CN114617540A - Low-cost magnetic nanoparticle imaging system and method - Google Patents
Low-cost magnetic nanoparticle imaging system and method Download PDFInfo
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Abstract
The invention relates to the field of magnetic particle imaging, in particular to a low-cost magnetic nanoparticle imaging system and a low-cost magnetic nanoparticle imaging method. The system comprises: the device comprises a magnetic field scanner, a main controller, an upper computer and an external supporting circuit, wherein the external supporting circuit is used for communicating the magnetic field scanner and the main controller; the support circuit includes: the device comprises a filter amplifier, an operational amplifier, a filter and an analog-to-digital converter; the invention leads the whole system to be lower in cost and integrated, realizes a low-cost compact magnetic nanoparticle imaging system and carries out two-dimensional imaging on the spatial distribution of superparamagnetic nanoparticles.
Description
Technical Field
The invention relates to the field of magnetic particle imaging, in particular to a low-cost magnetic nanoparticle imaging system and method.
Background
Medical imaging technology has advanced to a great extent over decades, with tomography taking an important position in medical imaging and playing an unachievable role in the prevention, diagnosis, treatment, and the like of diseases. With the proposition and development of precise medical treatment, the drug targeted delivery using magnetic materials as carriers becomes a research hotspot, has high requirements on the accuracy and efficiency of targeted drug therapy all the time, has important significance on detecting tracers with similar delivery effects on evaluating the final effect, and the existing tracer detection schemes with the most use mainly comprise: the technology comprises the following steps of firstly, Magnetic Resonance Imaging (MRI), secondly, Positron Emission Tomography (PET), thirdly, electron Computer Tomography (CT) and the like, but the technologies have various defects; for example, motion artifacts are easily introduced due to too long scanning time in MRI, CT tracers and devices themselves have radiation hazards, tracers used in PET imaging have radioactivity, and the like, which further restricts the detection of the tracers by the existing medical imaging method.
With the development of the subject of magnetic materials, a nano-sized magnetic nanoparticle has been developed, which has been rapidly and widely noticed due to its non-toxic, non-radiative and non-secondary-harmful properties to human body, and once it appears, the size of the particle is in nano-scale, when the diameter of the particle is smaller than a certain critical size, the magnetic substance has a mono-domain structure, when the ambient temperature is lower than the curie temperature and higher than the transition temperature, the ferromagnetic substance has superparamagnetism, the nano-particle (SPION) with superparamagnetism generates a non-linear magnetization response in the magnetic field, and the response can be described by using the langevin classical paramagnetic theory more specifically, that is, the alternating magnetic moment of the particle reaches the non-saturated state to generate a non-linear magnetization behavior, based on the characteristic, the nonlinear magnetization response can be detected by a hardware detection coil, and then imaging and subsequent analysis are carried out on the spatial distribution of the particles.
The Imaging mechanism described above is called Magnetic nanoparticle Imaging (MPI) technology, and this method and system are first proposed from 2005, and the first prototype in the world was constructed by Bernhard Gleich and coworkers sumen, and then after many years of development, certain achievements were achieved in Imaging speed and resolution, and hardware structures range from the first one-dimensional to three-dimensional, and FFP spatial traversal modes are also diverse, such as spiral trajectory, radial trajectory, cartesian trajectory, and so on, but most used is lissajous trajectory.
The MPI technology has been developed so far, and some simple systems have been constructed for verifying the imaging mechanism, but the following defects still exist:
1. these systems only stay in the verification stage of the novel local function designed in the system, such as verifying whether the novel FOV scanning trajectory is successful, verifying whether the novel magnetic field structure is successful in constructing a more optimized FFP, or verifying the innovative excitation signal working mode; these systems are not considered from the price of the system itself, and result in using, for example, a signal generator for generating a Field of View (FOV) driving FFP to traverse the space, and a data acquisition card for acquiring the SPION nonlinear magnetization response signal, and the use of various independent devices not only increases the weight of the system, but also has high price, which hinders the development of the system toward portability, so that the MPI system causes great difficulty in bedside detection, and the high price causes great obstacle to the popularization of the MPI technology.
2. The traditional MPI system uses a microcontroller (CPU) with a serial Von Neumann structure as a main controller, the running speed of the computer with the serial structure is influenced by the result of the previous step, the characteristic of calculating a plurality of tasks in each clock period cannot be achieved, the processing speed of high-speed data transmission, real-time storage, rapid image reconstruction and display is restricted, and once the processor solidifies a program, the running mechanism of an internal program cannot be changed, the flexibility of later debugging is reduced, and the use cost is further increased.
3. Because the development time of the MPI imaging system is relatively short compared with other computed tomography imaging technologies, the development of the whole machine and the expansion of the system space have a great promotion space. In the existing general MPI system, a two-dimensional and three-dimensional FOV is required to be generated, a three-dimensional electromagnetic coil is generally used for driving an FFP (fan filter), and the mode not only needs a complex coil cooling and water-cooling facility outside the electromagnetic coil and a high-power direct-current power supply for supplying power, but also increases the difficulty for the accurate control of the FFP, so that the mode for forming the two-dimensional and three-dimensional FOV not only increases the hardware cost, but also increases the volume of the system, and further hinders the general development of the MPI technology.
The present invention is proposed based on the above various drawbacks of the conventional MPI.
Disclosure of Invention
The embodiment of the invention provides a low-cost magnetic nanoparticle imaging system and a low-cost magnetic nanoparticle imaging method.
