Temperature measurement method under complex excitation magnetic field of two-dimensional magnetic nanoparticle imaging device

Abstract

The present invention discloses a temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, belonging to the field of nanomaterial testing technology. A magnetic nanometer temperature measurement method is proposed for the complex excitation magnetic field generated by the two-dimensional magnetic nanoparticle imaging device. Specifically, while utilizing the complex excitation signal to cause the magnetic nanoparticles to have a rich relationship between nonlinear magnetic susceptibility and temperature, the method also considers the influence of field strength and particle saturation magnetization on temperature measurement in actual two-dimensional MPI applications, establishes a compensation function, and provides a temperature measurement model when the dominant relaxation mechanism of the particles is Neel relaxation or Brownian relaxation. This realizes real-time temperature detection of magnetic nanoparticles on the two-dimensional magnetic nanoparticle imaging device, solving the problem that the current magnetic nanoparticle temperature measurement method cannot accurately measure temperature under the complex excitation magnetic field of the two-dimensional magnetic nanoparticle imaging device.

Description

Technical Field

[0001] The present invention belongs to the technical field of nanomaterial testing, and more specifically, relates to a temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device. Background Art

[0002] In recent years, magnetic nanoparticles (MNPs) have been widely used in various biomedical diagnostic and therapeutic fields due to their unique physical, chemical, and biological properties. Magnetic nanoparticle imaging (MPI) is a novel medical diagnostic method that can accurately locate the spatial distribution of MNPs. Magnetic hyperthermia using MNPs as thermogenic agents is considered a promising cancer treatment, offering excellent targeted hyperthermia within tissues. The integration of MPI diagnostics and magnetic hyperthermia is of great significance for the development of integrated diagnosis and treatment in the medical field. However, achieving this goal requires precise localization of the MNP thermogenic agents within the body while also accurately measuring the temperature of the tumor and surrounding tissues. Currently, in most magnetic hyperthermia experiments, temperature monitoring is performed using fiber optic thermometers, but this method is invasive and can cause additional trauma to the patient. Due to the excellent magnetothermal properties of MNPs and the good biopenetration of magnetic signals, magnetic nanothermometry is considered one of the most promising approaches to address the temperature detection challenge in magnetic hyperthermia. Therefore, combining MPI technology with magneto-nanothermometry to realize magneto-nano imaging and temperature measurement is of great significance for the integration of MPI-magnetic hyperthermia diagnosis and treatment.

[0003] In 2009, Weaver et al. first proposed a method based on the relationship between the ratio of the fifth and third harmonics of the magnetic nanoparticle's magnetization response and temperature, achieving temperature measurements with an accuracy of 0.3 K. Subsequently, magnetic nanothermometry attracted considerable attention. In 2012, W. Liu et al. constructed a temperature measurement model under DC magnetic field excitation based on the Langevin paramagnetic theorem. This method achieved a measurement accuracy of 0.55 K in the range of 310 K to 350 K. In 2016, L. He et al. proposed a linear magnetic nanoparticle temperature measurement method based on Debye theory, which calculates the AC magnetic susceptibility of magnetic nanoparticles. This method achieves temperature measurement accuracy exceeding 0.3 K and expands the applicability of magnetic nanoparticle temperature measurement to medium- and high-frequency weak magnetic fields. Research has revealed that the excitation magnetic fields used in these magnetic nanoparticle temperature measurement techniques are all DC or single AC excitation fields. However, in MPI technology, the excitation magnetic field is becoming increasingly complex. Utilizing the rich magnetic information provided by complex excitation fields can improve MPI imaging accuracy. For example, Viereck et al. introduced a multi-frequency alternating excitation magnetic field into the MPI technology, and ZWTay et al. introduced a pulsed excitation magnetic field into the MPI excitation magnetic field.

