Magnetic microbubble magnetothermoacoustic imaging method and device

Through the magnetic microbubble magnetothermal acoustic imaging method, the magnetothermal effect and thermal acoustic source are stimulated by the combination structure of magnetic nanoparticles and microbubble, the magnetothermal effect and thermal acoustic source are solved, the problem of insufficient sensitivity in the prior art is achieved, and the high sensitivity diagnosis of early cancer and metastasis is achieved, and radiation-free imaging with high contrast and depth is available.

CN116138738BActive Publication Date: 2025-08-12INST OF ELECTRICAL ENG CHINESE ACAD OF SCI
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Patent Information

Application Number
CN202310138388.0
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-02-20
Publication Date
2025-08-12
Estimated Expiration
2043-02-20

AI Technical Summary

Technical Problem

The existing magnetic nanoparticle magnetothermal acoustic imaging technology has insufficient sensitivity and concentration, making it difficult to achieve high sensitivity diagnosis of early cancers and metastasis. In addition, traditional imaging technology has limitations such as radiation hazards, high costs, and shallow detection depth.

Method used

Magnetic microbubbles are used as developer, and the combination structure of magnetic nanoparticles and microbubbles is used to generate magnetothermal effects and thermal sound sources through pulsed magnetic field excitation. Combined with an ultrasonic transducer to detect magnetothermal acoustic signals, reconstruct the thermal sound source and magnetic microbubbles concentration images to achieve dual enhanced magnetothermal acoustic imaging.

Benefits of technology

It realizes the early accurate diagnosis of the lesion, has high sensitivity, low cost, radiation-free magnetothermal acoustic imaging, can detect abnormalities at the level of disease molecules, and improves the contrast and depth of imaging.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention provides a magnetic microbubble magnetothermoacoustic imaging method and device. A pulsed power supply excites a coil to generate a pulsed magnetic field, which is applied to magnetic microbubbles. The magnetic microbubbles are composed of magnetic nanoparticles and microbubbles. Due to the presence of the magnetic nanoparticles, the magnetic microbubbles produce a magnetocaloric effect under the action of the pulsed magnetic field, forming a thermoacoustic source. This thermal expansion induces an ultrasonic signal, which is further amplified by the presence of the microbubbles. This ultrasonic signal, i.e., the magnetothermoacoustic signal, is detected by an ultrasonic transducer, thereby reconstructing an image of the thermoacoustic source and the magnetic microbubble concentration. The magnetic microbubble magnetothermoacoustic imaging device using the present method comprises a magnetic field excitation system, an electromagnetic field-temperature field-acoustic field coupling conversion unit, a detection system, and an imaging and display unit.
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Description

Technical Field

[0001] The present invention belongs to the field of medical imaging, and in particular relates to a magnetic microbubble magnetothermoacoustic imaging method and device. Background Art

[0002] Malignant tumors are among the most serious threats to human health. Conventional clinical diagnostic techniques often diagnose tumors in the middle or late stages. Early and accurate diagnosis is crucial for improving treatment efficacy and patient survival. There is an urgent need to develop imaging technologies for the early diagnosis of cancer and its metastasis.

[0003] From a pathological perspective, early-stage cancers, metastases, and lesions after treatment, which are difficult to detect with traditional imaging examinations, have generally undergone significant changes at the genetic and cellular levels. Understanding the malignant nature of tumors at the molecular level is a major challenge in cancer research, and there is an urgent need to observe the molecular activities that characterize the malignant nature of tumors. With the development and application of various types of targeted nanodiagnostic and therapeutic agents, molecular imaging technologies that can achieve precise diagnosis and treatment of cancer have attracted increasing attention. They conduct qualitative and quantitative research on biological processes at the cellular or molecular level, explore abnormalities at the cellular and molecular levels during the disease process, and can detect lesions at the molecular level before anatomical changes occur, achieving early and accurate diagnosis of lesions.

[0004] Existing molecular imaging technologies have limitations in clinical applications, such as radioactivity, insufficient sensitivity, high cost, or shallow detection depth. Therefore, there is an urgent need to develop new molecular imaging technologies that are radiation-free, have low production and detection costs, and have high sensitivity, large depth, and high resolution.

[0005] In recent years, coupled imaging methods that combine optical, electrical, acoustic, thermal, and magnetic technologies have become a trend in the development of emerging biomedical imaging methods, potentially opening up a broader research and application space for molecular imaging. Compared with single-field molecular imaging techniques, electromagnetic-ultrasound coupled imaging technology is low-cost, radiation-free, and does not require high-field magnets or radiation sources, thus overcoming the limitations of single-field imaging. Multi-physics imaging that combines electromagnetic and acoustic fields improves resolution while retaining the high contrast of dielectric imaging, and has become a research hotspot.

[0006] Magnetic nanoparticle magnetothermoacoustic imaging (MTA) has been developed based on traditional MTA. While MTA uses the electrical conductivity of biological tissue as an imaging parameter, MTA uses magnetic nanoparticles as a developer, leveraging their magnetization properties to enhance detection sensitivity. However, achieving high-sensitivity MTA with low concentrations of magnetic nanoparticles remains challenging. Currently, research on MTA with magnetic nanoparticles, both domestically and internationally, is largely limited to analyzing MTA properties and verifying the feasibility of thermoacoustic signal enhancement, with limited focus on specific application objectives. The concentration of magnetic nanoparticles used for imaging is relatively high for biological tissues, and the sensitivity of MTA with magnetic nanoparticles needs to be further improved.

[0007] Magnetic nanoparticles and ultrasonic microbubbles exhibit excellent magnetothermoacoustic imaging and echo-reflection ultrasound scattering response, respectively. Magnetic microbubbles, a novel micro-nanomaterial composed of nanoscale magnetic particles and encapsulated bubbles with specific structural and parameter combinations, can dually enhance magnetothermoacoustic signals and are expected to become a more sensitive, targeted magnetothermoacoustic coupled imaging agent. Currently, there are no published reports on the application of magnetic microbubbles in magnetothermoacoustic imaging research.

[0008] In summary, the application of magnetic microbubbles in magnetothermoacoustic imaging leverages two properties of magnetic microbubbles to achieve dual enhancement of a coupled imaging method: the magnetothermoacoustic response of magnetic microbubbles improves magnetothermoacoustic conversion efficiency, and the ultrasonic scattering properties of magnetic microbubbles further enhance the magnetothermoacoustic signal. This new method of magnetothermoacoustic imaging with magnetic microbubbles has great potential for application in precision diagnosis and treatment. Summary of the Invention

[0009] The purpose of the present invention is to achieve early and accurate diagnosis of lesions and to make up for the shortcomings of existing magnetic nanoparticle detection and imaging. A magnetic microbubble magnetothermoacoustic imaging method and device are proposed. The present invention can utilize the dual enhancement effect of magnetic microbubbles on magnetothermoacoustic signals to achieve higher sensitivity magnetothermoacoustic imaging.

