Magnetic particle imaging method and device based on magnetotactic bacterial magnetosomes

Abstract

The present invention relates to the field of biomedical imaging technology, and discloses a magnetic particle imaging method and device based on magnetotactic bacterial magnetosomes. The method comprises: obtaining target magnetosomes; wherein the target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement; generating an excitation field, a first target focusing field, and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetosomes, the frequencies of the first target focusing field and the second target focusing field are both lower than the frequency of the excitation field, and the excitation field is a low-frequency, high-amplitude sinusoidally varying magnetic field; under the action of the excitation field, the first target focusing field, and the second target focusing field, the signal of the target magnetosome is collected; wherein the signal of the target magnetosome is a signal with avalanche magnetic characteristics; the signal of the target magnetosome is reconstructed to obtain a reconstructed image corresponding to the target magnetosome. The present invention can improve the resolution of imaging.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical imaging, and in particular to a magnetic particle imaging method and device based on magnetotactic bacterial magnetosomes. Background Art

[0002] Magnetic particle imaging can quantitatively image the concentration and distribution of magnetic particles and has been widely used in scenarios such as vascular imaging, cell tracking, and tumor labeling.

[0003] At present, the tracers used in magnetic particle imaging are usually superparamagnetic nanoparticles. These particles will undergo a magnetization response under the action of a magnetic field, generating specific signals. These signals are then detected by the receiving coils of the imaging system. Next, the spatial distribution of the magnetic particles in the imaging area is determined by processing and analyzing the received signals. Using image reconstruction algorithms, images are reconstructed based on the detected magnetic particle signals.

[0004] However, due to the relatively gentle magnetization response of superparamagnetic nanoparticles, the point spread function during imaging is often wide, which ultimately leads to poor imaging resolution. Summary of the invention

[0005] In view of this, the present invention provides a magnetic particle imaging method and device based on magnetotactic bacterial magnetosomes to solve the technical problem that the tracer magnetization response of magnetic particle imaging is slow, resulting in a wide point spread function of imaging, thereby affecting the resolution of imaging.

[0006] In the first aspect, the present invention provides a magnetic particle imaging method based on magnetotactic bacterial magnetosomes, and the method is applied to an imaging system; wherein the method includes: obtaining target magnetosomes; wherein the target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement; generating an excitation field, a first target focusing field and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetosomes, and the frequencies of the first target focusing field and the second target focusing field are both lower than the frequencies of the excitation field; under the action of the excitation field, the first target focusing field and the second target focusing field, collecting signals of the target magnetosomes; wherein the signals of the target magnetosomes are signals with avalanche magnetization characteristics; and reconstructing the signals of the target magnetosomes to obtain reconstructed images corresponding to the target magnetosomes.

[0007] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment enables the target magnetosomes to generate an avalanche-like magnetization response signal during the imaging process through an excitation field, a first target focusing field and a second target focusing field, that is, a high-amplitude and low-frequency excitation field, and a focusing field with a lower frequency than the excitation field. The high amplitude of the excitation field ensures that the magnetic field amplitude is higher than the coercive force of the target magnetosomes, and the low frequency ensures that the magnetosomes can keep up with the response speed of the changes in the external magnetic field, thereby achieving more accurate positioning and signal extraction of target magnetosomes at different depths or positions, thereby improving the imaging resolution.

[0008] In addition, by reconstructing the original signal of the target magnetosome, the magnetic properties of the magnetosome and the performance advantages of the imaging system can be fully utilized to achieve a more accurate and clear imaging effect, and then obtain a high-resolution reconstructed image.

[0009] In addition, the target magnetosome has an avalanche response characteristic. The response of the magnetosome does not depend on the interaction between particles, but a single magnetosome itself has this characteristic. Even without the influence of other magnetosomes, a single magnetosome can produce an avalanche magnetization change when the external magnetic field reaches a certain intensity, so that the magnetosome can respond quickly when the magnetic field changes.

[0010] In an optional embodiment, the signal of the target magnetosome is reconstructed to obtain a reconstructed image corresponding to the target magnetosome, including: segmenting the signal of the target magnetosome to obtain multiple segments of first target signals, and averaging the multiple segments of the first target signals to obtain a second target signal; wherein the length of each segment of the first target signal is the least common multiple of the excitation period, the first target focusing field period and the second target focusing field period; obtaining a frequency response function of a link in the imaging system, and processing the frequency response function to obtain an inverse function corresponding to the frequency response function; based on the inverse function and the second target signal, determining a third target signal; wherein the third target signal is used to characterize a signal for time domain correction; determining the excitation magnetosome in the imaging system The derivative of the field with respect to time is obtained based on each point of the third target signal, and the first target point is obtained by dividing each point by the derivative; wherein the time point of each point of the third target signal corresponds to the time point of the derivative of the excitation magnetic field with respect to time; based on each first target point, a first target intermediate value that meets the preset conditions is determined; wherein the first target intermediate value is used to characterize the signal intensity of the target magnetosome of each first target point; the first amplitude corresponding to the first target focusing field and the second amplitude corresponding to the second target focusing field are gridded to obtain a grid; the first target intermediate value is filled into the grid according to the corresponding amplitude, so that the first target intermediate value is converted into image information with spatial distribution; based on the image information, a reconstructed image corresponding to the target magnetosome is constructed.

[0011] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment can effectively reduce random noise and interference by segmenting and averaging the signals of the target magnetosomes, so that the obtained second target signal is more stable and the signal quality is improved. The second target signal is corrected by using the inverse function of the frequency response function to ensure the accuracy of the signal in the time domain, making subsequent signal processing and analysis more accurate. Then, by determining the first target intermediate value that meets the preset conditions, the signal intensity of the target magnetosome at each first target point can be accurately reflected. Then, the first target intermediate value is filled into the grid according to the corresponding amplitude to obtain image information with spatial distribution, which can intuitively show the position and intensity distribution of the target magnetosome in the imaging field of view.

[0012] In an optional embodiment, before filling the first target intermediate value into the grid according to the corresponding amplitude to convert the first target intermediate value into image information with spatial distribution, the method also includes: obtaining the coercive force corresponding to the target magnetic body; dividing the intermediate value into a first group of intermediate values ​​and a second group of intermediate values ​​according to the positive and negative derivatives of the excitation magnetic field amplitude at the corresponding time point; wherein the first group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to the positive values ​​of the derivative of the excitation magnetic field amplitude, and the second group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to the negative values ​​of the derivative of the excitation magnetic field amplitude; subtracting the horizontal coordinate of the coercive force from each intermediate value in the first group of intermediate values ​​to obtain the first intermediate value; adding the horizontal coordinate of the coercive force to each intermediate value in the first group of intermediate values ​​to obtain the second intermediate value; and obtaining the first target intermediate value based on the first intermediate value and the second intermediate value.

[0013] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment divides the intermediate values ​​into two groups according to the positive and negative derivatives of the excitation magnetic field amplitude, and processes the signals under different magnetization directions respectively to eliminate or reduce the signal interference or error caused by different magnetization directions, thereby improving the reliability and stability of the signal. By adding and subtracting the coercive force horizontal coordinate operation to the first group of intermediate values, a more accurate first target intermediate value can be obtained, so that when the first target intermediate value is subsequently filled into the grid and converted into image information with spatial distribution, it can more accurately reflect the position and intensity distribution of the target magnetosome.

[0014] In an optional embodiment, the period corresponding to the frequency of the excitation field is greater than the relaxation time of the target magnetic body, and the amplitude of the excitation field is greater than the coercive force of the target magnetic body.

[0015] In the magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment, when the period of the excitation field frequency is greater than the relaxation time of the target magnetosome, the magnetosome has enough time to fully respond and reach a new magnetization state after each excitation, thereby ensuring that the magnetosome always maintains stability and high sensitivity during the measurement or application process. Secondly, the amplitude of the excitation field is greater than the coercive force of the target magnetosome, which means that the internal resistance of the magnetosome can be easily overcome, so that its magnetization direction quickly and completely follows the changes in the excitation field, achieving a fast and efficient magnetization process, and improving the response speed and performance of the magnetosome in related applications.

[0016] In an optional embodiment, the signal of the target magnetosome is reconstructed to obtain a reconstructed image corresponding to the target magnetosome, including: obtaining a point-like magnetosome mimetic; wherein the point-like magnetosome mimetic is the same as the target magnetosome; based on the first target focusing field and the second target focusing field, traversing the imaging field of view, and collecting a fourth target signal corresponding to the point-like magnetosome mimetic at each position; performing Fourier transform on the fourth target signal to obtain a frequency domain signal corresponding to each position; based on the frequency domain signal, determining a target frequency signal; wherein the target frequency signal is a signal in the frequency domain signal that satisfies an integer multiple of the frequency of the excitation magnetic field; arranging the target frequency signals at each position into a system matrix; and obtaining a reconstructed image based on the system matrix and the frequency domain signal.