[0004] The aforementioned magnetic nanothermometry method cannot accurately describe the relationship between the response of magnetic nanoparticles and temperature under complex excitation magnetic fields, which in turn affects temperature measurement accuracy and is not well applied to the complex excitation magnetic fields of MPI. Therefore, a temperature measurement method suitable for complex excitation magnetic fields is needed to promote the integrated development of MPI technology and magnetic nanothermometry technology. Summary of the Invention

[0005] In response to the above defects or improvement needs of the prior art, the present invention provides a temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, which aims to solve the problem that the current magnetic nanoparticle temperature measurement method cannot accurately measure temperature under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device.

[0006] To achieve the above object, according to one aspect of the present invention, a temperature measurement method in a two-dimensional magnetic nanoparticle imaging device under a complex excitation magnetic field is provided, comprising:

[0007] S1. Placing the magnetic nanoparticles to be tested in the sample chamber of a two-dimensional MPI imaging device and detecting the magnetization response signal of the magnetic nanoparticles under a complex excitation magnetic field; the complex excitation magnetic field refers to a non-single type of magnetic field;

[0008] S2. Calculate the third-order AC magnetic susceptibility phase and the fifth-order AC magnetic susceptibility phase of the magnetic nanoparticles;

[0009] S3. Simulate the magnetization response of particles under complex excitation magnetic fields, establish a compensation function related to field strength and saturation magnetization, and simultaneously establish the relationship between the phase of the cubic and quintic AC magnetic susceptibility and temperature to construct a temperature measurement model.

[0010] S4. Substitute the third-order AC magnetic susceptibility phase and the fifth-order AC magnetic susceptibility phase calculated in step S2 into the temperature measurement model to calculate the temperature.

[0011] Furthermore, when the particles exhibit Neel relaxation, the temperature measurement model is:

[0012]

[0013] K is the anisotropy constant, V m is the particle core volume, k B is the Boltzmann constant, T is the temperature, G 3,N (h mul ,m s ), G 5,N (h mul ,m s ) is the compensation function, m s is the saturation magnetization of the particle, h mul is the field intensity ratio of the multi-alternating excitation magnetic field in the complex excitation magnetic field, t0 is the diffusion relaxation time; θ3 is the phase of the third-order alternating magnetic susceptibility, and θ5 is the phase of the fifth-order alternating magnetic susceptibility;

[0014] When the particles exhibit Brownian relaxation, the constructed temperature measurement model is:

[0015]

[0016] η is the viscosity of the particle carrier liquid, V h is the hydrodynamic volume of the particle, G 3,B (h mul ,m s ), G 5,B (h mul ,m s ) is the compensation function.

[0017] Furthermore, the compensation function G 3,N (h mul ,m s ), G 3,B (h mul ,m s The specific numerical fitting process of ) is as follows:

[0018] (1) Calculate the magnetization response of magnetic nanoparticles under complex excitation magnetic fields according to the Fokker-Plank equation;

[0019] (2) Obtaining the tertiary magnetic susceptibility phase information of the particle based on the magnetization response of the particle;

[0020] (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, repeating steps (1) and (2) to obtain the corresponding compensation term value;

[0021] (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0022] (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

[0023] Furthermore, the compensation function G 5,N (h mul ,m s ), G 5,B (h mul ,m s The specific numerical fitting process of ) is as follows:

[0024] (1) Calculate the magnetization response of magnetic nanoparticles under complex excitation magnetic fields according to the Fokker-Plank equation;

[0025] (2) Obtain the fifth-order magnetic susceptibility phase information of the particle based on the magnetization response of the particle;

[0026] (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, and repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0027] (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0028] (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

[0029] Furthermore, the three-phase AC magnetic susceptibility is

[0030]

[0031] M3, Respectively represent the harmonic amplitude and phase of the magnetization response signal M(t) at the frequency f3; H3, They represent the cube of the complex excitation magnetic field H(t) 3 (t) Harmonic amplitude and phase at frequency f3.

[0032] Furthermore, the quintic AC magnetic susceptibility phase is

[0033]

[0034] M5, Respectively represent the harmonic amplitude and phase of M(t) at frequency f5; H5, They represent the fifth power of H(t) 5 (t) Harmonic amplitude and phase at frequency f5.

