processing unit, a low-voltage differential signal bus, and a field-programmable gate array demultiplexing, weak analog signals can be preliminarily processed and reconstructed near the contact points, which helps reduce channel crosstalk and long-distance transmission interference caused by high-density leads. In high-frequency steady-state acoustic field measurement scenarios, the multi-contact microelectrode module 10 can be configured as a tip-sensitive one-dimensional or two-dimensional probe array, and the acquisition can be performed layer by layer along the reverse direction of ultrasonic propagation using a stepping displacement stage. This allows the sensing contact points to preferentially obtain the acoustic-electric response before being affected by multiple scattering from the probe shaft in front of the incident wave, thus providing an alternative measurement path that reduces the overall disturbance of the probe array for ultra-high frequency or high-gradient acoustic fields with frequencies greater than 1 MHz.

[0020] Overall, the various technical means in this application are organically coordinated around the continuous technical contradictions of "difficulty in entering the low-intensity ultrasonic sound field inside the solid medium without disturbance, difficulty in reading it with anti-interference, and difficulty in inferring the spatial sound pressure from the local voltage". From the physical transduction mechanism, frequency domain anti-interference mechanism, spatial sampling mechanism to reverse reconstruction mechanism, a progressive synergistic relationship is formed. Its overall technical effect cannot be obtained independently by any single module or single existing technology.

[0021] The specification of this application contains numerous technical features distributed across various technical solutions. Listing all possible combinations of these technical features (i.e., technical solutions) would make the specification excessively lengthy. To avoid this problem, the various technical features disclosed in the above-described invention, the various technical features disclosed in the following embodiments and examples, and the various technical features disclosed in the accompanying drawings can be freely combined to form various new technical solutions (all of which are considered to have been described in this specification), unless such a combination of technical features is technically infeasible. For example, one example discloses feature A+B+C, and another example discloses feature A+B+D+E. Features C and D are equivalent technical means that serve the same function, and technically only one needs to be used; they cannot be used simultaneously. Feature E can technically be combined with feature C. Therefore, the solution A+B+C+D should not be considered as described because it is technically infeasible, while the solution A+B+C+E should be considered as described. Attached Figure Description

[0022] Figure 1 This is a block diagram illustrating the overall architecture and working principle of an in-situ ultrasonic field measurement system for solid media according to an embodiment of this application.

[0023] Figure 2 This is a schematic diagram of the structure of a three-dimensional multi-contact microelectrode array according to an embodiment of this application.

[0024] Figure 3 This is a schematic diagram of the spatial layout of an in-situ ultrasonic field measurement system for a phantom body according to an embodiment of this application.

[0025] Figure 4 This is a schematic diagram illustrating the principle of low-disturbance quasi-three-dimensional in-situ tomography scanning along the reverse direction of ultrasonic wave propagation using a stepper motor-driven tip-sensitive microelectrode array, according to an embodiment of this application.

[0026] Figure 5 This is a schematic diagram illustrating the frequency domain characteristics of the acoustic-electric heterodyne mixing effect and the principle of narrowband signal extraction according to an embodiment of this application.

[0027] Figure 6 This is a schematic diagram of the relative spatial configuration and voxel reconstruction of an ultrasonic transducer and microelectrode array during a three-dimensional tomographic scanning process according to an embodiment of this application.

[0028] Figure 7 This is a flowchart of the algorithm for acoustic field reconstruction and Wiener deconvolution inversion calculation based on the lead field kernel function according to an embodiment of this application.

[0029] Figure 8 This is a schematic diagram of the three-dimensional simulation setup and the local electrode setup near the acoustic focus according to an embodiment of this application.

[0030] Figure 9 This is a comparative schematic diagram of the reference sound pressure field, measured voltage envelope, and Wiener reconstruction results on different orthogonal planes according to embodiments of this application.

[0031] Figure 10 This is a schematic diagram comparing measured images and reconstructed images under different noise conditions according to embodiments of this application. Detailed Implementation

[0032] In the following description, many technical details are presented to help the reader better understand this application. However, those skilled in the art will understand that the technical solutions claimed in this application can be implemented even without these technical details and various variations and modifications based on the following embodiments.

[0033] Explanation of some concepts: The acoustic-electric effect (AE) refers to the physical effect in which the local physical mobility and collision cross-section of ions are affected by the dynamic pressure gradient carried by the sound wave and the changes in the density of the medium when the sound wave propagates in a medium containing mobile ions. This causes the local conductivity or resistivity of the medium to be transiently modulated with the sound pressure, and produces a detectable electrical response under the action of an applied electric field.

[0034] Heterodyning refers to a nonlinear physical multiplication effect. In this application, the low-frequency alternating current injected through the multi-contact microelectrode module 10 and the high-frequency ultrasonic sound field that causes changes in the resistivity of the medium generate a physical product in the control equation of the acousto-electric effect, thereby deriving a new carrier frequency component (i.e., the sum frequency signal and the difference frequency signal) in the frequency spectrum whose frequency is equal to the sum and difference of the two original frequencies.

[0035] The lead field refers to the spatial distribution of the measured signal intensity when a potential is measured using one or more pairs of electrodes on or within a dielectric surface. This field can be represented by the vector field of current density generated at various points in space when an equivalent current is injected into the measuring electrode. It is a core physical quantity describing the spatial selectivity of a measurement system in bioelectromagnetics and impedance tomography.

[0036] The spatial averaging effect refers to the physical phenomenon that when the effective sensitive area of ​​a sound field sensor is larger than the spatial variation scale of the sound field, the sound pressure at different positions on the sensitive surface cancels each other out during the integration process due to phase differences, resulting in an underestimation of the measured peak sound pressure.

[0037] Wiener deconvolution is a regularized deconvolution method that uses a pre-calibrated spatial lead field kernel function and noise power spectrum estimate to spatially invert the three-dimensional voltage envelope voxel matrix under the minimum mean square error criterion to reconstruct the three-dimensional ultrasonic sound pressure field distribution.

[0038] Transcranial ultrasound stimulation (TUS) is an emerging neuromodulation technique that uses focused ultrasound waves to penetrate the skull and reach specific brain regions, thereby non-invasively regulating neuronal activity through mechanical or acoustic effects.

[0039] Acoustoelectric Interaction Constant ( ) refers to a material property parameter that characterizes the proportional relationship between the relative change in local resistivity caused by sound wave propagation in a weakly conductive medium and the transient ultrasonic sound pressure. Its physical dimensions are . .

[0040] Solid or semi-solid media refer to media such as solid phantoms, semi-solid phantoms, ex vivo tissue specimens, or ex vivo skull specimens that contain mobile ions and can generate acoustic and electrical responses under the combined action of an external electric field and an ultrasonic field.

[0041] The target medium refers to the solid or semi-solid medium that is incorporated into the multi-contact microelectrode module 10 and receives high-frequency ultrasonic waves emitted by the ultrasonic transmitting unit 50 in this application.

[0042] A multi-contact microelectrode module refers to a microelectrode structure with multiple selectable contacts, capable of injecting low-frequency alternating current into the target medium 60 and receiving differential voltage signals, and is indicated by reference numeral 10 in this application.

[0043] An excitation contact pair refers to a pair of contacts in the multi-contact microelectrode module 10 that are selected for directional injection of low-frequency alternating current into the target medium 60.

[0044] A measurement contact pair refers to a pair of contacts in the multi-contact microelectrode module 10 that are selected to receive a differential voltage signal containing an acoustic-electric modulation component.

[0045] Low-frequency alternating current refers to the current generated by the dual signal generation and ultrasonic transmission module 20 and injected into the target medium 60 via the excitation contact to form a background current density field. Alternating current.

[0046] High-frequency ultrasound refers to ultrasound emitted by the ultrasonic transmitting unit 50 towards the target medium 60 and used to modulate the local conductivity of the target medium 60.

[0047] Acousto-electric modulation signal refers to an electrical signal carrying sound pressure information generated after low-frequency alternating current and high-frequency ultrasonic waves undergo heterodyne mixing in a target medium 60 through the acoustic-electric effect.

[0048] Difference frequency and sum frequency sideband refer to the frequencies after heterodyne mixing of acoustic and electrical frequencies. The frequency components formed at that location, among which It is a high-frequency ultrasonic wave. It is the frequency of low-frequency alternating current.

[0049] Broadband Discrete Time Series It refers to the time series data formed after the differential voltage signal is filtered by low-frequency fundamental wave, differentially amplified and digitally acquired.

[0050] A three-dimensional voltage envelope voxel matrix is ​​a three-dimensional voltage data matrix formed by arranging baseband acoustic-electric envelope signals at multiple spatial coordinates according to the physical location of the contact points.

[0051] The spatial lead field kernel function is a kernel function that characterizes the distribution of electrical sensitivity of different contact combinations of the multi-contact microelectrode module 10 to different spatial locations inside the target medium 60. In a physical sense, it is equivalent to the point spread function of the system.

[0052] Retreating reverse beam stepping refers to a tomographic measurement method in which, in a tip-sensitive probe array implementation, the probe array retreats layer by layer from far to near along the reverse direction of high-frequency ultrasonic wave propagation, and at each layer, electronic gating is used to collect acoustic and electrical signals.