[0010] In order to achieve the above object, the present invention adopts the following technical solutions:

[0011] A magnetic microbubble magnetothermoacoustic imaging method is described. A pulsed power supply excites a coil to generate a pulsed magnetic field, which is applied to magnetic microbubbles. The magnetic microbubbles are composed of magnetic nanoparticles and microbubbles. Due to the presence of the magnetic nanoparticles, the magnetic microbubbles generate a magnetocaloric effect under the pulsed magnetic field, forming a thermoacoustic source. This thermal expansion excites an ultrasonic signal, which is further amplified by the presence of the microbubbles. This ultrasonic signal, known as the magnetothermoacoustic signal, is detected by an ultrasonic transducer, thereby reconstructing an image of the thermoacoustic source and magnetic microbubble concentration. The magnetic microbubbles accumulate on diseased biological tissue, and based on the differences in electromagnetic and acoustic properties between the magnetic microbubbles and the tissue, their distribution is identified, thereby revealing the location and characteristics of the diseased tissue. Three structures of magnetic microbubbles used for magnetic microbubble magnetothermoacoustic imaging are available: one in which the magnetic nanoparticles are coupled to the outer surface of the microbubble; one in which the magnetic nanoparticles are embedded in the microbubble shell; and one in which the magnetic nanoparticles are embedded in the microbubble oil layer. Magnetic nanoparticles are chemically bonded to the microbubble surface. This structure imparts superior viscoelasticity to the microbubble shell, allowing for greater freedom than when magnetic nanoparticles are embedded within the microbubble shell, minimizing the inhibitory effect on microbubble vibrations, and resulting in a higher saturation magnetization. Magnetic nanoparticles and microbubbles exhibit excellent magnetothermoacoustic imaging and echo-reflection ultrasonic scattering response, respectively. Magnetic nanoparticles enhance the magnetothermoacoustic ultrasonic signal by altering acoustic impedance. The acoustic properties of magnetic microbubbles are related not only to the microbubbles themselves but also to the concentration of magnetic nanoparticles within the microbubbles.

[0012] Aiming at the medium environment of soft tissue and biological tissue containing bone, the thermal acoustic source function is introduced into the solid displacement field and fluid acoustic field at the same time, and an electromagnetic field-temperature field-solid displacement field-fluid acoustic field coupling model is established;

[0013] For the fluid-structure interaction model, the acoustic pressure fluctuation equation, boundary conditions, and initial conditions in the fluid region are described as follows:

[0014]

[0015] Where p(r,t) is the sound pressure at time t at position r, c s is the propagation velocity of longitudinal waves in the fluid, β is the volume expansion coefficient, C p is the specific heat capacity, S(r') is the spatial distribution of the thermal acoustic source generated by the magnetic microbubble under the action of the electromagnetic field, δ(t) is the step function, ρ0 is the medium density, n is the normal component of the fluid and solid interface, u is the displacement vector, and the sound source term includes the partial derivative of the thermal function S(r',t). The sound source term can be expressed as a function of the spatial distribution of the thermal acoustic source and the time term, that is, r' is the location of the thermal sound source, ▽ 2 is the Laplace operator, is the second-order partial derivative with respect to time, is the time partial derivative, ▽ is the differential operator, and fluid-solid represents the fluid-solid boundary;

[0016] When the magnetothermoacoustic signal encounters a solid material during propagation, the thermal equilibrium kinetic equation and boundary conditions are described by equation (2):

[0017]

[0018] Where λ and μ are Lame coefficients, u is the displacement vector, and β T =λβ, T is the temperature rise based on the reference temperature, ρ0 is the medium density, p is the sound pressure, n is the normal component of the fluid and solid interface, ▽ 2 is the Laplace operator, is the second-order partial derivative with respect to time, is the time partial derivative, ▽ is the differential operator, f| fluid-solid =-np| fluid-solid Represents the coupled boundary conditions of fluid and solid, fluid-solid represents the fluid-solid boundary, and f represents the force converted into by the sound pressure in the fluid when it encounters the solid interface;

[0019] When the excitation is a modulated signal alternating pulse magnetic field excitation, the expression of the thermal sound source is:

[0020]

[0021] Where μ0 is the vacuum permeability, H(r') is the amplitude of the magnetic field intensity, χ0 is the magnetic susceptibility of the magnetic microbubble, ω0 is the angular frequency, τ R is the relaxation time;

[0022] For different forms of excitation - narrow pulse single pulse magnetic field excitation, ignoring hysteresis loss, under adiabatic conditions, the magnetization energy accumulation is characterized as a thermoacoustic source, and the thermal function expression is:

[0023]

[0024] Where B0(r',t) represents the magnetic induction intensity in vacuum, and M(r',t) represents the equivalent magnetization intensity of magnetic microbubbles.

[0025] Since magnetic microbubbles are different from magnetic nanoparticle structures, they are new micro-nano materials composed of nanoscale magnetic particles and microbubbles combined with specific structures and parameters. When conducting theoretical analysis, it is difficult to use the performance of a single magnetic microbubble to characterize them. Their electromagnetic response properties such as magnetization curves and ultrasonic response properties can be macroscopically equivalent, and their equivalent parameters can be used to conduct electromagnetic field-temperature field-acoustic field coupling analysis.

[0026] Furthermore, the magnetic microbubbles used for magnetothermoacoustic imaging are composed of magnetic nanoparticles with good magnetothermoacoustic effect and microbubbles with good ultrasonic imaging performance. The electromagnetic, acoustic response and magnetothermoacoustic effect characteristics of the magnetic microbubbles are controlled by adjusting the structural relationship, particle size, quantity and concentration of the magnetic nanoparticles and microbubbles.

[0027] Furthermore, the excitation of the magnetothermoacoustic signal of the magnetic microbubble is a pulsed magnetic field in various forms, including a single pulse excitation with a certain repetition frequency or an alternating pulse excitation of a modulated signal with a certain width; different excitation modes excite the magnetothermoacoustic effects of the magnetic microbubbles, and the mechanism of magnetothermoacoustic generation of the magnetic microbubbles is magnetization energy accumulation, hysteresis effect or magnetic relaxation loss that absorbs energy from the non-radiative field; considering the magnetization process of the magnetic nanoparticles of the magnetic microbubbles, according to the Langevin theory, the magnetization intensity in the thermoacoustic source is expressed as an expression of the magnetic nanoparticle concentration of the magnetic microbubbles and the Langevin function; when considering the magnetic relaxation loss, since the magnetic nanoparticles connected to the surface of the magnetic microbubble are aggregated on the surface of the microbubble, the magnetic relaxation loss includes Neel relaxation and Brownian relaxation. Due to the different structures of the magnetic microbubbles and the magnetic nanoparticles, the magnetic nanoparticles aggregated on the surface of the microbubble of the magnetic microbubble may also have a hysteresis loss effect; the Green's function integral method and the time-domain finite element method are used to solve the acoustic field.