[0035] Furthermore, step S4 specifically involves obtaining the best estimated value of the temperature through a particle swarm algorithm.

[0036] The present invention also provides a temperature measurement device under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, comprising:

[0037] A magnetization response signal measurement module is used to detect the magnetization response signal of the magnetic nanoparticles to be tested placed in the sample chamber of the two-dimensional MPI imaging device under the application of a complex excitation magnetic field; the complex excitation magnetic field refers to a magnetic field of non-single type;

[0038] Hybrid AC magnetization phase calculation module, used to calculate the cubic AC magnetic susceptibility phase and quintic AC magnetic susceptibility phase of magnetic nanoparticles;

[0039] The simulation module is used to simulate the magnetization response of particles under complex excitation magnetic fields, establish a compensation function related to field strength and saturation magnetization, and establish the relationship between the phase of the cubic AC magnetic susceptibility and the phase of the quintic AC magnetic susceptibility and temperature in parallel to build a temperature measurement model;

[0040] The temperature calculation module is used to substitute the cubic AC magnetic susceptibility phase and the quintic AC magnetic susceptibility phase obtained by the hybrid AC magnetization phase calculation module into the temperature measurement model to calculate the temperature.

[0041] In general, the above technical solutions conceived by the present invention can achieve the following beneficial effects compared with the prior art.

[0042] (1) The present invention takes into account the multidimensional complexity of the excitation magnetic field in actual two-dimensional MPI applications, which makes the nonlinear magnetization response components of the particles rich. A temperature measurement model is constructed by combining the relationship between the third-order magnetic susceptibility phase and the fifth-order magnetic susceptibility phase and the temperature. At the same time, the influence of the field strength and the particle saturation magnetization intensity on the temperature measurement in actual two-dimensional MPI applications is also considered. A compensation function is added to the constructed temperature measurement model to make the model applicable to a wide range of excitation parameters (field strength, frequency, excitation signal type). This solves the problem of inaccurate temperature measurement of existing temperature measurement models under multi-dimensional non-single excitation magnetic fields and can avoid time-consuming calibration and calibration processes.

[0043] (2) The present invention constructs a temperature measurement model when the dominant relaxation mechanism of the magnetic nanoparticles is Neel relaxation or Brownian relaxation. Therefore, when the temperature of the magnetic nanoparticles changes with either Neel relaxation or Brownian relaxation as the dominant relaxation mechanism, the method proposed in the present invention can obtain the temperature of the particles. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 Flow chart of the method of the present invention;

[0045] Figure 2 When the complex excitation magnetic field is H(t)=H s +H x cos(2πf1t)+H y cos(2πf2t), compensation function G in the temperature range of 309K-335K 3,N (h mul ,m s )’s fitted image;

[0046] Figure 3 Schematic diagram of the change of the third-order magnetic susceptibility phase θ3 of the response signal with temperature in the temperature measurement experiment of sample A;

[0047] Figure 4 Schematic diagram of the change of the third-order magnetic susceptibility phase θ3 of the response signal with temperature in the temperature measurement experiment of sample B;

[0048] Figure 5 is the error between the temperature measured by the proposed method and the temperature measured by the fiber optic thermometer in the temperature measurement experiment of sample A;

[0049] Figure 6 is the error value between the temperature measured by the proposed method and the temperature measured by the fiber optic thermometer in the temperature measurement experiment of sample B. DETAILED DESCRIPTION

[0050] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely for the purpose of explaining the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

[0051] In the two-dimensional MPI imaging device, a complex excitation magnetic field is applied to the particles, that is, multiple excitation magnetic fields in different directions are superimposed. Compared with a single excitation magnetic field, a non-single type of complex excitation magnetic field will significantly change the time domain signal shape of the particle magnetization response. At the same time, the complex magnetic field enriches the nonlinear magnetization response components of the particles. At this time, the existing magnetic nanometer temperature measurement method proposed based on Langevin's theorem cannot accurately describe the magnetization response of the particles under a complex excitation magnetic field. Moreover, the existing magnetic nanometer temperature measurement method that only uses the linear magnetic susceptibility of the particles can only show the magnetization response information of the particles under a single fundamental frequency, and cannot reflect the effect of all excitation magnetic fields on the magnetization of the particles. These existing magnetic nanometer temperature measurement methods have limitations in application in complex excitation magnetic fields, which will affect the temperature measurement accuracy.