[0017] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment can fully obtain the response characteristics of the imaging system to the point-like magnetosomes at different positions by traversing the imaging field of view and collecting the fourth target signal corresponding to the point-like magnetosomes at various positions. The time domain signal is converted into a frequency domain signal by Fourier transform, and the target frequency signal (i.e., a signal that satisfies the integer multiple of the excitation magnetic field frequency) is determined, and unnecessary noise and interference components can be removed. Then, the frequency domain signal is processed using the system matrix, and a reconstructed image can be obtained quickly and effectively. And because the point-like magnetosomes are the same as the target magnetosomes, the system matrix constructed by the point-like magnetosomes can reflect the response characteristics of the imaging system to the target magnetosomes, so that the reconstructed image corresponding to the target magnetosomes can be obtained effectively and quickly.

[0018] In an optional embodiment, the target magnetosome is obtained by the following method: the magnetosome is ultrasonically treated by an ultrasonic module to obtain a first magnetosome; wherein the first magnetosome is used to characterize the easy-axis arrangement dispersion of the magnetosome, and the magnetosome is a single-domain magnetic nanoparticle having a complete lipid bilayer structure and composed of ferroferric oxide crystals; under the action of the uniform magnetic field of the magnetization module, the first magnetosome is magnetized to obtain the target magnetosome.

[0019] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment effectively changes the arrangement and dispersion state of the magnetosomes through ultrasonic treatment, so that the magnetosomes that were originally aggregated or orderly arranged become more dispersed and random, thereby enhancing the overall magnetic response performance of the magnetosomes, and then improving their flexibility and application effect in the external magnetic field. Then, under the action of the uniform magnetic field of the magnetization module, the first magnetosome can be accurately magnetized to obtain a target magnetosome with a specific magnetization direction and target magnetization intensity, thereby improving the magnetic properties of the magnetosome. In addition, the lipid bilayer structure can ensure the dispersibility of the magnetosomes and the appropriate inter-particle force.

[0020] In an optional embodiment, magnetosomes are obtained by: culturing a magnetotactic bacterial strain by a culture device; wherein the magnetotactic bacterial strain is used to synthesize magnetosomes; if the optical density of the bacterial liquid in the magnetotactic bacterial strain at a wavelength of 565 nanometers and the value of the characteristic parameter of the magnetotactic bacterial strain are both between 0.8 and 1.0, the target magnetotactic bacterial strain is lysed by a lysis device to obtain magnetosomes.

[0021] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment is a method in which the optical density of the bacterial solution in the magnetotactic bacterial strain at a wavelength of 565 nanometers and the value of the characteristic parameters of the magnetotactic bacterial strain are both between 0.8 and 1.0, and the target magnetotactic bacterial strain is lysed by a lysis device to obtain magnetosomes. This method can effectively control the growth of the magnetotactic bacterial strain and the synthesis of magnetosomes, thereby obtaining magnetosomes with a lipid bilayer structure.

[0022] In an optional embodiment, under the action of the first target focusing field and the second target focusing field, the signal of the target magnetic body is collected, including: based on a preset excitation signal, turning on the excitation coil and receiving the electromagnetic signal from the receiving coil; adjusting the fundamental frequency feedthrough in the electromagnetic signal by a feedthrough compensation device until the fundamental frequency feedthrough in the electromagnetic signal reaches a minimum value, and executing the step of collecting the signal of the target magnetic body under the action of the first target focusing field and the second target focusing field.

[0023] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment can effectively adjust the fundamental frequency feedthrough in the electromagnetic signal until it reaches the minimum value through the feedthrough compensation device. When the fundamental frequency feedthrough reaches the minimum value, the signal of the target magnetosome is collected. On the one hand, the interference of the fundamental frequency feedthrough on signal collection is reduced, thereby improving the purity and accuracy of the signal, and on the other hand, it ensures that the collected signal is more accurate.

[0024] In the second aspect, the present invention provides a magnetic particle imaging system based on magnetotactic bacterial magnetosomes, the device comprising: a target magnetosome acquisition module, used to acquire target magnetosomes; wherein the target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement; a generation module, used to generate a first target focusing field and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetosomes, and the frequency of the first target focusing field is lower than the frequency of the second target focusing field; a signal receiving module, used to collect signals of the target magnetosomes under the action of the first target focusing field and the second target focusing field; wherein the signals of the target magnetosomes are signals with avalanche-like magnetic properties; an image reconstruction module, used to reconstruct the signals of the target magnetosomes to obtain a reconstructed image corresponding to the target magnetosomes.

[0025] In a third aspect, the present invention provides a computer device, comprising: a memory and a processor, the memory and the processor being communicatively connected to each other, the memory storing computer instructions, and the processor executing the magnetic particle imaging method based on magnetotactic bacterial magnetosomes of the above-mentioned first aspect or any corresponding embodiment thereof by executing the computer instructions.

[0026] In a fourth aspect, the present invention provides a computer-readable storage medium having computer instructions stored thereon, the computer instructions being used to enable a computer to execute the magnetic particle imaging method based on magnetotactic bacterial magnetosomes of the above-mentioned first aspect or any corresponding embodiment thereof.

[0027] In a fifth aspect, the present invention provides a computer program product, comprising computer instructions for causing a computer to execute the magnetic particle imaging method based on magnetotactic bacterial magnetosomes of the first aspect or any corresponding embodiment thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0029] Figure 1 is a structural schematic diagram of an imaging system according to an embodiment of the present invention;

[0030] Figure 2 is another structural schematic diagram of an imaging system according to an embodiment of the present invention;

[0031] Figure 3 1 is a schematic flow chart of a magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to an embodiment of the present invention;

[0032] Figure 4 is a schematic diagram of avalanche response of a magnetosome according to an embodiment of the present invention;

[0033] Figure 5 Schematic diagram of the relationship between the FWHM of the magnetosomes, the bacterial solution concentration, and the signal intensity according to an embodiment of the present invention.

[0034] Figure 6 is a schematic flow chart of another magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to an embodiment of the present invention;

[0035] Figure 7 is a schematic diagram of the relationship between the FWHM of the magnetic body and the excitation field amplitude according to an embodiment of the present invention;

[0036] Figure 8 is a schematic diagram of the relationship between the FWHM of the magnetic body and the excitation field frequency according to an embodiment of the present invention;

[0037] Fig. 9 is a schematic flow chart of another magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to an embodiment of the present invention;

[0038] Fig.10 is a schematic diagram of a magnetic body according to an embodiment of the present invention;

[0039] Fig.11 is a structural block diagram of a magnetic particle imaging device based on magnetotactic bacterial magnetosomes according to an embodiment of the present invention;

[0040] Fig.12 It is a schematic diagram of the hardware structure of a computer device according to an embodiment of the present invention. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0042] Based on relevant technologies, magnetic particle imaging can quantitatively image the concentration and distribution of magnetic particles, and has been widely used in scenarios such as vascular imaging, cell tracking, and tumor labeling.

[0043] At present, the tracers used in magnetic particle imaging are usually superparamagnetic nanoparticles. These particles will undergo a magnetization response under the action of a magnetic field, generating specific signals. These signals are then detected by the receiving coils of the imaging system. Next, the spatial distribution of the magnetic particles in the imaging area is determined by processing and analyzing the received signals. Using image reconstruction algorithms, images are reconstructed based on the detected magnetic particle signals.

[0044] However, due to the relatively gentle magnetization response of superparamagnetic nanoparticles, the point spread function during imaging is often wide, which ultimately leads to poor imaging resolution.

[0045] Based on this, the present invention provides a magnetic particle imaging method and device based on magnetotactic bacterial magnetosomes, through the excitation field, the first target focusing field and the second target focusing field, that is, through the high-amplitude and low-frequency excitation field, and the focusing field with a lower frequency relative to the excitation field, the target magnetosome can generate an avalanche-like magnetization response signal during the imaging process, the high amplitude of the excitation field ensures that the magnetic field amplitude is higher than the coercive force of the target magnetosome, and the low frequency ensures that the magnetosome can keep up with the response speed of the external magnetic field change, thereby achieving more accurate positioning and signal extraction of target magnetosomes at different depths or positions, thereby improving the imaging resolution. In addition, by reconstructing the original signal of the target magnetosome, the magnetic properties of the magnetosome and the performance advantages of the imaging system can be fully utilized, thereby achieving a more accurate and clear imaging effect, and then obtaining a high-resolution reconstructed image. In addition, the target magnetosome has an avalanche response characteristic. Among them, the response of the magnetosome does not depend on the interaction between particles, but the single magnetosome itself has this characteristic. Even without the influence of other magnetosomes, a single magnetosome can produce an avalanche-like magnetization change when the external magnetic field reaches a certain intensity, enabling the magnetosome to respond quickly to changes in the magnetic field.