[0053] The following is a brief summary of some of the innovative aspects of this application: In summary, this application does not simply transfer known acoustic-electric effects to ultrasonic measurements, nor does it merely replace traditional hydrophones with multi-contact microelectrodes. Rather, it addresses the specific technical challenge of characterizing low-intensity ultrasonic sound fields within solid or semi-solid target media 60 in situ, by integrating the physical mechanism—high-frequency ultrasonic sound pressure—that originally belonged to two independent technical fields: acoustic metrology and bioelectromagnetics. The transient modulation of the local conductivity of the driving medium containing movable ions, and the connection field vector between adjacent contacts in the multi-contact microelectrode module 10. With current density field vector The sensitivity matrix formed by the dot product exhibits an exponential decay spatial collapse characteristic in the microscopic range—organized in a functional reuse and nonlinear coupling manner as an indivisible closed-loop measurement system with "sound pressure-conductivity modulation-heterodyne sideband extraction-lead field inversion" as the main line.

[0054] Specifically, such as Figure 1 and Figure 5 As shown, the dual signal generation and ultrasonic transmission module 20 establishes a frequency within the target medium 60 via excitation contacts. Low-frequency alternating current and its current density field Synchronously drive the ultrasonic transmitting unit 50 to form a frequency High-frequency ultrasound; when the two overlap in the same local space, acoustic-electric heterodyne mixing occurs, in The difference frequency and sum frequency sidebands generate an acoustic-electric modulation signal carrying sound pressure information. This mixing is not voltage multiplication in electronic circuits, but rather a physical product that only exists under the specific material condition of sound waves causing changes in ion mobility in a medium containing mobile ions. This is fundamentally different from traditional electronic heterodyne receivers. For example... Figure 2 and Figure 6 As shown, The signal is extracted differentially from the measurement contact pairs, and after being filtered by the signal conditioning and data acquisition module 30 to remove low-frequency fundamental frequencies and polarization drift, and subjected to anti-saturation differential amplification and digitization, a broadband discrete-time series is formed. Signal processing and inverse inversion module 40, such as Figure 7 The diagram shows the extraction of the baseband acoustic-electric envelope using Kaiser window frequency domain shaping and IQ quadrature demodulation, which is then stitched together in physical coordinates to form a three-dimensional voltage envelope voxel matrix; due to the sensitivity matrix The exponential attenuation within the microscopic range of the contact point degenerates the macroscopic volume integral into a localized weighted sampling within an extremely small spatial region. Combined with Wiener deconvolution using a pre-calibrated lead field kernel function, this reversely weakens the lead field smoothing effect, reconstructing the three-dimensional sound pressure field distribution within the target medium 60. This cascaded coupling across the boundaries of acoustics, electromagnetics, and signal processing cannot be readily achieved through isolated improvements or simple superposition of existing technologies in any single field.

[0055] Furthermore, the inventors of this application have discovered through long-term in-depth research that the difficulty in measuring the ultrasonic sound field inside a solid medium is not simply due to whether the sensor size is small enough, but rather because the traditional measurement paradigm relies on the mechanical deformation of the probe itself or the indirect response of a large imaging system to obtain sound pressure, making it difficult to decouple the measurement structure, the medium structure, and the sound field to be measured.

[0056] After in-depth analysis, the inventors discovered that traditional hydrophones rely on piezoelectric films to output electrical signals through macroscopic mechanical deformation. This mechanism requires a certain geometric area and acoustic backing structure at the sensor front end. However, when these structures are inserted into a solid medium, they create a macroscopic reflection interface around the probe that is mismatched with the acoustic impedance of the medium, leading to secondary sound field distortion. In other words, the measurement process itself disrupts the physical state of the measured object. The inventors further realized that the spatial resolution of a hydrophone depends on the effective sensitive element size related to frequency. In the mid-to-low frequency range, the expansion of the effective diameter far exceeds the physical size, resulting in a spatial averaging effect that underestimates the peak sound pressure. In addition, the factory calibration coefficients of commercial hydrophones based on pure water environments lose their direct applicability in solids due to the difference in acoustic impedance between solids and liquids. Regarding magnetic resonance acoustic field monitoring, the inventors found that the temperature rise and displacement generated by low-intensity transcranial ultrasound stimulation are extremely small, far below the sensitivity threshold of magnetic resonance thermometry and acoustic radiation force imaging. Furthermore, the method's reliance on a bulky scanner compromises the portability of the measurement.

[0057] Based on the aforementioned research, the inventors creatively recognized that if the target medium containing mobile ions is used as the acoustic-electric conversion carrier, and a separable sideband signal is generated by heterodyne mixing of low-frequency alternating current and high-frequency ultrasound in the same space, and then the local sound pressure is electronically gated and sampled using the spatial lead field of multi-contact microelectrodes, and deconvolution reconstruction is completed by combining it with a pre-calibrated lead field kernel function, it is possible to fundamentally bypass the aforementioned coupling dilemma. Based on this insight, this application proposes an in-situ measurement system and method for ultrasonic sound field inside a solid medium based on the acoustic-electric effect. The implementation process of this application is described in detail below through specific embodiments.

[0058] To make the objectives, technical solutions, and advantages of this invention clearer, the specific embodiments of this invention will be further described in detail below with reference to the accompanying drawings and specific examples. It should be understood that the embodiments described herein are only for explaining this invention and are not intended to limit the scope of protection of this invention. Where there is no conflict, the embodiments and technical features in these embodiments can be combined with each other.

[0059] Example 1: In-situ Measurement System of Ultrasonic Field Inside Solid Medium Based on Acoustoelectric Effect like Figure 1 As shown, this embodiment provides an in-situ measurement system for the ultrasonic field inside a solid medium based on the Acoustoelectric Effect (AE). The system consists of four highly coordinated core functional modules: a multi-contact microelectrode module, a dual signal generation and ultrasonic emission module, a signal conditioning and data acquisition module, and a signal processing and inverse inversion module. These four modules form a complete functional closed loop through hardware electrical connections and software timing control. The structure, function, and synergistic relationship between each module are described in detail below with reference to the accompanying drawings. In the following description, solid or semi-solid media containing mobile ions are collectively referred to as "target media." For example, target media include, but are not limited to, artificially doped polyurethane rubber or Ecoflex silicone brain tissue physical phantoms, cerebrospinal fluid-filled ex vivo skull specimens, and ex vivo brain tissue slices. These media share the common characteristic of containing mobile ion carriers capable of directional migration under the drive of an external electric field, which is the material basis for the occurrence of the acoustic-electric effect.

[0060] I. Physical Basis of the Acoustoelectric Effect The acousto-electric effect utilized in this invention is a known physical phenomenon. This invention is not a discovery of the effect itself, but rather its creative application to in-situ quantitative measurement of ultrasonic sound fields within solid or semi-solid media. When ultrasound propagates in a target medium, the pressure changes carried by the sound waves cause transient periodic changes in the microscopic physical mobility and concentration density of ions within the medium. Macroscopically, this manifests as a periodic alternation of the local resistivity of the medium with the frequency of the sound waves. The fundamental acousto-electric constitutive equation can be expressed as: In the formula, The initial static resistivity of the medium in the absence of ultrasonic interference; This represents the transient change in resistivity; The transient ultrasonic pressure field passing through this region; The acoustic-electric interaction constant (C0) depends on the ion concentration and composition of the medium. Equation 1 shows that when the sound pressure is in the compressed phase (pressure increases), the resistivity of the medium decreases (conductivity increases); when the sound pressure is in the rarefied phase, the resistivity increases. It should be noted that since minute changes in conductivity cannot spontaneously radiate electromagnetic waves, a background current field must be actively injected into the medium to detect this modulation of local resistivity.

[0061] Furthermore, when a frequency of [frequency value missing] is injected through a multi-contact microelectrode of the implantation medium... A low-frequency sinusoidal AC excitation electric field is generated, while an external ultrasonic transducer emits a frequency of... When a high-frequency continuous wave is emitted, according to the product-difference formula of trigonometric functions, a physical-level heterodyning effect will occur within the medium. The generated acoustic-electric signal will split into two new high-frequency components: the sum frequency and the difference frequency. In the formula, The frequency of high-frequency ultrasound. This refers to the frequency of the low-frequency alternating current. For example... Figure 5 As shown, this physical-level heterodyne mixing mechanism shifts and modulates the effective signal frequency carrying weak ultrasonic sound pressure information onto two high-frequency narrowband sidebands, which in the frequency domain helps to distinguish the co-frequency signals that may be generated by the driving ultrasonic transducer itself. High-voltage electromagnetic crosstalk artifacts are avoided, while low-frequency physiological noise and Thermal noise makes it possible to extract narrowband signals with high signal-to-noise ratio using high-gain amplifiers.

[0062] II. Multi-contact microelectrode module like Figure 2 and Figure 3 As shown, the multi-contact microelectrode module, serving as the front-end sensing unit for interaction between this system and the target medium, is configured to be placed inside the target medium. The core function of this module is to directionally inject low-frequency alternating current into the target medium through a selected pair of excitation contacts, and to acquire differential voltage signals through a selected pair of measurement contacts.