[0052] like Figure 1 As shown, the present invention provides a temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, comprising the following steps:

[0053] Step S1. Placing the magnetic nanoparticles to be tested in the sample chamber of a two-dimensional MPI imaging device and detecting the magnetization response signal M(t) of the magnetic nanoparticles under a complex excitation magnetic field H(t);

[0054] When magnetic nanoparticles are in different environmental states, such as when dissolved in a carrier liquid or fixed, the temperature sensitivity of their nonlinear response signals is different. In MPI bioimaging, when magnetic nanoparticles are internalized and fixed by biological tissues or cells, the particles mainly exhibit Neel relaxation, while when magnetic nanoparticles are free in the blood, the particles mainly exhibit Brownian relaxation. Different dominant relaxation mechanisms will affect the temperature sensitivity of the particles' nonlinear response, thereby affecting the accuracy of temperature measurement. The dominant relaxation mechanism of the magnetic nanoparticle samples to which this method is applicable can be either Neel relaxation or Brownian relaxation. The complex excitation magnetic field generated by the MPI excitation device refers to a non-single type of magnetic field. In this embodiment, the imaging surface of the two-dimensional MPI device is the XOY surface, and the complex excitation magnetic field H(t) is expressed as H(t)=H s +H x cos(2πf1t)+H y cos(2πf2t), where H s is the spatial DC gradient magnetic field, Magnetic nanoparticles will generate magnetization response signals under the stimulation of complex magnetic fields. The Hall-type magnetic sensor TLE4997A8D is used to detect the magnetic induction intensity M(t) of the object area to be measured. The magnetic sensor converts the sensed magnetic signal into an electrical signal. After subsequent signal conditioning circuits such as signal enhancement, filtering and denoising, the signal is collected by a data acquisition card and stored in a computer.

[0055] Step S2. Calculating the third-order AC magnetic susceptibility phase θ3 and the fifth-order AC magnetic susceptibility phase θ5 of the magnetic nanoparticles;

[0056] Since the complex excitation magnetic field will produce a rich mixture of frequencies, for the measured magnetic response signal M(t), a digital phase-sensitive detection algorithm is used to extract the harmonic amplitude M3 and phase θ of M(t) at frequency f3. M3 And the harmonic amplitude M5 and phase θ of M(t) at frequency f5 M5 The digital phase-sensitive detection algorithm is also used to extract the cube of H(t) 3 (t) Harmonic amplitude H3 and phase θ at frequency f3 H3 and H(t) to the fifth power H 5 (t) Harmonic amplitude H5 and phase θ at frequency f5 H5 The third-order mixing frequency f3 satisfies: f3 = N1f1 + N2f2 and N1 + N2 = 3, with N1 and N2 both being positive integers; the fifth-order mixing frequency f5 satisfies: f5 = N1f1 + N2f2 and N1 + N2 = 5, with N1 and N2 both being positive integers. In this embodiment, f3 = 2f1 + f2 and f5 = 3f1 + 2f2 are selected.

[0057] The harmonics of the particle's magnetic response M(t) and the corresponding magnetic susceptibility satisfy the following relationship: M(t) = H(t)χ1 + H 3 (t)χ3+H 5 (t)χ5+…. Then the third magnetic susceptibility Quintic magnetic susceptibility The phase of magnetic susceptibility can be obtained based on the real and imaginary parts of magnetic susceptibility. H3, Substituting the following formula, the third-order AC magnetic susceptibility phase θ3 of the response signal can be calculated:

[0058]

[0059] Similarly, the extracted M5, H5, Substituting the following formula, the third-order AC magnetic susceptibility phase θ5 of the response signal can be calculated:

[0060]

[0061] To ensure the algorithm extraction accuracy, the number of signal sampling points N of the digital phase-sensitive detection algorithm must meet and is an integer, where f s is the sampling frequency of the data acquisition card.

