CN115067918B - FFL-based high-definition real-time imaging device, system and method - Google Patents

Abstract

A high-definition real-time imaging device, an imaging system and an imaging method based on an FFL solve the problems that in the prior art, other operations cannot be performed on a sample during imaging, an imaging area is limited, large sample scanning is difficult to realize, the resolution of three-dimensional tomography is low, the scanning speed is low, and the practicability is poor. The magnetic field-free line scanning device comprises a magnetic field-free line scanning coil group I and a magnetic field-free line scanning coil group II which are arranged on a base and can form a movable magnetic field-free line, wherein an open magnetic field-free line scanning area is arranged between the magnetic field-free line scanning coil group I and the magnetic field-free line scanning coil group II; the magnetic field coverage area of the excitation winding coil and the detection area of the detection winding coil correspond to the magnetic field line-free scanning area. The magnetic field-free magnetic field imaging device is reasonable in design and compact in structure, can generate uniform magnetic field-free lines in an imaging area, and can enlarge a detection space and facilitate clinical continuous observation and intraoperative observation while ensuring imaging resolution.

Description

FFL-based high-definition real-time imaging device, system and method

Technical Field

The invention belongs to the technical field of medical detection devices, and particularly relates to high-definition real-time imaging equipment, an imaging system and an imaging method based on FFL.

Background

Magnetic Particle Imaging (MPI), a brand new Imaging method for in vivo Imaging using highly safe superparamagnetic iron oxide nanoparticles as tracers; compared with the existing imaging technologies such as MRI, CT, PET and the like, the magnetic resonance imaging system has the important technical advantages of high sensitivity and high resolution, capability of avoiding harmful ionizing radiation, high safety of contrast agents, capability of realizing dynamic targeted imaging and the like. In addition, magnetic particle imaging technology can bring innovative technological breakthrough to clinical medicine in the fields of intraoperative imaging, persistent disease monitoring, dynamic targeting drug delivery and the like, and has become one of brand new imaging technologies which are attracted attention globally in recent years.

Currently, there are several research teams around the world developing Magnetic Particle Imaging (MPI) devices, wherein the totally enclosed MPI devices are developed by the german philips hamburger research institute and the university of california at berkeley and the university of china science and technology, and form a pre-clinical prototype product for commercialization, which implements movement of FFP field-free points in three-dimensional space by applying ac magnetic fields with different phases in three directions; in the aspect of signal receiving, detection coils arranged in different directions are used for acquiring directional components of alternating-current magnetization response signals generated by the magnetic nanoparticle contrast agent, and three-dimensional imaging is realized through an image reconstruction method. However, these MPI apparatuses all adopt a closed system structure, so that the imaging cannot be performed on the sample at the same time, and the sample to be detected needs to be completely placed in the closed detection space, the imaging area is limited, and the scanning of the large sample is difficult to achieve, and such a structure limits the clinical application range of MPI.

In addition, turkish team has also conducted three-dimensional tomographic research on MPI imaging apparatuses, which generate FFL field-free lines rotatable in the XY plane by an up-down symmetrical structure and realize scanning in the Z direction by moving a sample, and a gradient coil can simultaneously realize functions of generating a gradient field and an offset field. The position of the sample in the Z-axis direction is changed through the shifting device to realize three-dimensional tomography, and the scanning mode has low resolution in the Z-axis direction, low scanning speed and poor practicability. There is therefore a need for improvements in prior art magnetic particle imaging apparatus, imaging systems and imaging methods.

Disclosure of Invention

The invention aims at the problems and provides high-definition real-time imaging equipment, an imaging system and an imaging method based on FFL (fringe field switching), which adopt an open imaging structure, have a larger imaging space, can generate uniform magnetic field-free lines in an imaging area and are convenient for clinical continuous observation and intraoperative observation; the intensity is only limited by the gradient field and is not limited by the excitation field, the direct-current gradient field intensity and the linear range can be increased under the condition of keeping the low excitation field intensity, and the whole electric displacement three-dimensional scanning of the sample is not required to be carried out by a displacement device; the imaging resolution is ensured, and meanwhile, the detection space is expanded, and the method has more clinical research significance.

The technical scheme adopted by the invention is as follows: the high-definition real-time imaging device based on the FFL comprises a base, wherein a magnetic field line-free scanning coil group I and a magnetic field line-free scanning coil group II which can form a movable magnetic field-free field are arranged on the base, and an open magnetic field line-free scanning area is arranged between the magnetic field line-free scanning coil group I and the magnetic field line-free scanning coil group II; the magnetic field coverage area of the excitation winding coil and the detection area of the detection winding coil correspond to the magnetic field-free line scanning area.

Preferably, the magnetic field-free line scanning coil group I and the magnetic field-free line scanning coil group II have the same structure and respectively comprise a plurality of groups of magnetic field-free line scanning coils which are arranged in central symmetry. To facilitate the formation and movement of non-magnetic field lines.

Furthermore, the field-free line scanning coil comprises a scanning coil winding framework, the scanning coil wound on the scanning coil winding framework comprises a gradient winding coil and an offset winding coil, and the offset winding coil and the gradient winding coil are arranged in an inner layer and an outer layer. The gradient winding coils are used for generating non-magnetic field lines at the geometric center of the surface of the non-magnetic field line scanning coil group, and variable low-frequency current is introduced into each offset winding coil, so that the offset winding coils generate variable offset magnetic fields and are coupled with the original gradient magnetic fields, and the non-magnetic field lines move in two directions.

Furthermore, in the field-free line scanning coils which are arranged in central symmetry, the directions of the magnetic fields generated by the gradient winding coils in the two groups of scanning coils which are positioned at the diagonal positions are the same, and the directions of the magnetic fields generated by the gradient winding coils in the two adjacent groups of scanning coils are opposite; and the directions of the magnetic fields generated by the offset winding coils in the two groups of scanning coils which are positioned at the diagonal positions are opposite. The gradient winding coils at two diagonal positions generate magnetic fields in the same direction, and two adjacent gradient winding coils generate magnetic fields in opposite directions, so that a non-magnetic field is generated at the middle position of the four gradient winding coils according to the right-hand rule, a gradient field is generated around the non-magnetic field, and the magnetic field intensity is larger as the gradient field is farther away from the non-magnetic field; meanwhile, the magnetic field intensity on one side of the gradient field is enhanced and the magnetic field intensity on the other side of the gradient field is weakened through the changed direct current introduced into the offset winding coil, so that the effect of moving the non-magnetic field line is achieved.

Preferably, the gradient winding coil and the offset winding coil arranged on the inner and outer layers are wound in a square shape. So as to be beneficial to controlling the movement of the magnetic field-free line in all directions.

Preferably, the lower end of the scanning coil winding framework is provided with a scanning framework fixing substrate, and the upper end of the scanning coil winding framework is provided with an upper flange; a winding groove is formed between the upper flange and the scanning framework fixing substrate, and the gradient winding coil and the offset winding coil are wound in the winding groove. The scanning coil winding framework is fixed on the coil fixing plate through the scanning framework fixing base plate on the lower side, and the offset winding coil and the gradient winding coil which are arranged on the inner layer and the outer layer are respectively wound in the winding groove between the upper flange and the scanning framework fixing base plate layer by layer.

Preferably, the scanning coil winding framework is made of a magnetic core material. So as to further enhance the direct current magnetic field, thereby enhancing the gradient magnetic field and improving the spatial resolution.

Preferably, the scanning coil set cooling shell is arranged outside the non-magnetic field line scanning coil set I and the non-magnetic field line scanning coil set II, and a cooling medium is filled in the sealed scanning coil set cooling shell. The temperature of the non-magnetic field line scanning coil group I and the non-magnetic field line scanning coil group II is reduced by using a cooling medium such as liquid nitrogen, liquid helium or transformer oil filled in the cooling shell of the scanning coil group, so that the resistance of the coils is greatly reduced, the thermal noise of a system and the power of a power supply are reduced, and the running stability of equipment is improved.

Preferably, a liquid inlet and a liquid outlet are respectively arranged on the scanning coil assembly cooling shell, and a coil wiring terminal is further arranged at the top of the scanning coil assembly cooling shell. So that the cooling medium flows into the cooling shell of the scanning coil group through the liquid inlet and then flows out of the liquid outlet, thereby realizing circular flow; and the connection between the internal field-free line scanning coil and the coil power supply is facilitated by utilizing the coil wiring terminal.

Preferably, the excitation winding coil is constituted by a helmholtz coil. To reduce the thermal noise impact of energizing the wound coils with a helmholtz coil structure.

Preferably, the two parts of coil structures of the Helmholtz coil are respectively wound in winding grooves of the excitation coil winding frameworks arranged at two sides of the excitation coil supporting seat; and a sample placing table is arranged at the middle part of the Helmholtz coil and the upper part of the excitation coil supporting seat. The exciting winding coil is fixed in the middle of the base through the exciting coil supporting seat, and the exciting winding coil is divided into a left section and a right section by the exciting coil winding frameworks arranged on two sides of the exciting coil supporting seat, so that a Helmholtz coil structure is formed.