[0028] Furthermore, the magnetic microbubbles are modified to prepare molecular probes, which are placed near diseased biological tissues. The molecular probes are composed of magnetic microbubbles, carriers, ligands or antibodies. The magnetic microbubbles serve as developers and as enhanced contrast agents for magnetothermoacoustic imaging. The ligands or antibodies are used to bind to receptors highly expressed in tumors. The molecular probes target diseased biological tissues and are developed through magnetic microbubbles to achieve molecular labeling imaging, thereby realizing the identification of diseased biological tissues.

[0029] Furthermore, the magnetic microbubbles generate thermoacoustic sources and magnetothermoacoustic signals under the action of magnetic field excitation. The analysis results and data of the magnetothermoacoustic signals are used to realize magnetic microbubble thermoacoustic source and concentration image reconstruction by adopting Wiener filter deconvolution, time inversion method, filtered back projection method, Tikhonov regularization, damped least squares method, and sensitive field real-time image reconstruction method. By using a tumor model containing magnetic microbubbles and numerical simulation analysis of the inverse problem of the acoustic field and electromagnetic field, the influence of the structural, electromagnetic, and acoustic characteristics of the magnetic microbubbles on the image reconstruction is obtained, the favorable conditions for image reconstruction are obtained, and the image reconstruction is optimized. By accurately extracting the position and concentration information of the targeted modified magnetic microbubbles, the corresponding relationship between its image characteristics and the target state is established.

[0030] The image reconstruction is performed using the Tikhonov regularization method. The normalized linear equation of the sound pressure detection value and the distribution of the magnetic microbubble thermal sound source is:

[0031] P=GS (5)

[0032] Among them, G is the system matrix, P is defined as the sound field distribution formed by the sound field reciprocity process, and S is the thermal sound source distribution.

[0033] Reconstruct the thermal sound source distribution, and its objective function is:

[0034]

[0035] Setting the derivative of equation (6) to zero, we get:

[0036] S=(G T G+λI) -1 G T P (7)

[0037] Among them, G T is the transposed matrix of G, λ is the regularization parameter, and I is the identity matrix.

[0038] The present invention also provides an imaging device for realizing the magnetic microbubble magnetothermoacoustic imaging method, wherein the imaging device is composed of a magnetic field excitation system, an electromagnetic field-temperature field-acoustic field coupling conversion unit, a detection system and an imaging and display unit; the magnetic field excitation system is composed of a synchronous trigger controller, a signal generating unit, a charging and discharging unit or a power amplifying unit, an excitation coil matching module and an excitation current acquisition module; the electromagnetic field-temperature field-acoustic field coupling conversion unit is composed of an excitation coil, a target body, an ultrasonic transducer array and a coupling medium; the detection system includes a low noise amplifier, a bandpass filter, a signal acquisition system, a mobile control system and A mobile platform; the imaging and display unit includes a data processing unit, an imaging module and an image display module; the magnetic field excitation system excites a pulsed magnetic field through an excitation coil, the pulsed magnetic field acts on the magnetic microbubbles, and excites magnetothermal acoustic signals; the magnetothermal acoustic signals are detected by an ultrasonic transducer, and after the signals are processed by a low-noise amplifier and a bandpass filter, a synchronous trigger signal controls a signal acquisition system to collect data; the signal acquisition system communicates with a mobile control system through a serial port, and the mobile control system controls the mobile platform to drive the ultrasonic transducer to perform linear or rotational scanning detection; the collected data is processed by the data processing unit, and image reconstruction and display are finally achieved.

[0039] Furthermore, the excitation source parameters of the pulsed magnetic field determine the characteristics of the excited ultrasonic signal, and adopt fast switching tubes suitable for inductive loads, high-frequency and high-power soft-switching inverter technology, and ultra-fast charging and discharging technology of capacitor energy storage to achieve single pulse excitation and modulated signal alternating pulse excitation with high repetition frequency and narrow pulse width; an ultrasonic transducer array matching the excitation source parameters of the pulsed magnetic field is adopted, including a linear arrangement array, a circular arrangement array, and a three-dimensional distribution arrangement array, combined with high-frequency filtering and amplification to suppress noise, and adopting pulse compression detection and multiple averaging acquisition mode processing methods to enhance the detection capability of the detection system and improve the detection signal-to-noise ratio and resolution of magnetothermoacoustic imaging; the signal acquisition system adopts a high-speed multi-channel acquisition card to achieve high-speed, large bandwidth, high-resolution and low-noise measurement, meeting the requirements of high-frequency ultrasonic transducer acquisition signals under high repetition frequency excitation; the mobile control system controls the mobile platform to realize μm-level high-precision automatic control scanning of the ultrasonic transducer and the ultrasonic transducer array in linear, circular and sector-shaped rotation in the x / y / z directions, meeting the signal acquisition requirements of different imaging methods.

[0040] The magnetic field excitation system is composed of a synchronous trigger controller, a signal generating unit, a charge and discharge unit or a power amplifying unit, an excitation coil matching module, and an excitation current acquisition module. The output end of the synchronous trigger controller is connected to the input end of the signal generating unit, the output end of the signal generating unit is connected to the input end of the charge and discharge unit or the power amplifying unit, the output end of the charge and discharge unit or the power amplifying unit is connected to the input end of the excitation coil matching module, and the output end of the excitation coil matching module is respectively connected to the input end of the excitation coil of the electromagnetic field-temperature field-acoustic field coupling conversion unit and the input end of the excitation current acquisition module; the synchronous trigger controller of the magnetic field excitation system outputs a signal to the input end of the signal generating unit and the detection system, the signal generating unit outputs a signal to the charge and discharge unit or the power amplifying unit, the charge and discharge unit or the power amplifying unit applies a pulse current to the excitation coil through the excitation coil matching module, and the excitation coil matching module outputs a signal to the excitation current acquisition module.

[0041] The electromagnetic field-temperature field-acoustic field coupling conversion unit consists of an excitation coil, a target object containing magnetic microbubbles and diseased tissue, an ultrasonic transducer array, and a coupling medium. The excitation coil is placed close to the target object, with the coupling medium between the target object and the ultrasonic transducer array. The excitation coil, under the influence of a magnetic field excitation system, excites a pulsed magnetic field. This pulsed magnetic field acts on the target object, generating a magnetothermal acoustic signal, which is then detected by the ultrasonic transducer array.

