Field Free Point Research Articles

Real-Time 3D MPI-Based Navigation Scheme for Microrobots With Flexible Field Free Point Trajectories and Virtual FFP Intuitive Manipulation

Real-Time 3D MPI-Based Navigation Scheme for Microrobots With Flexible Field Free Point Trajectories and Virtual FFP Intuitive Manipulation

A Novel Local Magnetic Fluid Hyperthermia Based on High Gradient Field Guided by Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI)-guided Magnetic Fluid Hyperthermia (MFH) has the potential for widespread utilization, as it allows for the prediction of magnetothermal dosage, real-time visualization of the thermal therapy process, and precise localization of the lesion area. However, the existing MPI-guided MFH (MPI-MFH) method is insensitive to concentration gradients of magnetic nanoparticles (MNPs) and is susceptible to causing damage to normal tissues with high MNP concentrations during MFH treatment, while inadequately heating tumor tissues with lower MNP concentrations. In this work, we established a relationship between MNP concentration and heating efficiency through simulations and phantom measurements, enabling the optimal selection of MFH parameters guided by MPI. Based on these findings, we developed a high-gradient field MPI-MFH method using a field-free point (FFP) approach to achieve precise local heating. Phantom experiments and in vivo glioma model experiments were conducted to validate this proposed method. The results demonstrated that the proposed method of MPI-MFH can improve the MNP concentration gradient sensitivity to ±1 mg/ml, thereby enabling more effective lesion-site heating without damaging normal tissues. This method not only reduced glioma size effectively but also holds promise for application in various other types of cancers.

Magnetic trap-based steering method for small-scale robots: Feasibility study

This paper proposes a novel method for steering a medical small-scale robot (SSR) based on a trapping magnetic field gradient (TMG). The proposed method steers a SSR in a desired direction by keeping and moving a SSR position via a TMG point changing. To create a TMG, a field-free point (FFP) is employed, and moreover a redefined FFP generation method is suggested to design a desired shape of a magnetic field map in a unidirectional mobile-type magnetic system with four electromagnetic coils. Herein, magnetic characteristics of a TMG were analyzed on a Multiphysics simulation and compared with previous methods for steering a SSR to confirm a TMG performance. Furthermore, the proposed method was implemented to validate a SSR steering ability in tubular environments. Consequently, the proposed method was verified by demonstrating a SSR targeting performance to a specific vascular branch via in-vitro experiments.

Development of a human-size magnetic particle imaging device for sentinel lymph node biopsy of breast cancer.

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8kHz@1.5mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30mm in the Z direction, and the sensitivity was about 10μg Fe SPIONs at 40mm distance with a spatial resolution of about 5mm. In the rat experiment, 54μg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.

Automatic Navigation Scheme for Micro-Robot Using Magnetic Potential Field Through Field Free Point

Automatic Navigation Scheme for Micro-Robot Using Magnetic Potential Field Through Field Free Point

Tomographic Magnetic Particle Imaging with a Single-Sided Field-Free Line Scanner.

Magnetic Particle Imaging (MPI) is a biomedical imaging modality that shows promise in enhancing clinical imaging capabilities. While there are current efforts to expand MPI hardware to enable wholebody and head imaging, this comes at a significant cost in terms of complexity and expense. A single-sided scanner can offer greater accessibility to the scanning area, as all hardware is located on one side of the device's surface, however, at the price of the limited penetration depth. Despite this, a single-sided device could serve as an open geometry preclinical scanner and a clinical instrument for local screening and procedures. The original single-sided device was introduced for a field-free point encoding gradient, which may limit its practical characteristics. We developed a field-free line single-sided device that has improved imaging characteristics, which is beneficial for preclinical applications and potential clinical translation. We demonstrated full tomographic imaging capabilities with the prototype of a single-sided MPI scanner and characterized the imaging performance of our imaging system. MPI has the potential to image various human body regions, particularly for breast cancer diagnosis. Our research tackles the crucial aspect of scalability in the emerging MPI technique.