Preferably, the detection winding coil is an assembly, the detection winding coil of the assembly structure comprises at least one differential winding coil, the differential winding coil comprises a detection coil forward winding section and a detection coil reverse winding section which are separated and continuously arranged, and the winding number, the winding length and the winding layer number of the detection coil forward winding section and the detection coil reverse winding section are the same. The weak magnetic signal is detected by using a winding coil of a differential structure formed by the same winding wire, and the influence of an environmental magnetic field and an excitation magnetic field on the detection signal is reduced; and two-dimensional or three-dimensional scanning is realized by analyzing signals measured by a detection winding coil consisting of one or more differential winding coils; namely: the detection winding coil formed by one differential winding coil can realize two-dimensional scanning, and the detection winding coil formed by two or more differential winding coils can realize three-dimensional scanning. For example: the two detection winding coils can capture two groups of signals, and the spatial position information of the magnetic particles is obtained by utilizing the deviation of the signals detected by the two detection winding coils.

Preferably, the forward winding section and the reverse winding section of the detection coil of the differential winding coil are respectively arranged at two sides of the non-magnetic field line scanning coil group I or the non-magnetic field line scanning coil group II; and one section of the detection coil close to the magnetic field line-free scanning area is used as a differential detection section coil, and the other section of the detection coil far away from the magnetic field line-free scanning area is used as a differential noise reduction section coil. In order to effectively reduce the excitation and twine the coil interference while, lengthen the distance between the differential detection section coil and the differential noise reduction section coil of detecting the winding coil as far as possible, namely: on the basis of the structural size of the existing exciting winding coil, the differential detection section coil positioned on the inner side is close to the sample in the magnetic field-free line scanning area as much as possible, the differential noise reduction section coil positioned on the outer side is far away from the sample as much as possible, and then the difference value between the signals detected by the differential detection section coil and the differential noise reduction section coil is large as much as possible (the folding loss is reduced), so that the measurement is convenient.

Furthermore, the differential detection section coil is wound on the detection section winding framework, and the detection section winding framework is positioned in the middle of the excitation winding coil; the differential noise reduction section coil is wound on the noise reduction section winding framework, and the noise reduction section winding framework is connected with the upper part of the reinforcing coil supporting seat. To reduce interference of exciting the winding coil with detecting the winding coil.

Furthermore, an excitation enhancement coil is also arranged on the enhancement coil supporting seat, and the excitation enhancement coil is composed of Helmholtz coils; two parts of coil structures of the Helmholtz coil are respectively wound in winding grooves of reinforcing coil winding frameworks arranged on two sides of the reinforcing coil supporting seat; the noise reduction section winding framework is positioned between the reinforcing coil winding frameworks on the two sides. The Helmholtz coil structures (excitation enhancing coils) arranged on two sides of the differential noise reduction section of the detection winding coil are used for further reducing the thermal noise influence of the excitation winding coil.

Preferably, the axial relative position of the noise reduction section winding framework and the noise enhancement coil winding framework can be adjusted. With the adjustment mechanism who sets up between section of making an uproar winding skeleton and the reinforcing coil winding skeleton of falling through making an uproar, change the relative position of the section coil of making an uproar between two parts of coils of the excitation reinforcing coil that constitutes by helmholtz coil structure of falling differential, and then utilize the fine adjustment of axial position, offset because the noise influence that test environment changes and arouse, make things convenient for the use of device.

Furthermore, the noise reduction section winding framework is movably connected with the sliding guide long round hole in the upper part of the reinforcing coil supporting seat through the noise reduction sliding adjusting seat. The relative positions of the differential noise reduction section coil and the excitation enhancement coil are finely adjusted by utilizing the reciprocating movement of the noise reduction sliding adjusting seat along the sliding guide long round hole, so that the purpose of reducing noise is achieved, and the detection is close to an ideal state.

Preferably, the middle part of the exciting coil winding framework of the exciting winding coil is provided with a detection framework mounting hole, and the detection section winding framework of the detection winding coil is arranged in the detection framework mounting hole. The compactness of the middle structure of the device is improved, so that the placing space of the sample placing table on the upper part of the exciting coil supporting seat is enlarged.

Preferably, the exciting winding coil is made of a multi-stranded wire. So as to effectively avoid the phenomenon that the equivalent alternating-current impedance of the coil is increased caused by high-frequency eddy current.

A sample containing a superparamagnetic particle tracer is also arranged in the open magnetic field-free line scanning areaThis is true. The superparamagnetic particle tracer is a biological functionalized ferric oxide nano material, and the core of the tracer is Fe with the thickness of several nm to tens of nm ₂ O ₃ Or Fe ₃ O ₄ A magnetic core. Tracer contrast agents commonly used for MPI magnetic particle imaging are iron oxide magnetic nanoparticles (Fe) ₃ O ₄ ) Also known as superparamagnetic Iron Oxide Nanoparticles (SPIONs), polymer-coated Magnetic Nanoparticles (MNPs). It is smaller than the smallest size that can be achieved by a common ferromagnetic body magnetic domain, so that all the internal atomic magnetic moments point to the same direction, and a huge single magnetic domain effect is achieved. Magnetic nuclei in this size are affected by thermal runaway and have a greater free spin capability than conventional ferromagnets, i.e., superparamagnetism. The active groups coupled to the shell can bind to a variety of biomolecules, such as proteins, enzymes, antigens, antibodies, nucleic acids, etc., to achieve their functionalization. Therefore, the superparamagnetic particle tracer composed of the magnetic nanoparticles has the characteristics of both magnetic particles and polymer particles, and has magnetic guidance, biocompatibility, small-size effect, surface effect, active groups and certain biomedical functions.

A high-definition real-time imaging system comprises the FFL-based high-definition real-time imaging equipment and further comprises a gradient coil power supply, wherein the gradient coil power supply is electrically connected with each gradient winding coil in a non-magnetic field line scanning coil group I and a non-magnetic field line scanning coil group II respectively, and each offset winding coil in the non-magnetic field line scanning coil group I and the non-magnetic field line scanning coil group II is electrically connected with the other offset coil power supply capable of generating variable direct current; the excitation winding coil is electrically connected with an excitation signal output end of an alternating current power supply; the detection winding coil is electrically connected with the signal input end of the phase-locked amplifier, the signal output end of the phase-locked amplifier is electrically connected with the signal input end of the signal acquisition equipment, and the signal output end of the signal acquisition equipment is electrically connected with an upper computer for image reconstruction. Exciting the magnetization intensity of the magnetic nano particles at the magnetic field-free line in the magnetic field-free line scanning area to generate periodic variation by an alternating magnetic field generated by an exciting winding coil connected with an alternating current power supply, and further generating an alternating current magnetization signal; meanwhile, the magnetic nano particles in the magnetic field line scanning area and other positions have less change of magnetization intensity because the magnetization intensity is saturated. Moreover, because the magnetization curve of the magnetic nanoparticles is nonlinear, the magnetization signal has nonlinear characteristics, and fundamental wave and each harmonic component of the magnetization signal can be obtained through Fourier change; and then the alternating current magnetization signal of the superparamagnetic particle tracer positioned at the non-magnetic field line is detected through the detection winding coil and the phase-locked amplifier, and fundamental wave and harmonic components of the alternating current magnetization signal are obtained, so that the concentration of the magnetic nanoparticles at the point can be reversely deduced.

Preferably, an excitation series resonance for reducing ac impedance is provided between the excitation signal output terminal of the ac power supply and the connection terminal of the excitation winding coil. The alternating current impedance of the exciting circuit is reduced by utilizing the exciting series resonance formed by the capacitor, so that the exciting circuit can realize the improvement of the current intensity on the premise of high frequency.

Preferably, a detection parallel resonance for improving the signal-to-noise ratio is arranged between the connection end of the detection winding coil and the detection signal input end of the lock-in amplifier. To greatly enhance the detected signal strength and suppress the passage of non-detected signal frequency noise through the use of a detection parallel resonance. It will be appreciated that the excitation series resonance provided between the ac power source and the excitation winding coil, and the detection parallel resonance provided between the detection winding coil and the lock-in amplifier, may be arranged separately or simultaneously, depending on the particular application.

A high-definition real-time imaging method uses the high-definition real-time imaging system and comprises the following steps:

step one, introducing direct current into each gradient winding coil in the magnetic field-free line scanning coil group I and the magnetic field-free line scanning coil group II to form uniform magnetic field-free lines in a magnetic field-free line scanning area;

step two, introducing variable direct current into each offset winding coil in the magnetic field-free line scanning coil group I and the magnetic field-free line scanning coil group II, further forming a variable offset field, coupling the variable offset field with an original gradient field, and realizing the movement of the magnetic field-free line in the magnetic field-free line scanning area;

placing a sample containing the superparamagnetic particle tracer in a magnetic field-free line scanning area, and then applying a high-frequency sinusoidal alternating magnetic field to the magnetic field-free line scanning area through an exciting winding coil; in addition, because the magnetization intensity of the magnetic nanoparticles in the non-magnetic field line scanning area and at other positions except the non-magnetic field line reaches saturation and the change of the magnetization intensity is small, only the magnetic nanoparticles at the non-magnetic field line are subjected to alternating current magnetization, and due to the nonlinear magnetization characteristic of the magnetic nanoparticles, fundamental wave and each subharmonic component of a magnetization signal are obtained through Fourier change;

detecting an alternating current magnetization signal of the superparamagnetic particle tracer in the sample at the position of a non-magnetic field line by detecting the wound coil, and obtaining fundamental wave and harmonic component of the magnetization signal by using a phase-locked amplifier;

acquiring a magnetic field or voltage distribution diagram through acquisition of fundamental wave and harmonic wave signals, and then, calculating and reconstructing the back to deduce the concentration of the magnetic nanoparticles in an upper computer so as to obtain the concentration distribution of the superparamagnetic particle tracer in the sample at each point in space and finish imaging of the organization structure; and taking a series of XY planes with different heights along the Z axis, respectively establishing a system function in the XY plane with each height, and restoring the detected magnetization response signal into the sample concentration on the XY plane with each height by using a least square method, thereby realizing the tomography in the Z direction.