[0063] Specifically, this module employs a structural design that reuses multiple contacts on the same probe. Several independent conductive sensing contacts are arranged axially along a single probe branch, with adjacent contacts electrically isolated from each other by an insulating layer. During system operation, a low-level timing control algorithm configures one pair of contacts as an "excitation contact pair" to directionally inject low-frequency alternating current into the medium; simultaneously, another pair of contacts adjacent to, interleaved with, or nested with it is configured as a "measurement contact pair" to extract differential voltage signals. The core technical advantage of this spatially tightly overlapping arrangement of excitation and measurement contact pairs lies in: enabling the current density field injected by the excitation contacts to... Spatial conduction field with measurement contact point The two fields overlap and superimpose highly in a localized space. Due to the extremely small spacing between the contact pairs, the spatial sensitivity matrix formed after the two fields are superimposed—that is... —The sound pressure level attenuates exponentially within the microscopic range of the contact surface. From a physical perspective, the piezoelectric film in a traditional piezoelectric hydrophone undergoes an indiscriminate two-dimensional rigid surface integral within its effective aperture. In a high-frequency focused sound field, this is highly susceptible to a severe spatial averaging effect due to phase cancellation at different locations, leading to a significant underestimation of the peak sound pressure level. In contrast, the spatial lead field weights utilized in this module exhibit an exponentially attenuating characteristic at the microscopic scale. This transforms the original macroscopic mean integral into a three-dimensional soft-weighted integral with a very high central weight, significantly reducing the broadband phase cancellation phenomenon from the hardware physics level and preserving high-fidelity high-frequency spatial components of the sound field for subsequent algorithms.

[0064] Furthermore, to improve the spatial sampling fidelity of the high-frequency ultrasonic sound field, the center-to-center distance between adjacent contacts in the multi-contact microelectrode module is adjusted along each axis. Optimization design based on the Nyquist-Shannon sampling theorem must satisfy: In the formula, The wavelength of the high-frequency ultrasonic wave to be measured is the wavelength of the wave propagating in the target medium. This criterion is beneficial in the spatial frequency domain for reducing the risk of signal aliasing and improving the fidelity of focal point morphology reconstruction. For example, for the center frequency... The wavelength of transcranial ultrasound in the tissue phantom is approximately 3 mm. According to Formula 3, the contact point spacing should be set to no more than 1.5 mm. Furthermore, the geometrical exposure area of ​​a single sensing contact point is limited to 100 μm. 2 Up to 2500 μm 2 Between these dimensions, this size is much smaller than the length of an ultrasonic wave, which can further reduce the spatial averaging effect at the physical level.

[0065] In terms of specific implementation, this invention is not limited to a particular structural form. Optional implementations include, but are not limited to: deep brain stimulation (DBS) electrodes, carbon fiber microfilament electrodes, microelectrode arrays based on rigid silicon microfilaments and fabricated using micro-electro-mechanical systems (MEMS) technology, or microelectrode arrays based on flexible polymer substrates (e.g., polyimide or parylene C). Regardless of the specific type chosen, their common structural feature is that the cross-sectional width of the probe branches is controlled at the tens of micrometer level. When implanted deep into the target medium, this effectively reduces mechanical compression and structural tearing of the medium, resulting in significantly less initial invasive damage compared to the complex and bulky probes of traditional hydrophones. Simultaneously, the combination of pure metal contacts and a polymer insulating layer endows it with extremely high mechanical durability, allowing it to operate stably for extended periods in high-pressure acoustic environments without physical failure.

[0066] More specifically, when the multi-contact microelectrode module is configured as a three-dimensional multi-contact microelectrode array (e.g.) Figure 2 and Figure 6 As shown, this array uses rigid silicon-based microfilaments or flexible polymers as a substrate to form a three-dimensional contact network with multiple depths and branches, integrating hundreds to thousands of independent sensing contacts at the micrometer level, covering the target sound field volume in the form of a physical three-dimensional grid. To solve the crosstalk and physical wiring bottlenecks that may be caused by high-density leads, the array directly integrates an application-specific integrated circuit (ASIC) or complementary metal-oxide-semiconductor (CMOS) front-end processing unit within the probe substrate. This front-end processing unit features active time-division multiplexing, low-noise in-situ primary signal amplification (Pixel Amplifier), and polarization impedance adaptive monitoring. The analog signals from each sensing contact are preprocessed and digitized locally by the front-end processing unit, and then transmitted to an external signal conditioning and data acquisition module via a low-voltage differential signaling (LVDS) bus. By placing analog signal preprocessing and digital gating logic inside the electrodes, this module significantly reduces the number of physical cables connecting to external devices to the level of a shared digital bus, while also reducing the risk of weak acoustic and electrical signals coupling with high-voltage electromagnetic interference during long-distance transmission.

[0067] During actual measurements, both the external focused ultrasound transmitter and the implanted microelectrode array remain relatively fixed in their macroscopic physical positions. The system dynamically allocates the function of each contact point through a low-level timing control algorithm: within a single phase detection cycle, a high-speed multiplexer selects two contacts at specific spatial coordinates in the array as excitation contact pairs to inject alternating background current, and simultaneously selects two other adjacent, interleaved, or nested contacts as measurement contact pairs to extract the acoustic-electric differential voltage signal within the local lead field of that coordinate. By performing millisecond-level high-speed electronic switching between three-dimensional spatial nodes, the system sequentially acquires the local sound pressure information of each discrete coordinate point within the array's coverage volume, thereby completing dense sampling of three-dimensional volume data without moving the ultrasound probe or the microelectrode body.

[0068] Furthermore, considering the interfacial polarization phenomenon caused by the probe remaining in the target medium containing conductive ions for a long time, the dynamic impedance dominated by the double-layer capacitance at the electrode-electrolyte interface will fluctuate over a wide range. The adaptive constant current source design at the back end of the system can effectively overcome the distortion of the injected electric field caused by this dynamic impedance fluctuation, which is beneficial to maintaining the constant amplitude of the directional injection current (see the relevant description of the dual signal generation and ultrasonic emission module below).

[0069] III. Signal Dual Generation and Ultrasonic Emission Module The dual signal generation and ultrasonic transmission module connects the multi-contact microelectrode module and the ultrasonic transmission unit, undertaking two core tasks requiring strict spatiotemporal synchronization: generating a low-frequency electrical excitation signal to drive the excitation contacts to inject low-frequency alternating current, and generating a high-frequency ultrasonic signal to drive the ultrasonic transmission unit to emit high-frequency ultrasonic waves toward the target medium. Strict temporal and spatial synchronization of the two signals is a prerequisite for the occurrence of the acoustic-electric heterodyne mixing effect.

[0070] like Figure 1 As shown, this module includes a multi-channel arbitrary waveform generator (AWG) and a voltage-to-current converter that share a common high-precision reference clock (e.g., a temperature-controlled crystal oscillator). The purpose of the shared clock is to reduce the impact of inherent clock drift between independent devices on the phase demodulation of extremely weak acoustic and electrical signals.

[0071] The low-frequency channel of the multi-channel arbitrary waveform generator drives a voltage-controlled constant current source to continuously inject a low-frequency alternating current with constant frequency and amplitude into the multi-contact microelectrode module. It should be noted that this AC voltage signal does not directly act on the probe, but rather serves as a control reference to drive the voltage-controlled constant current source with high impedance output characteristics. The high impedance output characteristic of the constant current source effectively overcomes the distortion of the injected electric field caused by the dynamic fluctuations of polarization impedance at the interface between the multi-contact microelectrode module and the target medium, maintaining the constant amplitude of the low-frequency alternating current. Optionally, the frequency of the low-frequency alternating current can be between 10 Hz and 10 kHz, and the amplitude can be between 0.1 mA and 2 mA. This microampere to milliampere current threshold not only effectively prevents thermal damage and electrochemical electrolysis effects in biological tissues, but also establishes and maintains a highly constant and pure background current density field within the target medium. .

[0072] Simultaneously, the high-frequency channel of the multi-channel arbitrary waveform generator generates continuous wave or pulse wave signals in the ultrasonic frequency band. After low-distortion amplification by a high-linearity radio frequency power amplifier, it drives the ultrasonic transmitting unit to emit high-frequency ultrasonic waves. Optionally, the center frequency of the high-frequency ultrasonic waves can cover the range of 0.5 MHz to 5 MHz.

[0073] During spatial scanning, the ultrasonic transmitting unit and the multi-contact microelectrode module remain relatively fixed in physical space. The front end of the ultrasonic transmitting unit is acoustically coupled to the surface of the solid medium under test via a water bladder or tank filled with degassed water to facilitate efficient transmission of acoustic energy. This system provides two selectable fully electronic acoustic coverage modes. The first is a wide-beam static envelope mode: the ultrasonic transmitting unit uses a single-element concave-focusing piezoelectric ceramic (PZT) transducer, ensuring that the resulting steady-state three-dimensional ultrasonic focal spot completely envelops the entire multi-contact microelectrode array region on a spatial scale. In this mode, spatial resolution is primarily determined by the high-speed electronic switching of the electrode contacts. The second is a phased array electronic deflection mode: the ultrasonic transmitting unit uses a multi-element ultrasonic phased array. With the transducer stationary, the phase and delay of the emitted waves from each element are adjusted to achieve electronic deflection of the ultrasonic focal point in three-dimensional space. Combined with time-division multiplexing gating within the multi-contact microelectrode module, this enables joint tracking of "acoustic field electronic deflection" and "electric field electronic gating," completing a purely electrical spatial scan (e.g., ...). Figure 6 (As shown).

[0074] IV. Signal Conditioning and Data Acquisition Module The signal conditioning and data acquisition module, connected to the multi-contact microelectrode module, is the core signal processing unit for high-fidelity extraction of weak acoustic and electrical signals from backgrounds of strong electromagnetic interference and complex baseline drift. For example... Figure 1As shown, the module includes a cascaded anti-saturation analog front end (AFE) and a high-speed analog-to-digital converter (ADC) array.