[0046] Figure 1 A structural schematic diagram of an imaging system is shown. The imaging system includes: an initial magnetic state adjustment device, a focusing field module, an excitation field module, a generation module, a control device, a power supply device, a signal receiving module, an image reconstruction module and a target magnetosome acquisition module.

[0047] The initial magnetic state adjustment device is used to generate a uniform magnetic field. The initial magnetic state adjustment device can be generated by a pair of permanent magnets placed in the same direction, and the amplitude of the magnetic field generated by the pair of permanent magnets is adjusted by relative distance, or it can be generated by an electromagnetic coil, and the amplitude of the magnetic field is adjusted by the magnitude of the DC current passed. The composition of the specific initial magnetic state adjustment module is not specifically limited here, and can be implemented by those skilled in the art.

[0048] Preferably, combined Figure 2As shown, the first permanent magnet 11 and the second permanent magnet 12 constitute an initial magnetic state adjustment device for generating a uniform magnetic field, which generates a uniform 50-90 mT magnetic field for adjusting the initial magnetic state of the magnetic body.

[0049] Preferably, the first permanent magnet 1 and the second permanent magnet 2 constitute permanent magnets that generate a gradient magnetic field. The two permanent magnets are placed opposite to each other to generate a magnetic field-free region in the center of the entire system with a main magnetic field gradient of 2.5 T / m. Within this region, the magnetic bodies will respond to the excitation field generated by the excitation coil. Outside the region, the magnetic bodies are saturated and do not generate any response signals.

[0050] The excitation field module is used to generate a low-frequency and high-amplitude excitation field. The excitation field module can be a solenoid or Helmholtz electromagnetic coil, etc., which is not specifically limited here.

[0051] Preferably, combined Figure 2 As shown, solenoid 7 is an excitation coil, and its function is to generate a low-frequency and high-amplitude excitation field of 1kHz and 30mT; solenoid 8 is a receiving coil, and its function is to receive the response signal generated by the magnetic body; solenoid 9 is an external receiving coil of the external compensation device, which is connected in series with the receiving coil in reverse, and its function is to compensate for the feed-through signal generated by the excitation coil in the receiving coil; solenoid 10 is an external excitation coil of the external compensation device, which is connected in series with the excitation coil, and its function is to generate the same gradient magnetic field as the excitation coil in the external receiving coil.

[0052] The focusing field module uses two pairs of Helmholtz coils to generate focusing fields in two perpendicular directions in space.

[0053] Preferably, combined Figure 2 As shown, the first Helmholtz coil 3 and the second Helmholtz coil 4 constitute a first focusing field coil for generating a first target focusing field, whose magnetic field strength is 22 mT and whose frequency is 10 Hz, and whose function is to cause the non-magnetic field area to be displaced in the horizontal non-excitation direction, and whose magnetic field amplitude is used for spatial positioning; the first Helmholtz coil 5 and the second Helmholtz coil 6 constitute a second focusing field coil for generating a first target focusing field, whose magnetic field amplitude is 45 mT and whose frequency is 1 Hz, and whose function is to cause the non-magnetic field area to be displaced in the vertical direction, and whose magnetic field amplitude is used for spatial positioning.

[0054] The control module is used to adjust the switch, amplitude and frequency of the above-mentioned excitation field and focusing field. The power supply module is used to supply power to the excitation field module and the focusing field module; the signal receiving module includes a receiving coil and a feedthrough compensation device, and the receiving coil is used to receive the signal of the target magnetic body; the feedthrough compensation device includes an external excitation and an external compensation coil, the external excitation coil and the solenoid of the excitation field module are connected in series, and the external compensation coil and the receiving coil are connected in series to offset the feedthrough signal generated by the excitation field, and the external excitation and external compensation coils can fine-tune the relative position through a mechanical device to adjust the feedthrough signal to the minimum; the image reconstruction module reconstructs the signal of the target magnetic body to obtain a reconstructed image.

[0055] In this embodiment, a magnetic particle imaging method based on magnetotactic bacterial magnetosomes is provided, which can be used in the above-mentioned imaging system. Figure 3 FIG. 1 is a flow chart of a magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to an embodiment of the present invention. Figure 3 As shown, the process includes the following steps:

[0056] Step S101, obtaining target magnetosomes; wherein the target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement.

[0057] The target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement. Specifically, the imaging system can obtain the target magnetosomes by placing the sample containing the magnetosomes at an appropriate position of the imaging system through a grabbing module in the imaging system, or by manually placing the sample containing the magnetosomes into the imaging system, etc. The specific method of placing the target magnetosomes is not specifically limited here, and can be implemented by those skilled in the art.

[0058] The target magnetosomes can be obtained by using an external strong magnetic field to align the magnetosomes, or by changing the surface properties of the magnetosomes by chemical methods to make them easy to align under an external magnetic field. The microchannels and flow fields in the microfluidic chip can also be used to accurately manipulate and arrange the magnetosomes. No specific limitations are made here and can be implemented by technical personnel in this field.

[0059] It should be noted that the target magnetosome has an avalanche response characteristic. The response of the magnetosome does not depend on the interaction between particles, but the single magnetosome itself has this characteristic. Even without the influence of other magnetosomes, a single magnetosome can produce an avalanche magnetization change when the external magnetic field reaches a certain intensity. Figure 4 As shown, Figure 4The middle curve is the hysteresis loop. Its ordinate is the degree of magnetization (Normalized Magnetization M), and its abscissa is the magnetic field intensity. The hysteresis loop of the magnetosome has a very steep rise at 20mT on the horizontal axis, where an avalanche response occurs.

[0060] Combination Figure 5 As shown, Figure 5 In the coordinate system of Concentration VS Signal ampulitude, the horizontal axis is the concentration of the bacterial solution (Signal ampulitude), and the vertical axis is the signal strength (Signal ampulitude). In the coordinate system of Concentration VS FWHM, the horizontal axis is the concentration of the bacterial solution (Signal ampulitude), and the vertical axis is a parameter for evaluating resolution (FWHM). Figure 5 It can be seen that the FWHM of magnetosomes is stable at different concentrations, and the signal intensity is linear, which proves that the properties of magnetosomes do not change with concentration, while the interaction is strongly related to the concentration, thus proving that magnetosomes do not rely on interaction. A parameter for evaluating resolution (Full Width at Half Maximum, FWHM) specifically refers to the width measured at half the maximum intensity of the signal or peak. Among them, the smaller the FWHM, the better, and the higher the signal intensity, the better.

[0061] Step S102, generating an excitation field, a first target focusing field and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetic body; and the frequencies of the first target focusing field and the second target focusing field are both lower than the frequencies of the excitation field.

[0062] The excitation field is a high-amplitude, low-frequency sinusoidal magnetic field. The high amplitude ensures that the magnetic field has strong energy to overcome the coercive force of the magnetic body and change its magnetization direction quickly. The low frequency ensures that the target magnetic body has enough time to fully respond and reach a new magnetization state, reducing the hysteresis effect and improving the measurement accuracy.

[0063] The first target focusing field and the second target focusing field can be a focusing field generated by a focusing field coil of the imaging system. Specifically, according to the parameter requirements of the focusing field, a magnetic field generating device capable of generating the required frequency and amplitude is selected or designed. Specifically, it can include an electromagnetic coil, a permanent magnet, etc.

[0064] Preferably, the first target focusing field and the second target focusing field are both low-frequency focusing fields. The first target focusing field can be generated by the first Helmholtz coil and the second Helmholtz coil, and the magnetic field strength is 22mT, the frequency is 10Hz, etc. The second target focusing field can be generated by the third Helmholtz coil and the fourth Helmholtz coil, and the magnetic field amplitude is 45mT, the frequency is 1Hz, etc., which is not specifically limited here and can be implemented by those skilled in the art.

[0065] Step S103, under the action of the excitation field, the first target focusing field and the second target focusing field, the signal of the target magnetosome is collected; wherein the signal of the target magnetosome is a signal with avalanche magnetic characteristics.

