Effect of tracer size distribution on magnetic particle imaging performance

The magnetic particle imaging (MPI) performance of collections of chains of magnetic nanoparticles with Néel and Brownian relaxation mechanisms was studied by carrying out simulations based on the Landau–Lifshitz–Gilbert equation and rotational Brownian dynamics, respectively. The effect of magnetic dipole–dipole interactions within chains on the time-domain average magnetic dipole moment and corresponding dynamic hysteresis loops, harmonic spectra, and point spread functions (PSFs) of the particle chains was evaluated. The results show that interactions within chains lead to ‘square-like’ dynamic hysteresis loops and enhanced MPI performance, compared to chains of non-interacting nanoparticles. For nanoparticles with the Brownian relaxation mechanism, subjected to a superimposed alternating and ramping magnetic field mimicking the magnetic field in MPI applications, we studied the dependence of x-space MPI performance of particle chains on parameters such as the amplitude of the alternating magnetic field, surface-to-surface separation between nanoparticles, solvent viscosity, and the number of nanoparticles in a chain. The results illustrate that magnetic dipole-dipole interactions within a chain contribute to enhanced MPI performance, and also suggest that there exist optimal values of the above parameters that lead to the best x-space MPI performance, i.e. maximum peak signal intensity and smallest full-width-at-half-maximum in PSFs.

Material for superconductive magnets

Recent advancements in medical imaging have brought forth various techniques such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and ultrasound, each contributing to improved diagnostic capabilities. Most recently, magnetic particle imaging (MPI) has become a rapidly advancing imaging modality with profound implications for medical diagnostics and therapeutics. By directly detecting the magnetization response of magnetic tracers, MPI surpasses conventional imaging modalities in sensitivity and quantifiability, particularly in stem cell tracking applications. Herein, this comprehensive review explores the fundamental principles, instrumentation, magnetic nanoparticle tracer design, and applications of MPI, offering insights into recent advancements and future directions. Novel tracer designs, such as zinc-doped iron oxide nanoparticles (Zn-IONPs), exhibit enhanced performance, broadening MPI's utility. Spatial encoding strategies, scanning trajectories, and instrumentation innovations are elucidated, illuminating the technical underpinnings of MPI's evolution. Moreover, integrating machine learning and deep learning methods enhances MPI's image processing capabilities, paving the way for more efficient segmentation, quantification, and reconstruction. The potential of superferromagnetic iron oxide nanoparticle chains (SFMIOs) as new MPI tracers further advanced the imaging quality and expanded clinical applications, underscoring the promising future of this emerging imaging modality.

Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluate its therapeutic effect using tumor-bearing mice. Materials and Methods: MNPs (Resovist?, 1.05 mg iron) were incorporated into the hemagglutinating virus of Japan-envelope (HVJ-E) vector (~5 × 109 particles) (HVJ-E/MNPs) by centrifugation at 10,000 × g for 5 min at 4°C. Tumor-bearing mice were prepared by inoculating Colon-26 cells subcutaneously into the backs of BALB/c mice. When the tumor volume reached ~100 mm3, HVJ-E/MNPs and/or BLM were injected directly into the tumor. The AMF was applied to the mice one hour after the injection of agents (AMF treatment). The mice injected with HVJ-E/MNPs were imaged using our magnetic particle imaging (MPI) scanner immediately (13 min) before, immediately (22 min) after, and 3, 7, and 14 days after the injection of agents, and the temporal changes of the average and maximum MPI pixel values in the tumor were quantitatively evaluated. The therapeutic effect was evaluated by calculating the relative tumor volume growth (RTVG) from the tumor volumes measured each day. Transmission electron microscopic (TEM) observation of resected tumors was also performed to confirm the intracellular distribution of MNPs. Results: The AMF treatment combined with BLM significantly decreased the RTVG value compared with AMF treatment alone at 9 to 14 days, and BLM alone at 3 to 5 days after AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14 days. TEM observation confirmed that most of the HVJ-E/MNPs were internalized into tumor cells within one hour after injection. Conclusion: A novel therapeutic strategy with use of AMF treatment and BLM was presented, and the time-dependent change of MNPs in tumors was evaluated using MPI. The present results suggest that this novel strategy can suppress tumor volume growth over AMF treatment or BLM alone, and can be performed repeatedly with a single injection of HVJ-E/MNPs. They also suggest that HVJ-E is effective for internalizing MNPs into cancer cells and that MPI allows for longitudinal monitoring of the distribution of MNPs in tumors.