Further, before actually scanning a sample containing a superparamagnetic particle tracer with unknown concentration, scanning a standard sample which is placed at a fixed position and contains a known superparamagnetic particle tracer with high concentration, and calculating the relationship between the position, concentration and the like of the tracer and a collected signal to form a system function; and then, scanning an actual sample (containing the superparamagnetic particle tracer with unknown concentration), and calculating the acquired magnetic field signal in a singular value decomposition or least square method or other modes to reduce the acquired magnetic field or voltage signal into a concentration distribution signal of the superparamagnetic particle tracer in the space, so as to realize image reconstruction.

Preferably, in the fifth step, multiple harmonic components generated by the nonlinear magnetization of the nano-magnetic particles are collected for imaging. The interference of other signals is effectively avoided by acquiring the signals of the harmonic signals under a fixed certain frequency; and signal interference generated by an excitation place exists when fundamental waves are collected.

Furthermore, only the third harmonic generated by the nonlinear magnetization of the nano magnetic particles is collected for imaging. The strongest third harmonic signal of the collected signal is fixed, which is beneficial to imaging.

Preferably, a dc component is added to the sinusoidal excitation field to collect even harmonics. To perform imaging with the second harmonic signal having a large amplitude.

The invention has the beneficial effects that: because the base is provided with the non-magnetic field line scanning coil group I and the non-magnetic field line scanning coil group II which can form a movable non-magnetic field line, an open non-magnetic field line scanning area is arranged between the non-magnetic field line scanning coil group I and the non-magnetic field line scanning coil group II; the magnetic field coverage area of the excitation winding coil and the detection area of the detection winding coil are in a structural form corresponding to the magnetic field line-free scanning area, so that the magnetic field line-free magnetic imaging device is reasonable in design and compact in structure, adopts an open type imaging structure, has a larger imaging space, can generate uniform magnetic field line-free lines in the imaging area, realizes in-vivo imaging, and is convenient for clinical continuous observation and intraoperative observation; moreover, the signal intensity detected by the detection winding coil is only limited by the gradient field and is not limited by the excitation field, and the direct current gradient field intensity and the linear range can be increased under the condition of keeping the low excitation field intensity; the imaging resolution is effectively improved, and meanwhile, the detection space is expanded. Meanwhile, the signal to noise ratio can be greatly improved and the imaging definition can be improved by cooling the cooling medium and acquiring harmonic imaging.

Compared with the traditional closed magnetic particle imaging device and system, the open magnetic particle imaging system has the advantage of open scanning space, can perform other operations on a sample while imaging, and has more clinical use value. In addition, because the two layers of the magnetic field-free line scanning coil group I and the magnetic field-free line scanning coil group II which are symmetrically arranged are used, compared with other open type MPI imaging equipment, the FFL (fringe field switching) imaging system can form an FFL (fringe field) magnetic field and a gradient magnetic field which are better in uniformity in a detection space, can restore the concentration of a sample more accurately, realizes more accurate three-dimensional image reconstruction, further achieves better image resolution, does not need omnibearing three-dimensional electronic scanning of a shifting device, and is strong in practicability.

Drawings

Fig. 1 is a schematic structural diagram of an FFL-based high-definition real-time imaging device according to the present invention.

Fig. 2 is a sectional view of an internal structure of fig. 1.

Fig. 3 is a partial schematic view of the excitation winding coil, the excitation boost coil i and the excitation boost coil ii of fig. 1 with the excitation winding coil, the excitation boost coil i and the excitation boost coil ii removed.

Fig. 4 is a schematic structural diagram of a magnetic field-free line scanning coil assembly i (magnetic field-free line scanning coil assembly ii) in the cooling housing of the scanning coil assembly in fig. 3.

Fig. 5 is a cross-sectional view of an internal structure of the cooling housing of the scanning coil assembly of fig. 3.

Fig. 6 is a schematic diagram of one configuration of the field-free line scanning coil of fig. 4.

Fig. 7 is a sectional view of the internal structure of fig. 6.

Fig. 8 is a partial structural diagram of fig. 1 with the cooling housing of the scanning coil assembly, the magnetic field-free line scanning coil assembly i and the magnetic field-free line scanning coil assembly ii removed.

Fig. 9 is a sectional view of the internal structure of fig. 8.

Fig. 10 is a schematic view of one configuration of the detection winding coil i and the detection winding coil ii in fig. 8.

Fig. 11 is a partial schematic view of the excitation boost coil i of fig. 8 at the location.

Fig. 12 is a partial schematic view of the field winding coil of fig. 8 at the location of the field winding coil.

FIG. 13 is a schematic diagram of an embodiment of a high definition real time imaging system of the present invention.

Fig. 14 is a circuit connection block diagram of fig. 13.

Fig. 15 is a waveform diagram of two sets of triangular wave currents applied to the offset winding coil by the offset coil power supply of fig. 13.

Fig. 16 is a schematic view showing a state of use in which the magnetic field lines are not formed by the magnetic field line-free scanning coil group i and the magnetic field line-free scanning coil group ii and move in the X-axis direction.

Fig. 17 is a schematic view showing a state of use in which the magnetic field lines are not formed by the magnetic field line-free scanning coil group i and the magnetic field line-free scanning coil group ii and move in the Y-axis direction.

Fig. 18 is a simulation diagram of the gradient-wound coils of the magnetic field-free line scanning coil set i and the magnetic field-free line scanning coil set ii generating magnetic field-free lines (magnetic field-free points) by the gradient magnetic field.

Fig. 19 is a simulation of the magnetic field-free line scanning coil set i and the magnetic field-free line scanning coil set ii in which the respective offset winding coils offset the magnetic field-free lines (magnetic field-free points).

Fig. 20 is a point spread function voltage distribution diagram in the embodiment of the present invention.

FIG. 21 is a voltage distribution diagram of a sample of "O" -type magnetic nanoparticles in an example of the present invention.

FIG. 22 is a graph showing the concentration distribution of the "O" type magnetic nanoparticle sample in the example of the present invention.

The sequence numbers in the figures illustrate: a base 1,2 no magnetic field line scanning coil group I, 3 no magnetic field line scanning coil group II, 4 scanning coil group cooling shell, 5 excitation winding coil, 6 excitation enhancing coil I, 7 excitation enhancing coil II, 8 no magnetic field line scanning area, 9 detection winding coil I, 10 detection winding coil II, 11 liquid inlet, 12 liquid outlet, 13 coil terminal, 14 coil fixing plate, 15 no field line scanning coil, 16 scanning framework fixing substrate, 17 scanning coil winding framework, 18 offset winding coil, 19 gradient winding coil, 20 upper flange, 21 framework connecting bolt, 22 enhancement coil supporting seat, 23 excitation coil supporting seat, 24 sample placing table, 25 difference detection section coil, 26 detection section winding framework, 27 difference noise reduction section coil, 28 noise reduction section winding framework, 29 enhancement coil winding framework, 30 noise reduction sliding adjusting seat, 31 sliding guiding oblong hole, 32 excitation coil winding framework, 33 detection framework placing hole, 34 gradient coil power supply, 35 offset coil power supply, 36 alternating current power supply, 37 excitation series resonance, 38 resonance imaging sample, 39 detection parallel resonance imaging, 40 phase-locked phase detection amplifier, 41 phase-locked loop signal acquisition equipment, 43 no magnetic field line signal acquisition equipment upper computer, 42 no magnetic field signal acquisition equipment.

Detailed Description

The specific structure of the present invention will be described in detail with reference to FIGS. 1 to 13. The high-definition real-time imaging device based on the FFL comprises a base 1, wherein a magnetic field line-free scanning coil group I2 and a magnetic field line-free scanning coil group II 3 which are used for forming magnetic field lines which can move freely are arranged on the base 1, and an open magnetic field line-free scanning area 8 is arranged between the magnetic field line-free scanning coil group I2 and the magnetic field line-free scanning coil group II 3 which are symmetrically arranged on the base 1 from left to right; by utilizing the two groups of scanning coil groups, more uniform FFL (fringe field free) magnetic field lines are generated in the imaging area in the middle part, so that the concentration of a sample is accurately reduced, and more accurate three-dimensional image reconstruction is facilitated. In addition, an excitation winding coil 5 is arranged in the magnetic field line-free scanning area 8, and the magnetic field coverage area of the excitation winding coil 5 corresponds to the magnetic field line-free scanning area 8; the base 1 is also provided with a detection winding coil, and the detection area of the detection winding coil corresponds to the magnetic field-free line scanning area 8. Other types of magnetic signal detection devices such as a magnetoresistive sensor may be used in place of the detection winding coil, as required.