[0062] Step S3. Constructing a temperature measurement model based on the relationship between the third-order magnetic susceptibility phase and the fifth-order magnetic susceptibility phase and temperature;

[0063] According to Debye theory, under ideal conditions (no interaction between particles and small enough AC magnetic field), the real and imaginary parts of the tertiary magnetic susceptibility of magnetic nanoparticles satisfy: Then tan(θ3)=2πf3t, and the real and imaginary parts of the fifth-order magnetic susceptibility of the magnetic nanoparticles satisfy: Therefore, tan(θ5) = 2πf5t. In actual 2D MPI bioimaging applications, the complex excitation magnetic field applied to the particles cannot meet the ideal condition of a sufficiently small AC magnetic field. This leads to errors in the model between the phase relationship between the third-order and fifth-order magnetic susceptibility and temperature constructed based on Debye theory.

[0064] In addition, the saturation magnetization m of the particle s Affected by temperature, it obeys Bloch's law:

[0065] m s =m s0 (1-α m T 3 / 2 )

[0066] Among them, m s0 The saturation magnetization at 0K is determined by the material density and the specific saturation magnetization, α m is a phenomenological parameter. It can be seen that changes in temperature will cause changes in the saturation magnetization of the particle. When constructing a temperature model, the influence of saturation magnetization and field strength on the temperature measurement model cannot be ignored. When the particle is in a fixed state, mainly showing Neel relaxation, the constructed temperature measurement model is:

[0067]

[0068] When the particles are dissolved in the carrier liquid and mainly exhibit Brownian relaxation, the temperature measurement model constructed is:

[0069]

[0070] Where f3 and f5 are the frequencies selected in step S2, t0 is the diffusion relaxation time, V m is the particle core volume, k B is the Boltzmann constant, K is the anisotropy constant, η is the viscosity of the particle carrier fluid, V h is the hydrodynamic volume of the particle, m s is the saturation magnetization of the particle, T is the temperature, and the compensation function G(h mul ,m s ) is obtained by numerical fitting, and its saturation magnetization m sIt is related to the field strength ratio of multiple alternating excitation magnetic fields in the complex excitation magnetic field.

[0071] Compensation function G 3,N (h mul ,m s The specific numerical fitting process of ) is as follows:

[0072] (1) According to the Fokker-Plank equation, the complex excitation magnetic field H(t) = H s +H x cos(2πf1t)+H y The magnetization response of magnetic nanoparticles under cos(2πf2t);

[0073] (2) Obtaining the tertiary magnetic susceptibility phase information of the particle based on the magnetization response of the particle;

[0074] (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, and repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0075] (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0076] (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

[0077] Figure 2 The complex excitation magnetic field is shown as H(t) = H s +H x cos(2πf1t)+H y cos(2πf2t), compensation function G in the temperature range of 309K-335K 3,N (h mul ,m s )’s fitted image.

[0078] The compensation function G can be obtained by the same steps as above. 3,B (h mul ,m s ).

[0079] Compensation function G 5,N (h mul ,m s The specific numerical fitting process of ) is as follows:

[0080] (1) According to the Fokker-Plank equation, the complex excitation magnetic field H(t) = H s +H xcos(2πf1t)+H y The magnetization response of magnetic nanoparticles under cos(2πf2t);

[0081] (2) Obtain the fifth-order magnetic susceptibility phase information of the particle based on the magnetization response of the particle;

[0082] (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, and repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0083] (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model;

[0084] (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

[0085] The compensation function G can be obtained through the same steps 5,B (h mul ,m s ).