Microfluidic formulation and characterization of size-tunable microparticle magnetic particle imaging tracers.

Magnetic particle imaging deblurring with dual contrastive learning and adversarial framework

The purpose of this work was to develop instrument markers that are visible in both magnetic particle imaging (MPI) and magnetic resonance imaging (MRI). The instrument markers were based on two different magnetic nanoparticle types (synthesized in-house KLB and commercial Bayoxide E8706). Coatings containing one of both particle types were fabricated and measured with a magnetic particle spectrometer (MPS) to estimate their MPI performance. Coatings based on both particle types were then applied on a segment of a nonmetallic guidewire. Imaging experiments were conducted using a commercial, preclinical MPI scanner and a preclinical 1 tesla MRI system. MPI image reconstruction was performed based on system matrices measured with dried KLB and Bayoxide E8706 coatings. The bimodal markers were clearly visible in both methods. They caused circular signal voids in MRI and areas of high signal intensity in MPI. Both the signal voids as well as the areas of high signal intensity were larger than the real marker size. Images that were reconstructed with a Bayoxide E8706 system matrix did not show sufficient MPI signal. Instrument markers with bimodal visibility are essential for the perspective of monitoring cardiovascular interventions with MPI/MRI hybrid systems.

For the success of biomedical applications of magnetic iron oxide nanoparticles (MION), such as magnetic hyperthermia and magnetic particle imaging, it is essential to understand the orientational dynamics of MION in a complex fluid under an alternating field. Here, using the magnetic linear dichroism (MLD) measurement, we directly observed the orientational behavior of MION in a hydrogel under a damped oscillating magnetic field (DOMF) of 33 kHz in frequency. Hydrophobically modified ethoxylated urethane (HEUR) is examined as the network polymer because the mesh size of the network is controllable with its concentration. We used two MIONs: a bare MION (MION1) and a MION coated with an amphiphilic polymer (MION2). Where the mesh size of the gel network is larger than the particle's hydrodynamic diameter, MION1 in the hydrogel rotates in the same manner in a simple solution, although the macroscopic rheological property of the medium is quite different. Meanwhile, the orientational behavior of MION2 is dramatically changed by the addition of HEUR molecules even below the minimum gelation concentration, indicating that MION2 is associated with the flower micelles of HEUR. By analyzing the MLD waveform, the orientational behavior of MION1 in the HEUR gel under a DOMF can be explained with single-mode relaxation, whereas that of MION2 is complicated; a rapid partial rotation near the particle and a whole slow rotation of the particle-flower micelle associate are superimposed. It is hard to distinguish this difference in orientational behaviors from the dynamic magnetization curve because the dominant magnetization reversal process is Néel rotation, the rotation of the magnetic moment in the particle. The MLD measurement is a potential tool for optimizing biomedical techniques utilizing MIONs and for nanorheology or colloid science in a complex matrix such as a hydrogel or cytoplasmic matrix.

Magnetic fluid hyperthermia (MFH) is a promising therapeutic strategy that targets malignant tissues by heating to 40-43 °C using magnetic nanoparticles (MNPs) subjected to an alternating magnetic field (AMF). In this study, novel magnetic iron(III) oxide nanoparticles doped with magnesium (Mg0.1-γ-Fe2O3(mPEG-silane)0.5) were synthesized, and their structural, chemical, and magnetic properties were analyzed using the following techniques: Fourier-transform infrared spectroscopy, Raman spectroscopy, vibrating magnetometer analysis, powder X-ray diffraction, inductively coupled plasma mass spectrometry, scanning electron microscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. The as-synthesized MNPs were used as water ferrofluids for MFH under an AMF in two calorimetric setups, namely phantom and lung cancer cell (A549) models. The as-synthesized MNPs were hexagonal or rhombohedral shaped, with an average size of 27 nm. They showed a typical soft ferromagnetic behavior based on the hysteresis profile, with a magnetic saturation of 70 emu g-1 and remnant magnetization of 1.6 emu g-1. In phantom studies, the ferrofluid (3.0 mg mL-1) exposed to an AMF (18.3 kA m-1, 110.1 kHz) heated up extremely quickly, reaching more than 90 °C in the first 10 min of magnetization. In cell studies, the ferrofluid (0.25 mg mL-1) under an AMF (16.7 kA m-1, 110.1 kHz) showed a slight increase in temperature within the first 12 min, reaching a peak of ca. 43-45 °C, which was stable up to the end of the AMF exposure (45 min). Under these conditions, a pronounced cytotoxic effect on the lung cancer cells was observed (viability ca. 15-20%). No such deleterious effects were observed when the cells were treated with MNPs only without an AMF. Specific absorption rate (SAR) measurements were performed using three mathematical approaches, namely the initial slope method, the corrected slope method, and the Box-Lucas method, which ranged from ca. 429 to 596 W g-1 for phantom and cell studies. Iron(III) oxide MNPs doped with magnesium were found to be candidates for MFH in lung cancer treatments.