According to an embodiment of the present invention, there is provided a low-cost magnetic nanoparticle imaging system, including: the device comprises a magnetic field scanner, a controller, an upper computer and an external supporting circuit, wherein the external supporting circuit is used for communicating the magnetic field scanner with the controller; the external support circuit includes: the device comprises a filter amplifier, an operational amplifier, a filter and an analog-to-digital converter; wherein, the first and the second end of the pipe are connected with each other,
the controller generates a driving signal based on a preset signal synthesis mode and sends the driving signal to the power amplifier;
the power amplifier is used for amplifying the driving signal and sending the driving signal to the magnetic field scanner;
when receiving the amplified driving signal, the magnetic field scanner is used for generating a magnetization reaction, generating a nonlinear magnetization signal and sending the nonlinear magnetization signal to the operational amplifier;
the operational amplifier is used for amplifying the nonlinear magnetization signal and sending the nonlinear magnetization signal to the filter;
the filter is used for filtering the amplified nonlinear magnetization signal and sending the filtered nonlinear magnetization signal to the analog-to-digital converter;
the analog-to-digital converter is used for converting the nonlinear magnetization signal after filtering processing into a digital signal and sending the digital signal to the controller;
the controller is used for transmitting the image digital signals to the upper computer for storage;
the upper computer is used for carrying out image reconstruction on the stored digital signals.
Further, the system adopts a programmable logic gate array as the controller.
Further, the controller synthesizes the driving signals by adopting a direct digital frequency mode.
Further, the system also comprises a guide rail driver, and when the guide rail driver receives the driving signal, the guide rail driver sends a phantom driving signal to the magnetic field scanner; the rail drive is used to movably test the phantom inside the system.
Further, the magnetic field scanner comprises a permanent magnet, a receiving coil and a driving coil; the driving coil is used for receiving the amplified driving signal and generating a driving magnetic field, the driving magnetic field excites the magnetic nano particles in the magnetic field scanner to send nonlinear magnetization reaction and generate nonlinear magnetization signals, and the receiving coil receives the nonlinear magnetization signals generated by the magnetization reaction; permanent magnets are used to build up the gradient magnetic field.
Furthermore, the distance between the permanent magnets is designed into a dynamic structure with adjustable distance, so that gradient magnetic fields with different gradient strengths are generated at different distances between the permanent magnets.
Further, the receiving coil adopts a differential structure design to receive the nonlinear magnetization signal.
Further, the controller uploads the digital signals received from the analog-to-digital converter to an upper computer for storage through an internal gigabit Ethernet integrated core.
Further, the upper computer carries out image reconstruction on the data based on a reconstruction algorithm of the X-Space.
According to another embodiment of the present invention, there is provided a low-cost method of magnetic nanoparticle imaging, the method comprising the steps of:
generating a driving signal based on a preset signal synthesis mode;
amplifying and transmitting the driving signal;
when receiving the amplified driving signal, generating a magnetization reaction and generating a nonlinear magnetization signal;
amplifying the nonlinear magnetization signal;
filtering the amplified nonlinear magnetization signal;
converting the nonlinear magnetization signal after filtering processing into a digital signal;
transmitting the digital signal to an upper computer for storage;
and carrying out image reconstruction on the stored digital signals.
The controller generates a driving signal based on a preset signal synthesis mode and sends the driving signal to a power amplifier; the power amplifier is used for amplifying the driving signal and sending the driving signal to the magnetic field scanner; when receiving the amplified driving signal, the magnetic field scanner is used for generating a magnetization reaction, generating a nonlinear magnetization signal and sending the nonlinear magnetization signal to the operational amplifier; the operational amplifier is used for amplifying the nonlinear magnetization signal and sending the nonlinear magnetization signal to the filter; the filter is used for filtering the amplified nonlinear magnetization signal and sending the filtered nonlinear magnetization signal to the analog-to-digital converter; the analog-to-digital converter is used for converting the nonlinear magnetization signal after filtering processing into a digital signal and sending the digital signal to the controller; the controller is used for transmitting the image digital signals to the upper computer for storage; the upper computer is used for carrying out image reconstruction on the stored digital signals. The invention leads the whole system to be lower in cost and integrated, realizes a low-cost compact magnetic nanoparticle imaging system and carries out two-dimensional imaging on the spatial distribution of superparamagnetic nanoparticles.
The beneficial effects of the invention at least comprise:
(1) compared with a traditional MPI system, the invention abandons the traditional CPU controller, adopts a Programmable Gate array (FPGA) as the controller of the system, and realizes stronger system flexibility and expandability while reducing power consumption by using the inherent parallel computation and Programmable capability; programmable logic development is carried out by calling a pre-designed kernel with an open source in the FPGA, complicated program writing in a CPU is omitted, and only the running logic of the whole control program needs to be designed, so that the development time cost and the capital cost are greatly reduced, and the MPI system is promoted to be developed towards low-cost discovery.
(2) Compared with the traditional MPI system, the invention uses an FPGA controller to control the synthesis of the driving signal and the receiving and transmission of the SPION nonlinear magnetization signal, and abandons the traditional signal generator, the traditional data acquisition card and various external water cooling, power supply and other equipment required by the electromagnetic coil, so that the whole system is more integrated and miniaturized, the occupied area and the manufacturing cost are greatly reduced, and the low-cost portable MPI system is realized.
(3) The scheme of the multi-dimensional MPI system is realized by using the controller to drive the movable guide rail driver to test the phantom, so that an electromagnetic coil used in the traditional MPI system is omitted, the stability of the system is improved, the cost is reduced, and the volume is reduced.
(4) The invention designs a permanent magnet structure with adjustable space area to generate FFP and a gradient magnetic field. The structure can flexibly adjust the distance between the two permanent magnets, not only can achieve the purpose of expanding and reducing the size of the area to be measured, but also realizes the advantage of adjustable gradient magnetic field value; according to Langmen classical paramagnetic theory, the gradient magnetic fields with different gradient strengths correspond to different detectable particle sizes; the invention can effectively enlarge the area to be measured and can meet the requirements of different sizes of particles used in different fields.