[0086] The Fokker-Plank equation can accurately describe the magnetization dynamics of particles numerically. Therefore, the present invention uses the complex excitation magnetic field H(t) = H s +H x cos(2πf1t)+H y The magnetic response of the particles was simulated under cos(2πf2t), and a compensation function related to the field strength and saturation magnetization intensity was established. According to the complexity of the excitation magnetic field of the two-dimensional MPI imaging device, the rich nonlinear relationship between the magnetic susceptibility and temperature caused by the complex excitation signal was utilized. By jointly constructing the relationship between the cubic magnetic susceptibility phase and the quintic magnetic susceptibility phase and temperature, an equation was constructed, and a magnetic nanothermometry model suitable for two-dimensional MPI imaging was proposed.

[0087] Step S4: Substitute the obtained third-order AC magnetic susceptibility phase θ3 and fifth-order AC magnetic susceptibility phase θ5 into the constructed temperature measurement model to obtain the best estimated value of the temperature T.

[0088] Since the constructed temperature measurement model is a nonlinear equation system about temperature T, the exact solution of temperature T cannot be directly obtained. The obtained cubic AC magnetic susceptibility phase θ3 and quintic AC magnetic susceptibility phase θ5 are substituted into the constructed temperature measurement model, and the optimal estimate of temperature T is obtained by particle swarm optimization.

[0089] Experimental example:

[0090] 1. Experimental steps and instructions:

[0091] To verify the feasibility of this method for measuring temperature under complex excitation magnetic fields, a magnetic nanoparticle sample (30 nm in size) was first prepared into sample A and sample B, with the particles in different states. Specifically, sample A was a 200 μL liquid sample with a carrier liquid of distilled water and a sample concentration of 25 mg / ml. In this case, the magnetic nanoparticles primarily exhibit Brownian relaxation. Sample B was prepared by mixing the magnetic nanoparticle sample solution with a 3.5% hot agarose solution at a 1:1 volume ratio, stirring thoroughly, and then allowing the solution to solidify at room temperature. In this case, the magnetic nanoparticles primarily exhibit Neel relaxation.

[0092] Next, the temperature measurement experiment is carried out on sample A and sample B respectively. The specific steps are as follows: after the sample A to be measured is heated in a water bath, it is placed in the sample chamber of the two-dimensional MPI imaging device. s +H x cos(2πf1t)+H y The temperature measurement experiment was carried out under cos(2πf2t), and the specific parameters of the excitation magnetic field were: frequency f1 = 135 Hz, f2 = 1695 Hz, H x =18mT / μ0,H y =1.8mT / μ0, and the gradient strength of the gradient magnetic field was 1.2T / m / μ0. Throughout the experiment, sample A was naturally cooled within the temperature range of 309K-335K, while a fiber optic thermometer was used to record the sample temperature in real time. The magnetic induction intensity signal generated by the magnetic nanoparticles was detected. After processing by the signal processing circuit, the third-order magnetic susceptibility phase θ3 and the fifth-order magnetic susceptibility phase θ5 of the response signal were extracted by computer using a data acquisition card and LabView program. The changes of the third-order magnetic susceptibility phase θ3 and the fifth-order magnetic susceptibility phase θ5 with temperature were obtained. In this experiment, the third-order mixing frequency f3 = 2f1 + f2 = 1965Hz and the fifth-order mixing frequency f5 = 3f1 + 2f2 = 5355Hz were selected. Similarly, the above experimental procedures were repeated for sample B.

[0093] The calculated tertiary magnetic susceptibility phase θ3 and quintic magnetic susceptibility phase θ5 information of sample A are brought into the temperature measurement model when Brownian relaxation dominates, and the optimal temperature estimate T is obtained by the particle swarm algorithm; similarly, the tertiary magnetic susceptibility phase θ3 and quintic magnetic susceptibility phase θ5 information of sample B calculated in the experiment are brought into the temperature measurement model when Neel relaxation dominates, and the optimal temperature estimate T is obtained by the particle swarm algorithm.