[0075] The anti-saturation analog front-end circuit consists of a cascaded physical high-pass filter (HPF) and a low-noise differential preamplifier (LNA). The cutoff frequency of the physical high-pass filter is configured to be higher than the frequency of the low-frequency alternating current. But at a frequency lower than high-frequency ultrasound Its design aims to isolate the injected fundamental frequency and electrochemical DC polarization drift caused by low-frequency alternating current. After baseline isolation, a low-noise differential preamplifier is cascaded to the subsequent stage, with an equivalent input voltage noise density of nV / The filtered signal is amplified by high-gain, untruncation-free differential amplification. This "filter-before-amplify" cascaded topology design is an anti-saturation front-end solution specifically designed for the characteristics of acoustic-electric modulation signals—the amplitude of the acoustic-electric modulation signal is extremely small (microvolts or nanovolts), but it is accompanied by a low-frequency injection current fundamental wave with an amplitude much larger than that and a solid dielectric polarized DC bias. If these are not effectively isolated before amplification, the subsequent amplifier circuit will inevitably experience voltage saturation and signal truncation, completely losing the ability to detect weak acoustic-electric signals.

[0076] The high-speed analog-to-digital converter array synchronously digitizes the amplified signals of each channel according to the oversampling rate that satisfies the Nyquist sampling theorem, and outputs a wideband discrete-time sequence corresponding to each spatial coordinate. .

[0077] When the multi-contact microelectrode module is configured as a three-dimensional multi-contact microelectrode array and integrates an ASIC / CMOS front-end processing unit, the signal conditioning and data acquisition module is equipped with a Field-Programmable Gate Array (FPGA). This FPGA utilizes a global hardware reference clock, originating from the same source as the signal dual generation and ultrasonic transmission modules, to synchronously receive high-speed serial data streams from the LVDS bus and perform digital demultiplexing, precisely reconstructing them into independent high-frequency digital time series that are strictly mapped to the spatial physical coordinates of the three-dimensional multi-contact microelectrode array. The reconstructed large-scale broadband data stream is continuously transmitted to the host computer system through a high-bandwidth data interface.

[0078] V. Signal Processing and Inverse Inversion Module The signal processing and inverse inversion module is connected to the signal conditioning and data acquisition module and is executed by the host computer workstation. Its purpose is to extract weak acoustic-electric modulation signals with high fidelity from the broadband noise returned by the high-density probe matrix and accurately reconstruct the spatial distribution of sound pressure. The core processing flow of this module includes two main stages: heterodyne frequency domain demodulation and spatial deconvolution reconstruction.

[0079] In the heterodyne frequency domain demodulation stage, the host computer workstation first uses a high-order Kaiser window to smooth and weight the time-domain data of the broadband discrete-time series, and then performs a Fast Fourier Transform (FFT) for frequency domain shaping. The Kaiser window, with its steep stopband attenuation characteristics and extremely high sidelobe suppression ratio, strictly confines the high-amplitude capacitive coupling crosstalk energy generated by the ultrasonic transducer at the high-frequency carrier to an extremely narrow main lobe, allowing the extremely weak sum and difference frequency signal peaks to be clearly identified in the amplitude spectrum. Subsequently, the system adopts an IQ quadrature amplitude demodulation scheme: in the digital domain, the bandpass-filtered signal is coupled to two local quadrature reference carriers—in-phase components. Orthogonal components —The signal is mixed and filtered out by a digital low-pass filter with a steep roll-off characteristic to remove harmonic components, thereby extracting the baseband acoustic-electric envelope signal that is unaffected by carrier phase distortion and multiple interface reflections. The amplitude fluctuation of this envelope on the time axis accurately maps the dynamic acoustic intensity response of the gate contact to its local microscopic space at a specific moment. The baseband acoustic-electric envelope signals from multiple spatial coordinates are stitched together to form a three-dimensional voltage envelope voxel matrix.

[0080] To establish a quantitative relationship between the measured voltage and the spatial sound field distribution, this system incorporates lead field theory from bioelectromagnetics. Based on the electromagnetic reciprocity theorem, the acoustic-electric modulation voltage recorded across the detection electrodes... It is the total volume of the medium. Volume integral of the internal acoustic polarization field: In the formula, The acoustic-electric interaction constant of the target medium; The initial static resistivity without ultrasonic interference; The measurement volume region inside the target medium; The spatial conduction field vector of the corresponding measurement contact pair in space is used to characterize the potential sensitivity of the measurement electrode pair at each point in space. The vector of the spatial current density field formed by low-frequency alternating current; Let be the transient ultrasonic sound pressure field to be reconstructed. Equation 4 reveals a core mathematical relationship: the final measured signal is the result of the sound pressure field and the equation... The electromagnetic sensitivity matrix is ​​formed by the convolution in space.

[0081] In the spatial deconvolution reconstruction stage, such as Figure 7 As shown, the system transforms the three-dimensional voltage envelope voxel matrix into the three-dimensional spatial frequency domain (k-space) using a three-dimensional fast Fourier transform (FFT), and then introduces Wiener deconvolution regularization to solve the inverse problem. Under the minimum mean square error (MMSE) criterion, this algorithm, combined with a pre-calibrated multi-contact microelectrode spatial lead field kernel function (which is equivalent to the system's point spread function in the spatial domain) and the system's background noise power spectrum, inversely compensates for the ambiguity caused by the electrode spatial integration effect, while effectively suppressing the divergence of high-frequency noise in the inverse operation. Finally, a high-resolution three-dimensional ultrasonic sound pressure field distribution map is reconstructed through a three-dimensional inverse Fourier transform (IFFT).

[0082] Alternatively, the solution to the spatial deconvolution or regularized inverse problem can be replaced by an inverse problem-solving algorithm based on Tikhonov regularization or the lumped-element method. Although these alternative algorithms differ in computational complexity, boundary condition dependence, or suppression of high-frequency background noise, they can all achieve the reverse elimination of spatial lead field ambiguity by introducing appropriate regularization parameters.

[0083] VI. Calibration Submodule This system further includes a calibration submodule, which provides the necessary spatial lead field kernel function for the signal processing and inverse inversion modules. Specifically, the calibration submodule performs physical scanning measurements on the multi-contact microelectrode module in a calibration medium with known acoustic field parameters (e.g., a degassed conductive aqueous solution environment or a standard phantom with precisely characterized acoustic properties). By spatially mapping the measured volume integral voltage envelope data with the known acoustic field parameters, a three-dimensional lead field kernel matrix characterizing the microscopic electromagnetic sensitivity of each contact is extracted. This matrix is ​​pre-stored in the system as the spatial lead field kernel function for the signal processing and inverse inversion modules when performing spatial deconvolution or regularized inverse problem solving. This kernel matrix is ​​physically equivalent to the point spread function (PSF) in an imaging system, and its accurate calibration is a prerequisite for subsequent Wiener deconvolution inversion.

[0084] VII. Cutting-edge sensitive alternatives for ultra-high frequency steady-state sound fields From the perspective of microscopic acoustic physics, the scattering mechanism of ultrasonic waves by obstacles in a solid medium depends on the dimensionless wavenumber-radius product. (in The probe radius is... (Wave number). When the frequency is low and the probe diameter meets the requirements... ( When the measurement frequency is greater than 1 MHz, causing a sharp decrease in wavelength, the probe is located in the Rayleigh scattering region, resulting in a negligible phase shift and disturbance to the sound field. However, when the measurement frequency is further increased to greater than 1 MHz, leading to a sharp decrease in wavelength, the dense three-dimensional microelectrode array will locally form an impedance fence structure similar to an acoustic metamaterial in the target area. Multiple scattering and backscattering will accumulate strongly within the array and coherently interfere, potentially even triggering a bandgap effect that causes a sharp drop in acoustic transmittance, thus introducing systematic errors into the sound field reconstruction.

[0085] For the aforementioned ultra-high frequency scenarios, this system provides an alternative solution. For example... Figure 4 (A schematic diagram of a low-disturbance quasi-three-dimensional in-situ tomography based on a stepper motor driven system is shown.) The multi-contact microelectrode module is configured as a tip-sensitive one-dimensional or two-dimensional probe array with sensing contacts concentrated at the physical tip. The probe body has an insulated, smooth, acoustically streamlined structure to minimize the forward geometric obstruction area. The system is also equipped with a high-precision stepper stage connected to the bottom of the multi-contact microelectrode module. During measurement, the stepper stage drives the tip-sensitive probe array to first penetrate to the farthest end of the target medium (the side away from the ultrasonic transducer), and then performs a layer-by-layer physical stepping motion in the opposite direction of high-frequency ultrasonic wave propagation, from far to near. Combined with electronic gating of the probe array plane, quasi-three-dimensional tomographic data acquisition is completed.

[0086] The core technical advantage of this scheme lies in its ability to physically avoid interference from the probe's structure on the forward propagation of sound waves. By limiting the sensing area to the probe tip and combining it with a step-by-step scanning in the opposite direction of the sound beam propagation, the system enables the sensing contact point to preferentially contact the initial incident wavefront—that is, the forward-propagating ultrasonic surface always preferentially interacts with the electrode tip contact point. Before the sound wave impacts the probe shaft and causes multiple scattering, distortion, and wake disturbance, its original sound intensity signal has been extracted in real time by the probe tip.