[0066] The signal of avalanche magnetic characteristics usually manifests as a sharp and significant change in magnetic response. The signal characteristics of avalanche magnetic characteristics are similar to the effect of an avalanche, that is, under certain conditions, the magnetic response will increase or decrease rapidly and significantly.

[0067] Specifically, when the external magnetic field or excitation reaches a certain threshold, materials or systems with avalanche magnetic properties will suddenly show a strong magnetic response. This response may manifest as a sharp increase in magnetization intensity, a rapid change in magnetic domain structure, or other forms of sudden changes in magnetic properties.

[0068] The state of the target magnetosome is a detectable state, and then the target magnetosome is selectively excited to generate a detectable signal. The signal of the target magnetosome is a signal with magnetic properties. A magnetic sensor or similar device is used to collect the signal of the target magnetosome under the action of the focusing field.

[0069] Optionally, the signal of magnetic characteristics may be a magnetic induction signal, a magnetization intensity signal, a magnetic resonance signal, a gradient field signal, etc., which is not specifically limited here and may be implemented by those skilled in the art.

[0070] Step S104, reconstructing the signal of the target magnetosome to obtain a reconstructed image corresponding to the target magnetosome.

[0071] After determining the signal of the target magnetosome, the signal of the target magnetosome can be reconstructed. Specifically, the signal of the target magnetosome can be reconstructed using an x-space algorithm, or the signal of the target magnetosome can be reconstructed using a system matrix reconstruction method, etc., which is not specifically limited here and can be implemented by those skilled in the art.

[0072] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment enables the target magnetosomes to generate an avalanche-like magnetization response signal during the imaging process through an excitation field, a first target focusing field and a second target focusing field, that is, a high-amplitude and low-frequency excitation field, and a focusing field with a lower frequency than the excitation field. The high amplitude of the excitation field ensures that the magnetic field amplitude is higher than the coercive force of the target magnetosomes, and the low frequency ensures that the magnetosomes can keep up with the response speed of the changes in the external magnetic field, thereby achieving more accurate positioning and signal extraction of target magnetosomes at different depths or positions, thereby improving the imaging resolution.

[0073] In addition, by reconstructing the original signal of the target magnetosome, the magnetic properties of the magnetosome and the performance advantages of the imaging system can be fully utilized to achieve a more accurate and clear imaging effect, and then obtain a high-resolution reconstructed image.

[0074] In addition, the target magnetosome has an avalanche response characteristic. The response of the magnetosome does not depend on the interaction between particles, but a single magnetosome itself has this characteristic. Even without the influence of other magnetosomes, a single magnetosome can produce an avalanche magnetization change when the external magnetic field reaches a certain intensity, so that the magnetosome can respond quickly when the magnetic field changes.

[0075] like Figure 6 As shown, in an optional embodiment, the signal of the target magnetosome is reconstructed in the above step S104 to obtain a reconstructed image corresponding to the target magnetosome, including:

[0076] Step S1041, segmenting the signal of the target magnetic body to obtain multiple segments of first target signals, and averaging the multiple segments of the first target signals to obtain the second target signal; wherein the length of each segment of the first target signal is the least common multiple of the excitation period, the first target focusing field period and the second target focusing field period.

[0077] The least common multiple of the excitation period, the first target focusing field period, and the second target focusing field period is used as the length of each segment of the first target signal. Then, according to the determined segment length, the signal of the target magnetosome is segmented. This can be implemented by programming, such as using the array slicing function in Python, etc., which is not specifically limited here. Then, all the extracted first target signals are averaged. This can be implemented by statistical methods, etc., which is not specifically limited here. The signal after average processing is the second target signal.

[0078] Preferably, if the signal of the target magnetosome has a last segment whose length is shorter than other segments, it is discarded, and then these segments are added and divided by the number of segments to obtain a second target signal.

[0079] Step S1042: acquiring a frequency response function of a link in the imaging system, and processing the frequency response function to obtain an inverse function corresponding to the frequency response function.

[0080] In an imaging system, the frequency response function of the link of the imaging system describes the response characteristics of the imaging system to signals of different frequencies. Specifically, without inserting a magnetic body, the imaging system first collects the common frequency response function of the receiving-compensation coil, filter, amplifier, and acquisition card in the receiving link by frequency scanning. Among them, the frequency response function of the link can be constructed by performing a frequency scan on the link of the imaging system through a network analyzer or other measuring equipment, measuring the response of the imaging system at different frequencies.

[0081] The inverse function of the frequency response function is the function required by the imaging system to perform an inverse transformation on the output signal to obtain the signal of the target magnetosome. Specifically, the inverse function of the frequency response function can be calculated by a mathematical algorithm, etc., which is not specifically limited here.

[0082] Step S1043, determining a third target signal based on the inverse function and the second target signal; wherein the third target signal is used to characterize the signal to be corrected in the time domain.

[0083] The second target signal is input into the inverse function to obtain the third target signal. Specifically, the second target signal is converted from the frequency domain back to the time domain to eliminate the distortion or delay introduced by the imaging system link.

[0084] Step S1044, determine the derivative of the excitation magnetic field with respect to time in the imaging system, and divide each point of the third target signal by the derivative to obtain the first target point; wherein the time point of each point of the third target signal corresponds one-to-one to the time point of the derivative of the excitation magnetic field with respect to time.

[0085] Determine the waveform of the current or voltage of the excitation coil in the imaging system that changes with time. Specifically, it can be obtained by measuring the parameters preset by the device or system, etc., and is not specifically limited here. Perform a derivative operation on the current or voltage waveform of the excitation coil to obtain its derivative. The derivative can be used to characterize the rate of change of the current or voltage over time. Specifically, if the current or voltage waveform is a discrete data point, the differential method can be used to approximate the derivative; if the current or voltage waveform is continuous, the calculus method can be used to calculate the derivative, etc., which is not specifically limited here and can be implemented by those skilled in the art. Since the time points of each point of the third target signal correspond one-to-one to the time points of the excitation magnetic field with respect to the time derivative, by dividing each point of the third target signal by the excitation magnetic field with respect to the time derivative at the corresponding time point, that is, after point-by-point division, the new signal obtained is the first target point.

[0086] Step S1045, based on each first target point, determine a first target intermediate value that meets a preset condition; wherein the first target intermediate value is used to characterize the signal strength of the target magnetosome at each first target point.

[0087] The preset condition may be that the signal strength exceeds a threshold value. The threshold value may be X, Y, etc., which is not specifically limited here. Specifically, when determining each first target point, it is determined which points among the first target points have a signal strength exceeding the threshold value, and then the signal strength of the first target point exceeding the threshold value is used as the first target intermediate value.

[0088] Step S1046, gridding the first amplitude corresponding to the first target focusing field and the second amplitude corresponding to the second target focusing field to obtain a grid.

[0089] The first amplitude corresponding to the first target focusing field and the second amplitude of the second target focusing field are used as coordinate values ​​to divide the imaging field of view into grids.

[0090] Specifically, a suitable grid size is selected, wherein the grid size determines the size of each cell after division. Then, a grid is created within the range of the first amplitude and the second amplitude using the selected grid size.

[0091] Step S1047, filling the first target intermediate value into the grid according to the corresponding amplitude, so that the first target intermediate value is converted into image information with spatial distribution.

[0092] Each grid cell in the grid created in step S1046 corresponds to a specific amplitude range. The corresponding relationship between the first target intermediate value and the amplitude is determined, and each first target intermediate value is filled into the corresponding grid cell.

[0093] Preferably, if a magnitude range corresponds to multiple intermediate values ​​(eg, due to interpolation or averaging), an appropriate strategy (eg, maximum, minimum, average, etc.) is selected to determine the final value of the grid cell.

[0094] Step S1048: construct a reconstructed image corresponding to the target magnetosome based on the image information.

[0095] Specifically, a visual image can be rendered according to the image data created in step S1047 through image processing or visualization libraries (such as OpenCV, Matplotlib, etc.). Specifically, the image contrast, brightness, resolution and other parameters are adjusted as needed to more clearly display the spatial distribution of the target magnetosomes.

[0096] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment can effectively reduce random noise and interference by segmenting and averaging the signals of the target magnetosomes, so that the obtained second target signal is more stable and the signal quality is improved. The second target signal is corrected by using the inverse function of the frequency response function to ensure the accuracy of the signal in the time domain, making subsequent signal processing and analysis more accurate. Then, by determining the first target intermediate value that meets the preset conditions, the signal intensity of the target magnetosome at each first target point can be accurately reflected. Then, the first target intermediate value is filled into the grid according to the corresponding amplitude to obtain image information with spatial distribution, which can intuitively show the position and intensity distribution of the target magnetosome in the imaging field of view.