[0042] The detection system includes a low-noise amplifier, a bandpass filter, a signal acquisition system, a mobile control system, and a mobile platform. The output end of the ultrasonic transducer array is connected to the input end of the low-noise amplifier of the detection system, the output end of the low-noise amplifier is connected to the input end of the bandpass filter, the output end of the bandpass filter is connected to the input end of the signal acquisition system, the signal acquisition system is connected to the mobile control system, the mobile control system is connected to the mobile platform, and the output end of the mobile platform is connected to the ultrasonic transducer array. The magnetothermoacoustic signal detected by the ultrasonic transducer array is output to the low-noise amplifier, the low-noise amplifier outputs a signal to the bandpass filter, the bandpass filter outputs a signal to the signal acquisition system, and the signal acquisition system outputs a signal to the imaging and display unit. The signal acquisition system and the mobile control system communicate via a serial port. The mobile control system controls the movement of the mobile platform and receives position information returned by the mobile platform via serial communication. The mobile platform controls the movement of the ultrasonic transducer array.

[0043] The imaging and display unit includes a data processing unit, an imaging module, and an image display module. The output of the data processing unit is connected to the input of the imaging module, which in turn is connected to the input of the image display module. The signal acquisition system of the detection system outputs a signal to the input of the data processing unit, the data processing unit outputs data to the imaging module, and the imaging module outputs an image to the image display module.

[0044] The operation of the magnetic microbubble magnetothermoacoustic imaging device is controlled by control and display imaging software. The software system is used in conjunction with the magnetothermoacoustic imaging device hardware system and has automatic testing, system configuration and motion console debugging functions. At the same time, the serial port connection status between the signal acquisition system, mobile control system and mobile platform is displayed, system error reporting is realized, and the current position of the probe is displayed. Among them, the automatic test interface performs the operation of starting acquisition, realizes automatic scanning and acquisition and display according to the motion trajectory, and the software interface displays the magnetothermoacoustic signal waveform of the ultrasonic transducer single point test and the imaging results of single or multiple ultrasonic transducers. During the ultrasonic transducer scanning process, the current status of the system is displayed, including the serial port connection status, whether the system has an error, the current position of the probe, the number of points the probe has moved to during the acquisition process, whether acquisition is in progress, and whether acquisition is completed. The system configuration interface configures the waveform display, including the sampling rate, the delay time after triggering, the average number of times and the number of sampling points for each record, the serial port name, the motion trajectory mode, the motion speed, and the acquisition data storage path. The motion console debugging interface is used to debug the mobile control system and mobile platform, including movement tests in different directions, setting and testing the axis, movement distance, movement speed and movement acceleration, and performing reset queries and reset operations.

[0045] Beneficial effects:

[0046] Unlike the existing magnetothermoacoustic method targeting the electrical conductivity of biological tissue targets, the mechanism of magnetothermoacoustic generation in the existing magnetothermoacoustic imaging method of biological tissue targets is ohmic loss, and the difference in electrical conductivity between diseased and normal biological tissue targets is used for imaging and disease diagnosis; unlike the existing magnetic nanoparticle magnetothermoacoustic imaging method, the existing magnetic nanoparticle magnetothermoacoustic imaging uses magnetic nanoparticles as developers to enhance the magnetothermoacoustic effect; the magnetic microbubble magnetothermoacoustic imaging method of the present invention uses magnetic microbubbles as developers, and the magnetic nanoparticle magnetothermoacoustic imaging method cannot be directly applied to magnetic microbubble magnetothermoacoustic imaging. The magnetic microbubbles used for magnetothermoacoustic imaging are composed of magnetic nanoparticles with good magnetothermoacoustic effect and microbubbles with good ultrasonic imaging performance. The electromagnetic, acoustic response and magnetothermoacoustic effect characteristics of the magnetic microbubbles are controlled by adjusting parameters such as the structural relationship, particle size, quantity, and concentration of the magnetic nanoparticles and microbubbles.

[0047] The magnetic microbubble magnetothermoacoustic imaging method and device of the present invention utilize the characteristics of magnetic microbubble developers with dual enhanced magnetothermoacoustic signals to achieve high-sensitivity imaging under low-concentration magnetic nanomaterial conditions. Combined with magnetic microbubble molecular probes, they can detect abnormalities at the molecular level of diseases, and have higher contrast than tissue imaging, thereby achieving early and accurate diagnosis of lesions. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 Schematic diagram of the magnetic microbubble magnetothermoacoustic imaging method of the present invention;

[0049] Figure 2 Schematic diagram of the magnetothermoacoustic effect of magnetic microbubbles stimulated by excitation signals;

[0050] Figure 3 Image reconstruction principle diagram;

[0051] Figure 4 Schematic diagram of the magnetic microbubble magnetothermoacoustic imaging device;

[0052] Figure 5 Schematic diagram of the magnetothermoacoustic imaging test software. DETAILED DESCRIPTION

[0053] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other. The method of the present invention excites magnetic microbubbles through electromagnetic excitation to stimulate magnetothermoacoustic signals, and reflects the location and state of the lesion through magnetic microbubble thermoacoustic source images and concentration images. Using molecular probes with magnetic microbubbles as developer, labeled imaging can be achieved. The imaging method of electromagnetic and ultrasonic coupling for magnetic microbubbles can achieve higher sensitivity detection of molecular-level abnormalities in deeper tissues, providing a new means for molecular imaging technology.

[0054] like Figure 1 As shown, the magnetic microbubble magnetothermoacoustic imaging method of the present invention involves a pulsed power supply excitation coil generating a pulsed magnetic field. The pulsed magnetic field is applied to magnetic microbubbles, which are composed of magnetic nanoparticles and microbubbles. Due to the presence of the magnetic nanoparticles, the magnetic microbubbles generate a magnetocaloric effect under the action of the pulsed magnetic field, forming a thermoacoustic source, causing thermal expansion and exciting an ultrasonic signal. The presence of the microbubbles further enhances the ultrasonic signal, which is detected by an ultrasonic transducer as a magnetothermoacoustic signal, thereby reconstructing an image of the thermoacoustic source and magnetic microbubble concentration. The magnetic microbubbles accumulate on diseased biological tissue, and based on the differences in electromagnetic and acoustic properties between the magnetic microbubbles and the biological tissue, the distribution of the magnetic microbubbles is identified, thereby reflecting the location and characteristics of the diseased biological tissue. There are three types of magnetic microbubbles used for magnetic microbubble magnetothermoacoustic imaging: one in which the magnetic nanoparticles are coupled to the outer surface of the microbubble; one in which the magnetic nanoparticles are embedded in the microbubble shell; and one in which the magnetic nanoparticles are embedded in the microbubble oil layer. Magnetic nanoparticles are chemically bonded to the microbubble surface. This structure imparts superior viscoelasticity to the microbubble shell, allowing for greater freedom than when magnetic nanoparticles are embedded within the microbubble shell, minimizing the inhibitory effect on microbubble vibrations, and resulting in a higher saturation magnetization. Magnetic nanoparticles and microbubbles exhibit excellent magnetothermoacoustic imaging and echo-reflection ultrasonic scattering response, respectively. Magnetic nanoparticles enhance the magnetothermoacoustic ultrasonic signal by altering acoustic impedance. The acoustic properties of magnetic microbubbles are related not only to the microbubbles themselves but also to the concentration of magnetic nanoparticles within the microbubbles.

