Applications Of Magnetic Particle Imaging Research Articles

Recent Developments in Magnetic Hyperthermia Therapy (MHT) and Magnetic Particle Imaging (MPI) in the Brain Tumor Field: A Scoping Review and Meta-Analysis.

Magnetic hyperthermia therapy (MHT) is a promising treatment modality for brain tumors using magnetic nanoparticles (MNPs) locally delivered to the tumor and activated with an external alternating magnetic field (AMF) to generate antitumor effects through localized heating. Magnetic particle imaging (MPI) is an emerging technology offering strong signal-to-noise for nanoparticle localization. A scoping review was performed by systematically querying Pubmed, Scopus, and Embase. In total, 251 articles were returned, 12 included. Articles were analyzed for nanoparticle type used, MHT parameters, and MPI applications. Preliminary results show that MHT is an exciting treatment modality with unique advantages over current heat-based therapies for brain cancer. Effective application relies on the further development of unique magnetic nanoparticle constructs and imaging modalities, such as MPI, that can enable real-time MNP imaging for improved therapeutic outcomes.

Machine Learning and Deep Learning Applications in Magnetic Particle Imaging.

In recent years, magnetic particle imaging (MPI) has emerged as a promising imaging technique depicting high sensitivity and spatial resolution. It originated in the early 2000s where it proposed a new approach to challenge the low spatial resolution achieved by using relaxometry in order to measure the magnetic fields. MPI presents 2D and 3D images with high temporal resolution, non-ionizing radiation, and optimal visual contrast due to its lack of background tissue signal. Traditionally, the images were reconstructed by the conversion of signal from the induced voltage by generating system matrix and X-space based methods. Because image reconstruction and analyses play an integral role in obtaining precise information from MPI signals, newer artificial intelligence-based methods are continuously being researched and developed upon. In this work, we summarize and review the significance and employment of machine learning and deep learning models for applications with MPI and the potential they hold for the future. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

Magnetic nanoparticles for magnetic particle imaging (MPI): design and applications.

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.

Harmonic response of Gd-doped Mn-ferrite nanoparticles under AC magnetic field and optimization of Gd doping for MPI applications

This study synthesized Gd-doped Mn-ferrite nanoparticles for magnetic particle imaging (MPI) applications with doping levels (x) of 0, 0.05, 0.07, and 0.10. Analyses using X-ray diffraction measurements unequivocally confirmed the presence of a spinel-type crystal structure in the synthesized particles and X-ray absorption fine-structure spectroscopy confirmed the incorporation of Gd atoms in place of Mn within the crystal lattice. Magnetization and harmonic measurements under an AC magnetic field revealed that particles with a high initial permeability and low coercivity showed a high response intensity. Notably, particles possessing a Gd doping level of x = 0.07 displayed the highest response and were considered promising as MPI materials.

Small zinc doped iron oxide tracers for magnetic particle imaging

Magnetic particle imaging (MPI) has garnered significant attention in biomedical imaging research due to its excellent signal intensity that is generated directly from superparamagnetic iron oxide nanoparticles (SPIONs). Small nanoparticle tracers with high saturation magnetisation are crucial for MPI as they can prolong circulation, crossing the blood brain barrier and enhance cellular uptake. In this work, we demonstrate small zinc doped iron oxide nanoparticles (Zn-IONPs) are excellent MPI tracers. Our Zn-IONPs exhibited up to 37 % and 64% enhancement in saturation magnetisation (Msat) value and MPI signal intensity respectively compared to Fe3O4 of the same size. As a result, the polymer encapsulated Zn-IONPs achieved up to 2.7-fold enhancement in MPI signal intensity compared to VivoTrax. Furthermore, these polymer encapsulated NPs were also determined to be non-toxic hence making these Zn-IONPs ideal for many biomedical applications in MPI where small size is critical to prolong circulation time and crossing the blood brain barrier.

SMART RHESINs-Superparamagnetic Magnetite Architecture Made of Phenolic Resin Hollow Spheres Coated with Eu(III) Containing Silica Nanoparticles for Future Quantitative Magnetic Particle Imaging Applications.