[0097] In order to reduce signal interference or error caused by different magnetization directions, in an optional implementation, before the above step S1047, the above method further includes:

[0098] Step a1, obtaining the coercive force corresponding to the target magnetic body.

[0099] Coercivity refers to the ability of a target magnetosome to maintain its own magnetism under the action of an external magnetic field. Specifically, the coercivity can be calculated by a cyclic method based on the magnetization characteristics of the target magnetosome, wherein the coercivity is calculated by the ratio of the magnetic field strengths when the external magnetic field is increased and decreased multiple times until the magnetic field finally disappears.

[0100] Preferably, combined Figure 7 as well as Figure 8 As shown, in the pre-magnetization of the magnetosome, the product of the pre-magnetization time and the pre-magnetization intensity is approximately about 800 (in seconds and mT, respectively), that is, 10s pre-magnetization in 80mT or 20s pre-magnetization in 40mT. The parameters of the magnetosome excitation can also be appropriately changed, and the limits of the change are: the excitation amplitude needs to be greater than the coercive force, and the excitation frequency should be as low as possible (1kHz); among them, the excitation amplitude is necessary, otherwise the high-resolution effect will completely disappear, and the excitation frequency is not necessary. When the frequency increases to a certain value (not exceeding 35kHz), the effect will be slightly reduced, but it will not disappear. Among them, the FWHM and the excitation field amplitude (Amplitude) of the magnetosome have a significant decrease at around 23mT, proving that the magnetic field amplitude needs to be greater than this value (i.e., coercive force); the relationship between the FWHM and the excitation field frequency (Frequency) of the magnetosome is that as the excitation field frequency increases, the effect of FWHM becomes worse and worse.

[0101] Step a2, divide the intermediate values ​​into a first group of intermediate values ​​and a second group of intermediate values ​​according to the positive or negative nature of the derivative of the excitation magnetic field amplitude at the corresponding time point; wherein the first group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to when the derivative of the excitation magnetic field amplitude is a positive value, and the second group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to when the derivative of the excitation magnetic field amplitude is a negative value.

[0102] The first group of intermediate values ​​is used to characterize that the derivative of the excitation magnetic field amplitude is a positive value, and the second group of intermediate values ​​is used to characterize that the derivative of the excitation magnetic field amplitude is a negative value. Specifically, all time points and corresponding intermediate values ​​are traversed. For each time point, the positive and negative nature of the derivative of the excitation magnetic field amplitude is checked. If the derivative is positive, the corresponding intermediate value is assigned to the first group of intermediate values; if the derivative is negative, the corresponding intermediate value is assigned to the second group of intermediate values.

[0103] Step a3, subtracting the abscissa of the coercive force from each intermediate value in the first group of intermediate values ​​to obtain a first intermediate value.

[0104] Step a4, adding the abscissa of the coercive force to each intermediate value in the first group of intermediate values ​​to obtain a second intermediate value.

[0105] The horizontal coordinate of the coercive force usually refers to the magnetic field intensity value corresponding to the coercive force on the hysteresis loop. Specifically, the horizontal coordinate values ​​of the coercive force are subtracted from the first set of intermediate values ​​(these intermediate values ​​correspond to the time points when the derivative of the excitation magnetic field amplitude is positive) to obtain a new set of intermediate values, namely the first intermediate values. The horizontal coordinate values ​​of the coercive force are subtracted from the second set of intermediate values ​​(these intermediate values ​​correspond to the time points when the derivative of the excitation magnetic field amplitude is negative) to obtain a new set of intermediate values, namely the second intermediate values.

[0106] Step a5, obtaining a first target intermediate value based on the first intermediate value and the second intermediate value.

[0107] The first intermediate value and the second intermediate value are combined, specifically, they may be formed into a set or averaged, etc. This may be determined by specific application scenarios and analysis requirements, and is not specifically limited here.

[0108] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment divides the intermediate values ​​into two groups according to the positive and negative derivatives of the excitation magnetic field amplitude, and processes the signals under different magnetization directions respectively to eliminate or reduce the signal interference or error caused by different magnetization directions, thereby improving the reliability and stability of the signal. By adding and subtracting the coercive force horizontal coordinate operation to the first group of intermediate values, a more accurate first target intermediate value can be obtained, so that when the first target intermediate value is subsequently filled into the grid and converted into image information with spatial distribution, it can more accurately reflect the position and intensity distribution of the target magnetosome.

[0109] like Fig. 9As shown, in an optional embodiment, the signal of the target magnetosome is reconstructed in the above step S104 to obtain a reconstructed image corresponding to the target magnetosome, including:

[0110] Step S2041, obtaining a dot-shaped magnetosome mimetic; wherein the dot-shaped magnetosome mimetic is identical to the target magnetosome.

[0111] The dot-shaped magnetosome mimic is used to simulate or replace the target magnetosome. Specifically, the physical and chemical properties of the dot-shaped magnetosome mimic are ensured to be as similar as possible to the target magnetosome, so that a signal similar to the target magnetosome can be generated in the subsequent imaging process.

[0112] Step S2042: based on the first target focusing field and the second target focusing field, traverse the imaging field of view and collect fourth target signals corresponding to each position of the point-shaped magnetic body phantom.

[0113] By changing the position of the magnetosome phantom, the signal generated by it is collected under different focusing fields. Specifically, the magnetosome phantom is moved within the imaging field of view using the first target focusing field and the second target focusing field, and the signal generated by it is collected at each position. Among them, the signal may include magnetic flux, magnetic induction intensity, etc., which is not specifically limited here and can be implemented by those skilled in the art.

[0114] Step S2043, performing Fourier transform on the fourth target signal to obtain frequency domain signals corresponding to each position; based on the frequency domain signal, determining the target frequency signal; wherein the target frequency signal is a signal in the frequency domain signal that satisfies an integer multiple of the frequency of the excitation magnetic field.

[0115] The collected time domain signal is converted into a frequency domain signal, and the target frequency signal related to the target excitation magnetic field frequency is identified. Specifically, the time domain signal is converted into a frequency domain signal through Fourier transform, so as to analyze and identify different frequency components. Signals that meet the integer multiple frequency of the excitation magnetic field frequency are screened out from the frequency domain signal, and these signals will be used for subsequent image reconstruction.

[0116] Step S2044, arranging the target frequency signals at each position into a system matrix.

[0117] Step S2045: obtaining a reconstructed image based on the system matrix and the frequency domain signal.

[0118] The selected target frequency signals are arranged into a system matrix according to their positions, which contains information about the position and signal strength of the magnetosome phantom. Then, based on the system matrix and the original frequency domain signal, a certain algorithm (such as inverse transformation, interpolation, etc.) is used to reconstruct the final image.

[0119] Preferably, the reconstructed image can be obtained by the formula S=SM×c; wherein SM is the system matrix, S is the frequency domain signal, c is the reconstructed image, and the solution method is the augmented Lagrangian method (Alternating Direction Method of Multipliers, ADMM) method or the randomized Kaczmarz method.

[0120] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment can fully obtain the response characteristics of the imaging system to the point-like magnetosomes at different positions by traversing the imaging field of view and collecting the fourth target signal corresponding to the point-like magnetosomes at various positions. The time domain signal is converted into a frequency domain signal by Fourier transform, and the target frequency signal (i.e., a signal that satisfies the integer multiple of the excitation magnetic field frequency) is determined, and unnecessary noise and interference components can be removed. Then, the frequency domain signal is processed using the system matrix, and a reconstructed image can be obtained quickly and effectively. And because the point-like magnetosomes are the same as the target magnetosomes, the system matrix constructed by the point-like magnetosomes can reflect the response characteristics of the imaging system to the target magnetosomes, so that the reconstructed image corresponding to the target magnetosomes can be obtained effectively and quickly.

[0121] In an optional embodiment, the period corresponding to the frequency of the excitation field is greater than the relaxation time of the target magnetic body, and the amplitude of the excitation field is greater than the coercive force of the target magnetic body.

[0122] The relaxation time is the time required for a magnetosome to transition from one magnetization state to another. If the period of the excitation field is too short, the magnetosome may not be able to keep up with its changes, resulting in incomplete or unstable magnetization. Therefore, ensuring that the excitation field period is greater than the relaxation time allows the magnetosome to reach the desired magnetization state after each excitation. Coercivity is the ability of a magnetosome to resist the change of its magnetization direction by an external magnetic field. Only when the amplitude of the excitation field exceeds this threshold will the magnetosome change its magnetization direction in response to the excitation field.