The structure of the magnetic field line-free scanning coil group i 2 and the magnetic field line-free scanning coil group ii 3 which are symmetrically arranged is the same, and each of the magnetic field line-free scanning coil groups includes four groups (or eight groups) of magnetic field line-free scanning coils 15 which are centrosymmetrically arranged, the four groups of magnetic field line-free scanning coils 15 are arranged in a shape like a Chinese character 'tian' (as shown in fig. 4), and the four groups of magnetic field line-free scanning coils 15 are fixedly arranged on the coil fixing plate 14, so that the formation of magnetic field lines and the movement of the magnetic field lines in the magnetic field line-free scanning area 8 are facilitated.

The field-free scanning coil 15 includes a scanning coil winding bobbin 17 having a square longitudinal cross section, the scanning coil wound on the scanning coil winding bobbin 17 includes a gradient winding coil 19 and an offset winding coil 18, and the offset winding coil 18 and the gradient winding coil 19 are arranged in inner and outer layers. Namely: the gradient winding coil 19 is directly wound on the scanning coil winding framework 17, and the offset winding coil 18 is wound outside the gradient winding coil 19; then, each gradient winding coil 19 is utilized to generate a non-magnetic field line at the geometric center of the surfaces of the non-magnetic field line scanning coil group I2 and the non-magnetic field line scanning coil group II 3, and the non-magnetic field lines formed by the non-magnetic field line scanning coil group I2 and the non-magnetic field line scanning coil group II 3 are overlapped; and a varying low frequency current is passed through each of the off-set coils 18 to cause the off-set coils 18 to generate a varying off-set magnetic field and to couple with the original gradient magnetic field, thereby achieving bidirectional movement of the field-free lines. It will be appreciated that the offset winding coil 18 may be wound directly on the scan coil winding former 17, while the gradient winding coil 19 may be wound outside the offset winding coil 18; in this case, the field-less line scanning coil 15 can be used normally as well, but the arrangement in which the offset winding coil 18 is located inside has a small offset range of the field-less line.

In the four sets of field-free scanning coils 15 arranged in central symmetry in the field-free scanning coil set i 2 and the field-free scanning coil set ii 3, the directions of the magnetic fields generated by the gradient winding coils 19 in two sets (set a and set B) of scanning coils located at diagonal positions are the same, the directions of the magnetic fields generated by the gradient winding coils 19 in two adjacent sets of scanning coils are opposite (as shown in fig. 16 and 17), and the directions of the magnetic fields of the two sets of gradient winding coils 19 are kept unchanged; the two sets of gradient winding coils 19 may also be made of permanent magnets, depending on the particular application. Meanwhile, the directions of the magnetic fields generated by the offset winding coils 18 in the two sets of scanning coils located at diagonal positions are opposite, and the directions of the magnetic fields of the two sets of offset winding coils 18 can be periodically changed. Furthermore, currents with the same magnitude and different directions are respectively introduced into two groups of four gradient winding coils 19 with the same specification, or currents with the same magnitude and the same direction are introduced into two groups of gradient winding coils 19 with opposite winding directions, so that the gradient winding coils 19 at two diagonal positions generate magnetic fields with the same direction, and two adjacent gradient winding coils 19 generate magnetic fields with opposite directions; therefore, according to the right-hand rule, the non-magnetic field lines are generated at the intermediate positions of the four gradient winding coils 19, and the gradient field is generated around the non-magnetic field lines, and the field intensity increases as the gradient field is farther from the non-magnetic field lines. At the same time, the changing direct current (as shown in fig. 15) flowing through the offset winding coil 18 increases the magnetic field strength on one side of the gradient field and decreases the magnetic field strength on the other side, thereby achieving the effect of moving the non-magnetic field (as shown in fig. 16 and 17).

In order to facilitate the control of the movement of the magnetic field-free lines in all directions, the gradient winding coil 19 and the offset winding coil 18 which are arranged in the inner layer and the outer layer of the magnetic field-free line scanning coil 15 and are arranged in the central symmetry manner in the magnetic field-free line scanning coil group I2 and the magnetic field-free line scanning coil group II 3 are both wound in a square manner, namely: the longitudinal cross-sections of the gradient winding coil 19 and the offset winding coil 18 are both square. The scanning coil winding backbone 17 of each field line free scanning coil 15 may be made of a magnetic core material (e.g., a soft magnetic core material) to further enhance the dc magnetic field, thereby enhancing the gradient magnetic field and increasing spatial resolution.

A scanning framework fixing substrate 16 is arranged at the lower end of the scanning coil winding framework 17, and an upper flange 20 is arranged at the upper end of the scanning coil winding framework 17; the scanning bobbin fixing substrate 16 is connected to the scanning coil winding bobbin 17 by a bobbin connecting bolt 21. A winding groove is formed between the upper flange 20 of the scanning coil winding bobbin 17 and the lower scanning bobbin fixing substrate 16, and the gradient winding coil 19 and the offset winding coil 18 are wound in the winding groove layer by layer. A scanning coil winding bobbin 17 is fixed to the coil fixing plate 14 through a lower scanning bobbin fixing base plate 16, and windings (nonmagnetic wires) of an offset winding coil 18 and a gradient winding coil 19, which are arranged on inner and outer layers, are wound in a winding groove between an upper flange 20 and the scanning bobbin fixing base plate 16, respectively, layer by layer.

And a cooling shell 4 of the scanning coil group is respectively arranged outside the non-magnetic field line scanning coil group I2 and the non-magnetic field line scanning coil group II 3, and a cooling medium (liquid nitrogen, liquid helium or transformer oil) is filled in the sealed cooling shell 4 of the scanning coil group. A liquid inlet 11 and a liquid outlet 12 which are convenient for a cooling medium to flow are respectively arranged on the scanning coil group cooling shell 4, and a coil wiring terminal 13 is also arranged at the top of the scanning coil group cooling shell 4; so that the cooling medium flows into the cooling shell 4 of the scanning coil assembly through the liquid inlet 11 and then flows out of the liquid outlet 12 to realize circular flow; and facilitates connection of the internal field-line-less scanning coils 15 (gradient winding coil 19 and offset winding coil 18) to coil power supplies (gradient coil power supply 34 and offset coil power supply 35), respectively, using coil terminals 13. And then through the flow of the cooling medium such as liquid nitrogen, liquid helium or transformer oil filled in the cooling shell 4 of the scanning coil group, the temperature of the non-magnetic field line scanning coil group I2 and the non-magnetic field line scanning coil group II 3 is reduced, so that the resistance of the coils is greatly reduced, the thermal noise of the system and the power supply power are reduced, and the running stability of the equipment is improved.

The excitation winding coil 5 provided in the magnetic field-free line scanning region 8 is constituted by a helmholtz coil to reduce the thermal noise influence of the excitation winding coil 5 by using a helmholtz coil structure. Windings (non-magnetic wires) of two coil structures of the Helmholtz coil are respectively wound in winding grooves of the excitation coil winding frameworks 32 on two sides of the excitation coil supporting seat 23 arranged in the middle of the base 1; the excitation coil winding former 32 may be made of a non-magnetic, non-conductive non-metallic material. Further, a sample placement stage 24 on which an imaging sample 38 is placed is provided in the middle of the excitation winding coil 5 and above the excitation coil support base 23 of the helmholtz coil structure. Therefore, the excitation winding coil 5 is fixed in the middle of the base 1 through the excitation coil support seat 23, and the excitation winding coil 5 is divided into a left section and a right section by the excitation coil winding frameworks 32 arranged on the two sides of the excitation coil support seat 23, so as to form a helmholtz coil structure.

The detection winding coil is of an assembly structure and comprises at least one differential winding coil (for example, two differential winding coils of a detection winding coil I9 and a detection winding coil II 10 are adopted), the differential winding coil comprises a detection coil forward winding section and a detection coil reverse winding section which are separated from each other and continuously arranged, and the winding number, the winding length and the winding layer number of the detection coil forward winding section and the detection coil reverse winding section are the same. The method comprises the steps of detecting weak magnetic signals by using a winding coil of a differential structure formed by the same winding (non-magnetic wire), and reducing the influence of an environmental magnetic field and an excitation magnetic field on detection signals; and the three-dimensional scanning of the sample is realized by analyzing the signals measured by the detection winding coil consisting of the detection winding coil I9 and the detection winding coil II 10 which are of two differential winding coils. Meanwhile, the detection winding coil formed by one differential winding coil can realize two-dimensional scanning, and the detection winding coil formed by two or more differential winding coils can realize three-dimensional scanning. For example: the two detection winding coils can capture two groups of signals, and the spatial position information of the magnetic particles is obtained by utilizing the deviation of the signals detected by the two detection winding coils.