Magnetic particle imaging (MPI) is a powerful and rapidly growing tomographic imaging technique that allows for the non-invasive visualization of superparamagnetic nanoparticles (NPs) in living matter. Despite its potential for a wide range of applications, the intrinsic quantitative nature of MPI has not been fully exploited in biological environments. In this study,a novel NP architecture that overcomes this limitation by maintaining a virtually unchanged effective relaxation (Brownian plus Néel) even when immobilized is presented. This superparamagnetic magnetite architecture made of phenolic resin hollow spheres coated with Eu(III) containing silica nanoparticles (SMART RHESINs)wassynthesized and studied. Magnetic particle spectroscopy (MPS) measurements confirm their suitability for potential MPI applications. Photobleaching studies show an unexpected photodynamic due to the fluorescence emission peak of the europium ion in combination with the phenol formaldehyde resin (PFR). Cell metabolic activity and proliferation behavior are not affected. Colocalization experiments revealthe distinct accumulation of SMART RHESINs near the Golgi apparatus. Overall, SMART RHESINs show superparamagnetic behavior and special luminescent properties without acute cytotoxicity, making them suitable for bimodal imaging probes for medical use like cancer diagnosis and treatment. SMART RHESINs have the potential to enable quantitative MPS and MPI measurements both in mobile and immobilized environments.

Application of magnetic particle imaging to evaluate nanoparticle fate in rodent joints.

Nanoparticles are a promising approach for improving intra-articular drug delivery and tissue targeting. However, techniques to non-invasively track and quantify their concentration in vivo are limited, resulting in an inadequate understanding of their retention, clearance, and biodistribution in the joint. Currently, fluorescence imaging is often used to track nanoparticle fate in animal models; however, this approach has limitations that impede long-term quantitative assessment of nanoparticles over time. The goal of this work was to evaluate an emerging imaging modality, magnetic particle imaging (MPI), for intra-articular tracking of nanoparticles. MPI provides 3D visualization and depth-independent quantification of superparamagnetic iron oxide nanoparticle (SPION) tracers. Here, we developed and characterized a polymer-based magnetic nanoparticle system incorporated with SPION tracers and cartilage targeting properties. MPI was then used to longitudinally assess nanoparticle fate after intra-articular injection. Magnetic nanoparticles were injected into the joints of healthy mice, and evaluated for nanoparticle retention, biodistribution, and clearance over 6weeks using MPI. In parallel, the fate of fluorescently tagged nanoparticles was tracked using in vivo fluorescence imaging. The study was concluded at day 42, and MPI and fluorescence imaging demonstrated different profiles in nanoparticle retention and clearance from the joint. MPI signal was persistent over the study duration, suggesting NP retention of at least 42days, much longer than the 14days observed based on fluorescence signal. These data suggest that the type of tracer - SPIONs or fluorophores - and modality of imaging can affect interpretation of nanoparticle fate in the joint. Given that understanding particle fate over time is paramount for attaining insights about therapeutic profiles in vivo, our data suggest MPI may yield a quantitative and robust method to non-invasively track nanoparticles following intra-articular injection on an extended timeline.

First Dedicated Balloon Catheter for Magnetic Particle Imaging

Vascular interventions are a promising application of Magnetic Particle Imaging enabling a high spatial and temporal resolution without using ionizing radiation. The possibility to visualize the vessels as well as the devices, especially at the same time using multi-contrast approaches, enables a higher accuracy for diagnosis and treatment of vascular diseases. Different techniques to make devices MPI visible have been introduced so far, such as varnish markings or filling of balloons. However, all approaches include challenges for in vivo applications, such as the stability of the varnishing or the visibility of tracer filled balloons in deflated state. In this contribution, we present for the first time a balloon catheter that is molded from a granulate incorporating nanoparticles and can be visualized sufficiently in MPI. Computed tomography is used to show the homogeneous distribution of particles within the material. Safety measurements confirm that the incorporation of nanoparticles has no negative effect on the balloon. A dynamic experiment is performed to show that the inflation as well as deflation of the balloon can be imaged with MPI.

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.

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.