(5) Compared with a direct signal coupling coil used in a traditional MPI system, the receiving coil with the differential structure filters most of driving signals from a source, reduces the bandwidth requirement of an external filter, and further reduces the cost of the system.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the invention without limiting the invention. In the drawings:
FIG. 1 is a schematic diagram of a low cost magnetic nanoparticle imaging system of the present invention;
FIG. 2 is a flow chart of a low cost magnetic nanoparticle imaging method of the present invention;
FIG. 3 is a diagram of a DDS synthesized drive signal according to the present invention;
FIG. 4 is a schematic diagram of the test phantom SPION moving left and right inside the receiving coil according to the invention;
FIG. 5 is a flow chart of the logic diagram for driving the SPION movement of the test phantom according to the present invention;
FIG. 6 is a model diagram of the gradient magnetic field of the magnetic field scanner of the present invention;
FIG. 7 is a pictorial representation of a gradient magnetic field of the magnetic field scanner of the present invention;
FIG. 8 is a schematic diagram of a drive coil for providing a drive magnetic field according to the present invention;
FIG. 9 is a schematic diagram of the present invention in which the drive coil and the resonant capacitor are matched in series resonance;
FIG. 10 is a schematic diagram of a differential structure coil of the receiver coil of the present invention;
FIG. 11 is a diagram illustrating an Ethernet-based data transmission protocol according to the present invention;
FIG. 12 is an experimental schematic diagram of superparamagnetic nanoparticles according to the present invention;
FIG. 13 is a schematic diagram of the basic two-dimensional imaging functionality of the system of the present invention;
FIG. 14 is a diagram illustrating the spatial resolution test results of the system of the present invention.
Reference numerals: 1-driving coil, 2-receiving coil, 3-permanent magnet, 4-SPION, and 5-adjustable handle.
Detailed Description
In order to make the technical solutions of the present invention better understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, shall fall within the protection scope of the present invention.
It should be noted that the terms "first," "second," and the like in the description and claims of the present invention and in the drawings described above are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the invention described herein are capable of operation in other sequences than those illustrated or described herein. Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
Example 1
As shown in fig. 1 to 14, according to an embodiment of the present invention, there is provided a low-cost magnetic nanoparticle imaging system, as shown in fig. 1, including: the device comprises a magnetic field scanner, a controller, an upper computer and an external supporting circuit, wherein the external supporting circuit is used for communicating the magnetic field scanner and the controller; the support circuit includes: a filter amplifier, an operational amplifier, a filter and an analog-to-digital converter; the main controller generates a driving signal based on a preset signal synthesis mode and sends the driving signal to the power amplifier; the power amplifier is used for amplifying the driving signal and sending the driving signal to the magnetic field scanner; when receiving the amplified driving signal, the magnetic field scanner is used for generating a magnetization reaction, generating a nonlinear magnetization signal and sending the nonlinear magnetization signal to the operational amplifier; the operational amplifier is used for amplifying the nonlinear magnetization signal and sending the nonlinear magnetization signal to the filter; the filter is used for filtering the nonlinear magnetization signal and sending the nonlinear magnetization signal after filtering to the analog-to-digital converter; the analog-to-digital converter is used for converting the nonlinear magnetization signal after filtering processing into a digital signal and sending the digital signal to the controller; the main controller is used for transmitting the digital signals to an upper computer for storage; and the upper computer is used for using the stored digital signals for image reconstruction.
In the embodiment, the whole MPI system is lower in cost and integrated through the scheme of the invention, and the low-cost compact magnetic nanoparticle imaging system is realized to perform two-dimensional imaging on the spatial distribution of superparamagnetic nanoparticles.
The system of the invention is described in detail below with specific examples:
the method comprises the following steps: the main controller generates a driving signal based on a preset signal synthesis mode and sends the driving signal to the power amplifier; the controller is used for generating, receiving and transmitting signals, and the invention synthesizes the Digital form of the driving signal by using a Direct Digital Synthesizer (DDS) mode, which can generate relatively pure signals, thereby saving external filters and reducing equipment cost. The DDS logic kernel is contained in the Programmable logic Gate array (FPGA) used in the invention and can be directly called, thereby saving time cost and research and development complexity and further reducing cost.
As a preferred scheme, an FPGA is used as a controller, and a driving signal required by the MPI system is synthesized by Direct Digital Synthesizer (DDS) synthesis and sent to a power amplifier for amplification, so that a traditional signal generator is not used directly.
Step two: the power amplifier is used for amplifying the driving signal and sending the driving signal to the magnetic field scanner; the drive signal is amplified by a power amplifier and then the amplified drive signal is transmitted to a drive coil 1 in the magnetic field scanner.
Step three: when receiving the amplified driving signal, the magnetic field scanner is used for generating a magnetization reaction, generating a nonlinear magnetization signal and sending the nonlinear magnetization signal to the operational amplifier; a driving coil 1 in the magnetic field scanner receives a driving signal, an FFP (fringe field) is generated on the driving coil 1 to excite a SPION (spin on Material) to generate a nonlinear magnetization reaction or a driving magnetic field, the driving magnetic field generated by the driving coil 1 excites magnetic nano particles to generate a nonlinear magnetization reaction or response, a receiving coil 2 receives the magnetization response and generates a nonlinear magnetization signal of the SPION, and the nonlinear magnetization signal is output to an operational amplifier for amplification.
Step four: the operational amplifier is used for amplifying the nonlinear magnetization signal and sending the nonlinear magnetization signal to the filter; the operational amplifier amplifies the nonlinear magnetization signal, and the amplified nonlinear magnetization signal is sent to the filter.
Step five: the filter is used for filtering the nonlinear magnetization signal and sending the nonlinear magnetization signal after filtering to the analog-to-digital converter; and the filter carries out filtering processing on the amplified nonlinear magnetization signal and sends the nonlinear magnetization signal after the filtering processing to the analog-to-digital converter.
Step six: the analog-to-digital converter converts the received or collected nonlinear magnetization signal into a digital signal and transmits the digital signal to the FPGA controller.