[0087] Example 2: In-situ Measurement Method of Ultrasonic Field Inside Solid Medium Based on Acoustoelectric Effect This embodiment provides an in-situ measurement method for ultrasonic sound fields inside solid media based on the acousto-electric effect, using the in-situ measurement system for ultrasonic sound fields inside solid media described in Embodiment 1. Figure 5 and Figure 7 As shown, the method includes the following sequential and cooperative steps. Step 100 corresponds to step S1, step 200 corresponds to step S2, step 300 corresponds to step S3, step 400 (including steps 410, 420, and 430) corresponds to step S4, and step 500 corresponds to step S5.

[0088] Step 100: Synchronously transmit low-frequency electrical excitation and high-frequency ultrasound. A low-frequency electrical excitation signal is sent to the multi-contact microelectrode module placed within the target medium via a dual signal generation and ultrasound transmission module. This signal is converted into a low-frequency alternating current with constant amplitude via a voltage-controlled constant current source and injected into the target medium through a selected pair of excitation contacts, establishing a stable and pure background current density field around the microelectrode. Simultaneously, the dual signal generation and ultrasound transmission module drives the ultrasound transmission unit to emit high-frequency ultrasound waves into the target medium. The front end of the ultrasound transmission unit achieves acoustic coupling with the medium surface through a degassed water bladder. Throughout the execution of steps 100 and subsequent steps, the ultrasound transmission unit and the multi-contact microelectrode module remain relatively fixed in physical space, without any macroscopic mechanical displacement.

[0089] Step 200: Heterodyne mixing driven by the acoustic-electric effect. Under the dual-field excitation conditions established in Step 100, according to the acoustic-electric constitutive equation revealed by Equation 1, the local conductivity of the target medium along the propagation path of the high-frequency ultrasonic wave is dynamically modulated by the sound pressure. Since Step 100 simultaneously establishes a background current density field in the medium, the conductivity change caused by the sound pressure forces the system to satisfy the current continuity equation by generating an additional acoustic-electric polarization field. According to the frequency relationship in Equation 2, the above physical multiplication produces a nonlinear heterodyne mixing effect, shifting the sound pressure information and generating a frequency carried on the high-frequency difference frequency (…). ) and frequency ( The high-frequency acoustic-electric modulation signal on the sideband. This step requires no human intervention and is a physicochemical process naturally initiated in the medium by the dual-field excitation conditions in step 100.

[0090] Step 300: Acoustic-Electronic Signal Extraction and Front-End Conditioning. Using a pair of measurement contacts selected by the multi-contact microelectrode module, the differential voltage signal of the aliased high-frequency acoustic-electric modulation signal is extracted differentially. After receiving the differential voltage signal, the signal conditioning and data acquisition module performs the following processing sequentially: First, a physical high-pass filter filters out the injected fundamental wave and electrochemical DC polarization drift caused by low-frequency alternating current; second, a low-noise differential preamplifier performs high-gain, anti-saturation differential amplification on the filtered signal; finally, a high-speed analog-to-digital converter array digitizes the signal at an oversampling rate, outputting a broadband discrete-time sequence corresponding to each spatial coordinate.

[0091] Step 400: Heterodyne frequency domain demodulation and three-dimensional voltage envelope voxel matrix construction. The signal processing and inverse inversion module receives the broadband discrete-time series, and the host computer workstation executes the heterodyne frequency domain demodulation algorithm, which includes Kaiser window weighting and IQ quadrature amplitude processing.

[0092] Step 410 involves frequency domain shaping and interference isolation: The time-domain data is smoothed and weighted using a high-order Kaiser window, followed by a Fast Fourier Transform. The steep stopband attenuation of the window function is utilized to suppress spectral leakage from high-frequency crosstalk in the ultrasonic transducer, accurately extracting the mixing frequency from the amplitude spectrum. High-frequency mixing signal spikes at the location.

[0093] Step 420 is IQ quadrature amplitude demodulation and envelope extraction: the extracted high-frequency mixing signal is compared with the in-phase component. and orthogonal components Two orthogonal reference carriers are mixed, and the harmonic components are filtered out by a digital low-pass filter to obtain a baseband acoustic envelope signal that is robust to carrier phase drift and multiple boundary reflections. The amplitude fluctuation of this envelope on the time axis accurately maps the dynamic acoustic intensity response of a specific gate contact to its local microscopic space.

[0094] Step 430 involves constructing a three-dimensional voxel matrix: Millisecond-level high-speed electronic gating is performed on contact pairs at different spatial coordinates in the multi-contact microelectrode module. Steps 100 to 420 are repeated sequentially to acquire the baseband acoustic-electric envelope signals of each discrete spatial node. The multi-point envelope data are then arranged and stitched together according to physical coordinates to form a three-dimensional voltage envelope voxel matrix. For example... Figure 6 As shown, this process enables pure electrical three-dimensional sound field volume sampling without mechanical displacement.

[0095] Step 500: Reconstruction of the 3D sound pressure field based on spatial deconvolution. (e.g.) Figure 7As shown, the signal processing and inverse inversion module, based on the pre-calibrated spatial lead field kernel function corresponding to the multi-contact microelectrode module within the system, solves the three-dimensional voltage envelope voxel matrix in the three-dimensional spatial frequency domain using spatial deconvolution or regularization inverse problem solving. Specifically, the system first performs a three-dimensional fast Fourier transform on the three-dimensional voltage envelope voxel matrix to convert it to... - In space, a same-dimensional Fourier transform is performed on the pre-calibrated spatial lead field kernel matrix to obtain its frequency domain transfer function. - In spatial geometry, Wiener deconvolution regularization is employed, and the inverse problem is solved by combining the system's background noise power spectrum estimation under the minimum mean square error criterion, thereby eliminating the smoothing and blurring effect caused by the hardware's macroscopic aperture. Finally, the true three-dimensional ultrasonic sound pressure field distribution inside the target medium is restored and analyzed through three-dimensional inverse Fourier transform.

[0096] Prerequisite for Step 500 – Pre-calibration Step. Before introducing the spatial lead field kernel function to solve the inverse problem in Step 500, the system must independently perform a pre-calibration step. The multi-contact microelectrode module is placed in a calibration medium or degassed conductive aqueous solution with known three-dimensional true focal parameters for physical scanning measurements, recording the measured volume integral voltage envelope data for each spatial coordinate. Based on the physical spatial mapping relationship between the measured data and the known parameters, a back-calculation algorithm is used to extract the three-dimensional lead field kernel matrix characterizing the microscopic electromagnetic sensitivity of different contacts. This matrix is ​​pre-stored in the system as the spatial lead field kernel function for spatial deconvolution point diffusion inversion correction in Step 500.

[0097] Example 3: Alternative Implementation The following describes alternative implementation methods for several key aspects of the technical solution of this invention in order to fully reveal the adaptability of this invention under different engineering scenarios and design constraints.

[0098] Alternative Implementation Method 1: Inverse Acoustic Beam Stepping Scanning of a Tip-Sensitive Probe Array. When the multi-contact microelectrode module is configured as a tip-sensitive probe array in a dimensionally reduced manner, the construction method of the three-dimensional voltage envelope voxel matrix in step 430 of Embodiment 2 is adjusted accordingly: a high-precision stepping stage is used to drive the tip-sensitive probe array to first penetrate to the farthest end of the target medium, and then step back layer by layer along the reverse direction of high-frequency ultrasonic wave propagation. At each tomographic position, steps 100 to 420 are repeated in combination with electronic gating in the probe array plane, so that the tip sensing contact always completes signal acquisition before the incident sound wave undergoes structural scattering. The acoustic envelopes of each layer and each spatial coordinate obtained are stitched together to form a three-dimensional voltage envelope voxel matrix.

[0099] Alternative Implementation Method Two: Broadband Pulse Ultrasound and Hilbert Transform Envelope Extraction. In step 100, the ultrasound transmitting unit alternatively transmits broadband short-pulse ultrasound or coded excitation ultrasound (such as Barker code or linear frequency modulated pulse Chirp). Correspondingly, in step 400, a broadband bandpass filter is used to extract the high-frequency acoustic-electric signal components from the differential voltage signal, and then the signal envelope is extracted using the Hilbert Transform or a matched filter to construct a three-dimensional voltage envelope voxel matrix. This alternative method can provide additional depth spatial resolution based on ultrasound time-of-flight, but its signal-to-noise ratio improvement effect against low-frequency electromagnetic interference differs from that of the continuous wave heterodyne mixing scheme.

[0100] Alternative Implementation Method 3: Mechanical Tomography of Single-Channel Microelectrodes. When system cost is limited or real-time requirements are not high, multi-contact microelectrode modules can be alternatively configured as single-channel microelectrodes. In steps 300 to 400, a high-precision three-dimensional stepper motor is used to perform relative physical translation between the ultrasonic transmitting unit and the single-channel microelectrode. Steps 100 to 420 are repeated sequentially for mechanical tomography of different spatial coordinates of the target medium. The acoustic envelopes of each spatial coordinate obtained together constitute the three-dimensional voltage envelope voxel matrix required in step 500. This alternative method trades measurement time for spatial resolution. Combined with the acoustic demodulation algorithm of this invention, it can also complete the in-situ three-dimensional reconstruction of the sound field inside the solid medium.