[0123] In the magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment, when the period of the excitation field frequency is greater than the relaxation time of the target magnetosome, the magnetosome has enough time to fully respond and reach a new magnetization state after each excitation, thereby ensuring that the magnetosome always maintains stability and high sensitivity during the measurement or application process. Secondly, the amplitude of the excitation field is greater than the coercive force of the target magnetosome, which means that the internal resistance of the magnetosome can be easily overcome, so that its magnetization direction quickly and completely follows the changes in the excitation field, achieving a fast and efficient magnetization process, and improving the response speed and performance of the magnetosome in related applications.

[0124] In an optional embodiment, the target magnetosomes are obtained by:

[0125] Step b1, ultrasonically treating the magnetosomes through an ultrasonic module to obtain first magnetosomes; wherein the first magnetosomes are used to characterize the easy axis arrangement dispersion of the magnetosomes, and the magnetosomes are single-domain magnetic nanoparticles with a complete lipid bilayer structure and ferroferric oxide crystals.

[0126] Magnetosomes are nanoparticles with special magnetic properties, which are composed of ferroferric oxide crystals and a complete lipid bilayer structure.

[0127] Ultrasonic treatment is a method that uses the energy of ultrasound to change the physical or chemical properties of a substance. Specifically, the ultrasound module is used to perform ultrasonic treatment on magnetosomes. Ultrasonic treatment may change certain properties of magnetosomes, such as size, shape, dispersion, etc.

[0128] The first magnetosome is used to characterize a magnetosome with dispersed easy axis arrangement. The easy axis is an important concept in magnetic materials, which represents the direction with the strongest magnetism. Specifically, the magnetosome is ultrasonically treated by the ultrasonic module, so that the easy axis arrangement of the magnetosome can be dispersed to form the first magnetosome.

[0129] Step b2: magnetizing the first magnetic body under the action of the uniform magnetic field of the magnetization module to obtain the target magnetic body.

[0130] Under the action of the uniform magnetic field of the magnetization module, the easy axes of the magnetosomes are aligned, so that different magnetosomes can produce consistent responses under the external magnetic field. Among them, "consistent response" is used to characterize that different magnetosomes will respond to exactly the same signal, and the signal will become very sharp at this time.

[0131] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment effectively changes the arrangement and dispersion state of the magnetosomes through ultrasonic treatment, so that the magnetosomes that were originally aggregated or orderly arranged become more dispersed and random, thereby enhancing the overall magnetic response performance of the magnetosomes, and then improving their flexibility and application effect in the external magnetic field. Then, under the action of the uniform magnetic field of the magnetization module, the first magnetosome can be accurately magnetized to obtain a target magnetosome with a specific magnetization direction and target magnetization intensity, thereby improving the magnetic properties of the magnetosome. In addition, the lipid bilayer structure can ensure the dispersibility of the magnetosomes and the appropriate inter-particle force.

[0132] In an optional embodiment, the magnetosomes are obtained by:

[0133] Step c1, culturing the magnetotactic bacterial strain using a culturing device; wherein the magnetotactic bacterial strain is used to synthesize magnetosomes.

[0134] Magnetotactic bacteria are a special type of bacteria that can synthesize magnetosomes in cells. These magnetosomes can move along the direction of the Earth's magnetic field. Specifically, magnetotactic bacterial strains are placed in a culture device to provide suitable growth conditions. Among them, the growth conditions may be specific temperatures, pH values, nutrients, and oxygen levels, etc., which are not specifically limited here. By optimizing these conditions, it can be ensured that the magnetotactic bacterial strains can regulate and change the particle size and morphology of the synthesized magnetosomes, etc., which are not specifically limited here and can be implemented by those skilled in the art.

[0135] Step c2: if the optical density of the bacterial solution in the magnetotactic bacterial strain at a wavelength of 565 nanometers and the value of the characteristic parameter of the magnetotactic bacterial strain are both between 0.8 and 1.0, the target magnetotactic bacterial strain is lysed by a lysis device to obtain magnetosomes.

[0136] After the cultivation process is completed, the growth status of the magnetotactic bacterial strain needs to be evaluated, including two key indicators: the optical density of the bacterial solution at a wavelength of 565 nanometers and the characteristic parameters of the magnetotactic bacterial strain.

[0137] Optical density is a method of measuring the concentration of a substance in a solution. By measuring the light absorption of the bacterial solution at a specific wavelength (here 565 nanometers), it can indirectly reflect the number and growth status of bacteria. Characteristic parameters can include the morphology, size, magnetism and other characteristics of bacteria. Fig.10 As shown, specifically, when the values ​​of these two indicators are within the range of 0.8 to 1.0, it means that the magnetotactic bacterial strain has synthesized enough magnetosomes. At this time, the target magnetotactic bacterial strain can be lysed by a lysis device. Lysis is used to characterize the destruction of bacterial cell walls and cell membranes by physical or chemical methods, thereby releasing magnetosomes in the cells.

[0138] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment is a method in which the optical density of the bacterial solution in the magnetotactic bacterial strain at a wavelength of 565 nanometers and the value of the characteristic parameters of the magnetotactic bacterial strain are both between 0.8 and 1.0, and the target magnetotactic bacterial strain is lysed by a lysis device to obtain magnetosomes. This method can effectively control the growth of the magnetotactic bacterial strain and the synthesis of magnetosomes, thereby obtaining magnetosomes with a lipid bilayer structure.

[0139] In an optional embodiment, in the above step S103, under the action of the first target focusing field and the second target focusing field, the signal of the target magnetosome is collected, including:

[0140] Step d1, based on a preset excitation signal, turning on the excitation coil and receiving an electromagnetic signal from the receiving coil.

[0141] The preset excitation signal is used to characterize an electrical signal with a specific frequency and amplitude, and is used to drive the excitation coil. The preset excitation signal can be M or N, etc., which is not specifically limited here. Specifically, when the excitation coil is turned on and the preset excitation signal is passed, the receiving coil will generate a corresponding electromagnetic signal. The electromagnetic signal includes the magnetic field information generated by the coil, as well as other possible interference signals.

[0142] Step d2, adjusting the fundamental frequency feedthrough in the electromagnetic signal by a feedthrough compensation device until the fundamental frequency feedthrough in the electromagnetic signal reaches a minimum value, and then executing the step of collecting the signal of the target magnetic body under the action of the first target focusing field and the second target focusing field.

[0143] The feedthrough compensation device is a device for adjusting or eliminating fundamental frequency feedthrough. The feedthrough compensation device reduces or eliminates interference by analyzing the fundamental frequency feedthrough component in the electromagnetic signal and applying a corresponding compensation algorithm or circuit. Among them, by adjusting the parameters or configuration of the feedthrough compensation device, the fundamental frequency feedthrough component in the electromagnetic signal can be gradually reduced until a minimum value is reached. When the fundamental frequency feedthrough reaches the minimum value, the step of collecting the signal of the target magnetic body under the action of the first target focusing field and the second target focusing field can be performed.

[0144] The magnetic particle imaging method based on magnetotactic bacterial magnetosomes provided in this embodiment can effectively adjust the fundamental frequency feedthrough in the electromagnetic signal until it reaches the minimum value through the feedthrough compensation device. When the fundamental frequency feedthrough reaches the minimum value, the signal of the target magnetosome is collected. On the one hand, the interference of the fundamental frequency feedthrough on signal collection is reduced, thereby improving the purity and accuracy of the signal, and on the other hand, it ensures that the collected signal is more accurate.

[0145] In this embodiment, a magnetic particle imaging device based on magnetotactic bacteria magnetosomes is also provided, which is used to implement the above embodiments and preferred embodiments, and the descriptions that have been made will not be repeated. As used below, the term "module" can be a combination of software and / or hardware that implements a predetermined function. Although the device described in the following embodiments is preferably implemented in software, the implementation of hardware, or a combination of software and hardware, is also possible and conceivable.

[0146] This embodiment provides a magnetic particle imaging device based on magnetotactic bacterial magnetosomes. Fig.11As shown, it includes: a target magnetosome acquisition module 1101, used to acquire the target magnetosome; wherein the target magnetosome is used to characterize the magnetosome with consistent easy axis arrangement; a generation module 1102, used to generate an excitation field, a first target focusing field and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetosome, and the frequencies of the first target focusing field and the second target focusing field are lower than the frequency of the excitation field; a signal receiving module 1103, used to collect the signal of the target magnetosome under the action of the excitation field, the first target focusing field and the second target focusing field; wherein the signal of the target magnetosome is a signal with avalanche magnetization characteristics; an image reconstruction module 1104, used to reconstruct the signal of the target magnetosome to obtain a reconstructed image corresponding to the target magnetosome.