Manganese doped-iron oxide nanoparticles and their potential as tracer agents for magnetic particle imaging (MPI)

Manganese doped iron oxide nanoparticles based on the chemical formula MnxFe3-xO4 (where × = 0.00, 0.50, and 1.00) have been prepared with different concentrations of manganese-oleate, and iron-oleate by thermal treatment method. To prevent nanoparticle from agglomeration and increase surface functioning, oleate was employed as a capping agent to create stable nanoparticles for magnetic particle imaging (MPI). Mn-doped magnetite nanoparticles (MnxFe3-xO4) were synthesized by the thermal decomposition method. Manganese-based iron oxides were morphologically assessed by x-ray diffraction (XRD), fourier transformed infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Manganese-based iron oxides were also magnetically examined with electron-spin resonance (ESR), physical properties measurement system (PPMS), and magnetic particle relaxometer (MPR). Additionally, phase composition and iron concentration of the manganese-based nanoparticles were determined with the Mossbauer spectra (MS) technique. The crystallite size of 11–18 nm was achieved with the XRD technique for MnxFe3-xO4. MnFe2O4 (x = 1.00) revealed high stability at higher temperatures according to TGA analysis and high saturation magnetization at room temperature as compared to other manganese concentrations. MPR demonstrated the shortest relaxation time of MnFe2O4 as compared to commercially MPI tracer agents such as Vivotrax (magnetic insight) and Perimag (micromod). The finding of this study emphasizes that manganese ferrites have the immense potential to become the optimum tracer agent for MPI applications.

Applications of Magnetic Particle Imaging in Biomedicine: Advancements and Prospects.

Magnetic particle imaging (MPI) is a novel emerging noninvasive and radiation-free imaging modality that can quantify superparamagnetic iron oxide nanoparticles tracers. The zero endogenous tissue background signal and short image scanning times ensure high spatial and temporal resolution of MPI. In the context of precision medicine, the advantages of MPI provide a new strategy for the integration of the diagnosis and treatment of diseases. In this review, after a brief explanation of the simplified theory and imaging system, we focus on recent advances in the biomedical application of MPI, including vascular structure and perfusion imaging, cancer imaging, the MPI guidance of magnetic fluid hyperthermia, the visual monitoring of cell and drug treatments, and intraoperative navigation. We finally optimize MPI in terms of the system and tracers, and present future potential biomedical applications of MPI.

System Matrix Based Reconstruction for Pulsed Sequences in Magnetic Particle Imaging.

Improving resolution and sensitivity will widen possible medical applications of magnetic particle imaging. Pulsed excitation promises such benefits, at the cost of more complex hardware solutions and restrictions on drive field amplitude and frequency. State-of-the-art systems utilize a sinusoidal excitation to drive superparamagnetic nanoparticles into the non-linear part of their magnetization curve, which creates a spectrum with a clear separation of direct feed-through and higher harmonics caused by the particles response. One challenge for rectangular excitation is the discrimination of particle and excitation signals, both broad-band. Another is the drive-field sequence itself, as particles that are not placed at the same spatial position, may react simultaneously and are not separable by their signal phase or shape. To overcome this potential loss of information in spatial encoding for high amplitudes, a superposition of shifting fields and drive-field rotations is proposed in this work. Upon close view, a system matrix approach is capable to maintain resolution, independent of the sequence, if the response to pulsed sequences still encodes information within the phase. Data from an Arbitrary Waveform Magnetic Particle Spectrometer with offsets in two spatial dimensions is measured and calibrated to guarantee device independence. Multiple sequence types and waveforms are compared, based on frequency space image reconstruction from emulated signals, that are derived from measured particle responses. A resolution of 1.0 mT (0.8 mm for a gradient of (-1.25,-1.25,2.5) Tm-1) in x- and y-direction was achieved and a superior sensitivity for pulsed sequences was detected on the basis of reference phantoms.

Comprehensive Evaluation of Magnetic Particle Imaging (MPI) Scanners for Biomedical Applications

Magnetic particle imaging (MPI) is an emerging tomographic imaging technique that tracks and quantitatively measures the spatial distribution of the superparamagnetic iron oxide nanoparticles (SPIONs). It is a radiation-free, background-free, and signal attenuation-free imaging modality that utilizes the non-linear behavior of the tracer response. The lowest acquisition time, high spatial resolution, and extreme sensitivity make it ideal for medical imaging in the future in comparison to magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). SPIONs are the main source of signal generation and have a significant influence on MPI characteristics. Many groups in the world are working to produce optimal tracer agents with a low toxicity profile for MPI applications. Versatile MPI scanners are developed and implemented at the pre-clinical stage to evaluate the performance of the system parameters. This review aims at giving an overview of the current developments and significant achievements of the tracers, imager design, image reconstruction, and potential applications of MPI since its first exposure to the scientific world in 2005.