A detection coil forward winding section and a detection coil reverse winding section of the detection winding coil I9 and the detection winding coil II 10 are respectively arranged on two sides of the magnetic field-free line scanning coil group I2 and two sides of the magnetic field-free line scanning coil group II 3; further, one detection coil near the middle field-free line scanning region 8 is used as a differential detection coil 25, and the other detection coil far from the field-free line scanning region 8 is used as a differential noise reduction coil 27 (see fig. 9 and 10). Further, while effectively reducing the interference of the excitation winding coil 5, the distance between the differential detection section coil 25 (detection coil forward winding section) and the differential noise reduction section coil 27 (detection coil reverse winding section) of the detection winding coil is lengthened as much as possible, that is: on the basis of the structural size of the existing exciting winding coil 5, the differential detection section coil 25 positioned on the inner side is made to be as close to the sample in the magnetic field line-free scanning area 8 as possible, the differential noise reduction section coil 27 positioned on the outer side is made to be as far away from the sample as possible, and then the difference value between the signals detected by the differential detection section coil 25 and the differential noise reduction section coil 27 is made to be as large as possible (the breakage is reduced), so that the measurement is convenient.

A differential detection section coil 25 of the detection winding coil I9 and the detection winding coil II 10 is wound on a detection section winding framework 26, and the detection section winding framework 26 is positioned in the middle of an excitation coil winding framework 32 of the excitation winding coil 5; the differential noise reduction section coil 27 of the detection winding coil I9 and the detection winding coil II 10 is wound on a noise reduction section winding framework 28, and the noise reduction section winding framework 28 is connected with the upper part of the enhanced coil supporting seat 22; two enhancement coil supporting seats 22 are respectively arranged at the outer sides of the magnetic field-free line scanning coil group I2 and the magnetic field-free line scanning coil group II 3, and the bottoms of the enhancement coil supporting seats 22 are connected with the base 1 so as to reduce the interference of the exciting winding coil 5 on the detection winding coil. Detection section winding skeleton 26 and fall and make an uproar section winding skeleton 28 and make by non-magnetic, non-conductive non-metallic material, and still be provided with the opening of arranging on detection section winding skeleton 26 and the section of falling an uproar section winding skeleton 28 to the wire winding that comes the detection winding coil through the opening of arranging is in the business turn over of winding skeleton winding groove, and guarantees the unanimity of the section coil 25 of differential detection and the section coil 27 of falling a difference winding number of turns, effectively avoids the appearance of tiny turn number error.

Excitation enhancement coils I6 and excitation enhancement coils II 7 which are symmetrically arranged are further arranged on the enhancement coil supporting seats 22 at the two ends of the base 1 respectively, and the excitation enhancement coils I6 and the excitation enhancement coils II 7 are both formed by Helmholtz coils; and further eliminating the conditions that the aluminum plates of the gradient winding coil 19 and the scanning coil group cooling shell 4 influence the excitation winding coil 5, so that the differential structure of the detection winding coil I9 and the detection winding coil II 10 is asymmetric, and the basic noise is overlarge. Meanwhile, two Helmholtz coil structures of the excitation enhancement coil are respectively wound in winding grooves of enhancement coil winding frameworks 29 arranged on two sides of the enhancement coil supporting seat 22; and the noise reduction section winding bobbin 28 of the detection winding coil is located between the reinforcing coil winding bobbins 29 on both sides thereof. And then, the excitation enhancement coil I6 and the excitation enhancement coil II 7 of Helmholtz coil structures arranged on two sides of the differential noise reduction section coil 27 of the detection winding coil are used for providing differential alternating current signals, so that the thermal noise influence of the excitation winding coil 5 is further reduced.

The axial relative position of the noise reduction section winding framework 28 on the reinforcing coil supporting seat 22 and the reinforcing coil winding frameworks 29 on the two sides of the noise reduction section winding framework can be adjusted; the adjusting mechanism that sets up between section of making an uproar winding skeleton 28 and the enhancement coil winding skeleton 29 in order to fall changes the relative position of the difference section of making an uproar coil 27 of making an uproar between excitation enhancement coil I6 and the two parts helmholtz coil of excitation enhancement coil II 7 that detects winding coil I9 and detection winding coil II 10, and then utilizes the fine adjustment of axial position, offsets because the noise influence that the test environment changes and arouses, facilitates the use of device.

The noise reduction section winding framework 28 is movably connected with sliding guide oblong holes 31 at two sides of the upper part of the reinforcing coil supporting seat 22 through a noise reduction sliding adjusting seat 30 at the bottom (as shown in fig. 11); it will be appreciated that other configurations for fine positioning may be used depending on the particular application. Therefore, the relative positions of the differential noise reduction section coil 27 and the excitation enhancement coil I6 and the excitation enhancement coil II 7 are finely adjusted by utilizing the reciprocating movement of the noise reduction sliding adjusting seat 30 along the sliding guide long round hole 31, so that the purpose of reducing noise is achieved, and the detection is close to an ideal state.

Two excitation coils of the excitation winding coil 5 of the Helmholtz coil structure are wound on the middle part of the framework 32 and are respectively provided with a detection framework placing hole 33; the detection section winding frameworks 26 of the detection winding coil I9 and the detection winding coil II 10 are respectively arranged in the detection framework arrangement holes 33 (as shown in FIG. 12); so as to improve the compactness of the middle structure of the device and further increase the placing space of the sample placing table 24 at the upper part of the exciting coil supporting seat 23.

In order to effectively avoid the phenomenon of increasing the equivalent direct current resistance of the coil caused by high-frequency eddy current, a plurality of stranded wires (litz wires) formed by stranding or weaving a plurality of independent insulated wires are used for manufacturing an excitation winding coil 5, an excitation enhancement coil I6 and an excitation enhancement coil II 7 which have a Helmholtz coil structure. The detection winding coil i 9 and the detection winding coil ii 10, and the gradient winding coil 19 and the offset winding coil 18 of the field-free line scanning coil 15 are made of a common single strand of copper wire (non-magnetic wire).

The invention uses liquid nitrogen, liquid helium or transformer oil and other cooling media to cool the non-magnetic field line scanning coil group I2 and the non-magnetic field line scanning coil group II 3 in the scanning coil group cooling shell 4 of the imaging device, and when the coil temperature is reduced to the temperature of the cooling media, the coil resistance is greatly reduced. Under the condition, the thermal noise of the system is reduced, the stability is increased, and the power of the power supply is reduced. For example: the detection winding coil is made of high-temperature superconducting materials, so that the direct-current resistance is reduced to zero under the cooling of liquid nitrogen, the thermal noise of the coil is reduced, and the detection sensitivity is improved; if the detection winding coil is made of low-temperature superconducting materials, direct current resistance is reduced to zero under the cooling of liquid helium, so that the thermal noise of the coil is reduced, and the detection sensitivity is improved. When the gradient winding coil 19 and the offset winding coil 18 in the non-magnetic field scanning coil set are made of high-temperature superconducting materials, the direct-current resistance is reduced to zero under the cooling of liquid nitrogen, the power of a power supply is reduced, and therefore the gradient field strength is improved by using larger direct current and the scanning range of the offset winding coil 18 is enlarged; if the gradient winding coil 19 and the offset winding coil 18 are made of low-temperature superconducting materials, the direct-current resistance is reduced to zero under the cooling of liquid helium, and the power supply power is reduced; to increase the gradient field strength and extend the scan range of the offset wrap coils 18 with a larger dc current.

And a sample containing a superparamagnetic particle tracer agent is also arranged in the open type magnetic field-free line scanning area 8 between the magnetic field-free line scanning coil group I2 and the magnetic field-free line scanning coil group II 3. The super paramagnetic particle tracer (magnetic nano particle) used in magnetic particle imaging is a biological functionalized ferric oxide nano material, and the core of the material is Fe with the thickness of several nm to tens of nm ₂ O ₃ Or Fe ₃ O ₄ A magnetic core. Tracer contrast agents commonly used for MPI magnetic particle imaging are iron oxide magnetic nanoparticles (Fe) ₃ O ₄ ) Also known as superparamagnetic Iron Oxide Nanoparticles (SPIONs), polymer-coated Magnetic Nanoparticles (MNPs). Which is smaller than the smallest dimension that can be achieved by a typical ferromagnetic body domain, so that all the internal atomic magnetic moments point in the same directionAnd has huge single magnetic domain effect. Magnetic nuclei in this size are affected by thermal runaway and have a greater free spin capability than conventional ferromagnets, i.e., superparamagnetism. The active groups coupled to the shell can bind to a variety of biomolecules, such as proteins, enzymes, antigens, antibodies, nucleic acids, etc., to achieve their functionalization. Therefore, the superparamagnetic particle tracer composed of the magnetic nanoparticles has the characteristics of magnetic particles and polymer particles, and has magnetic guidance, biocompatibility, small-size effect, surface effect, active group and certain biomedical function.