[0055] Aiming at the medium environment of soft tissue and biological tissue containing bone, the thermal acoustic source function is introduced into the solid displacement field and fluid acoustic field at the same time, and an electromagnetic field-temperature field-solid displacement field-fluid acoustic field coupling model is established;

[0056] For the fluid-structure interaction model, the acoustic pressure fluctuation equation, boundary conditions, and initial conditions in the fluid region are described as follows:

[0057]

[0058] Where p(r,t) is the sound pressure at time t at position r, c s is the propagation velocity of longitudinal waves in the fluid, β is the volume expansion coefficient, C p is the specific heat capacity, S(r') is the spatial distribution of the thermal acoustic source generated by the magnetic microbubble under the action of the electromagnetic field, δ(t) is the step function, ρ0 is the medium density, n is the normal component of the fluid and solid interface, u is the displacement vector, and the sound source term includes the partial derivative of the thermal function S(r',t). The sound source term can be expressed as a function of the spatial distribution of the thermal acoustic source and the time term, that is, r' is the location of the thermal sound source, ▽ 2 is the Laplace operator, is the second-order partial derivative with respect to time, is the time partial derivative, ▽ is the differential operator, and fluid-solid represents the fluid-solid boundary;

[0059] When the magnetothermoacoustic signal encounters a solid material during propagation, the thermal equilibrium kinetic equation and boundary conditions are described by equation (2):

[0060]

[0061] Where λ and μ are Lame coefficients, u is the displacement vector, and β T =λβ, T is the temperature rise based on the reference temperature, ρ0 is the medium density, p is the sound pressure, n is the normal component of the fluid and solid interface, ▽ 2 is the Laplace operator, is the second-order partial derivative with respect to time, is the time partial derivative, ▽ is the differential operator, f| fluid-solid =-np| fluid-solid Represents the coupled boundary conditions of fluid and solid, fluid-solid represents the fluid-solid boundary, and f represents the force converted into by the sound pressure in the fluid when it encounters the solid interface;

[0062] When the excitation is a modulated signal alternating pulse magnetic field excitation, the expression of the thermal sound source is:

[0063]

[0064] Where μ0 is the vacuum permeability, H(r') is the amplitude of the magnetic field intensity, χ0 is the magnetic susceptibility of the magnetic microbubble, ω0 is the angular frequency, τ R is the relaxation time;

[0065] For different forms of excitation - narrow pulse single pulse magnetic field excitation, ignoring hysteresis loss, under adiabatic conditions, the magnetization energy accumulation is characterized as a thermoacoustic source, and the thermal function expression is:

[0066]

[0067] Where B0(r',t) represents the magnetic induction intensity in vacuum, and M(r',t) represents the equivalent magnetization intensity of magnetic microbubbles;

[0068] Since magnetic microbubbles are different from magnetic nanoparticle structures, they are new micro-nano materials composed of nanoscale magnetic particles and microbubbles combined with specific structures and parameters. When conducting theoretical analysis, it is difficult to use the performance of a single magnetic microbubble to characterize them. Their electromagnetic response properties such as magnetization curves and ultrasonic response properties can be macroscopically equivalent, and their equivalent parameters can be used to conduct electromagnetic field-temperature field-acoustic field coupling analysis.

[0069] The magnetic microbubble magnetothermoacoustic imaging method of the present invention uses magnetic microbubbles as a developer, and the magnetic nanoparticle magnetothermoacoustic imaging method cannot be directly applied to magnetic microbubble magnetothermoacoustic imaging. The magnetic microbubbles used for magnetothermoacoustic imaging are composed of magnetic nanoparticles with good magnetothermoacoustic effect and microbubbles with good ultrasonic imaging performance. The electromagnetic and acoustic responses and magnetothermoacoustic effect characteristics of the magnetic microbubbles are controlled by adjusting the structural relationship, particle size, number and concentration of the magnetic nanoparticles and microbubbles.

[0070] Figure 2 The figure shows the principle of magnetothermoacoustic effect of magnetic microbubbles stimulated by excitation signals. The excitation of magnetothermoacoustic signals of magnetic microbubbles is a pulsed magnetic field in various forms, including single pulse excitation with a certain repetition frequency or alternating pulse excitation of a modulated signal with a certain width. Different excitation modes stimulate different magnetothermoacoustic effects of magnetic microbubbles. The mechanism of magnetothermoacoustic generation of magnetic microbubbles is magnetization energy accumulation, hysteresis effect or magnetic relaxation loss of energy absorbed from non-radiative fields. Considering the magnetization process of magnetic microbubbles and magnetic nanoparticles, according to Langevin theory, the magnetization intensity in the thermoacoustic source is expressed as an expression of magnetic nanoparticle concentration and Langevin function. When magnetic relaxation loss is considered, since the magnetic nanoparticles connected to the surface of the magnetic microbubbles are aggregated on the surface of the microbubbles, the magnetic relaxation loss includes Neel relaxation and Brownian relaxation. Due to the different structures of magnetic microbubbles and magnetic nanoparticles, the magnetic nanoparticles aggregated on the surface of the microbubbles of magnetic microbubbles also have hysteresis loss effect. The acoustic field is solved by Green's function integration method and time-domain finite element method.

[0071] Figure 3The image reconstruction principle diagram is shown. Magnetic microbubbles, under magnetic field excitation, generate thermoacoustic sources and magnetothermoacoustic signals. Using the analysis results and data from these signals, Wiener filter deconvolution, time reversal, filtered back projection, Tikhonov regularization, damped least squares, and sensitive field real-time image reconstruction are employed to reconstruct magnetic microbubble thermoacoustic source and concentration images. Using a tumor model containing magnetic microbubbles and numerical simulation of inverse acoustic and electromagnetic field problems, the effects of the structural, electromagnetic, and acoustic characteristics of the magnetic microbubbles on image reconstruction are analyzed, favorable conditions for image reconstruction are identified, and image reconstruction is optimized. By accurately extracting the location and concentration information of the targeted, modified magnetic microbubbles, a correspondence between their image features and target status is established.

[0072] The image reconstruction is performed using the Tikhonov regularization method. The normalized linear equation of the sound pressure detection value and the distribution of the magnetic microbubble thermal sound source is:

[0073] P=GS (5)

[0074] Among them, G is the system matrix, P is defined as the sound field distribution formed by the sound field reciprocity process, and S is the thermal sound source distribution.

[0075] Reconstruct the thermal sound source distribution, and its objective function is:

[0076]

[0077] Setting the derivative of equation (6) to zero, we get:

[0078] S=(G T G+λI) -1 G T P (7)

[0079] Among them, G T is the transposed matrix of G, λ is the regularization parameter, and I is the identity matrix.