[0147] In some optional embodiments, the image reconstruction module 1104 includes: a segmented averaging unit, which is used to segmentally process the signal of the target magnetosome to obtain multiple segments of the first target signal, and average the multiple segments of the first target signal to obtain the second target signal; wherein the length of each segment of the first target signal is the least common multiple of the excitation period, the first target focusing field period and the second target focusing field period; a first acquisition unit, which is used to acquire the frequency response function of the link in the imaging system, and process the frequency response function to obtain the inverse function corresponding to the frequency response function; a first determination unit, which is used to determine the third target signal based on the inverse function and the second target signal; wherein the third target signal is used to characterize the signal for time domain correction; a second determination unit, which is used to determine the derivative of the excitation magnetic field in the imaging system with respect to time. , and based on each point of the third target signal divided by the derivative, the first target point is obtained; wherein the time point of each point of the third target signal corresponds to the time point of the derivative of the excitation magnetic field with respect to time; a third determination unit is used to determine the first target intermediate value that meets the preset conditions based on each first target point; wherein the first target intermediate value is used to characterize the signal intensity of the target magnetosome of each first target point; a division unit is used to grid the first amplitude corresponding to the first target focusing field and the second amplitude corresponding to the second target focusing field to obtain a grid; a filling unit is used to fill the first target intermediate value into the grid according to the corresponding amplitude, so that the first target intermediate value is converted into image information with spatial distribution; a construction unit is used to construct a reconstructed image corresponding to the target magnetosome based on the image information.

[0148] In some optional embodiments, the above-mentioned device also includes: a coercive force acquisition module, used to obtain the coercive force corresponding to the target magnetic body; a division module, used to divide the intermediate values ​​into a first group of intermediate values ​​and a second group of intermediate values ​​according to the positive and negative derivatives of the excitation magnetic field amplitude at the corresponding time point; wherein the first group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to the positive values ​​of the derivative of the excitation magnetic field amplitude, and the second group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to the negative values ​​of the derivative of the excitation magnetic field amplitude; a first calculation module, used to subtract the horizontal coordinate of the coercive force from each intermediate value in the first group of intermediate values ​​to obtain a first intermediate value; a second calculation module, used to add the horizontal coordinate of the coercive force to each intermediate value in the first group of intermediate values ​​to obtain a second intermediate value; a third calculation module, used to obtain a first target intermediate value based on the first intermediate value and the second intermediate value.

[0149] In some optional embodiments, the period corresponding to the frequency of the first target focusing field and the period corresponding to the frequency of the second target focusing field are both smaller than the relaxation time of the target magnetosomes, and the amplitude of the first target focusing field and the amplitude of the second target focusing field are both larger than the coercive force of the target magnetosomes.

[0150] In some optional embodiments, the image reconstruction module 1104 includes: a second acquisition unit, used to acquire a point-like magnetosome mimetic; wherein the point-like magnetosome mimetic is the same as the target magnetosome; a traversal unit, used to traverse the imaging field of view based on the first target focusing field and the second target focusing field, and collect fourth target signals corresponding to the point-like magnetosome mimetic at each position; a Fourier transform processing unit, used to perform Fourier transform on the fourth target signal to obtain frequency domain signals corresponding to each position; a fourth determination unit, used to determine the target frequency signal based on the frequency domain signal; wherein the target frequency signal is a signal in the frequency domain signal that satisfies an integer multiple of the frequency of the excitation magnetic field; an arrangement unit, used to arrange the target frequency signals at each position into a system matrix; and a calculation unit, used to obtain a reconstructed image based on the system matrix and the frequency domain signal.

[0151] In some optional embodiments, the above-mentioned device also includes: an ultrasonic processing module, which is used to perform ultrasonic processing on the magnetosome through the ultrasonic module to obtain a first magnetosome; wherein the first magnetosome is used to characterize the easy-axis arrangement dispersion of the magnetosome, and the magnetosome is a single-domain magnetic nanoparticle composed of a complete lipid bilayer structure and ferroferric oxide crystals; a magnetization module, which is used to magnetize the first magnetosome under the action of the uniform magnetic field of the magnetization module to obtain a target magnetosome.

[0152] In some optional embodiments, the above-mentioned device also includes: a culture module, used to culture the magnetotactic bacterial strain through the culture device; wherein the magnetotactic bacterial strain is used to synthesize magnetosomes; a lysis module, used to lyse the target magnetotactic bacterial strain through the lysis device to obtain magnetosomes if the optical density of the bacterial liquid in the magnetotactic bacterial strain at a wavelength of 565 nanometers and the value of the characteristic parameter of the magnetotactic bacterial strain are both between 0.8 and 1.0.

[0153] In some optional embodiments, the signal receiving module 1103 includes: a start receiving unit, which is used to start the excitation coil based on a preset excitation signal and receive the electromagnetic signal from the receiving coil; an adjustment execution unit, which is used to adjust the fundamental frequency feedthrough in the electromagnetic signal through a feedthrough compensation device until the fundamental frequency feedthrough in the electromagnetic signal reaches a minimum value, and then execute the step of collecting the signal of the target magnetic body under the action of the first target focusing field and the second target focusing field.

[0154] The further functional description of each of the above modules and units is the same as that of the above corresponding embodiments and will not be repeated here.

[0155] The magnetic particle imaging device based on magnetotactic bacterial magnetosomes in this embodiment is presented in the form of a functional unit, where the functional unit refers to an ASIC (Application Specific Integrated Circuit) circuit, a processor and memory that executes one or more software or fixed programs, and / or other devices that can provide the above functions.

[0156] The embodiment of the present invention also provides a computer device having the above Fig.11 The magnetic particle imaging device based on magnetotactic bacterial magnetosomes is shown.

[0157] See also Fig.12 , Fig.12 is a schematic diagram of the structure of a computer device provided by an optional embodiment of the present invention, such as Fig.12As shown, the computer device includes: one or more processors 1000, memory 2000, and interfaces for connecting various components, including high-speed interfaces and low-speed interfaces. Various components are connected to each other using different buses for communication, and can be installed on a common mainboard or installed in other ways as needed. The processor can process the instructions executed in the computer device, including instructions stored in or on the memory to display the graphical information of the GUI on an external input / output device (such as, a display device coupled to the interface). In some optional embodiments, if necessary, multiple processors and / or multiple buses can be used together with multiple memories and multiple memories. Similarly, multiple computer devices can be connected, and each device provides part of the necessary operations (for example, as a server array, a group of blade servers, or a multi-processor system). Fig.12 A processor 1000 is taken as an example.

[0158] The processor 1000 may be a central processing unit, a network processor or a combination thereof. The processor 1000 may further include a hardware chip. The hardware chip may be a dedicated integrated circuit, a programmable logic device or a combination thereof. The programmable logic device may be a complex programmable logic device, a field programmable gate array, a general purpose array logic or any combination thereof.

[0159] The memory 2000 stores instructions executable by at least one processor 1000, so that at least one processor 1000 executes the method shown in the above embodiment.

[0160] The memory 2000 may include a program storage area and a data storage area, wherein the program storage area may store an operating system, an application required by at least one function; the data storage area may store data created according to the use of the computer device, etc. In addition, the memory 2000 may include a high-speed random access memory, and may also include a non-transient memory, such as at least one disk storage device, a flash memory device, or other non-transient solid-state storage device. In some optional embodiments, the memory 2000 may optionally include a memory remotely arranged relative to the processor 1000, and these remote memories may be connected to the computer device via a network. Examples of the above-mentioned network include, but are not limited to, the Internet, an intranet, a local area network, a mobile communication network, and combinations thereof.

[0161] The memory 2000 may include a volatile memory, such as a random access memory; the memory 2000 may also include a non-volatile memory, such as a flash memory, a hard disk or a solid state drive; the memory 2000 may also include a combination of the above types of memory.

[0162] The computer device also includes a communication interface 3000, which is used for the computer device to communicate with other devices or a communication network.