To propose an alternative method of thermoacoustic wave generation based on heating of magnetic nanoparticles (MNPs) using alternating magnetic field (AMF). The feasibility of thermoacoustic wave generation from MNPs by applying a short-burst of AMF or a frequency-modulated AMF is theoretically analyzed. As the relaxation of MNPs is strongly dependent upon the amplitude and frequency of AMF, either an amplitude modulated, fixed frequency AMF (termed time-domain AMF) or a frequency modulated, constant amplitude AMF (termed frequency-domain AMF) will result in time-varying heat dissipation from MNPs, which has the potential to generate thermoacoustic waves. Following Rosensweig's model of specific power loss of MNPs in a steady-state AMF, the time-resolved heat dissipations of MNPs of superparamagnetic size when exposed to a short bursting of AMF and∕or to a linearly frequency chirped AMF are derived, and the resulted acoustic propagation is presented. Based on experimentally measured temperature-rise characteristics of a superparamagnetic iron-oxide nanoparticle (SPION) matrix in a steady-state AMF of various frequencies, the heat dissipations of the SPION under time-domain and frequency-domain AMF configurations that could have practical utility for thermoacoustic wave generation are estimated. The initial rates of the temperature-rise of the SPION matrix were measured at an iron-weight concentration of 0.8 mg∕ml and an AMF frequency of 88.8 kHz to 1.105 MHz. The measured initial rates of temperature-rise were modeled by Rosensweig's theory, and projected to 10 MHz AMF frequency, at which a 1 μs bursting corresponding to a 1.55 mm axial resolution of acoustic detection could contain 10 complete cycles of AMF oscillation and the power dissipation is approximately 84 times of that at 1 MHz. Exposing the SPION matrix to a 1 μs bursting of AMF at 10 MHz frequency and 100 Oe field intensity would produce a volumetric heat dissipation of 7.7 μJ∕cm(3) over the microsecond duration of the AMF burst. If the SPION matrix is exposed to a 1 ms long AMF train at 100 Oe field intensity that chirps linearly from 1 to 10 MHz, the volumetric heat dissipation produced over each 2π phase change of the AMF oscillation is estimated to increase from 0.15 to 1.1 μJ∕cm(3) within the millisecond duration of the chirping of AMF. The heat dissipations upon SPION (∼1 mg∕ml iron-weight concentration) by a 1 μs bursting of 100 Oe AMF at 10 MHz and a 1 ms train of 100 Oe AMF that chirps linearly from 1 to 10 MHz were estimated to determine the potential of thermal-acoustic wave generation. Although thermoacoustic wave generation from MNPs by time- or frequency-domain AMF applications is predicted, the experimental generation of such a wave remains challenging.

We studied the magnetic resonance imaging liver contrast agent Resovist by a variety of magnetic measurement techniques, in order to understand the physical mechanism of their high magnetic particle imaging (MPI) performance, with a focus on the size-dependent contributions to the MPI signal. To this end, we used asymmetric flow field-flow fractionation to separate Resovist into a set of fractions with defined hydrodynamic diameters. The individual fractions were magnetically characterized by static magnetization and magnetorelaxometry measurements to obtain the corresponding effective magnetic anisotropy and effective size distribution parameters. In addition, the MPI performance of each fraction was assessed by magnetic particle spectroscopy. We observed an MPI signal gain of about 100% with respect to their iron amount for the best fraction. Relating these finding to the results from magnetic characterization provides more insight into the mechanisms of MPI performance of Resovist. This knowledge may help to improve the design of novel MPI tracers.