Step seven: the controller is used for transmitting the digital signals to an upper computer for storage; the FPGA controller uploads the received data to an upper computer for storage in real time at a transmission speed of 1Gb/s through an internal gigabit Ethernet integrated kernel.
Step eight: then, image reconstruction is carried out on the spatial distribution of the SPION by using a reconstruction algorithm based on X-Space; the process is executed through an ARM inner core contained in the FPGA, so that high-speed data transmission is realized, a multi-task cooperative operation mechanism is realized, and the expandability and the flexibility of the system are improved.
The beneficial effects of the invention at least comprise:
(1) compared with a traditional MPI system, the invention abandons the traditional CPU controller, adopts a Programmable Gate array (FPGA) as the controller of the system, and realizes stronger system flexibility and expandability while reducing power consumption by using the inherent parallel computation and Programmable capability; programmable logic development is carried out by calling a pre-designed kernel with an open source in the FPGA, complicated program writing in a CPU is omitted, and only the running logic of the whole control program needs to be designed, so that the development time cost and the capital cost are greatly reduced, and the MPI system is promoted to be developed towards low-cost discovery.
(2) Compared with the traditional MPI system, the invention uses an FPGA controller to control the synthesis of the driving signal and the receiving and transmission of the SPION nonlinear response signal, and abandons the traditional signal generator, the traditional data acquisition card and various external water cooling, power supply and other equipment required by the electromagnetic coil, so that the whole system is more integrated and miniaturized, the occupied area and the manufacturing cost are greatly reduced, and the low-cost portable MPI system is realized.
(3) The scheme of the multi-dimensional MPI system is realized by using the controller to drive the movable guide rail driver to test the phantom, so that an electromagnetic coil used in the traditional MPI system is omitted, the stability of the system is improved, the cost is reduced, and the volume is reduced.
(4) The invention designs a permanent magnet 3 structure with adjustable space area to generate FFP and a gradient magnetic field. The structure can flexibly adjust the distance between the two permanent magnets 3, not only can achieve the purpose of expanding and reducing the size of the area to be measured, but also realizes the advantage of adjustable gradient magnetic field value; according to Langmen classical paramagnetic theory, the gradient magnetic fields with different gradient strengths correspond to different detectable particle sizes; the invention can effectively enlarge the area to be measured and can meet the requirements of different sizes of particles used in different fields.
(5) Compared with a direct signal coupling coil used in a traditional MPI system, the receiving coil 2 with a differential structure filters most of driving signals from a source, reduces the bandwidth requirement of an external filter, and further reduces the cost of the system.
In the embodiment, the system adopts a programmable logic gate array as a controller; compared with a traditional MPI system, the invention abandons the traditional CPU controller, adopts a Programmable Gate array (FPGA) as the controller of the system, and realizes stronger system flexibility and expandability while reducing the power consumption by using the inherent parallel computation and Programmable capabilities; programmable logic development is carried out by calling a pre-designed kernel of an open source in the FPGA, complicated program writing in a CPU is omitted, and only the running logic of the whole control program needs to be designed, so that the development time cost and the capital cost are greatly reduced, and the MPI system is promoted to be developed towards low-cost discovery.
In this embodiment, the controller synthesizes the driving signal by using a direct digital frequency method; the FPGA controller synthesizes driving signals required by the MPI system in a Direct Digital Synthesizer (DDS) synthesis mode, so that a signal generator is abandoned; the DDS mode not only has ultrahigh-speed frequency conversion time, but also can keep the continuity of the phase, thereby easily realizing frequency, phase and amplitude modulation; in the embodiment, the driving signal is synthesized by using a DDS mode; in other embodiments, the manner of synthesizing the driving signal further includes other manners, such as a pulse width modulation manner, which is not described herein.
The DDS synthesized driving signal of the present invention is explained in detail below with specific embodiments:
in the process of constructing the traditional MPI system, in order to generate an alternating driving signal meeting the requirement, a signal generator is directly used, so that the cost of the system is directly increased, the volume of the system is increased, and the portability of the system is inconvenient, therefore, a single-board controller is used for generating the driving signal in the invention, the used method is a DDS (direct digital synthesis) method, of course, the method for synthesizing the alternating driving signal is not only a DDS method, but also a pulse width modulation method and the like, but the DDS method not only has ultrahigh-speed frequency conversion time, but also can keep the continuity of the phase, so that the frequency, the phase and the amplitude modulation are easily realized, and the output digital signal can be directly input to a driving coil 1 to drive an FFP after being converted into an analog signal by a DAC (digital-to-analog converter) by virtue of the purity, and an external filter is omitted, the cost of the system is saved. The DDS main body part mainly comprises the following parts: frequency control words, a phase accumulator, a phase converter and a digital-to-analog converter, fig. 3 shows a block diagram of a main part of a driving magnetic field signal, wherein an output frequency is expressed by a formula as follows;
wherein f isOUTFor the frequency of the final synthesized drive signal, N represents the number of clocks that the phase accumulator outputs the minimum incremental phase change, fclkM represents the number of bits of the phase accumulator, which is the reference clock of the DDS, and then the output frequency can be adjusted by adjusting the phase accumulator and the number of pulses. The FPGA used in the invention contains a DDS integrated kernel which can be directly called, and the required driving signal can be synthesized only by modifying parameters such as a reference clock, an output frequency digit, an initial phase and the like, so that the development time cost is reduced, and the volume of the system is reduced. As shown in fig. 3, in the process of data transmission formed by the driving signals, one sinusoidal amplitude signal output from a look-up table (LUT) and output by the DDS is input to the DAC through the driving module, and then the analog driving signals are output through digital-to-analog conversion.