Space-Specific Mixing Excitation for High-SNR Spatial Encoding in Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI) is a radiation-free tracer-based imaging technology that visualizes the spatial distribution of superparamagnetic iron oxide nanoparticles. Conventional spatial encoding methods in MPI rely on a gradient magnetic field with a constant gradient strength to generate a field-free point or line for spatial scanning. However, increasing the gradient strength can enhance theoretical spatial resolution but also lead to a decrease in the Signal-to-Noise Ratio (SNR) and sensitivity of the imaging system. This poses a technical challenge in balancing spatial resolution and sensitivity, necessitating intricate hardware design. To address this, we present a Space-Specific Mixing Excitation (SSME) technique for achieving high-SNR spatial encoding in MPI. By utilizing a dual-frequency excitation magnetic field with a non-homogeneous field strength, magnetic particles at each position generate unique intermodulation responses. By performing multi-channel acquisitions across the entire field of view, high SNR MPI signals can be acquired. When combined with reconstruction techniques based on system matrix, multi-dimensional SSME-MPI can be achieved. The effectiveness of the proposed method was validated through phantom and in vivo imaging experiments. The results demonstrate significant improvements in sensitivity (3.6-fold improvement) and spatial resolution (better than 1 mm) without any hardware modifications. These findings demonstrate the capability of SSME to enhance both the spatial resolution and sensitivity of MPI. This method provides a solution to the ongoing challenge of balancing spatial resolution and sensitivity in MPI, potentially facilitating the implementation of MPI in a wider range of medical applications.

Relaxation spectral analysis in multi-contrast vascular magnetic particle imaging.

Magnetic nanoparticles (MNPs) are used as tracers without ionizing radiation in vascular imaging, molecular imaging, and neuroimaging. The relaxation mechanisms of magnetization in response to excitation magnetic fields are important features of MNPs. The basic relaxation mechanisms include internal rotation (Néel relaxation) and external physical rotation (Brownian relaxation). Accurate measurement of these relaxation times may provide high sensitivity for predicting MNP types and viscosity-based hydrodynamic states. It is challenging to separately measure the Néel and Brownian relaxation components using sinusoidal excitation in conventional MPI. We developed a multi-exponential relaxation spectral analysis method to separately measure the Néel and Brownian relaxation times in the magnetization recovery process in pulsed vascular MPI. Synomag-D samples with different viscosities were excited using pulsed excitation in a trapezoidal-waveform relaxometer. The samples were excited at different field amplitudes ranging from 0.5 to 10 mT at intervals of 0.5 mT. The inverse Laplace transform-based spectral analysis of the relaxation-induced decay signal in the field-flat phase was performed by using PDCO, a primal-dual interior method for convex objectives. Néel and Brownian relaxation peaks were elucidated and measured on samples with various glycerol and gelatin concentrations. The sensitivity of viscosity prediction of the decoupled relaxation times was evaluated. A digital vascular phantom was designed to mimic a plaque with viscous MNPs and a catheter with immobilized MNPs. Spectral imaging of the digital vascular phantom was simulated by combining a field-free point with homogeneous pulsed excitation. The relationship between the Brownian relaxation time from different tissues and the number of periods for signal averages was evaluated for a scan time estimation in the simulation. The relaxation spectra of synomag-D samples with different viscosity levels exhibited two relaxation time peaks. The Brownian relaxation time had a positive linear relationship with the viscosity in the range 0.9 to 3.2 mPa · s. When the viscosity was >3.2 mPa · s, the Brownian relaxation time saturated and did not change with increasing viscosity. The Néel relaxation time decreased slightly with an increase in the viscosity. The Néel relaxation time exhibited a similar saturation effect when the viscosity level was >3.2 mPa · s for all field amplitudes. The sensitivity of the Brownian relaxation time increased with the field amplitude and was maximized at approximately 4.5 mT. The plaque and catheter regions were differentiated from the vessel region in the simulated Brownian relaxation time map. The simulation results show that the Néel relaxation time was 8.33±0.09 μs in the plaque region, 8.30±0.08 μs in the catheter region, and 8.46±0.11 μs in the vessel region. The Brownian relaxation time was 36.60±2.31 μs in the plaque region, 30.17±1.24 μs in the catheter region, and 31.21±1.53 μs in the vessel region. If we used 20 excitation periods for image acquisition in the simulation, the total scan time of the digital phantom was approximately 100 s. Quantitative assessment of the Néel and Brownian relaxation times through inverse Laplace transform-based spectral analysis in pulsed excitation, highlighting their potential for use in multi-contrast vascular MPI.

Specific absorption rate of randomly oriented magnetic nanoparticles in a static magnetic field.

Numerical simulations using the stochastic Landau-Lifshitz equation are performed to study magnetization dynamics of dilute assemblies of iron oxide nanoparticles exposed to an alternating (ac) magnetic field with an amplitude H ac = 200 Oe and a frequency f = 300 kHz and a static (dc) magnetic field in the range H dc = 0-800 Oe. The specific absorption rate (SAR) of the assemblies is calculated depending on the angle between the directions of the ac and dc magnetic fields. For the case of an inhomogeneous dc magnetic field created by two opposite magnetic fluxes, the spatial distribution of the SAR in the vicinity of the field-free point is obtained for assemblies with different nanoparticle size distributions. The results obtained seem to be helpful for the development of a promising joint application of magnetic nanoparticle imaging and magnetic hyperthermia.