[0163] The embodiment of the present invention also provides a computer-readable storage medium. The method according to the embodiment of the present invention can be implemented in hardware, firmware, or can be implemented as a computer code that can be recorded in a storage medium, or can be implemented as a computer code that is originally stored in a remote storage medium or a non-temporary machine-readable storage medium and will be stored in a local storage medium through a network download, so that the method described herein can be stored in such software processing on a storage medium using a general-purpose computer, a dedicated processor, or programmable or dedicated hardware. Among them, the storage medium can be a magnetic disk, an optical disk, a read-only storage memory, a random access memory, a flash memory, a hard disk or a solid-state hard disk, etc.; further, the storage medium can also include a combination of the above types of memories. It can be understood that a computer, a processor, a microprocessor controller, or programmable hardware includes a storage component that can store or receive software or computer code. When the software or computer code is accessed and executed by a computer, a processor, or hardware, the method shown in the above embodiment is implemented.

[0164] A part of the present invention may be applied as a computer program product, such as a computer program instruction, which, when executed by a computer, can call or provide the method and / or technical solution according to the present invention through the operation of the computer. Those skilled in the art should understand that the existence of the computer program instruction in a computer-readable medium includes, but is not limited to, a source file, an executable file, an installation package file, etc., and accordingly, the way in which the computer program instruction is executed by the computer includes, but is not limited to: the computer directly executes the instruction, or the computer compiles the instruction and then executes the corresponding compiled program, or the computer reads and executes the instruction, or the computer reads and installs the instruction and then executes the corresponding installed program. Here, the computer-readable medium may be any available computer-readable storage medium or communication medium accessible to the computer.

[0165] Although the embodiments of the present invention have been described in conjunction with the accompanying drawings, those skilled in the art may make various modifications and variations without departing from the spirit and scope of the present invention, and such modifications and variations are all within the scope defined by the appended claims.

Claims

1. A magnetic particle imaging method based on magnetotactic bacterial magnetosomes, characterized in that: The method comprises: Obtaining target magnetosomes; wherein the target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement; Generate an excitation field, a first target focusing field and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetic body, and the frequencies of the first target focusing field and the second target focusing field are both lower than the frequency of the excitation field; wherein the excitation field is a low-frequency excitation field; Under the action of the excitation field, the first target focusing field and the second target focusing field, the signal of the target magnetosome is collected; wherein the signal of the target magnetosome is a signal having avalanche magnetization characteristics; The signal of the target magnetosome is reconstructed to obtain a reconstructed image corresponding to the target magnetosome.

2. The magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to claim 1, characterized in that: The reconstructing the signal of the target magnetosome to obtain a reconstructed image corresponding to the target magnetosome includes: Processing the signal of the target magnetic body in segments to obtain multiple segments of first target signals, and averaging the multiple segments of the first target signals to obtain a second target signal; wherein the length of each segment of the first target signal is the least common multiple of the excitation period, the first target focusing field period, and the second target focusing field period; Acquire a frequency response function of a link in the imaging system, and process the frequency response function to obtain an inverse function corresponding to the frequency response function; Based on the inverse function and the second target signal, determining a third target signal; wherein the third target signal is used to characterize the signal to be corrected in the time domain; Determine the derivative of the excitation field with respect to time in the imaging system, and obtain the first target point based on each point of the third target signal divided by the derivative; wherein the time point of each point of the third target signal corresponds one-to-one to the time point of the derivative of the excitation field with respect to time; Based on each of the first target points, determining a first target intermediate value that meets a preset condition; wherein the first target intermediate value is used to characterize the signal strength of the target magnetosome at each of the first target points; Performing grid division on a first amplitude corresponding to the first target focusing field and a second amplitude corresponding to the second target focusing field to obtain a grid; Filling the first target intermediate value into the grid according to the corresponding amplitude, so that the first target intermediate value is converted into image information with spatial distribution; Based on the image information, a reconstructed image corresponding to the target magnetosome is constructed.

3. The magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to claim 2, characterized in that: Before filling the first target intermediate value into the grid according to the corresponding amplitude so as to convert the first target intermediate value into image information with spatial distribution, the method further includes: Obtaining the coercive force corresponding to the target magnetic body; Dividing the intermediate values ​​into a first group of intermediate values ​​and a second group of intermediate values ​​according to the positive and negative values ​​of the derivatives of the excitation field amplitude at the corresponding time points; wherein the first group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to when the derivatives of the excitation field amplitude are positive, and the second group of intermediate values ​​is used to characterize the intermediate values ​​corresponding to when the derivatives of the excitation field amplitude are negative; Subtract the abscissa of the coercive force from each intermediate value in the first group of intermediate values ​​to obtain a first intermediate value; Adding each intermediate value in the first group of intermediate values ​​to the abscissa of the coercive force to obtain a second intermediate value; The first target intermediate value is obtained based on the first intermediate value and the second intermediate value.

4. The magnetic particle imaging method based on magnetotactic bacteria magnetosomes according to claim 1, characterized in that: The period corresponding to the frequency of the excitation field is greater than the relaxation time of the target magnetic body, and the amplitude of the excitation field is greater than the coercive force of the target magnetic body.

5. The magnetic particle imaging method based on magnetotactic bacteria magnetosomes according to claim 1, characterized in that: The reconstructing the signal of the target magnetosome to obtain a reconstructed image corresponding to the target magnetosome includes: Obtaining a dot-shaped magnetosome mimetic; wherein the dot-shaped magnetosome mimetic is identical to the target magnetosome; Based on the first target focusing field and the second target focusing field, traverse the imaging field of view, and collect fourth target signals corresponding to the point-shaped magnetic body phantom at various positions; Performing Fourier transform on the fourth target signal to obtain frequency domain signals corresponding to each position; Based on the frequency domain signal, determine a target frequency signal; wherein the target frequency signal is a signal in the frequency domain signal that satisfies an integer multiple of the frequency of the excitation field; Arrange the target frequency signals at various positions into a system matrix; The reconstructed image is obtained based on the system matrix and the frequency domain signal.

6. The magnetic particle imaging method based on magnetotactic bacteria magnetosomes according to claim 1, characterized in that: The target magnetosomes are obtained by the following method: Ultrasonic treatment is performed on the magnetosomes by an ultrasonic module to obtain first magnetosomes; wherein the first magnetosomes are used to characterize the easy axis arrangement dispersion of the magnetosomes, and the magnetosomes are single-domain magnetic nanoparticles having a complete lipid bilayer structure and composed of ferroferric oxide crystals; Under the action of the uniform magnetic field of the magnetization module, the first magnetic body is magnetized to obtain the target magnetic body.

7. The magnetic particle imaging method based on magnetotactic bacteria magnetosomes according to claim 6, characterized in that: The magnetosomes are obtained by the following method: Cultivating the magnetotactic bacterial strain by a cultivation device; wherein the magnetotactic bacterial strain is used to synthesize magnetosomes; If the optical density of the bacterial solution in the magnetotactic bacterial strain at a wavelength of 565 nanometers and the value of the characteristic parameter of the magnetotactic bacterial strain are both between 0.8 and 1.0, the target magnetotactic bacterial strain is lysed by a lysis device to obtain the magnetosomes.

8. The magnetic particle imaging method based on magnetotactic bacteria magnetosomes according to claim 1, characterized in that: The step of collecting signals of the target magnetic bodies under the action of the excitation field, the first target focusing field and the second target focusing field comprises: Based on a preset excitation signal, the excitation coil is turned on, and an electromagnetic signal from the receiving coil is received; The fundamental frequency feedthrough in the electromagnetic signal is adjusted by a feedthrough compensation device until the fundamental frequency feedthrough in the electromagnetic signal reaches a minimum value, and then the step of collecting the signal of the target magnetic body under the action of the first target focusing field and the second target focusing field is performed.

9. A magnetic particle imaging device based on magnetotactic bacterial magnetosomes, characterized in that: The device comprises: A target magnetosome acquisition module is used to acquire target magnetosomes; wherein the target magnetosomes are used to characterize magnetosomes with consistent easy axis arrangement; A generating module, used to generate an excitation field, a first target focusing field and a second target focusing field; wherein the amplitude of the excitation field is higher than the coercive force amplitude of the target magnetic body, and the frequencies of the first target focusing field and the second target focusing field are lower than the frequency of the excitation field; wherein the excitation field is a low-frequency excitation field; A signal receiving module, used for collecting the signal of the target magnetosome under the action of the excitation field, the first target focusing field and the second target focusing field; wherein the signal of the target magnetosome is a signal with avalanche magnetization characteristics; The image reconstruction module is used to reconstruct the signal of the target magnetosome to obtain a reconstructed image corresponding to the target magnetosome.

10. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores computer instructions, and the computer instructions are used to enable a computer to execute the magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to any one of claims 1 to 8.

11. A computer program product, characterized in that The method comprises computer instructions for causing a computer to execute the magnetic particle imaging method based on magnetotactic bacterial magnetosomes according to any one of claims 1 to 8.

Images