The high-definition real-time imaging system for magnetic particle imaging by using the high-definition real-time imaging equipment based on the FFL further comprises a gradient coil power supply 34, wherein the gradient coil power supply 34 is electrically connected with each gradient winding coil 19 in the non-magnetic field line scanning coil group I2 and the non-magnetic field line scanning coil group II 3 respectively; each offset winding coil 18 in the non-magnetic field line scanning coil set I2 and the non-magnetic field line scanning coil set II 3 is electrically connected with another offset coil power supply 35 which can generate variable direct current. The excitation winding coil 5, the excitation enhancement coil I6 and the excitation enhancement coil II 7 are electrically connected with an excitation signal output end of an alternating current power supply 36. The detection winding coil I9 and the detection winding coil II 10 are electrically connected with the signal input end of the lock-in amplifier 40, the signal output end of the lock-in amplifier 40 is electrically connected with the signal input end of the signal acquisition device 41, and the signal output end of the signal acquisition device 41 is electrically connected with the upper computer 42 for image reconstruction; and the imaging system is cooled using liquid nitrogen, liquid helium or transformer oil. Thus, the magnetization of the magnetic nanoparticles at the field-free lines in the field-free line scanning region 8 is excited to periodically change by the alternating magnetic field generated by the excitation winding coil 5 connected to the alternating current signal source (alternating current power source 36) to generate an alternating current magnetization signal; meanwhile, the magnetic nano particles in the non-magnetic field line scanning area 8 and other positions have saturated magnetization intensity, so that the change of the magnetization intensity is small. Moreover, because the magnetization curve of the magnetic nanoparticles is nonlinear, the magnetization signal has nonlinear characteristics, and fundamental wave and each harmonic component of the magnetization signal can be obtained through Fourier change; and detecting the alternating current magnetization signal of the superparamagnetic particle tracer at the position without the magnetic field lines through the detection winding coil I9, the detection winding coil II 10 and the lock-in amplifier 40, and obtaining fundamental waves and harmonic components of the alternating current magnetization signal so as to reversely deduce the concentration of the magnetic nanoparticles at the position.

An excitation series resonance 37 for reducing alternating current impedance is arranged between an excitation signal output end of the alternating current power supply 36 and connecting ends of the excitation winding coil 5, the excitation enhancement coil I6 and the excitation enhancement coil II 7; the ac impedance of the excitation circuit is reduced by the excitation series resonance 37 formed by the capacitor, so that the excitation circuit can realize the improvement of the current intensity on the premise of high frequency. The excitation frequency is determined by the relaxation time of the superparamagnetic nanoparticles, i.e. for superparamagnetic particles which are not bound to the detected object, the excitation period is far less than the denier relaxation time of the superparamagnetic particles and slightly greater than or equal to the brownian relaxation time thereof is satisfied. Generally, magnetic nuclei above 20nm can meet the Neille relaxation time requirements, while Brownian relaxation times are generally availableτ _B = πη d _H ³ /2k _B TIs shown in whichηIn order to obtain the viscosity of the solution,k _B Tin order to be a thermal energy,d _H is the magnetic particle hydraulic diameter.

The detection winding coil I9 and the detection winding coil II 10 are used for detecting alternating current magnetization signals generated by magnetic particles, and because the superparamagnetic particles have nonlinear magnetization properties, in order to reduce excitation noise interference, a harmonic signal detection method is adopted to detect the signals. The magnetic sensitive immunity detection device can detect the magnetic particle signals in an odd harmonic mode or an even harmonic mode. When the excitation field is a pure AC field, i.e. only AC excitation current is passed through the excitation winding coil 5I _ac Then the superparamagnetic particles will generate odd harmonic signals; when the excitation field is an AC/DC coupling field, that is, an AC excitation current and a DC excitation current are simultaneously introduced into the excitation coilI _dc Then, odd and even harmonic signals will be generated simultaneously; preferably, the intensity ratio of the multiple harmonic signals is used to further reduce the ambient temperature or solventThe detection sensitivity is improved by the influence of liquid viscosity change and the like on detection signals.

And a detection parallel resonance 39 for improving the signal-to-noise ratio is arranged between the connecting end of the detection winding coil I9 and the detection winding coil II 10 and the detection signal input end of the phase-locked amplifier 40. The use of the detection parallel resonance 39 greatly enhances the detection signal strength and suppresses the passage of non-detection signal frequency noise. Quality factor available for signal-to-noise enhancementQ = ωL/RIs shown in whichωIn order to detect the angular frequency of the wave,Lin order to detect the inductance of the coil,Rthe equivalent direct current resistance of the detection coil is obtained. Therefore, to obtain largerQThe excitation and detection signal frequencies need to be increased. However, as before, the excitation and detection signal frequencies are determined by the relaxation times of the superparamagnetic nanoparticles. In the traditional alternating current detection, magnetic particles have larger hydraulic diameter, for example, the Brownian relaxation time of the magnetic particles with the particle size of 250nm in pure water solution is about 5.9ms at room temperature, the excitation frequency of the magnetic particles is lower than 169.5Hz, the third harmonic frequency is lower than 508.5Hz, and the resonance is detected at the frequencyQValues often only slightly above 1, the parallel resonance does not have the effect of enhancing the signal-to-noise ratio. In order to obtain better signal-to-noise ratio, superparamagnetic particles with smaller hydraulic diameter are optimally used, for example, the Brownian relaxation time of magnetic particles with the particle diameter of 90nm is about 0.27ms, the excitation frequency is 3704Hz, the third harmonic frequency is 11112Hz, and under the frequency, the quality factor of more than 10 times can be easily obtained. It will be appreciated that the excitation series resonance 37 provided between the ac power supply 36 and the excitation winding coil 5, the excitation boost coil i 6 and the excitation boost coil ii 7, and the detection parallel resonance 39 provided between the detection winding coil i 9 and the detection winding coil ii 10 and the lock-in amplifier 40, may be arranged separately or simultaneously, depending on the particular application. The excitation winding coil 5, the excitation enhancement coil I6 and the excitation enhancement coil II 7 which are made of multi-stranded wires can effectively avoid the phenomenon that the equivalent direct current resistance of the coil is increased due to high-frequency eddy current, and under the condition, the quality factor of more than 30 times can be obtained.

The high-definition real-time imaging method of the high-definition real-time imaging system comprises the following steps:

step one, introducing direct current into each gradient winding coil 19 in the magnetic field line-free scanning coil group I2 and the magnetic field line-free scanning coil group II 3, so that the two gradient winding coils 19 at the diagonal positions generate magnetic fields with the same direction, and the two adjacent gradient winding coils 19 generate magnetic fields with opposite directions, as shown in fig. 18, a magnetic field-free field is formed in the magnetic field line-free scanning area 8; and a gradient field is generated around the magnetic field-free line, and the farther the gradient field is away from the magnetic field-free line, the larger the field intensity is.

And step two, as shown in fig. 19, a variable direct current is supplied to each offset winding coil 18 in the magnetic field line-free scanning coil group i 2 and the magnetic field line-free scanning coil group ii 3, so that the magnetic field strength on one side of the gradient field is increased, the magnetic field strength on the other side is decreased, a variable offset field is formed and coupled with the original gradient field, and the magnetic field-free field moves in the magnetic field line-free scanning area 8.

Thirdly, placing a sample containing the superparamagnetic particle tracer in the magnetic field-free line scanning area 8, and then applying a high-frequency sinusoidal alternating magnetic field to the magnetic field-free line scanning area 8 through the exciting winding coil 5; meanwhile, because the magnetization intensity of the magnetic nanoparticles in the non-magnetic field line scanning region 8 and at other positions except the non-magnetic field lines is saturated and the change of the magnetization intensity is small, only the magnetic nanoparticles at the non-magnetic field lines are subjected to alternating current magnetization (the magnetization intensity is subjected to periodic change); and due to the nonlinear magnetization characteristic of the magnetic nanoparticles, fundamental wave and each subharmonic component of a magnetization signal are obtained through Fourier change. Before actually scanning a sample containing a superparamagnetic particle tracer with unknown concentration, a standard sample which is placed at a fixed position and contains a known high-concentration superparamagnetic particle tracer needs to be scanned, and the relationship between the position, concentration and the like of the tracer and an acquired signal is calculated to form a system function; and then, scanning an actual sample (containing the superparamagnetic particle tracer with unknown concentration), and calculating the acquired magnetic field signal in a singular value decomposition or least square method or other modes to reduce the acquired magnetic field or voltage signal into a concentration distribution signal of the superparamagnetic particle tracer in the space, so as to realize image reconstruction.

And step four, detecting the alternating current magnetization signal of the superparamagnetic particle tracer in the sample at the position without the magnetic field line by detecting the winding coil I9 and the winding coil II 10, and obtaining the fundamental wave and harmonic component of the magnetization signal by using the phase-locked amplifier 40.

Acquiring fundamental wave and harmonic wave signals to obtain a magnetic field or voltage distribution map; then, in the upper computer 42, the concentration of the magnetic nanoparticles is deduced through calculation and reconstruction, so that the concentration distribution of the superparamagnetic particle tracer in the sample at each point in space is obtained, and the imaging of the tissue structure is completed. Because signal interference generated by an excitation field exists in the acquisition of fundamental waves, multiple harmonic components generated by nonlinear magnetization of nano magnetic particles can be acquired for imaging; by collecting the signals under a fixed certain frequency of the harmonic signals, the interference of other signals is effectively avoided. And, can also only fix and gather the third harmonic that the nanometer magnetic particle non-linear magnetization produced, the signal is strongest and image. Theoretically, several harmonics in the harmonic component can be collected; however, the harmonic wave of higher order than the third harmonic wave is weaker in signal and more difficult to collect. Meanwhile, direct current components can be added into the sine excitation field, and alternating current and direct current are added in a mixing manner to collect even harmonics; and then the second harmonic signal with larger amplitude is used for imaging.