[0094] 2. Temperature measurement test results:

[0095] Figure 3 Schematic diagram of the change of the third-order magnetic susceptibility phase θ3 of the response signal with temperature in the temperature measurement experiment of sample A; Figure 4Schematic diagram of the change of the third-order magnetic susceptibility phase θ3 of the response signal with temperature in the temperature measurement experiment of sample B; Figure 5 is the error between the temperature measured by the proposed method and the temperature measured by the fiber optic thermometer in the temperature measurement experiment of sample A; Figure 6 is the error between the temperature measured by the proposed method and the temperature measured by the fiber optic thermometer in the temperature measurement experiment of sample B.

[0096] The experimental results show that the temperature error of the proposed method is generally within 0.2 K. Therefore, this magnetic nanometer temperature measurement method based on the temperature sensitivity of the nonlinear magnetic susceptibility phase at the mixing frequency of magnetic nanoparticles can achieve non-contact temperature measurement under the complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, broadening the application range of magnetic nanometer temperature measurement technology.

[0097] 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 temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, characterized in that: include: S1. Placing the magnetic nanoparticles to be tested in the sample chamber of a two-dimensional MPI imaging device and detecting the magnetization response signal of the magnetic nanoparticles under a complex excitation magnetic field; the complex excitation magnetic field refers to a non-single type of magnetic field; S2. Calculate the third-order AC magnetic susceptibility phase and the fifth-order AC magnetic susceptibility phase of the magnetic nanoparticles; S3. Simulate the magnetization response of particles under complex excitation magnetic fields, establish a compensation function related to field strength and saturation magnetization, and simultaneously establish the relationship between the phase of the cubic and quintic AC magnetic susceptibility and temperature to construct a temperature measurement model. S4. Substitute the three-time AC magnetic susceptibility phase and the five-time AC magnetic susceptibility phase calculated in step S2 into the temperature measurement model to calculate the temperature; When the particles exhibit Neel relaxation, the temperature measurement model is: K is the anisotropy constant, V m is the particle core volume, k B is the Boltzmann constant, T is the temperature, G 3,N (h mul ,m s ), G 5,N (h mul ,m s ) is the compensation function, m s is the saturation magnetization of the particle, h mul is the field intensity ratio of the multi-alternating excitation magnetic field in the complex excitation magnetic field, τ0 is the diffusion relaxation time; θ3 is the phase of the third-order alternating magnetic susceptibility, θ5 is the phase of the fifth-order alternating magnetic susceptibility; f3 and f5 are the third-order mixing frequency and the fifth-order mixing frequency, respectively; When the particles exhibit Brownian relaxation, the constructed temperature measurement model is: η is the viscosity of the particle carrier liquid, V h is the hydrodynamic volume of the particle, G 3,B (h mul ,m s ), G 5,B (h mul ,m s ) is the compensation function; m s is the saturation magnetization of the particle, h mul is the field strength ratio of the multiple alternating excitation magnetic fields in the complex excitation magnetic field, T is the temperature, k B is the Boltzmann constant; θ3 is the cubic AC magnetic susceptibility phase, θ5 is the quintic AC magnetic susceptibility phase; f3 and f5 are the cubic mixing frequency and the quintic mixing frequency, respectively; Compensation function G 3,N (h mul ,m s ), G 3,B (h mul ,m s The specific numerical fitting process of ) is as follows: (1) Calculate the magnetization response of magnetic nanoparticles under complex excitation magnetic fields according to the Fokker-Plank equation; (2) Obtaining the tertiary magnetic susceptibility phase information of the particle based on the magnetization response of the particle; (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, repeating steps (1) and (2) to obtain the corresponding compensation term value; (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model; (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

2. The temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device according to claim 1, characterized in that: Compensation function G 5,N (h mul ,m s ), G 5,B (h mul ,m s The specific numerical fitting process of ) is as follows: (1) Calculate the magnetization response of magnetic nanoparticles under complex excitation magnetic fields according to the Fokker-Plank equation; (2) Obtain the fifth-order magnetic susceptibility phase information of the particle based on the magnetization response of the particle; (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, and repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model; (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model; (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

3. The temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device according to claim 1, characterized in that: The phase of the three-phase AC magnetic susceptibility is M3, Respectively represent the harmonic amplitude and phase of the magnetization response signal M(t) at the frequency f3; H3, They represent the cube of the complex excitation magnetic field H(t) 3 (t) Harmonic amplitude and phase at frequency f3.