[0101] Alternative inversion reconstruction algorithms. When reconstructing the three-dimensional sound pressure field distribution from the three-dimensional voltage envelope voxel matrix, in addition to the Wiener deconvolution algorithm mentioned above, alternative inverse problem-solving algorithms based on Tikhonov regularization or the finite element lumped parameter method can also be used. By introducing appropriate regularization parameters, these alternative algorithms can also achieve the inverse elimination of spatial lead field ambiguity effects.

[0102] Instructions for use The in-situ measurement system and method for ultrasound fields within solid media described in this invention are particularly suitable for focus measurement applications in low-intensity transcranial ultrasound stimulation (TUS) neuromodulation. In this application, the physical carrier of the measurement object is limited to ex vivo tissue specimens, ex vivo skull specimens, or solid physical phantoms of brain tissue (such as...) not intended for disease diagnosis or treatment. Figure 3As shown, this is used for in-situ calibration and measurement of the real acoustic focus within a physical object, characterizing its three-dimensional distribution, and performing ultrasound safety dosimetry on the target area. The technical significance of this application lies in providing a reliable means for in-situ calibration of the real acoustic focus within a physical object for the development and preclinical evaluation of transcranial ultrasound stimulation devices, without relying on expensive and bulky magnetic resonance imaging equipment. In these applications, conductive agents (such as physiological saline or conductive gel) can be pre-incorporated into the phantom or ex vivo specimen to meet the acoustic-electric effect excitation conditions of a "solid or semi-solid medium containing mobile ions."

[0103] Example 4: Three-dimensional numerical simulation verification To verify the feasibility and noise resistance of the spatial deconvolution reconstruction method based on the lead field kernel function proposed in this invention, a set of exemplary three-dimensional numerical simulation results are given below.

[0104] A uniform equivalent conductive dielectric numerical phantom with dimensions of 48 mm × 48 mm × 64 mm was constructed, with a discrete mesh of 96 × 96 × 128 voxels and a voxel spacing of 0.5 mm. The dielectric sound velocity was taken as 1540 m / s, corresponding to a 500 kHz ultrasonic wave length of approximately 3.08 mm. This simulation was mainly used to verify the sound pressure amplitude envelope, lead field spatial integration, and deconvolution reconstruction process. Acousto-electric coupling, conductivity, and injected current amplitude were uniformly incorporated into the normalized response coefficients. The output results are expressed as normalized voltage envelope and normalized sound pressure amplitude.

[0105] The reference sound field was constructed using a three-dimensional focused Gaussian sound pressure amplitude distribution, with the focal point located at a depth of approximately 35 mm. The transverse -6 dB full width was 3.0 mm, and the axial -6 dB full width was 12.0 mm. The microelectrodes were used along... The multi-contact linear electrode model with directional insertion has 5 contacts near the focal point with a spacing of 1.5 mm between adjacent contacts. Its spatial sensitivity is represented by the three-dimensional equivalent lead field kernel function, with a transverse FWHM of 2.0 mm and an axial FWHM of 3.0 mm.

[0106] like Figure 8 As shown, in the forward simulation, the reference sound pressure field and the lead field kernel function are convolved in three dimensions to simulate the spatial integration and ambiguity effect of the microelectrode lead field on the local acoustic-electric signal, and Gaussian white noise is superimposed on the obtained three-dimensional voltage envelope voxel matrix. Subsequently, frequency domain Wiener deconvolution is used to recover the sound pressure amplitude distribution, and the reconstruction result is processed by non-negative truncation and peak normalization.

[0107] like Figure 9As shown, under the baseline condition that the noise standard deviation is 2% of the peak value of the noiseless measurement envelope, the three-dimensional voxel correlation coefficient between the reconstructed sound field and the reference sound field in the normalized numerical simulation example is about 0.92, and the focus localization error is about 0.87 mm.

[0108] like Figure 10 As shown, further stress tests were conducted by increasing the noise level to 10%, 50%, 100%, and 200%. The results show that under low to medium noise conditions, the reconstructed focal position remains stable. Under extreme noise conditions, although the background artifacts across the entire field increase significantly, the main focal region can still be formed near the reference focal point after Wiener deconvolution. These results demonstrate that the spatial deconvolution method based on the lead field kernel function can recover the three-dimensional sound pressure amplitude distribution inside solid or semi-solid media in numerical simulations and has a certain degree of noise robustness for focal point localization and main lobe geometry parameters.

[0109] Example 5: Quantitative Analysis of System Equivalent Input Noise and Expected Signal-to-Noise Ratio The following quantitative estimates of the equivalent input noise and expected signal-to-noise ratio of the system of the present invention under typical implementation conditions are presented to support the technical feasibility of effectively extracting acoustic and electrical signals at the nanovolt to microvolt level.

[0110] In an exemplary embodiment, the anti-saturation analog front-end employs a cascaded topology of "physical high-pass filter + low-noise differential preamplifier + high-speed ADC". The physical high-pass filter is used to suppress low-frequency injected fundamental, electrode polarization drift, and DC bias before high-gain amplification, reducing the risk of saturation in subsequent amplifier stages. The equivalent input voltage noise density of the differential preamplifier can be configured to be in the range of 3–10 nV / √Hz, and the total gain link can be configured to be 40–80 dB, adjusted according to the input dynamic range and the full-scale range of the ADC.

[0111] When using the acoustic sideband frequency When performing narrowband IQ demodulation centered on a given point, if the equivalent noise bandwidth is... The input equivalent integral noise contributed by the preamplifier can be estimated as: For example, take , At that time, the integral noise is approximately If the equivalent bandwidth is reduced to 100 Hz or 10 Hz by extending the sampling time or by repeated averaging, the integral noise can be reduced to approximately 50 nV or 16 nV. Taking into account electrode thermal noise, constant current source noise, ADC noise, and residual electromagnetic crosstalk, the total input equivalent noise of the system can be controlled in the range of tens to hundreds of nanovolts RMS.

[0112] The amplitude of the acoustic-electric signal can be estimated from the acoustic-electric modulation relationship. When the acoustic-electric interaction constant... Pick magnitude, focal sound pressure level When the local resistivity is between 0.1 and 1 MPa, the relative modulation amount Approximately to If the effective background voltage formed by the low-frequency alternating current in the measurement lead field is... The overlap efficiency between the sound field and the guide field is Then the single-sided acoustic-electric sideband voltage can be approximately expressed as: by , , For example, the single-sided acoustic-electric sideband signal can be in the range of several nanovolts to several microvolts. For macroscopic bionic electrodes, the background alternating current can be on the order of 0.1–1 mA; for micrometer-scale contact electrodes, a charge-balanced alternating excitation on the order of μA is preferable to reduce the risk of electrode polarization and electrochemical reactions. Thus, under narrowband demodulation, repetitive averaging, and good shielding conditions, nanovolt to microvolt-level acoustic-electric modulation signals are detectable.

[0113] Example 6: Functional Architecture of ASIC / CMOS On-Chip Front-End Processing Unit When the multi-contact microelectrode module is configured as a three-dimensional multi-contact microelectrode array, the functional modules of the ASIC or CMOS on-chip front-end processing unit integrated within its probe array substrate include: an analog multiplexed switch matrix, a configurable gain low-noise differential amplifier, a bandpass filter array, a contact impedance monitoring circuit, and a successive approximation high-speed analog-to-digital converter. Its overall signal chain can be summarized as: multi-contact microelectrode array → contact gating → low-noise differential amplification → filtering and gain adjustment → on-chip ADC → high-speed digital output → external FPGA / host computer processing. Each channel is digitized on-chip and output via an SPI serial interface or LVDS bus.

[0114] The aforementioned ASIC / CMOS front-end processing unit can refer to the functional architecture of existing multi-channel neurophysiological recording chips or high-density microelectrode array readout chips, such as Intan Technologies' RHD2164 64-channel digital neural interface chip. It should be noted that conventional neural recording chips are mostly designed for low-frequency neural electrical signals. When this invention is used to acquire high-frequency acoustic-electric heterodyne sidebands, the front-end bandwidth, filter parameters, and ADC sampling rate should be adapted according to the actual ultrasound frequency and electrical excitation frequency.

[0115] Example 7: Fabrication process and optional products of three-dimensional multi-contact microelectrode arrays Three-dimensional multi-contact microelectrode arrays can be fabricated using mature silicon-based MEMS microfabrication processes. The basic process path includes: defining probes or multi-branch electrode structures using photolithography; forming silicon-based microneedles / microprobes through deep reactive ion etching (DRIE) or wet etching; forming conductive contacts and interconnects such as platinum, gold, and iridium oxides through metal thin film sputtering, evaporation, or electroplating; and finally, insulating and encapsulating the electrodes with materials such as silicon dioxide, silicon nitride, polyimide, or Parylene C, and exposing the electrode surface by opening windows in the contact area.

[0116] This type of structure can refer to mature manufacturing routes for existing neural microelectrode arrays, such as the fabrication methods for the Utah Array or the Michigan Probe. Commercially available reference products include BlackRock Microsystems' Utah multi-electrode array (containing 96 silicon-based electrode needles with a needle spacing of 400 μm and selectable needle length), NeuroNexus Technologies' multi-branched silicon-based probe arrays (such as the A series or Poly series, with probe branch widths of approximately 50–70 μm), or Cambridge NeuroTech's high-density flexible polymer electrode arrays. Alternatively, flexible polymer substrate processes can be used, such as using polyimide or Parylene C as a substrate, to form multi-contact flexible probes through metal thin film patterning, multilayer interconnection, and flexible encapsulation. For complex three-dimensional structures, three-dimensional contact arrangements can also be achieved by combining micro-assembly, micro / nano 3D printing, or two-photon polymerization processes.