[0080] Figure 4The figure shows a magnetic microbubble magneto-thermoacoustic imaging device, which consists of a magnetic field excitation system, an electromagnetic field-temperature field-acoustic field coupling conversion unit, a detection system, and an imaging and display unit. The output of the magnetic field excitation system is connected to the input of the electromagnetic field-temperature field-acoustic field coupling conversion unit, which in turn is connected to the input of the detection system. The output of the detection system is connected to the input of the imaging and display unit. The magnetic field excitation system consists of a synchronous trigger controller, a signal generation unit, a charge and discharge unit or a power amplifier unit, an excitation coil matching module, and an excitation current acquisition module. The electromagnetic field-temperature field-acoustic field coupling conversion unit consists of an excitation coil, a target, an ultrasonic transducer array, and a coupling medium. The detection system includes a low-noise amplifier, a bandpass filter, a signal acquisition system, a motion control system, and a mobile platform. The imaging and display unit includes a data processing unit, an imaging module, and an image display module. The magnetic field excitation system excites a pulsed magnetic field through an excitation coil. The pulsed magnetic field acts on magnetic microbubbles and excites magnetothermal acoustic signals. The magnetothermal acoustic signals are detected by an ultrasonic transducer array. After being processed by the detection system's low-noise amplifier and bandpass filter, the magnetothermal acoustic signals are controlled by a synchronous trigger signal to collect data in a signal acquisition system. The signal acquisition system communicates with the mobile control system through a serial port. The mobile control system controls the mobile platform to drive the ultrasonic transducer to perform linear or rotational scanning detection. The collected data is processed by the imaging and display unit to ultimately achieve image reconstruction and display.

[0081] The parameters of the pulsed magnetic field excitation source determine the characteristics of the excited ultrasonic signal. Fast switching tubes suitable for inductive loads, high-frequency, high-power soft-switching inverter technology, and ultra-fast charging and discharging technology for capacitor energy storage are used to achieve single-pulse excitation and modulated signal alternating pulse excitation with high repetition frequency and narrow pulse width. Ultrasonic transducer arrays matching the excitation source parameters of the pulsed magnetic field are used, including linearly arranged arrays, annularly arranged arrays, and three-dimensionally distributed arrays. Combined with high-frequency filtering and amplification to suppress noise, pulse compression detection and multiple averaging acquisition mode processing methods are used to enhance the detection capability of the detection system and improve the detection signal-to-noise ratio and resolution of magnetothermoacoustic imaging. The signal acquisition system uses a high-speed multi-channel acquisition card to achieve high-speed, large-bandwidth, high-resolution, and low-noise measurements, meeting the requirements for high-frequency ultrasonic transducer signal acquisition under high repetition frequency excitation. The mobile control system controls the mobile platform to achieve μm-level high-precision automatic control scanning of the ultrasonic transducer and ultrasonic transducer array in linear, circular, and sector-shaped rotation in the x / y / z directions, meeting the signal acquisition requirements of different imaging methods.

[0082] The magnetic field excitation system is composed of a synchronous trigger controller, a signal generating unit, a charge and discharge unit or a power amplifying unit, an excitation coil matching module, and an excitation current acquisition module. The output end of the synchronous trigger controller is connected to the input end of the signal generating unit, the output end of the signal generating unit is connected to the input end of the charge and discharge unit or the power amplifying unit, the output end of the charge and discharge unit or the power amplifying unit is connected to the input end of the excitation coil matching module, and the output end of the excitation coil matching module is respectively connected to the input end of the excitation coil of the electromagnetic field-temperature field-acoustic field coupling conversion unit and the input end of the excitation current acquisition module; the synchronous trigger controller of the magnetic field excitation system outputs a signal to the input end of the signal generating unit and the detection system, the signal generating unit outputs a signal to the charge and discharge unit or the power amplifying unit, the charge and discharge unit or the power amplifying unit applies a pulse current to the excitation coil through the excitation coil matching module, and the excitation coil matching module outputs a signal to the excitation current acquisition module.

[0083] The electromagnetic field-temperature field-acoustic field coupling conversion unit consists of an excitation coil, a target object containing magnetic microbubbles and diseased tissue, an ultrasonic transducer array, and a coupling medium. The excitation coil is placed close to the target object, with the coupling medium between the target object and the ultrasonic transducer array. The excitation coil, under the influence of a magnetic field excitation system, excites a pulsed magnetic field. This pulsed magnetic field acts on the target object, generating a magnetothermal acoustic signal, which is then detected by the ultrasonic transducer array.

[0084] The detection system includes a low-noise amplifier, a bandpass filter, a signal acquisition system, a mobile control system, and a mobile platform. The output end of the ultrasonic transducer array is connected to the input end of the low-noise amplifier of the detection system, the output end of the low-noise amplifier is connected to the input end of the bandpass filter, the output end of the bandpass filter is connected to the input end of the signal acquisition system, the signal acquisition system is connected to the mobile control system, the mobile control system is connected to the mobile platform, and the output end of the mobile platform is connected to the ultrasonic transducer array. The magnetothermoacoustic signal detected by the ultrasonic transducer array is output to the low-noise amplifier, the low-noise amplifier outputs a signal to the bandpass filter, the bandpass filter outputs a signal to the signal acquisition system, and the signal acquisition system outputs a signal to the imaging and display unit. The signal acquisition system and the mobile control system communicate via a serial port. The mobile control system controls the movement of the mobile platform and receives position information returned by the mobile platform via serial communication. The mobile platform controls the movement of the ultrasonic transducer array.

[0085] The imaging and display unit includes a data processing unit, an imaging module, and an image display module. The output of the data processing unit is connected to the input of the imaging module, which in turn is connected to the input of the image display module. The signal acquisition system of the detection system outputs a signal to the input of the data processing unit, the data processing unit outputs data to the imaging module, and the imaging module outputs an image to the image display module.

[0086] Figure 5 The figure shows a schematic diagram of the magnetothermoacoustic imaging test software. The operation of the magnetic microbubble magnetothermoacoustic imaging device is controlled by the control and display imaging software, namely the magnetothermoacoustic imaging test software. The software system works in conjunction with the magnetothermoacoustic imaging device hardware system and has automatic testing, system configuration, and motion console debugging functions. It also displays the serial port connection status between the signal acquisition system, motion control system, and mobile platform, implements system error reporting, and displays the current position of the probe. The automatic test interface starts the acquisition operation, realizes automatic scanning, acquisition, and display according to the motion trajectory. The software interface displays the magnetothermoacoustic signal waveform of the ultrasonic transducer single-point test and the imaging results of single or multiple ultrasonic transducer scans. During the ultrasonic transducer scanning process, the current system status is displayed, including the serial port connection status, whether the system has errors, the current position of the probe, the probe movement point during the acquisition process, whether acquisition is in progress, and whether acquisition is complete. The system configuration interface configures the waveform display, including the sampling rate, post-trigger delay time, average count and number of sampling points per record, serial port name, motion trajectory mode, motion speed, and acquisition data storage path. The motion console debugging interface is used to debug the mobile control system and mobile platform, including movement tests in different directions, setting and testing the axis, movement distance, movement speed and movement acceleration, and performing reset queries and reset operations.