A magnetic particle imaging in anisotropic magnetic manipulation platform

Magnetic particle imaging (MPI) has been demonstrated as the most promising imaging technology for monitoring distribution of magnetic nanoparticles (MNPs) at high sensitivity, high resolution, and fast imaging speed. Up to now, most published researches use the symmetric setups with multiple orthogonal pairs of coils. However, this poses a size and controllable degrees-of-freedom limitation for 3D manipulation tasks. The difficulties of field-free point (FFP) estimation and interferences of the core materials limit the MPI integration into other types of magnetic configuration. Thus, this paper presents a feasibility study of the integration of the MPI function in the anisotropic magnetic platform. A FFP generation method in anisotropic structures with various magnetic sources is derived and numerically investigated. The tracking performances are then demonstrated in both in-vitro and in-vivo experiments using one of the selected anisotropic structures. To date, the function of the proposed system is limited to tracking the particle. The experimental results on tracking the MNPs show a tracking accuracy of around 1 mm. Our proposed methodology allows the current magnetic actuation systems to upgrade the functionalities of simultaneous manipulation and localization.

Development of Magnetic Particle Imaging (MPI) Scanner for Phantom Imaging of Tracer Agents

This article presents the design and implementation of the magnetic particle imaging (MPI) scanner for phantom imaging of the potential tracer agents for MPI applications. The field-free point (FFP)-based spatial encoding of 4.3 T/m was implemented so that it helps to localize the superparamagnetic iron oxide nanoparticles (SPIONs) response inside the field of view (FOV). Solenoid drive coil and gradiometric receive coil were constructed to achieve 15 mT (peak amplitude) at 9.3 kHz. Moreover, a magnetic particle spectrometer (MPS) was utilized at 9.9 kHz for the characterization of relaxation time, frequency spectrum, and full-width at half-maximum (FWHM) of the particle signals in response to the excitation field at 9.9 kHz. The X-space algorithm was designed for the post-processing of the particle signals in the MPI scanner. Dextran-coated Perimag and carboxydextran-coated Vivotrax plus were characterized with MPS followed by the phantom imaging with MPI scanner. Perimag was found as fast relaxation sample (low relaxation time), narrow pulsewidth (high spatial resolution), and higher signal intensity compared to the Vivotrax plus.

1D imaging of a superparamagnetic iron oxide nanoparticle distribution by a single-sided FFL magnetic particle imaging scanner.

Magnetic Particle Imaging (MPI) is an emerging imaging modality that has a potential of complimenting other imaging modalities in clinical practice. Despite many efforts to scale up MPI hardware to date no MPI systems have been demonstrated to accommodate full body imaging. Previously, we introduced hardware and characterized a prototype of a single-sided MPI scanner, where all coils are confined to a single-side of the device, which provides a subject with unrestricted access to the scanning area although with a limited penetration depth. The major difference in our design from the first reported single-sided scanner is in incorporating a field-free line instead of a field-free point, which generally promises higher sensitivity and more robust image reconstruction. However, as inherent to any single-sided configurations the fields in our device are spatially inhomogeneous making it challenging to apply existing imaging techniques. For our specific geometry we implemented spatial encoding scheme and imaging in time-domain making the image reconstruction fast. In this work we present one dimensional imaging of multiple rods phantoms with a single-sided field-free line MPI scanner. The results demonstrate that our scanner is capable of one dimensional imaging of phantoms with a spatial resolution of at least 7 mm without image processing.

Evaluation of Harmonic Signals Derived From Multiple Spatially Separated Samples for Magnetic Particle Imaging

We studied the harmonic components of signals derived from magnetization of magnetic nanoparticles depending on the direct current magnetic field at magnetic particle imaging (MPI). When single sample was located, the field free point confirmed that the third harmonic has the maximum value and the second harmonic has the minimum value. We proposed a new analytical method that takes the ratio of the third harmonic to the second harmonic to improve the resolution. Moreover, the complex signal obtained from separately located two samples was measured under a gradient magnetic field. We discussed the important issues with respect to the even harmonics in application of MPI for diagnostics in human body.