Example (b):

as shown in FIGS. 13 and 14, when the present invention is used, the illustrated device is used, the gradient coil power supply 34 is an ITECH DC power supply, the offset coil power supply 35 is a KP3000GS power supply of NF company, the AC power supply 36 is a 4610 power supply, the PLL amplifier 40 is an LI5645 PLL amplifier 40 of NF company, and the signal acquisition device 41 is an NI USB-6361 data acquisition card. The frequency used to energize the wound coil 5 is 20kHz and the lock-in amplifier 40 locks in the sample third harmonic signal, i.e. 60kHz. The gradient winding coil 19 is electrified with 26A direct current to generate a 4.0T/m gradient magnetic field; triangular wave current with the peak value of 30A is introduced into the offset winding coil 18, the size of the magnetic field-free line scanning area 8 is 40mm multiplied by 40mm, and alternating current with the peak value of 30A is introduced into the excitation winding coil 5.

The gradient winding coil 19 in each of the non-field line scanning coils 15 of the non-field line scanning coil group i 2 and the non-field line scanning coil group ii 3 is 800 turns, the offset winding coil 18 wound around the outer side of each gradient winding coil 19 is 480 turns, and the gradient winding coil 19 and the offset winding coil 18 are both in the same plane. A DC power of 26A is applied to the gradient winding coil 19, and a linear gradient magnetic field of 4T/m can be generated near the center of the surface of the gradient winding coil 19, and the linear range is 40X 40mm. And, two sets of triangular wave currents (as shown in fig. 15) are fed to the offset winding coil 18, wherein one set of triangular wave currents is superposed on the direct-current magnetic field which is gradually increased in each planar scanning, one set of triangular wave currents is superposed on the direct-current magnetic field which is gradually decreased in each planar scanning, and the frequencies of the two sets of triangular wave currents are both 10Hz, so that the magnetic field-free line can be completely scanned 10 times in the magnetic field line-free scanning area 8 every second. The exciting winding coil 5 is arranged in an open space between the magnetic field-free line scanning coil group I2 and the magnetic field-free line scanning coil group II 3 (two groups of gradient winding coils 19), a sample containing the superparamagnetic particle tracer is positioned between two coil structures of the exciting winding coil 5, and the differential detection winding coil is arranged in the magnetic field-free line scanning area 8. The collected voltage signal intensity is Vs =2 pi fN (pi D2/4) Bs, where: vs is the signal voltage, f is the frequency of the excitation field, D is the coil diameter of the detection winding coil, and Bs is the magnetization signal of the superparamagnetic particle tracer. According to the calculation formula: the voltage signal Vs is proportional to the frequency f of the excitation field, and as the frequency f increases, the voltage Vs of the detection winding coil also increases.

The existing research shows that when the frequency of an excitation magnetic field is more than 20kHz or the strength of an orthogonal alternating current magnetic field is more than 3mT, the human body can generate weak peripheral nerve stimulation and heating effects; therefore, in the present embodiment, the signal is detected by using a magnetic field strength of 2mT at a frequency of 20 kHZ. Since the excitation winding coil 5 has a large ac impedance at the excitation frequency, the impedance of the excitation winding coil 5 is reduced using the excitation series resonance 37. The inductance of the excitation winding coil 5 is 0.1mH and the capacitance of the excitation series resonance 37 is calculated to be 25nF. In order to avoid the situation that the equivalent direct current resistance of the coil is increased due to the skin effect of the current and effectively prevent the thermal noise interference, the excitation winding coil 5 adopts a multi-strand litz wire instead of a common single wire.

And detecting the superparamagnetic particle tracer in the sample by detecting the winding coil. The imaging sample 38 is placed in the magnetic field-free line scanning area 8, the magnetic field-free line scanning area 8 is located in an open space between the magnetic field-free line scanning coil group I2 and the magnetic field-free line scanning coil group II 3, and the size of the scanning area is 40mm multiplied by 40mm. Meanwhile, in order to improve the sensitivity of detecting the winding coil, that is: and the signal-to-noise ratio S/N of the detection winding coil is improved, and a completely symmetrical differential winding coil is adopted. The winding directions of the two sections of coils of the differential winding coil of the detection winding coil I9 and the detection winding coil II 10 are opposite, and the number of turns of the two sections is 150, so that an excitation field reaches a balanced state at the detection winding coil, and excitation interference is reduced. The detection winding coil simultaneously uses the LC detection parallel resonance 39 to collect the third harmonic to improve signal strength. The inductance of the detection winding coil was 410uH, and the capacitance of the detection parallel resonance 39 was calculated to be 17nF. The area of the LC circuit on the circuit board is about 2cm ² The direction of the magnetic field is vertical to the excitation field, and after the circuit board is shielded, the circuit board is extended to a position far away from the excitation winding coil 5 and the detection winding coil by using a connecting wire so as to reduce excitation interference; and the grounding end of the detection winding coil is connected to the metal platform which is close to the excitation field to obtain better grounding effect.

The data information is transmitted to the upper computer 42 by the signal acquisition equipment 41, and then image reconstruction is performed by the upper computer 42. And the image reconstruction adopts a non-negative least square method, converts the voltage signal into a superparamagnetic particle tracer concentration distribution signal in the space through a system function measured in advance, and reduces the signal into a tissue structure to finish the imaging of the tracer.

The specific process of image reconstruction is as follows: first, the Point Spread Function (PSF) of MPI is measured, i.e. a very small volume of a high concentration MNP sample (sample containing superparamagnetic particle tracer) is used to obtain a voltage cloud of the system point spread function. Then, a system matrix a is obtained by a point spread function. The spatial resolution of the voltage cloud image preliminarily scanned by the system is low, so that the obtained voltage cloud image is reconstructed by using the system matrix A, and the voltage value is reduced to the sample concentration value so as to improve the spatial resolution. Expressing the concentration of MNP sample as n (x, y, z), n (x, y, z) can be expressed by vector nj (j =1,2, \8230;, K), and the relationship between V and n can be expressed as:

V=An

in the formula: v is the voltage signal value measured by the LabVIEW program.

Then, image reconstruction is performed with a non-negative least squares (NNLS): imaging of a 40mm x 40mm area was performed once in about 5 seconds, with a scan area of 40mm x 40mm per slice. A voltage cloud plot of the point spread function obtained when the MNP sample was 15mm below the sense wrap coil as shown in fig. 20 was first obtained using the LabVIEW control program. The voltage cloud shown in fig. 20 is a circle with the MNP sample located at the center of the circle. The point spread function in fig. 20 can be approximated by a two-dimensional normal distribution.

An "o" type MNP sample placed in the center of the detection area was measured and a voltage cloud was obtained as shown in fig. 21. From fig. 21, the sample morphology can be identified with a spatial resolution of about 5mm.

To improve the spatial resolution of MNP detection, fig. 21 was analyzed using NNLS. A point spread function as shown in fig. 20 is obtained using a small-volume high-concentration MNP sample at the very center of the detection region, and a system matrix a is constructed using the point spread function, and is expressed as Vi (i =1,2, \8230;, K) by a vector, and K =1681.

Solving the equation V = An, the voltage cloud can be converted into a concentration profile of the MNP sample as shown in fig. 22. Therefore, an NNLS algorithm is used, and an MNP concentration distribution graph is obtained through a Matlab image reconstruction program; the concentration profile of MNPs was estimated from the voltage cloud shown in fig. 22. It is evident that the reconstructed o-shaped sample is better able to recover the sample size than in the case of fig. 21. It was found that the spatial resolution of the concentration n is higher than the spatial resolution of the voltage cloud, about 1mm.

Compared with a traditional closed magnetic particle imaging device and system, the magnetic particle imaging system has the advantages that the movable magnetic field-free lines in high-strength and high-linearity ranges are formed by controlling the gradient winding coil 19 and the offset winding coil 18 in the magnetic field-free line scanning coil group I2 and the magnetic field-free line scanning coil group II 3 which are arranged on two sides of a sample, open magnetic particle imaging scanning is realized, the gradient field strength is not limited by the excitation field strength, and the spatial resolution and the scanning space are improved conveniently. Compared with other living body imaging technologies (such as MRI or X-ray and the like), the invention has the advantages of higher detection speed, higher sensitivity and spatial resolution and can provide an open imaging space.

Claims (25)

1. A high definition real-time imaging device based on FFL, includes base (1), its characterized in that: a magnetic field-free line scanning coil group I (2) and a magnetic field-free line scanning coil group II (3) which can form a movable magnetic field-free line are arranged on the base (1), and an open magnetic field-free line scanning area (8) is arranged between the magnetic field-free line scanning coil group I (2) and the magnetic field-free line scanning coil group II (3); the magnetic field coverage area of the excitation winding coil (5) and the detection area of the detection winding coil correspond to the magnetic field line-free scanning area (8); the non-magnetic field line scanning coil group I (2) and the non-magnetic field line scanning coil group II (3) are the same in structure and respectively comprise a plurality of groups of non-magnetic field line scanning coils (15) which are arranged in central symmetry; the field-free scanning coil (15) comprises a scanning coil winding framework (17), the scanning coil wound on the scanning coil winding framework (17) comprises a gradient winding coil (19) and an offset winding coil (18), and the offset winding coil (18) and the gradient winding coil (19) adopt the structural form of inner and outer layer arrangement.