In an embodiment, the system further comprises a rail driver, and the rail driver sends out a phantom driving signal to the magnetic field scanner when receiving the driving signal; the guide rail driver sends a phantom driving signal to the driving coil 1 for testing a phantom inside the system; the invention adopts a scheme of mechanically moving the test phantom in the FOV to realize the multi-dimensional MPI system, further improves the accuracy of the system, reduces the cost compared with the electromagnetic coil, and improves the stability of the system.
The design of the guide rail drive according to the invention is explained in detail below with specific embodiments:
in order to reduce the cost and ensure the accuracy of the system, the invention abandons the scheme of using a multidimensional electromagnetic coil to drive the FFP to traverse in the FOV, adopts a novel mode of mechanically moving a test phantom to form a two-dimensional FOV space, uses a movable guide to complete the movement of the test phantom (SPION) in the other direction, and as shown in the schematic diagram that the arrow of the SPION in FIG. 4 shows that the SPION fixed at the other end of the guide rail moves left and right in the receiving coil 2, the FFP is driven to move along the direction vertical to the paper by combining with the driving coil 1, so as to form a two-dimensional FOV plane; fig. 5 is a logic diagram of a specific driving test phantom to move, which includes a data storage process, wherein the test phantom is moved by 5mm in the left-right direction by means of a guide rail, and the driving coil 1 is combined to drive the FFP by a distance of 20mm in the vertical direction, so as to form a FOV plane of 10mm × 20 mm.
In this embodiment, the magnetic field scanner includes a permanent magnet, a receiving coil 2, and a driving coil 1; the driving coil 1 is used for receiving the amplified driving signal and generating a driving magnetic field, the driving magnetic field excites the magnetic nano particles in the magnetic field scanner to generate a nonlinear magnetization reaction, and the receiving coil 2 is used for generating a nonlinear magnetization signal; the permanent magnet 3 is used to build up a gradient magnetic field. In this embodiment, the distance between the permanent magnets 3 is designed to be a dynamic structure with adjustable distance, and the adjustable handle 5 is used for adjusting, so that different distances between the permanent magnets 3 generate gradient magnetic fields with different gradient strengths.
The construction of the magnetic field scanner, as shown in fig. 4 to 9, is roughly divided into two parts, and the following is a detailed description of the construction of the magnetic field scanner according to the present invention by way of specific embodiments:
(1) simulation and construction of gradient magnetic fields
The magnetic field scanner plays a central role in the present invention because it controls the SPION to generate a non-linear magnetization signal. The invention abandons the traditional scheme of using an electromagnetic coil to generate a gradient magnetic field, because the electromagnetic coil is difficult to control the generation and the stability of the magnetic field, and a large amount of water cooling and direct current power supplies are needed outside, thereby greatly increasing the manufacturing cost of the system and being difficult to popularize the MPI technology; therefore, the permanent magnet 3 with neodymium iron boron (NdFe35) as the main material is used as the main material for constructing the gradient magnetic field, the neodymium iron boron has high stability and low manufacturing cost, is easy to obtain in the market, shortens the manufacturing time and accelerates the construction of the system.
Firstly, modeling simulation is carried out on the gradient magnetic field which plays a role in coding, the gradient magnetic field with composite specific strength is constructed, and in a certain range, the larger the gradient value of the gradient magnetic field is, the smaller the particle size of the detected particles is, and the higher the sensitivity of the system is. During modeling, a permanent magnet material with the outer diameter of 124mm and the height of 20mm is selected, the S poles of the two permanent magnets 3 are opposite, an FFP point and a gradient magnetic field required in the MPI system are generated, and the magnetic field intensity changes linearly within a certain range near the FFP point, so that the position of the SPION is subjected to space coding by utilizing the proportional relation between the magnetic field intensity of the gradient and the distance.
In the invention, in order to increase the flexibility and imaging area of the system, the permanent magnets 3 are designed into a dynamic structure with adjustable spacing, so that gradient magnetic field values with different gradient strengths are generated at different distances between the permanent magnets 3, and the different gradient magnetic field values can detect particles with different particle sizes according to the Lawnian theorem, thereby increasing the expandability of the system, so that the system not only can provide the performance with different spatial resolutions (the spatial resolution refers to the minimum spatial distance between adjacent particle clusters which can be observed), but also can expand the imaging range.
(2) Simulation and construction of the driving magnetic field:
the invention preliminarily designs the FOV to be 10mm multiplied by 20mm, wherein 20mm is arranged in the y direction and 10mm is arranged in the x direction in the figures 6 and 7; when the distance between the permanent magnets 3 is 100mm, a gradient magnetic field value of 1.7T/m can be generated, so that a driving magnetic field with a single peak value of 17mT is designed for generating a driving magnetic field with a length of 20mm in the y direction; in order to drive the FFP to traverse the SPION uniformly in the FOV, wherein the drive magnetic field needs to be designed to be relatively uniform enough to meet the requirement, the invention uses the drive coil 1 of the solenoid structure to generate the drive magnetic field; in order to avoid the current skin effect generated by using a single-strand copper wire, the invention uses the multi-strand wound litz wire as a current carrier, thereby not only avoiding the uneven distribution of a magnetic field, but also greatly reducing the heating and energy dissipation of the wire and saving the system energy.
A modeled image of the proposed drive coil 1 is shown in fig. 8; in the simulation platform, firstly, a modeling tool is used for modeling the solenoid, then, a corresponding 0.1mm multiplied by 1200 strand litz wire with the outer diameter of 5mm is selected as a lead material for modeling simulation to obtain a required 17mT driving magnetic field single peak value, the inner diameter of the solenoid is 50mm, the outer diameter of the solenoid is 90mm, the solenoid is wound by 80 turns in total and divided into four layers, and the system can meet the requirement by providing a current value of about 21A.