[0087] The magnetic microbubbles are modified to prepare molecular probes, which are placed near diseased biological tissues. The molecular probes consist of magnetic microbubbles, carriers, ligands or antibodies. The magnetic microbubbles serve as a developer and an enhanced contrast agent for magnetothermoacoustic imaging. The ligands or antibodies are used to bind to receptors highly expressed in tumors. The molecular probes target diseased biological tissues and are developed by magnetic microbubbles to achieve molecular labeling imaging, thereby realizing the identification of diseased biological tissues.

[0088] The magnetic microbubble magnetothermoacoustic imaging method and device of the present invention utilize the characteristics of magnetic microbubble developers with dual enhanced magnetothermoacoustic signals to achieve high-sensitivity imaging under low-concentration magnetic nanomaterial conditions. Combined with magnetic microbubble molecular probes, they can detect abnormalities at the molecular level of diseases, and have higher contrast than tissue imaging, thereby achieving early and accurate diagnosis of lesions.

[0089] It will be easily understood by those skilled in the art that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A magnetic microbubble magnetothermoacoustic imaging method, characterized in that: The imaging method comprises a pulse power supply exciting coil to generate a pulse magnetic field, and the pulse magnetic field is applied to magnetic microbubbles, which are composed of magnetic nanoparticles and microbubbles. Due to the presence of magnetic nanoparticles, the magnetic microbubbles generate a magnetocaloric effect under the action of the pulse magnetic field, forming a thermoacoustic source, causing thermal expansion to excite ultrasonic signals. Due to the presence of microbubbles, the magnetic microbubbles further enhance the ultrasonic signal, which is detected by an ultrasonic transducer, i.e., a magnetocaloric signal, and then an image of the thermoacoustic source and magnetic microbubble concentration is reconstructed; the magnetic microbubbles gather on the diseased biological tissue, and the distribution of the magnetic microbubbles is identified based on the differences in electromagnetic properties and acoustic source properties between the magnetic microbubbles and the biological tissue, thereby reflecting the location of the diseased biological tissue and the characteristics of the diseased biological tissue; magnetic microbubbles for magnetic microbubble magnetocaloric imaging There are three structures: one is that magnetic nanoparticles are coupled to the outer surface of the microbubble; one is that magnetic nanoparticles are embedded in the microbubble shell; and another is that magnetic nanoparticles are embedded in the microbubble oil layer; the magnetic nanoparticles are connected to the microbubble surface through a chemical reaction. This structure makes the microbubble shell have better viscoelasticity, has greater freedom than the magnetic nanoparticles embedded in the microbubble shell, has less inhibitory effect on the vibration of the microbubble, and has a higher saturation magnetization intensity; the magnetic nanoparticles and microbubbles have good magnetothermoacoustic imaging performance and good echo reflection ultrasonic scattering response performance, respectively. The magnetic nanoparticles enhance the magnetothermoacoustic ultrasonic signal by changing the acoustic impedance. The acoustic performance of the magnetic microbubble is not only related to the microbubble, but also to the concentration characteristics of the magnetic nanoparticles in the magnetic microbubble. Aiming at the medium environment of soft tissue and biological tissue containing bone, the thermal acoustic source function is introduced into the solid displacement field and fluid acoustic field at the same time, and an electromagnetic field-temperature field-solid displacement field-fluid acoustic field coupling model is established; For the fluid-structure interaction model, the acoustic pressure fluctuation equation, boundary conditions, and initial conditions in the fluid region are described as follows: Where p(r,t) is the sound pressure at time t at position r, c s is the propagation velocity of longitudinal waves in the fluid, β is the volume expansion coefficient, C p is the specific heat capacity, S(r') is the spatial distribution of the thermal acoustic source generated by the magnetic microbubble under the action of the electromagnetic field, δ(t) is the step function, ρ0 is the medium density, n is the normal component of the fluid and solid interface, u is the displacement vector, and the sound source term includes the partial derivative of the thermal function S(r',t). The sound source term can be expressed as a function of the spatial distribution of the thermal acoustic source and the time term, that is, r' is the position of the thermal sound source, is the Laplace operator, is the second-order partial derivative with respect to time, is the time partial derivative, is the differential operator, fluid-solid represents the fluid-solid boundary; When the magnetothermoacoustic signal encounters a solid material during propagation, the thermal equilibrium kinetic equation and boundary conditions are described by equation (2): Where λ and μ are Lame coefficients, u is the displacement vector, and β T =λβ, T is the temperature rise based on the reference temperature, ρ0 is the medium density, p is the sound pressure, n is the normal component of the fluid and solid interface, ▽ 2 is the Laplace operator, is the second-order partial derivative with respect to time, is the time partial derivative, is the differential operator, f| fluid-solid =-np| fluid-solid Represents the coupled boundary conditions of fluid and solid, fluid-solid represents the fluid-solid boundary, and f represents the force converted into by the sound pressure in the fluid when encountering the solid interface; When the excitation is a modulated signal alternating pulse magnetic field excitation, the expression of the thermal sound source is: Where μ0 is the vacuum permeability, H(r') is the amplitude of the magnetic field intensity, χ0 is the magnetic susceptibility of the magnetic microbubble, ω0 is the angular frequency, τ R is the relaxation time; For different forms of excitation - narrow pulse single pulse magnetic field excitation, ignoring hysteresis loss, under adiabatic conditions, the magnetization energy accumulation is characterized as a thermoacoustic source, and the thermal function expression is: Where B0(r',t) represents the magnetic induction intensity in vacuum, and M(r',t) represents the equivalent magnetization intensity of magnetic microbubbles.

2. The magnetic microbubble magneto-thermoacoustic imaging method according to claim 1, characterized in that: The magnetic microbubbles used for magnetothermoacoustic imaging are composed of magnetic nanoparticles with good magnetothermoacoustic effect and microbubbles with good ultrasonic imaging performance. The electromagnetic, acoustic response and magnetothermoacoustic effect characteristics of the magnetic microbubbles are controlled by adjusting the structural relationship, particle size, number and concentration of the magnetic nanoparticles and microbubbles.