[0117] Example 8: Wiener deconvolution regularization parameter selection strategy and lead field kernel matrix pre-calibration process Regularization parameters in Wiener deconvolution This is used to suppress noise amplification caused by the excessively small amplitude of the lead field kernel function at high spatial frequencies. Its value can be determined based on the system noise level, the reference sound field power spectrum, and reconstruction stability. In practice, background noise can be collected under conditions of no ultrasonic emission or no current injection to estimate the system noise power spectrum; then, combined with the signal power spectrum from known sound field calibration experiments or numerical simulations, a suitable value can be selected. In engineering implementation, A fixed constant can be used, or it can be adaptively adjusted according to different spatial frequency components; its value can be determined by the L-curve method, the generalized cross-validation (GCV) method, or the method of minimizing reconstruction error in the calibration data, so as to achieve a balance between spatial resolution and noise suppression.

[0118] The pre-calibration of the lead field kernel matrix can be completed in a calibration medium with a known sound field distribution. The specific procedure is as follows: First, a reference three-dimensional sound pressure distribution is obtained using a standard hydrophone or a focusing transducer with known parameters. Acoustic numerical simulation can be used as initial values ​​for calibration, parameter constraints, or consistency checks. Subsequently, a multi-contact microelectrode module of the same model as that used in the actual measurement is placed in the calibration medium, and the corresponding acousto-electric voltage envelope matrix is ​​acquired under the same low-frequency current injection, ultrasonic emission, signal conditioning, and demodulation parameters. The two satisfy an approximate spatial convolution relationship: in The lead field kernel matrix to be calibrated. This represents the noise term. Subsequently, an inversion method with regularization constraints is used in the three-dimensional frequency domain to estimate the lead field transfer function. To improve calibration stability, calibration can be repeated at multiple focal locations, multiple sound pressure levels, or multiple electrode gating combinations, and the resulting kernel matrix is ​​averaged, normalized, and smoothed as necessary.

[0119] Example 9: Differences in the Implementation of Solid Phantom Measurement and In Vivo Measurement The following explains the differences in the implementation of the technical solution of the present invention in two application scenarios: solid phantom measurement and in vivo measurement.

[0120] In solid phantom or ex vivo specimen measurement scenarios, the target medium can be prepared using polyvinyl alcohol hydrogel, agar / gelatin hydrogel, or other aqueous semi-solid materials. Its conductivity can be adjusted to approximate the electrical properties of brain tissue, cerebrospinal fluid, or specific ex vivo tissues by incorporating sodium chloride solution, conductive gel, or other ionicly conductive components. The geometry, sound velocity, sound attenuation coefficient, conductivity, and acoustic-electric interaction constant of this type of phantom can be obtained through pre-calibration and typically remain approximately stable during short-term measurements. Therefore, it is suitable for system parameter calibration, lead field kernel matrix inversion, sound field reconstruction algorithm verification, and ex vivo metrological calibration of transcranial ultrasound focal positions.

[0121] In the aforementioned solid phantom measurement scenarios, multi-contact microelectrode modules can be pre-embedded in the target area before phantom casting or gel curing, or inserted into a predetermined spatial position after phantom molding via puncture, catheter guidance, or a three-dimensional stepping platform. Since the phantom does not involve damage to living tissue or affect neural function, the electrode positions can be repeatedly adjusted according to the experimental design, and the spatial coverage can be optimized through mechanical scanning or multi-point pre-embedding. For ex vivo skull, ex vivo brain tissue, or composite brain tissue phantoms, electrode placement can also be repeatedly fixed using image localization, 3D printing fixtures, or positioning supports.

[0122] In in vivo measurement scenarios, if used as an alternative implementation method for research animal experiments, such as in ethically approved intracranial ultrasound field studies in small animals, multi-contact microelectrode modules must be implanted into the target brain region via craniotomy, micro-drilling, or catheter access, following standard stereotactic surgical procedures. Unlike in phantom scenarios, extensive and repeated movement is generally not advisable after implantation in vivo to avoid additional tissue damage, bleeding, inflammatory responses, or interference with neurological function. Therefore, in in vivo scenarios, pre-planned fixed implantation paths, small-sized microelectrodes, lower injection currents, and shorter measurement windows are more suitable.

[0123] Regarding safety thresholds, solid-state phantom measurements primarily focus on engineering issues such as electrode polarization, electrolytic bubbles, material heating, signal saturation, and measurement repeatability. In contrast, in vivo measurements, in addition to the aforementioned factors, require strict control of parameters such as injection current, charge density, stimulation duration, ultrasound intensity, temperature rise, and mechanical index to avoid thermal damage to nerve tissue, unintended electrical stimulation, blood-brain barrier effects, or local tissue damage. Solid-state phantom scenarios can utilize a wider parameter scanning range for system calibration and sensitivity verification, while in vivo scenarios should employ conservative parameters after safety assessment and should be prioritized for research measurements not intended for diagnostic or therapeutic purposes.

[0124] It should be noted that in this application, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one" does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element. In this application, if a reference is made to performing an action based on an element, it means performing the action at least based on that element, including two cases: performing the action only based on that element, and performing the action based on that element and other elements. Expressions such as "multiple," "repeatedly," and "various" include two, two times, two kinds, and more than two, more than two times, and more than two kinds.

[0125] Furthermore, it should be understood that after reading the above disclosure of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the scope of protection claimed in this application.

Claims

1. A system for in-situ measurement of ultrasonic sound field inside a solid medium based on the acousto-electric effect, characterized in that, include: A multi-contact microelectrode module is configured to be placed inside a solid or semi-solid medium containing mobile ions, for injecting low-frequency alternating current into the solid or semi-solid medium through a selected pair of excitation contacts, and for acquiring differential voltage signals through a selected pair of measurement contacts. The dual signal generation and ultrasonic emission module connects the multi-contact microelectrode module and the ultrasonic emission unit. It generates a low-frequency electrical excitation signal to drive the pair of excitation contacts to inject the low-frequency alternating current, and generates a high-frequency ultrasonic signal to drive the ultrasonic emission unit to emit high-frequency ultrasonic waves toward the solid or semi-solid medium. Utilizing the acoustic pressure of the high-frequency ultrasonic waves to modulate the local conductivity of the solid or semi-solid medium at the same frequency, the low-frequency alternating current and the high-frequency ultrasonic waves undergo heterodyne mixing, generating a high-frequency acoustic-electric modulation signal carrying acoustic pressure information on the difference frequency and sum frequency sidebands, which is then extracted by the pair of measurement contacts as the differential voltage signal. The signal conditioning and data acquisition module is connected to the multi-contact microelectrode module and is used to receive the differential voltage signal, sequentially perform low-frequency fundamental wave filtering, anti-saturation differential amplification and digital acquisition on the differential voltage signal, and output the broadband discrete time sequence corresponding to the differential voltage signal. The signal processing and inverse inversion module, connected to the signal conditioning and data acquisition module, is used to receive the broadband discrete-time series, perform heterodyne frequency domain demodulation on the broadband discrete-time series to extract the baseband envelope and generate a three-dimensional voltage envelope voxel matrix; and based on the pre-calibrated spatial lead field kernel function corresponding to the multi-contact microelectrode module, solve the spatial deconvolution or regularization inverse problem of the three-dimensional voltage envelope voxel matrix to reconstruct the three-dimensional ultrasonic sound pressure field distribution map inside the solid or semi-solid medium.

2. The in-situ ultrasonic field measurement system inside a solid medium according to claim 1, characterized in that, The multi-contact microelectrode module is configured to reuse multiple contacts on the same probe: a pair of contacts is configured as the excitation contacts, and another pair of contacts adjacent to, intersecting or nested with them is configured as the measurement contacts, so that the injected current density field coincides and overlaps with the measured spatial conduction field, and a localized spatial sensitivity distribution with exponentially rapid decay is formed in the microscopic range of the contact surface. The center-to-center distance between adjacent contacts of the multi-contact microelectrode module in each axial direction Satisfying the Nyquist sampling theorem ,in The wavelength of the high-frequency ultrasonic wave in the solid or semi-solid medium is given, and the exposure area of ​​a single contact point is between 100 μm. 2 Up to 2500 μm 2 between; The multi-contact microelectrode module is selected from one of the following types: deep brain stimulation electrode, carbon fiber microfilament electrode, microelectromechanical system microelectrode array based on rigid silicon microfilament, or microelectrode array based on flexible polymer substrate; wherein the flexible polymer substrate includes polyimide or parylene.

3. The in-situ ultrasonic field measurement system inside a solid medium according to claim 1, characterized in that, The dual signal generation and ultrasonic transmission module includes a multi-channel arbitrary waveform generator and a voltage-controlled constant current source sharing a common high-precision reference clock. The multi-channel arbitrary waveform generator drives the voltage-controlled constant current source to continuously inject a low-frequency alternating current with a frequency between 10 Hz and 10 kHz and an amplitude between 0.1 mA and 2 mA into the multi-contact microelectrode module. The voltage-controlled constant current source overcomes the distortion of the injected electric field caused by the dynamic fluctuation of the polarization impedance at the interface between the multi-contact microelectrode module and the solid or semi-solid medium with its high impedance output characteristics, and maintains the constant amplitude of the low-frequency alternating current. The multi-channel arbitrary waveform generator drives the ultrasonic transmitting unit to emit high-frequency ultrasonic waves with a frequency between 0.5 MHz and 5 MHz through a high-frequency channel. During spatial scanning, the ultrasonic transmitting unit and the multi-contact microelectrode module remain relatively fixed. The ultrasonic transmitting unit uses a single-element concave-focusing piezoelectric ceramic transducer to form a wide-beam static envelope mode covering the multi-contact microelectrode module, or uses a multi-element ultrasonic phased array to achieve three-dimensional electronic deflection of the focal point by adjusting the phase and delay of the emitted wave, and cooperates with the time-division multiplexing gating in the multi-contact microelectrode module to complete the pure electrical spatial scanning.