When a driving magnetic field is simulated, only ideal conditions are considered, the resistance value of a coil obtained through actual measurement is 5 ohms, and the ohm law shows that a voltage value of 105V is needed to achieve a current value of 21A, an expensive alternating current power amplifier capable of outputting 105V is needed to be used, if a signal output by a power amplifier is directly used for driving a coil 1, a large voltage value is needed, and therefore the voltage output capacity of the power amplifier is greatly tested, and therefore, in the invention, a series resonance mode is adopted to reduce the cost of the power amplifier; as shown in fig. 8, in this way, the coil and the capacitor can be matched to form a series resonance mode, and the effect of small voltage and large current can be easily realized at the resonance point according to the characteristics of the series resonance, so that the current output requirement is met, an expensive power amplifier is not required to be prepared, and the cost is reduced.
In this embodiment, the receiving coil 2 receives the nonlinear magnetization signal by adopting a differential structure design; the driving coil 1 generates an FFP (fringe field) to excite the SPION to generate a driving magnetic field with a nonlinear magnetization response, the driving magnetic field generated by the driving coil 1 excites the magnetic nano-particles to send the nonlinear magnetization response and generate a nonlinear magnetization signal, and the receiving coil 2 receives the SPION nonlinear magnetization signal generated by the magnetization response.
The invention adopts a receiving coil 2 with a space structure and a differential structure to receive the nonlinear magnetization signal of SPION; the specific description is as follows:
after the SPION is excited, according to the Raney's theorem, the particles can generate nonlinear magnetization response, and in the invention, a receiving coil 2 with a space structure and a differential structure is used for receiving SPION nonlinear magnetization signals; fig. 10 shows a basic structure of the receiving coil 2, in which the left coil and the right coil are wound in opposite directions, the left part is the main receiving coil 2 for coupling the driving signal and the response signal of the SPION, and the right part is the coil of the differential structure; the right coil has the same parameters except that the winding mode is opposite to that of the left coil, and the number of winding turns is more than that of the left coil; because the SPION is placed in the coil on the left and is far away from the differential coil on the right, the Faraday's electromagnetic induction theorem can know that the coil on the right is only coupled to the driving signal which has a phase difference of pi with the receiving coil 2 on the left, and because the coils are connected in series and the differential coil on the right is far away from the SPION, the driving signal coupled to the coil on the right and the driving signal coupled to the coil on the left are superposed into an offsetting mode, so that only the nonlinear magnetization signal of the SPION in the coil on the left is reserved, and further the driving signal is offset to a greater extent and the SPION signal is reserved, so that the driving signal is directly removed from the source under the condition of not introducing other clutter, the bandwidth requirement of a filter in a receiving link is reduced, the system cost is further reduced, the receiving coil is inserted into the driving coil 1 when in use, and the coil on the left and the driving coil 1 are placed in parallel, the center of which coincides with the center of the drive coil 1.
Because various noises are inevitably introduced in the actual environment, an external active filter is always inevitable, and the operational amplifier amplifies the received nonlinear magnetization signal of the SPION and adds a filter; the filter carries out filtering processing on the nonlinear magnetization signal, and 3-order and 5-order main harmonic signals of the SPION are processed and reserved; the received signals are converted into digital signals through an integrated analog-to-digital converter and transmitted to a main controller, the main controller transmits the original data to an upper computer in a gigabit Ethernet interface mode, and the upper computer stores the data and then carries out further image reconstruction for use.
As shown in fig. 11, the following describes the main transmission protocol of the gigabit ethernet used in the present invention in detail by using a specific embodiment:
the method comprises the following steps: an FPGA board card information request; and the PC terminal sends an information request to the FPGA controller so as to acquire the board card information of the FPGA, such as the ID model of the controller.
Step two: the FPGA responds to the request; the FPGA controller receives the information request of the terminal and responds to the request of the terminal.
Step three: requesting a data length; and the terminal sends a transmission data length instruction to the FPGA controller.
Step four: starting to transmit data; and after receiving the data request command, the FPGA controller starts to transmit corresponding data to the terminal according to the command of the requested data length.
The PC terminal or the upper computer firstly obtains the ID model of the main controller through the first step and the second step, then sends a data transmission preparation instruction to the FPGA controller, and the FPGA controller responds to the data transmission instruction and transmits the SPION original signal with the corresponding length to the terminal upper computer; due to the high speed of 1Gb/s of the gigabit Ethernet, the real-time property of the original data can be ensured; and repeating the process of the third step and the process of the fourth step to meet the requirement of real-time display and storage of the original data on the upper computer. In the embodiment, the controller is used for realizing the tasks of synthesis of the driving signal, output of the guide rail motion signal, receiving and transmission of the SPION original signal and the like, and a signal generator and a data acquisition card are replaced, so that the cost is greatly reduced, the system is more integrated and miniaturized, the system is guided to develop towards the direction of portability, and the bedside inspection becomes possible.
In the embodiment, the controller integrates an IP core through an internal gigabit Ethernet and uploads a digital signal received from the analog-to-digital converter to an upper computer for storage; the controller receives or collects the digital signal through the analog-to-digital converter and transmits the digital signal to the upper computer in real time at a transmission speed of 1Gb/s in a gigabit Ethernet mode; the upper computer stores the digital signals for image reconstruction, and the task is executed through an ARM inner core contained in the FPGA, so that high-speed data transmission is realized, a multi-task cooperative operation mechanism is realized, and the expandability and flexibility of the system are improved.
In the embodiment, the upper computer carries out image reconstruction on the image data based on a reconstruction algorithm of X-Space.