4. The temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device according to claim 1, characterized in that: The phase of the quintic AC magnetic susceptibility is M5, Respectively represent the harmonic amplitude and phase of M(t) at frequency f5; H5, They represent the fifth power of H(t) 5 (t) Harmonic amplitude and phase at frequency f5.

5. A temperature measurement method under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device according to any one of claims 1 to 4, characterized in that: Step S4 specifically involves obtaining the best estimated value of the temperature through a particle swarm algorithm.

6. A temperature measurement device under a complex excitation magnetic field of a two-dimensional magnetic nanoparticle imaging device, characterized in that: include: A magnetization response signal measurement module is used to detect the magnetization response signal of the magnetic nanoparticles to be tested placed in the sample chamber of the two-dimensional MPI imaging device under the application of a complex excitation magnetic field; the complex excitation magnetic field refers to a magnetic field of non-single type; Hybrid AC magnetization phase calculation module, used to calculate the cubic AC magnetic susceptibility phase and quintic AC magnetic susceptibility phase of magnetic nanoparticles; The simulation module is used to simulate the magnetization response of particles under complex excitation magnetic fields, establish a compensation function related to field strength and saturation magnetization, and establish the relationship between the cubic AC magnetic susceptibility phase and the quintic AC magnetic susceptibility phase and temperature in parallel to construct a temperature measurement model. The temperature calculation module is used to substitute the cubic AC magnetic susceptibility phase and the quintic AC magnetic susceptibility phase obtained by the hybrid AC magnetic phase calculation module into the temperature measurement model to calculate the temperature. When the particles exhibit Neel relaxation, the temperature measurement model is: K is the anisotropy constant, V m is the particle core volume, k B is the Boltzmann constant, T is the temperature, G 3,N (h mul ,m s ), G 5,N (h mul ,m s ) is the compensation function, m s is the saturation magnetization of the particle, h mul is the field intensity ratio of the multi-alternating excitation magnetic field in the complex excitation magnetic field, τ0 is the diffusion relaxation time; θ3 is the phase of the third-order alternating magnetic susceptibility, θ5 is the phase of the fifth-order alternating magnetic susceptibility; f3 and f5 are the third-order mixing frequency and the fifth-order mixing frequency, respectively; When the particles exhibit Brownian relaxation, the constructed temperature measurement model is: η is the viscosity of the particle carrier liquid, V h is the hydrodynamic volume of the particle, G 3,B (h mul ,m s ), G 5,B (h mul ,m s ) is the compensation function; m s is the saturation magnetization of the particle, h mul is the field strength ratio of the multiple alternating excitation magnetic fields in the complex excitation magnetic field, T is the temperature, k B is the Boltzmann constant; θ3 is the cubic AC magnetic susceptibility phase, θ5 is the quintic AC magnetic susceptibility phase; f3 and f5 are the cubic mixing frequency and the quintic mixing frequency, respectively; Compensation function G 3,N (h mul ,m s ), G 3,B (h mul ,m s The specific numerical fitting process of ) is as follows: (1) Calculate the magnetization response of magnetic nanoparticles under complex excitation magnetic fields according to the Fokker-Plank equation; (2) Obtaining the tertiary magnetic susceptibility phase information of the particle based on the magnetization response of the particle; (3) changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field without changing the saturation magnetization intensity of the particles, repeating steps (1) and (2) to obtain the corresponding compensation term value; (4) changing the particle saturation magnetization intensity corresponding to different temperatures, but not changing the field intensity ratio of the multiple alternating magnetic fields in the complex excitation magnetic field, repeating steps (1) and (2) to obtain the corresponding compensation term value in the constructed model; (5) Fitting the obtained multiple discrete compensation item values ​​to obtain a compensation item fitting function.

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