2. The FFL-based high definition real time imaging device of claim 1, wherein: in the field-free line scanning coils (15) which are arranged in central symmetry, the directions of magnetic fields generated by the gradient winding coils (19) in two groups of scanning coils which are positioned at diagonal positions are the same, and the directions of the magnetic fields generated by the gradient winding coils (19) in two adjacent groups of scanning coils are opposite; the magnetic fields generated by the offset winding coils (18) in the two diagonally-positioned sets of scanning coils are in opposite directions.

3. The FFL-based high definition real time imaging device of claim 1, wherein: the gradient winding coil (19) and the offset winding coil (18) which are arranged on the inner layer and the outer layer are both wound in a square shape.

4. The FFL based high definition real time imaging device of claim 1, wherein: a scanning framework fixing substrate (16) is arranged at the lower end of the scanning coil winding framework (17), and an upper flange (20) is arranged at the upper end of the scanning coil winding framework (17); a winding groove is formed between the upper flange (20) and the scanning framework fixing base plate (16), and the gradient winding coil (19) and the offset winding coil (18) are wound in the winding groove.

5. The FFL-based high definition real time imaging device of claim 1, wherein: the scanning coil winding framework (17) is made of magnetic core materials.

6. The FFL based high definition real time imaging device of claim 1, wherein: and a cooling shell (4) of the scanning coil assembly is arranged outside the non-magnetic field line scanning coil assembly I (2) and the non-magnetic field line scanning coil assembly II (3), and a cooling medium is filled in the sealed cooling shell (4) of the scanning coil assembly.

7. The FFL based high definition real time imaging device of claim 6, wherein: a liquid inlet (11) and a liquid outlet (12) are respectively arranged on the scanning coil assembly cooling shell (4), and a coil wiring terminal (13) is further arranged at the top of the scanning coil assembly cooling shell (4).

8. The FFL-based high definition real time imaging device of claim 1, wherein: the excitation winding coil (5) is formed by a Helmholtz coil.

9. The FFL based high definition real time imaging device of claim 8, wherein: the two parts of coil structures of the Helmholtz coil are respectively wound in winding grooves of excitation coil winding frameworks (32) arranged at two sides of the excitation coil supporting seat (23); and a sample placing table (24) is arranged at the middle part of the Helmholtz coil and the upper part of the excitation coil supporting seat (23).

10. The FFL based high definition real time imaging device of claim 1, wherein: the detection winding coil is an assembly, the detection winding coil of the assembly structure comprises at least one differential winding coil, the differential winding coil comprises a detection coil forward winding section and a detection coil reverse winding section which are separated from each other and continuously arranged, and the winding number, the winding length and the winding layer number of the detection coil forward winding section and the detection coil reverse winding section are the same.

11. The FFL based high definition real time imaging device of claim 10, wherein: the positive winding section and the negative winding section of the detection coil of the differential winding coil are respectively arranged at two sides of the non-magnetic field line scanning coil group I (2) or the non-magnetic field line scanning coil group II (3); and one section of the detection coil close to the non-magnetic field line scanning area (8) is used as a differential detection section coil (25), and the other section of the detection coil far away from the non-magnetic field line scanning area (8) is used as a differential noise reduction section coil (27).

12. The FFL based high definition real time imaging device of claim 11, wherein: the differential detection section coil (25) is wound on the detection section winding framework (26), and the detection section winding framework (26) is positioned in the middle of the excitation winding coil (5); the differential noise reduction section coil (27) is wound on the noise reduction section winding framework (28), and the noise reduction section winding framework (28) is connected with the upper part of the enhanced coil supporting seat (22).

13. The FFL-based high definition real time imaging device of claim 12, wherein: an excitation enhancement coil is also arranged on the enhancement coil supporting seat (22), and the excitation enhancement coil is formed by Helmholtz coils; the two parts of coil structures of the Helmholtz coil are respectively wound in winding grooves of reinforcing coil winding frameworks (29) arranged at two sides of a reinforcing coil supporting seat (22); the noise reduction section winding framework (28) is located between the reinforcing coil winding frameworks (29) on the two sides.

14. The FFL-based high definition real time imaging device of claim 13, wherein: the axial relative position of the noise reduction section winding framework (28) and the reinforcing coil winding framework (29) can be adjusted.

15. The FFL-based high definition real time imaging device of claim 14, wherein: the noise reduction section winding framework (28) is movably connected with a sliding guide long circular hole (31) at the upper part of the reinforcing coil supporting seat (22) through a noise reduction sliding adjusting seat (30).

16. The FFL-based high definition real time imaging device of claim 12, wherein: the middle part of the excitation coil winding framework (32) of the excitation winding coil (5) is provided with a detection framework placing hole (33), and the detection section winding framework (26) of the detection winding coil is arranged in the detection framework placing hole (33).

17. The FFL-based high definition real time imaging device of claim 1, wherein: the excitation winding coil (5) is made of a plurality of twisted wires.

18. The FFL-based high definition real time imaging device of claim 1, wherein: and a sample containing a superparamagnetic particle tracer is also arranged in the open magnetic field-free line scanning area (8).

19. A high definition real time imaging system comprising the FFL based high definition real time imaging apparatus of claim 1, wherein: the gradient coil power supply (34) is respectively and electrically connected with each gradient winding coil (19) in the non-magnetic field line scanning coil group I (2) and the non-magnetic field line scanning coil group II (3), and each offset winding coil (18) in the non-magnetic field line scanning coil group I (2) and the non-magnetic field line scanning coil group II (3) is electrically connected with the other offset coil power supply (35) which can generate variable direct current; the excitation winding coil (5) is electrically connected with an excitation signal output end of an alternating current power supply (36); the detection winding coil is electrically connected with a signal input end of the phase-locked amplifier (40), a signal output end of the phase-locked amplifier (40) is electrically connected with a signal input end of the signal acquisition equipment (41), and a signal output end of the signal acquisition equipment (41) is electrically connected with an upper computer (42) for image reconstruction.

20. The high definition real time imaging system of claim 19, wherein: an excitation series resonance (37) is arranged between an excitation signal output end of the alternating current power supply (36) and a connecting end of the excitation winding coil (5), and/or a detection parallel resonance (39) is arranged between a connecting end of the detection winding coil and a detection signal input end of the phase-locked amplifier (40).

21. A high definition real-time imaging method using the high definition real-time imaging system of claim 19, characterized in that: the method comprises the following steps:

step one, introducing direct current into each gradient winding coil (19) in the magnetic field-free line scanning coil group I (2) and the magnetic field-free line scanning coil group II (3) to form uniform magnetic field-free lines in the magnetic field-free line scanning area (8);

step two, introducing variable direct current into each offset winding coil (18) in the magnetic field-free line scanning coil group I (2) and the magnetic field-free line scanning coil group II (3) so as to form a variable offset field and couple the variable offset field with an original gradient field, thereby realizing the movement of the magnetic field-free lines in the magnetic field-free line scanning area (8);

placing a sample containing the superparamagnetic particle tracer in the magnetic field-free line scanning area (8), and then applying a high-frequency sinusoidal alternating magnetic field to the magnetic field-free line scanning area (8) through an exciting winding coil (5); in addition, because the magnetization intensity of the magnetic nano particles in the magnetic field line-free scanning area (8) and other positions except the magnetic field line-free scanning area reaches saturation and the change of the magnetization intensity is small, only the magnetic nano particles at the magnetic field line-free scanning area generate alternating current magnetization, and due to the nonlinear magnetization characteristic of the magnetic nano particles, fundamental wave and each subharmonic component of a magnetization signal are obtained through Fourier change;

detecting an alternating current magnetization signal of the superparamagnetic particle tracer in the sample at the position without the magnetic field line by detecting the winding coil, and obtaining fundamental wave and harmonic component of the magnetization signal by using a phase-locked amplifier (40);

acquiring a magnetic field or voltage distribution diagram through acquisition of fundamental wave and harmonic wave signals, then reversely deducing the concentration of the magnetic nanoparticles through calculation and reconstruction in an upper computer (42), further acquiring the concentration distribution of the superparamagnetic particle tracer in the sample at each point in space, and finishing the imaging of the organization structure; and taking a series of XY planes with different heights along the Z axis, respectively establishing a system function in the XY plane with each height, and restoring the detected magnetization response signal into the sample concentration on the XY plane with each height by using a least square method, thereby realizing the tomography in the Z direction.

22. The high-definition real-time imaging method of claim 21, wherein: before actually scanning a sample containing a superparamagnetic particle tracer with unknown concentration, firstly scanning a standard sample which is placed at a fixed position and contains a known superparamagnetic particle tracer with high concentration, and calculating the relationship between the position, concentration and the like of the tracer and an acquired signal to form a system function; and then, scanning the actual sample, and calculating the acquired magnetic field signal in a singular value decomposition or least square method or other modes to reduce the acquired magnetic field or voltage signal into a concentration distribution signal of the superparamagnetic particle tracer in the space, so as to realize image reconstruction.

23. The high-definition real-time imaging method of claim 21, wherein: and fifthly, collecting multiple harmonic components generated by nonlinear magnetization of the nano magnetic particles for imaging.

24. The high-definition real-time imaging method of claim 23, wherein: and only collecting the third harmonic generated by the nonlinear magnetization of the nano magnetic particles for imaging.

25. The high-definition real-time imaging method of claim 23, wherein: a dc component is added to the sinusoidal excitation field to collect even harmonics.

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