The image reconstruction of the present invention is explained in detail below with specific examples:
(1) selecting materials:
in the invention, a novel magnetic nanoparticle is used, the particle has the characteristics of no toxicity and no radiation, the SPION with water-based property is used as an experimental material in the invention and is not easy to aggregate, the carrier can be easily expanded to various application aspects, such as targeted drug release, cancer thermotherapy, blood vessel development and the like, side effects cannot be generated in a human body, the carrier can be easily discharged out of the body through renal circulation, and a non-toxic and non-radiation MPI system is really realized, because the particle has the diameter of less than 100nm, the particle is converted from paramagnetic to superparamagnetic, and the physical property of the superparamagnetic guides the particle to have the characteristic of single-domain magnetism, a nonlinear magnetization process can be generated in an alternating magnetic field, and the response can be coupled by a receiving coil 2 for imaging, and is the superparamagnetic nanoparticle used as shown in figure 12; FIG. 12 is a left side view (a) of a solution bottle containing 50nm SPION particles, which is horizontally placed as shown in the right side view (b) of FIG. 11, and a permanent magnet 3 is attached to the left side of the solution bottle in the b view; it can be seen that in the solution bottle in the b picture, the solution on the left side is more than that on the right side due to the action of the permanent magnet 3; this indicates that the permanent magnet 3 tests for paramagnetism contained in the liquid.
(2) Description of the image reconstruction procedure:
the invention carries out image reconstruction based on a reconstruction algorithm of X-Space, and the brief expression of the algorithm is as follows:
wherein ρ (x) [ particles/m ]3]Representing the spatial distribution of SPION, xs(t)Represents the instantaneous position of the FFP inside the FOV in an alternating motion over time (the drive signal is an alternating signal); b is1[T/A]Is the sensitivity of the receiving coil 2; m [ Am ]2]Is the magnetic moment of SPION; g [ A/m ]2]Is the gradient strength value of the gradient magnetic field; hsat(t)[A/m]Represents the saturation magnetization of SPION; s (t) represents the received time-varying signal of SPION, h (x) represents the derivative of the Langmuir function, which is an inherent property of SPION; the spatial distribution of SPION, the intensity value and the concentration of SPION can be obtained by solving the algorithm formula,The particle size and the volume of the test sample are in direct proportion.
In the invention, two groups of experiments are carried out to verify the function of the system, one group is that a group of test phantoms are manufactured by using SPION0.1ml with the grain diameter of 25mg/ml and 50nm to carry out basic two-dimensional imaging functional verification, as shown in a diagram a and a diagram b in fig. 13, the system can reconstruct 20 x 20 images, and the spatial distribution of basic SPION can be distinguished from the images; the other set is test phantoms with different pitches made by using 6 sets of SPION with the same parameters, the spatial resolution of the test system is shown in the a and b plots of FIG. 14, and it can be seen from the result graph that the system can achieve 4.5mm spatial resolution, and the more the SPION is concentrated in the middle of FOV, the stronger the signal.
From the above results, it can be seen that the system proposed and constructed by the present invention can perform basic imaging and 4.5mm spatial resolution on the spatial distribution of SPION.
Example 2
As shown in fig. 1 to 14, according to another embodiment of the present invention, there is provided a low-cost magnetic nanoparticle imaging method including the steps of:
s101: generating a driving signal based on a preset signal synthesis mode;
s102: amplifying and transmitting the driving signal;
s103: when receiving the amplified driving signal, generating a magnetization reaction and generating a nonlinear magnetization signal;
s104: amplifying the nonlinear magnetization signal;
s105: filtering the nonlinear magnetization signal;
s106: converting the nonlinear magnetization signal after filtering processing into a digital signal;
s107: transmitting the digital signal to an upper computer for storage;
s108: the stored digital signals are used for image reconstruction.
The process of the invention is illustrated in detail below with specific examples:
the method comprises the following steps: the main controller generates a driving signal based on a preset signal synthesis mode and sends the driving signal to the power amplifier; the controller is used for generating, receiving and transmitting signals, and the invention synthesizes the Digital form of the driving signal by using a Direct Digital Synthesizer (DDS) mode, and the mode can generate relatively pure signals, thereby saving external filters and reducing equipment cost. The DDS logic kernel is contained in the Programmable logic Gate array (FPGA) used in the invention and can be directly called, thereby saving time cost and research and development complexity and further reducing cost.
As a preferred scheme, an FPGA is used as a controller, and a driving signal required by the MPI system is synthesized by Direct Digital Synthesizer (DDS) synthesis and sent to a power amplifier for amplification, so that a traditional signal generator is not used directly.
Step two: the power amplifier is used for amplifying the driving signal and sending the driving signal to the magnetic field scanner; the drive signal is amplified by a power amplifier and then the amplified drive signal is transmitted to a drive coil 1 in the magnetic field scanner.
Step three: when receiving the amplified driving signal, the magnetic field scanner is used for generating a magnetization reaction, generating a nonlinear magnetization signal and sending the nonlinear magnetization signal to the operational amplifier; a driving coil 1 in the magnetic field scanner receives a driving signal, an FFP (fringe field) is generated on the driving coil 1 to excite a SPION (spin on Material) to generate a driving magnetic field with nonlinear magnetization response, the driving magnetic field generated by the driving coil 1 excites magnetic nano particles to generate nonlinear magnetization response, a receiving coil 2 receives the magnetization response and generates a nonlinear magnetization signal of the SPION, and the nonlinear magnetization signal is output to an operation method device for amplification processing.
Step four: the operational amplifier is used for amplifying the nonlinear magnetization signal and sending the nonlinear magnetization signal to the filter; the operational amplifier amplifies the nonlinear magnetization signal, and the amplified nonlinear magnetization signal is sent to the filter.
Step five: the filter is used for filtering the nonlinear magnetization signal and sending the nonlinear magnetization signal after filtering to the analog-to-digital converter; the filter carries out filtering processing on the amplified nonlinear magnetization signal and sends the nonlinear magnetization signal after filtering processing to the analog-to-digital converter;
step six: the analog-to-digital converter converts the received or collected nonlinear magnetization signal into a digital signal and transmits the digital signal to the FPGA controller.
Step seven: the controller is used for transmitting the digital signals to an upper computer for storage; the FPGA controller uploads the received data to an upper computer for storage in real time at a transmission speed of 1Gb/s through an internal gigabit Ethernet integrated kernel.