3. The magnetic microbubble magnetothermoacoustic imaging method according to claim 1, characterized in that: The excitation of the magnetothermoacoustic signal of the magnetic microbubble is a pulsed magnetic field in various forms, including a single pulse excitation with a certain repetition frequency or a modulated signal alternating pulse excitation with a certain width; different excitation modes excite different magnetothermoacoustic effects of the magnetic microbubbles, and the mechanism of magnetothermoacoustic generation of the magnetic microbubbles is magnetization energy accumulation, hysteresis effect or magnetic relaxation loss that absorbs energy from the non-radiative field; considering the magnetization process of the magnetic nanoparticles of the magnetic microbubbles, according to the Langevin theory, the magnetization intensity in the thermoacoustic source is expressed as an expression of the magnetic nanoparticle concentration of the magnetic microbubbles and the Langevin function; when considering the magnetic relaxation loss, since the magnetic nanoparticles connected to the surface of the magnetic microbubble are aggregated on the surface of the microbubble, the magnetic relaxation loss includes Neel relaxation and Brownian relaxation; due to the different structures of the magnetic microbubbles and the magnetic nanoparticles, the magnetic nanoparticles aggregated on the surface of the microbubble of the magnetic microbubble have a hysteresis loss effect; the Green's function integral method and the time-domain finite element method are used to solve the acoustic field.

4. The magnetic microbubble magneto-thermoacoustic imaging method according to claim 1, characterized in that: The magnetic microbubbles are modified to prepare molecular probes, which are placed near diseased biological tissues. The molecular probes consist of magnetic microbubbles, carriers, ligands or antibodies. The magnetic microbubbles serve as a developer and an enhanced contrast agent for magnetothermoacoustic imaging. The ligands or antibodies are used to bind to receptors highly expressed in tumors. The molecular probes target diseased biological tissues and are developed by magnetic microbubbles to achieve molecular labeling imaging, thereby realizing the identification of diseased biological tissues.

5. The magnetic microbubble magneto-thermoacoustic imaging method according to claim 1, characterized in that: The magnetic microbubbles generate a thermoacoustic source and a magnetothermoacoustic signal under the action of a magnetic field. The analysis results and data of the magnetothermoacoustic signal are used to implement magnetic microbubble thermoacoustic source and concentration image reconstruction by employing Wiener filter deconvolution, time reversal method, filtered back projection method, Tikhonov regularization, damped least squares method, and sensitive field real-time image reconstruction method. A tumor model containing magnetic microbubbles is used to analyze the inverse problem of acoustic and electromagnetic fields to obtain the influence of the structural, electromagnetic, and acoustic characteristics of the magnetic microbubbles on image reconstruction, obtain favorable conditions for image reconstruction, and achieve image reconstruction optimization. By accurately extracting the position and concentration information of the targeted modified magnetic microbubbles, a corresponding relationship between their image characteristics and target state is established. The image reconstruction is performed using the Tikhonov regularization method. The normalized linear equation of the sound pressure detection value and the distribution of the magnetic microbubble thermal sound source is: P=GS(5) Where G is the system matrix, P is defined as the sound field distribution formed by the sound field reciprocity process, and S is the thermal sound source distribution; Reconstruct the thermal sound source distribution, and its objective function is: Setting the derivative of equation (6) to zero, we get: S=(G T G+λI) -1 G T P(7) Among them, G T is the transposed matrix of G, λ is the regularization parameter, and I is the identity matrix.

6. An imaging device for implementing the magnetic microbubble magnetothermoacoustic imaging method according to any one of claims 1 to 5, characterized in that: The imaging device comprises a magnetic field excitation system, an electromagnetic field-temperature field-acoustic field coupling conversion unit, a detection system, and an imaging and display unit. The magnetic field excitation system comprises a synchronous trigger controller, a signal generating unit, a charging and discharging unit or a power amplifying unit, an excitation coil matching module, and an excitation current acquisition module. The electromagnetic field-temperature field-acoustic field coupling conversion unit comprises an excitation coil, a target body, an ultrasonic transducer array, and a coupling medium. The detection system comprises a low-noise amplifier, a bandpass filter, a signal acquisition system, a mobile control system, and a mobile platform. The imaging and display unit comprises a data processing unit, an imaging module, and an image display module. The magnetic field excitation system excites a pulsed magnetic field through the excitation coil, which acts on magnetic microbubbles to excite magnetothermal acoustic signals. The magnetothermal acoustic signals are detected by the ultrasonic transducer, and after being processed by the low-noise amplifier and the bandpass filter, the synchronous trigger signal controls the signal acquisition system to collect data. The signal acquisition system communicates with the mobile control system via a serial port, and the mobile control system controls the mobile platform to drive the ultrasonic transducer to perform linear or rotational scanning detection. The collected data is processed by the data processing unit, ultimately achieving image reconstruction and display.

7. The imaging device according to claim 6, wherein The excitation source parameters of the pulsed magnetic field determine the characteristics of the excited ultrasonic signal, and adopt fast switching tubes suitable for inductive loads, high-frequency and high-power soft-switching inverter technology, and ultra-fast charging and discharging technology of capacitor energy storage to achieve single pulse excitation and modulated signal alternating pulse excitation with high repetition frequency and narrow pulse width; an ultrasonic transducer array matching the excitation source parameters of the pulsed magnetic field is adopted, including a linear arrangement array, a circular arrangement array, and a three-dimensional distribution arrangement array, combined with high-frequency filtering and amplification for noise suppression, and a processing method using pulse compression detection and multiple averaging acquisition modes to enhance the detection capability of the detection system and improve the detection signal-to-noise ratio and resolution of magnetothermoacoustic imaging; the signal acquisition system adopts a high-speed multi-channel acquisition card to achieve high-speed, large bandwidth, high-resolution and low-noise measurement, meeting the requirements of high-frequency ultrasonic transducer signal acquisition under high repetition frequency excitation; the mobile control system controls the mobile platform to achieve μm-level high-precision automatic control scanning of the ultrasonic transducer and the ultrasonic transducer array in linear, circular and sector-shaped rotation in the x / y / z directions, meeting the signal acquisition requirements of different imaging methods; The operation of the magnetic microbubble magnetothermoacoustic imaging device is controlled by control and display imaging software. The software system is used in conjunction with the hardware system of the magnetothermoacoustic imaging device, and has automatic testing, system configuration and motion console debugging functions. At the same time, the serial port connection status between the signal acquisition system, the mobile control system and the mobile platform is displayed to realize system error reporting and display the current position of the probe. Among them, the automatic test interface starts the acquisition operation, realizes automatic scanning and acquisition and display according to the motion trajectory, and the software interface displays the magnetothermoacoustic signal waveform of the ultrasonic transducer single-point test and the imaging results of single or multiple ultrasonic transducers scanning. The ultrasonic transducer scans During the process, the current status of the system is displayed, including the serial port connection status, whether the system has an error, the current position of the probe, the point the probe has moved to during the acquisition process, whether acquisition is in progress, and whether acquisition is completed; the system configuration interface is used to configure the waveform display, including the sampling rate, delay time after triggering, average times and the number of sampling points for each record, serial port name, motion trajectory mode, motion speed, and acquisition data storage path; the motion console debugging interface is used to debug the mobile control system and mobile platform, including movement tests in different directions, setting and testing the axis, movement distance, movement speed and movement acceleration, and performing reset queries and reset operations.

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