4. The in-situ ultrasonic field measurement system inside a solid medium according to claim 1, characterized in that, The signal conditioning and data acquisition module includes a cascaded anti-saturation analog front-end circuit and a high-speed analog-to-digital converter array; The anti-saturation analog front-end circuit includes a physical high-pass filter and a low-noise differential preamplifier. The cutoff frequency of the physical high-pass filter is configured to be greater than the frequency of the low-frequency alternating current and lower than the frequency of the high-frequency ultrasound, used to isolate the injected fundamental wave and electrochemical DC polarization drift caused by the low-frequency alternating current. The low-noise differential preamplifier is cascaded in the subsequent stage to amplify the filtered signal with high gain. The high-speed analog-to-digital converter array performs oversampling and digital acquisition on the amplified signal to output the broadband discrete-time sequence corresponding to each spatial coordinate. The mixing frequency of the sum and difference frequency sidebands generated by the heterodyne mixer. satisfy: ,in The frequency of the high-frequency ultrasound is [the frequency of the ultrasound wave]. The frequency of the low-frequency alternating current; The signal processing and inverse inversion module is executed by the host computer workstation. The heterodyne frequency domain demodulation includes: using a high-order Kaiser window to perform smooth weighting and fast Fourier transform frequency domain shaping on the time-domain data of the broadband discrete-time series; using stopband attenuation to suppress co-frequency crosstalk spectral leakage; and extracting the frequency located at the mixing frequency. The high-frequency mixing signal at the location is processed by IQ quadrature amplitude demodulation of in-phase and quadrature components, and the harmonic components are filtered out by digital low-pass filter to extract the baseband acoustic-electric envelope signal that is not affected by carrier phase distortion and interface reflection. The three-dimensional voltage envelope voxel matrix is ​​formed by splicing multiple points.

5. The in-situ ultrasonic field measurement system inside a solid medium according to claim 1, characterized in that, The time domain value of the differential voltage signal It conforms to the following formula for volume integral of the lead field: In the formula, The acoustic-electric interaction constant of the solid or semi-solid medium is given. The initial static resistivity without ultrasonic interference; The measurement volume region is located inside the solid or semi-solid medium. This corresponds to the spatial lead field vector of the measurement contact point in space; The spatial current density field vector formed by the low-frequency alternating current; The transient ultrasonic pressure field to be reconstructed; When the signal processing and inverse inversion module is executed, the three-dimensional voltage envelope voxel matrix is ​​transformed to the three-dimensional spatial frequency domain, and the Wiener deconvolution algorithm is introduced. The inverse problem is solved by combining the spatial lead field kernel function and the system background noise power spectrum. Subsequently, the fuzzy divergence caused by the sensor spatial smoothing integral effect is compensated by the three-dimensional Fourier inverse transform inverse inversion, and the three-dimensional ultrasonic sound pressure field distribution map is restored. Alternatively, the solution of the spatial deconvolution or regularization inverse problem can be replaced by an inverse problem solution algorithm based on Tikhonov regularization or the finite element lumped parameter method.

6. The in-situ ultrasonic field measurement system inside a solid medium according to claim 1, characterized in that, It also includes a calibration submodule, which is used to perform physical scanning measurements on the multi-contact microelectrode module in a calibration medium with known acoustic field parameters. By spatially mapping the measured volume integral voltage envelope data with the known acoustic field parameters, a three-dimensional lead field kernel matrix characterizing the microscopic electromagnetic sensitivity of each contact is extracted. This matrix is ​​then used as the spatial lead field kernel function when the signal processing and inverse inversion module performs the spatial deconvolution or regularization inverse problem solution.

7. A method for in-situ measurement of ultrasonic sound field inside a solid medium based on the acousto-electric effect, using the in-situ measurement system for ultrasonic sound field inside a solid medium as described in any one of claims 1 to 6, characterized in that, It includes the following sequential and co-operating steps: Step S1: A low-frequency electrical excitation signal is sent to a multi-contact microelectrode module placed in a solid or semi-solid medium containing mobile ions through a dual signal generation and ultrasonic emission module, so as to directionally inject low-frequency alternating current into the solid or semi-solid medium, and at the same time drive the ultrasonic emission unit to emit high-frequency ultrasonic waves into the solid or semi-solid medium. Step S2: The acoustic-electric effect of modulating the local conductivity of the solid or semi-solid medium at the same frequency by the sound pressure of the high-frequency ultrasonic wave causes the low-frequency alternating current and the high-frequency ultrasonic wave to undergo nonlinear heterodyne mixing, thereby shifting the sound pressure information and generating a high-frequency acoustic-electric modulation signal carried on the high-frequency difference frequency and sum frequency sidebands. Step S3: The differential voltage signal of the aliased high-frequency acoustic-electric modulation signal is extracted using a pair of measurement contacts selected by the multi-contact microelectrode module; after the signal conditioning and data acquisition module performs physical high-pass fundamental filtering and high-gain differential amplification on the differential voltage signal, it performs oversampling and digital output as the corresponding broadband discrete time series. Step S4: The signal processing and inverse inversion module receives the broadband discrete time series, executes the heterodyne frequency domain demodulation algorithm including Kaiser window weighting and IQ orthogonal amplitude processing, removes electromagnetic crosstalk and phase distortion at the same frequency, extracts acoustic envelope features and reconstructs the three-dimensional voltage envelope voxel matrix. Step S5: The signal processing and inverse inversion module, based on the pre-calibrated spatial lead field kernel function corresponding to the multi-contact microelectrode module within the system, solves the three-dimensional voltage envelope voxel matrix in the three-dimensional spatial frequency domain using spatial deconvolution or regularization inverse problem, inversely eliminating the smoothing and blurring effect caused by the hardware macroscopic aperture, and restoring and resolving the true three-dimensional ultrasonic sound pressure field distribution map inside the solid or semi-solid medium.

8. The method for in-situ measurement of ultrasonic field inside a solid medium according to claim 7, characterized in that, During the execution of steps S1 to S4, the ultrasonic transmitting unit and the multi-contact microelectrode module remain relatively fixed in physical space; the construction of the three-dimensional voltage envelope voxel matrix in step S4 is achieved by performing millisecond-level high-speed electronic gating switching on the contact pairs at different spatial coordinates in the multi-contact microelectrode module, and repeating steps S1 to S3 in sequence to collect the baseband acoustic-electric envelope signal of each discrete spatial node, thereby completing the pure electrical three-dimensional sound field volume sampling without mechanical displacement; Before introducing the spatial lead field kernel function in step S5 to solve the inverse problem, a pre-calibration step is also included, which is performed independently: the multi-contact microelectrode module is placed in a calibration medium or degassed conductive aqueous solution with known three-dimensional real focus parameters for physical scanning measurement, and the measured volume integral voltage envelope data of each spatial coordinate is recorded. Based on the physical spatial mapping relationship between the measured volume integral voltage envelope data and the known three-dimensional true focus parameters, a back-inference algorithm is used to analyze and extract the three-dimensional lead field kernel matrix that characterizes the microscopic electromagnetic sensitivity of different contact points. This matrix is ​​pre-stored in the system as the spatial lead field kernel function for spatial deconvolution point diffusion inversion correction in step S5.

9. The method for in-situ measurement of ultrasonic field inside a solid medium according to claim 7, characterized in that, In step S1, the ultrasonic transmitting unit alternatively transmits broadband short-pulse ultrasonic waves or coded excitation ultrasonic waves; in step S4, a broadband bandpass filter is used to extract the high-frequency acoustic-electric signal components in the differential voltage signal, and then Hilbert transform or matched filter is used to extract the signal envelope to form the three-dimensional voltage envelope voxel matrix; or, the multi-contact microelectrode module is alternatively configured as a single-channel microelectrode, and in steps S3 to S4, a high-precision three-dimensional stepper motor is used to perform relative physical translation between the ultrasonic transmitting unit and the single-channel microelectrode, and mechanical tomography scans are performed on different spatial coordinates of the solid or semi-solid medium by repeating steps S1 to S4 in sequence, and the acoustic envelopes of each spatial coordinate obtained together constitute the three-dimensional voltage envelope voxel matrix required in step S5.

10. The use of the in-situ measurement system for ultrasonic field inside a solid medium according to any one of claims 1 to 6 or the in-situ measurement method for ultrasonic field inside a solid medium according to any one of claims 7 to 9 in the application of low-intensity transcranial ultrasound stimulation for neuromodulation, characterized in that, The physical carrier of the measurement object is limited to ex vivo tissue specimens, ex vivo skull specimens, or solid physical phantoms of brain tissue that are not for disease diagnosis and treatment purposes. These phantoms are used for in-situ calibration and measurement of the real sound wave focus inside the entity, the three-dimensional distribution morphology, and the target area ultrasound safety dosimetry.

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