Implementation and imaging with a versatile 180 mm magnetic-particle-imaging field-generator

Magnetic Particle Imaging (MPI) is a non-invasive imaging technique based on the detection of the non-linear magnetization curve of magnetic nanoparticles. The spatial encoding of the particle-distribution measurement relies on the combination of an alternating magnetic field, the excitation field, and a constant or slowly changing field, the selection field. The homogeneous excitation field undergoes a harmonic distortion caused by the particles. This distortion can be assigned to a certain location within the measurement field by utilizing the selection field. MPI scanners presented so far use coil designs that lead to selection fields with a field free point or a field free line and have a bore diameter between 30 mm and 120 mm. A recently published system has an elliptical bore with 190 mm width in the narrower dimension. Since the invention of MPI, the bore diameter of MPI systems has not changed significantly. Here, we show the entire process of the design, implementation, and operation of an MPI system that offers a bore diameter of 180 mm. It includes the hardware which enables the generation of a selection field with a field free point and one with a field free line, which accounts for the versatility of the scanner. It enables the preclinical investigation of laboratory animals with the corresponding dimensions by imaging a field of view of 40 mm × 40 mm. This study is an incremental step towards the design and operation of larger MPI scanners to finally reach clinical applications.

Selection field generation using permanent magnets and electromagnets for a magnetic particle imaging scanner

This paper presents a comprehensive study on modeling and implementation of the selection field using NdFeB permanent magnets, electromagnetic coils, and a hybrid system for magnetic particle imaging (MPI). Selection fields were designed for 71 mm internal workspace and their size was based on an 11.25% enhanced ratio of Maxwell configuration. The magnetic particle imaging technique uses a gradient field to define a field of view (FOV) and generate a field-free point (FFP) which is applied to localize superparamagnetic nanoparticles (SPIONs). This study aims to develop a selection field for a new 3D magnetic particle imaging scanner at (−2.15, −2.15, 4.3) T/m gradient field in (x, y, z) directions, respectively. Three different topologies for gradient fields were numerically modeled in COMSOL and analytically calculated in MATLAB for magnetic flux density (mT) and gradient field strength (T/m). A selection field with NdFeB permanent magnets was practically implemented and its result was compared with the outcomes of a numerical simulation model. Experimental results of permanent magnets selection field topology agreed well with the numerical results from COMSOL. Numerical and analytical results of other selection field topologies were in good agreement. Spatial homogeneity of the selection field topologies was investigated over a range of 40 mm symmetric across the FFP and cost-effective analysis was performed to choose an optimum topology. A hybrid system resulted in better homogeneity over the permanent magnet and electromagnetic topologies with 96.8% spatial homogeneity, and 0.30% relative gradient field strength error. High spatial homogeneity of the gradient field minimizes the image artifacts of the MPI.

Optimization of Field-Free Point Position, Gradient Field and Ferromagnetic Polymer Ratio for Enhanced Navigation of Magnetically Controlled Polymer-Based Microrobots in Blood Vessel.

Microscale and nanoscale robots, frequently referred to as future cargo systems for targeted drug delivery, can effectively convert magnetic energy into locomotion. However, navigating and imaging them within a complex colloidal vascular system at a clinical scale is exigent. Hence, a more precise and enhanced hybrid control navigation and imaging system is necessary. Magnetic particle imaging (MPI) has been successfully applied to visualize the ensemble of superparamagnetic nanoparticles (MNPs) with high temporal sensitivity. MPI uses the concept of field-free point (FFP) mechanism in the principal magnetic field. The gradient magnetic field (|∇B|) of MPI scanners can generate sufficient magnetic force in MNPs; hence, it has been recently used to navigate nanosized particles and micron-sized swimmers. In this article, we present a simulation analysis of the optimized navigation of an ensemble of microsized polymer MNP-based drug carriers in blood vessels. Initially, an ideal two-dimensional FFP case is employed for the basic optimization of the FFP position to achieve efficient navigation. Thereafter, a nine-coil electromagnetic actuation simulation system is developed to generate and manipulate the FFP position and |∇B|. Under certain vessel and fluid conditions, the particle trajectories of different ferromagnetic polymer ratios and |∇B| were compared to optimize the FFP position.