Step eight: then, image reconstruction is carried out on the spatial distribution of the SPION by using a reconstruction algorithm based on X-Space; the process is executed through an ARM inner core contained in the FPGA, so that high-speed data transmission is realized, a multi-task cooperative operation mechanism is realized, and the expandability and the flexibility of the system are improved.
The beneficial effects of the invention at least comprise:
(1) compared with a traditional MPI system, the invention abandons the traditional CPU controller, adopts a Programmable Gate array (FPGA) as the controller of the system, and realizes stronger system flexibility and expandability while reducing power consumption by using the inherent parallel computation and Programmable capability; programmable logic development is carried out by calling a pre-designed kernel of an open source in the FPGA, complicated program writing in a CPU is omitted, and only the running logic of the whole control program needs to be designed, so that the development time cost and the capital cost are greatly reduced, and the MPI system is promoted to be developed towards low-cost discovery.
(2) Compared with the traditional MPI system, the invention uses an FPGA controller to control the synthesis of the driving signal and the receiving and transmission of the SPION nonlinear response signal, and abandons the traditional signal generator, the traditional data acquisition card and various external water cooling, power supply and other equipment required by the electromagnetic coil, so that the whole system is more integrated and miniaturized, the occupied area and the manufacturing cost are greatly reduced, and the low-cost portable MPI system is realized.
(3) The scheme of the multi-dimensional MPI system is realized by using the controller to drive the movable guide rail driver to test the phantom, so that an electromagnetic coil used in the traditional MPI system is omitted, the stability of the system is improved, the cost is reduced, and the volume is reduced.
(4) The invention designs a permanent magnet 3 structure with adjustable space area to generate FFP and a gradient magnetic field. The structure can flexibly adjust the distance between the two permanent magnets 3, not only can achieve the purpose of expanding and reducing the size of the area to be measured, but also realizes the advantage of adjustable gradient magnetic field value; according to the Langewan classical paramagnetic theory, the gradient magnetic fields with different gradient strengths correspond to different detectable particle sizes; the invention can effectively enlarge the area to be measured and can meet the requirements of different sizes of particles used in different fields.
(5) Compared with a direct signal coupling coil used in a traditional MPI system, the receiving coil 2 with a differential structure filters most of driving signals from a source, reduces the bandwidth requirement of an external filter, and further reduces the cost of the system.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. A low cost magnetic nanoparticle imaging system, comprising: the device comprises a magnetic field scanner, a controller, an upper computer and an external supporting circuit, wherein the external supporting circuit is used for communicating the magnetic field scanner with the controller; the external support circuit includes: the device comprises a filter amplifier, an operational amplifier, a filter and an analog-to-digital converter; wherein the content of the first and second substances,
the controller generates a driving signal based on a preset signal synthesis mode and sends the driving signal to the power amplifier;
the power amplifier is used for amplifying the driving signal and sending the driving signal to the magnetic field scanner;
when the amplified driving signal is received, the magnetic field scanner is used for generating a magnetization reaction, generating a nonlinear magnetization signal and sending the nonlinear magnetization signal to the operational amplifier;
the operational amplifier is used for amplifying the nonlinear magnetization signal and sending the nonlinear magnetization signal to the filter;
the filter is used for filtering the amplified nonlinear magnetization signal and sending the filtered nonlinear magnetization signal to the analog-to-digital converter;
the analog-to-digital converter is used for converting the nonlinear magnetization signal after filtering processing into a digital signal and sending the digital signal to the controller;
the controller is used for transmitting the image digital signal to an upper computer for storage;
and the upper computer is used for carrying out image reconstruction on the stored digital signals.
2. The low-cost magnetic nanoparticle imaging system of claim 1, wherein the system employs a programmable gate array as the controller.
3. The low-cost magnetic nanoparticle imaging system of claim 1, wherein the controller synthesizes the drive signals using direct digital frequency.
4. The low-cost magnetic nanoparticle imaging system of claim 1, further comprising a rail driver that, upon receiving the drive signal, sends a phantom drive signal to the magnetic field scanner; the rail drive is used for movably testing a phantom inside the system.
5. The low-cost magnetic nanoparticle imaging system of claim 1, wherein the magnetic field scanner comprises a permanent magnet, a receive coil, and a drive coil; the driving coil is used for receiving the amplified driving signal and generating a driving magnetic field, the driving magnetic field excites the magnetic nanoparticles in the magnetic field scanner to send nonlinear magnetization reaction and generate nonlinear magnetization signals, and the receiving coil receives the nonlinear magnetization signals generated by the magnetization reaction; the permanent magnet is used for constructing a gradient magnetic field.
6. The low-cost magnetic nanoparticle imaging system of claim 5, wherein the pitch of the permanent magnets is designed in a dynamic configuration with adjustable pitch such that different distances between the permanent magnets produce the gradient magnetic fields of different gradient strengths.
7. The low-cost magnetic nanoparticle imaging system of claim 5, wherein the receive coil is configured to receive the non-linear magnetization signal using a differential configuration.
8. The low-cost magnetic nanoparticle imaging system of claim 1, wherein the controller uploads the digital signals received from the analog-to-digital converter to the host computer for storage via an internal gigabit ethernet integrated core.
9. The low-cost magnetic nanoparticle imaging system of claim 8, wherein the upper computer reconstructs the data based on an X-Space reconstruction algorithm.
10. A low-cost magnetic nanoparticle imaging method, comprising the steps of:
generating a driving signal based on a preset signal synthesis mode;
amplifying and transmitting the driving signal;
when the amplified driving signal is received, a magnetization reaction is carried out, and a nonlinear magnetization signal is generated;
amplifying the nonlinear magnetization signal;
filtering the amplified nonlinear magnetization signal;
converting the nonlinear magnetization signal after filtering processing into a digital signal;
transmitting the digital signal to an upper computer for storage;
and performing image reconstruction on the stored digital signals.
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