In magnetic particle imaging (MPI), nanoparticle relaxation delays the response of the super paramagnetic iron oxide nanoparticles (SPIO) magnetization to the applied magnetic field [1-7]. Relaxation can be a significant issue in MPI, since the delayed response can deteriorate the quality of MPI images: due to relaxation, both the resolution and the signal-to-noise ratio (SNR) of the MPI images will worsen. Previously, the SPIO relaxation effect in MPI was modeled as a single time constant using the first-order Debye relaxation process [5,8-9]. While this model provided a good fit to the experimental data, it does not capture the full response of the SPIOs: instantaneous magnitude of the sinusoidal drive field is time-varying, which in turn will cause the relaxation time to vary. In this work, we analyze the effects of field dependent relaxation time on MPI images reconstructed with the x-space technique [2].

We report a simple one step protocol for the preparation of fairly monodisperse and highly water-soluble magnetic iron oxide nanoparticles (MIONs) through a co-precipitation method using a novel multifunctional, biocompatible and water-soluble polymer ligand dodecanethiol-polymethacrylic acid (DDT-PMAA). DDT-PMAA owing to its several intrinsic properties, not only efficiently controls the size of the MIONs but also gives them excellent water solubility, long time stability against aggregation and oxidation, biocompatibility and multifunctional surface rich in thioether and carboxylic acid groups. The molecular weight and concentration of the polymer ligand were optimized to produce ultrasmall (4.6 ± 0.7 nm) MIONs with high magnetization (50 emu g-1). The MIONs obtained with 1.5 mM DDT-PMAA (5330 g mol-1) are highly stable in solution as well as in dry powder form for an extended period of time. These MIONs show a high degree of monodispersity and are superparamagnetic at room temperature. The polymer ligand and MIONs@Polymer were characterized by GPC, 1H NMR, DLS, TEM, FTIR-Raman, XRD, TGA and VSM. In order to demonstrate the bio-applications of these magnetic nanoparticles (NPs), their toxicity was determined by MTT assay and they were found to be non-toxic and biocompatible. Finally, MIONs were conjugated with the anti-cancer drug doxorubicin (DOX) and its efficacy, as a model drug delivery system, was determined using HepG2 cells. The efficiency of the drug-NP conjugates i.e., covalently bound DOX-MIONs and electrostatically loaded DOX/MIONs, was found to be significantly higher than that of the free drug (DOX).

Hybrid nanogels, composed of thermoresponsive polymers and superparamagnetic nanoparticles, are attractive nanocarriers for biomedical applications, being able-as a polymer matrix-to uptake and release high quantities of chemotherapeutic agents and-as magnetic nanoparticles-to be heated when exposed to an alternative magnetic field (AMF), better known as magnetic hyperthermia. Herein, biocompatible, pH-responsive, magnetoresponsive, and thermoresponsive nanogels, based on oligo(ethylene glycol) methyl ether methacrylate monomers and a methacrylic acid comonomer were prepared by conventional precipitation radical copolymerization in water, post-assembled by complexation with iron oxide magnetic nanoparticles (MNPs) of maghemite (γ-Fe2O3), and loaded with an anticancer drug (doxorubicin, DOX), for remotely controlled drug release by a "hot spot", as an athermal magnetic hyperthermia strategy against cancer. These nanogels, denoted MagNanoGels, with a hydrodynamic diameter from 328 to 460 nm, as a function of the MNP content, have a swelling-deswelling behavior at their volume phase temperature transition around 47 °C in a physiological medium (pH 7.5), which is above the human body temperature (37 °C). Applying an alternative magnetic field increases the release of DOX by 2-fold, while no macroscopic heating was recorded. This enhanced drug release is due to a shrinking of the polymer network by local heating, as illustrated by the MagNanoGel size decrease under an AMF. In cancer cells, not only do the DOX-MagNanoGels internalize DOX more efficiently than free DOX, but also DOX intracellular release can be remotely triggered under an AMF, in athermal conditions, thus enhancing DOX cytotoxicity.

Magnetite nanoparticle (MNP) tracers can be optimized for Magnetic Particle Imaging (MPI) by tuning their magnetic core size and size distribution. In previous work, our group showed that ~15 nm MNPs were optimal at 250 khz by synthesizing a series of tracers with tuned size and narrow size distributions. This optimization approach is general, and here we present experimental results that demonstrate that the same principles apply at 25 khz excitation. The key result of this work is that MPI spatial resolution can be improved by the appropriate selection of MNPs.KeywordsOptimization ApproachPoint Spread FunctionNarrow Size DistributionMagnetite NanoparticlePoint SpreadThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.