Maghemite nanoparticles coated by methacrylamide-based polymer for magnetic particle imaging

A wise selection of tracers is critical for magnetic particle imaging (MPI). Most of the current tracers are based on superparamagnetic iron oxide nanoparticles (SPIONs) with a suitable coating. We prepared maghemite cores (γ-Fe2O3) by coprecipitation of Fe(II) and Fe(III) salts with ammonium hydroxide followed by oxidation with hydrogen peroxide and stabilization as an anionic (γ-Fe2O3⊖) or cationic colloid (γ-Fe2O3⨁). The cores were coated by poly(N-(2-hydroxypropyl)methacrylamide)-co-N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide. The particles were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, Mössbauer spectroscopy, tested in vitro in a field-free point MPI scanner, and compared to nanoparticles prepared by oxidation with sodium hypochlorite and to the commercially available Resovist®. The cores had an average diameter of 8.0 nm (γ-Fe2O3⨁) and 8.7 nm (γ-Fe2O3⊖); the hydrodynamic diameter was 88 nm. Zeta potential values for both positively charged (+52 mV) and negatively charged particles (–60 mV) provided for good colloidal stabilization. Spinel structure of maghemite was confirmed by Mössbauer spectroscopy. The uncoated γ-Fe2O3⨁ particles yielded an MPI signal lower (by 16 %) than Resovist; the coated ones reached 88 % of the Resovist signal. Anionic γ-Fe2O3⊖ particles reached a higher (uncoated particles, by 15 %) or comparable (coated ones) signal relative to Resovist with a substantially lower signal dispersion. Control particles prepared by oxidation with sodium hypochlorite scored the weakest results. To conclude, a suitable size, narrow size distribution, and colloidal stability predispose the synthetized particles for use as a tracer for MPI. The anionic particles provided a higher signal with a lower dispersion than commercial tracers.

High-Frequency Néel Relaxation Response for Submillimeter Magnetic Particle Imaging Under Low Field Gradient

Magnetic particle imaging (MPI) is beneficial for bioanalytical cellular imaging, due to its lack of both attenuation and background signal, but it typically requires a very high field gradient to achieve submillimeter resolution. The authors use the N\'eel relaxation response of the tracers to encode the coordinates of the field-free point (FFP) while magnetically scanning the phantom image under a low field gradient. This approach identifies the FFP steering frequencies and trajectory density as important parameters for refining the spatial resolution, and unlocks the possibility for noninvasive submillimeter imaging of cells or small-animal models.

A Magnetic Particle Imaging-Based Navigation Platform for Magnetic Nanoparticles Using Interactive Manipulation of a Virtual Field Free Point to Ensure Targeted Drug Delivery

Magnetic nanoparticles (MNPs) exhibiting certain superparamagnetic properties are optimal for drug delivery because they facilitate imaging and targeting of biological interactions at the cellular and molecular levels. In terms of monitoring, magnetic particle imaging (MPI) yields real-time MNPs position and concentration data, and guides MNPs to desired positions if an actuation function is available. Here, we describe a new, user-driven steering scheme for MNPs based on a virtual field free point (FFP). The scheme utilizes a general MPI system, with no need for additional hardware. The scheme facilitates interactive user manipulation with real-time imaging and MNPs actuation within the body. An FFP with four coils is used to model the resultant magnetic force and a virtual FFP to linearize that force with respect to the relative positions of the MNPs and the real FFP. Simulations and experiments confirm that the direction and magnitude of the forces exerted on MNPs via manipulation of the virtual FFP are controllable. An intuitive guidance system featuring real-time MPI at 2 Hz and user-driven virtual FFP manipulation (via a computer mouse) is employed to show that MNPs trajectories can be controlled. Our MPI-based navigation platform allows the user to effectively guide MNPs using real-time visual feedback, facilitating targeted drug delivery.

Localization and Actuation for MNPs Based on Magnetic Field-Free Point: Feasibility of Movable Electromagnetic Actuations.

Targeted drug delivery (TDD) based on magnetic nanoparticles (MNPs) and external magnetic actuation is a promising drug delivery technology compared to conventional treatments usually utilized in cancer therapy. However, the implementation of a TDD system at a clinical site based on considerations for the actual size of the human body requires a simplified structure capable of both external actuation and localization. To address these requirements, we propose a novel approach to localize drug carriers containing MNPs by manipulating the field-free point (FFP) mechanism in the principal magnetic field. To this end, we devise a versatile electromagnetic actuation (EMA) system for FFP generation based on four coils affixed to a movable frame. By the Biot–Savart law, the FFP can be manipulated by appropriately controlling the gradient field strength at the target area using the EMA system. Further, weighted-norm solutions are utilized to correct the positions of FFP to improve the accuracy of FFP displacement in the region of interest (ROI). As MNPs, ferrofluid is used to experiment with 2D and 3D localizations in a blocked phantom placed in the designed ROI. The resultant root mean square error of the localizations is observed to be approximately 1.4 mm in the 2D case and 1.6 mm in the 3D case. Further, the proposed movable EMA is verified to be capable of simultaneously scanning multiple points as well as the actuation and imaging of MNPs. Based on the success of the experiments in this study, further research is intended to be conducted in scale-up system development to design precise TDD systems at clinical sites.