A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation.

There is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumor behavior, and metastatic properties observed in the original tumor. To study PDX cells preclinically, we used both bioluminescence imaging (BLI) to evaluate cell viability and magnetic particle imaging (MPI), an emerging imaging technology to allow for detection and quantification of iron nanoparticles. The goal of this study was to develop the first successful iron labeling method of breast cancer cells derived from patient brain metsastases and validate this method with imaging during tumor development. The overall workflow of this labeling method is as follows: adherent and non-adherent luciferase expressing human breast cancer PDX cells (F2-7) are dissociated and concurrently labeled after incubation with micron-sized iron oxide particles (MPIO; 25 μg Fe/ml), with labeling validated by cellular imaging with MPI and BLI. In this study, NOD/SCID/ILIIrg-/- (n = 5) mice Received injections of 1 × 106 iron-labeled F2-7 cells into the fourth mammary fat pad (MFP). BLI was performed longitudinally to day 49 and MPI was performed up to day 28. In vivo BLI revealed that signal increased over time with tumor development. MPI revealed decreasing signal in the tumors over time. Here, we demonstrate the first application of MPI to monitor the growth of a PDX MFP tumor and the first successful labeling of PDX cells with iron oxide particles. Imaging of PDX cells provides a powerful system to better develop personalized therapies targeting breast cancer brain metastasis.

Tailored Magnetic Multicore Nanoparticles for Use as Blood Pool MPI Tracers

For the preclinical development of magnetic particle imaging (MPI) in general, and the exploration of possible new clinical applications of MPI in particular, tailored MPI tracers with surface properties optimized for the intended use are needed. Here we present the synthesis of magnetic multicore particles (MCPs) modified with polyethylene glycol (PEG) for use as blood pool MPI tracers. To achieve the stealth effect the carboxylic groups of the parent MCP were activated and coupled with pegylated amines (mPEG-amines) with different PEG-chain lengths from 2 to 20 kDa. The resulting MCP-PEG variants with PEG-chain lengths of 10 kDa (MCP-PEG10K after one pegylation step and MCP-PEG10K2 after a second pegylation step) formed stable dispersions and showed strong evidence of a successful reaction of MCP and MCP-PEG10K with mPEG-amine with 10 kDa, while maintaining their magnetic properties. In rats, the mean blood half-lives, surprisingly, were 2 and 62 min, respectively, and therefore, for MCP-PEG10K2, dramatically extended compared to the parent MCP, presumably due to the higher PEG density on the particle surface, which may lead to a lower phagocytosis rate. Because of their significantly extended blood half-life, MCP-PEG10K2 are very promising as blood pool tracers for future in vivo cardiovascular MPI.

The Reconstruction of Magnetic Particle Imaging: Current Approaches Based on the System Matrix.

Magnetic particle imaging (MPI) is a novel non-invasive molecular imaging technology that images the distribution of superparamagnetic iron oxide nanoparticles (SPIONs). It is not affected by imaging depth, with high sensitivity, high resolution, and no radiation. The MPI reconstruction with high precision and high quality is of enormous practical importance, and many studies have been conducted to improve the reconstruction accuracy and quality. MPI reconstruction based on the system matrix (SM) is an important part of MPI reconstruction. In this review, the principle of MPI, current construction methods of SM and the theory of SM-based MPI are discussed. For SM-based approaches, MPI reconstruction mainly has the following problems: the reconstruction problem is an inverse and ill-posed problem, the complex background signals seriously affect the reconstruction results, the field of view cannot cover the entire object, and the available 3D datasets are of relatively large volume. In this review, we compared and grouped different studies on the above issues, including SM-based MPI reconstruction based on the state-of-the-art Tikhonov regularization, SM-based MPI reconstruction based on the improved methods, SM-based MPI reconstruction methods to subtract the background signal, SM-based MPI reconstruction approaches to expand the spatial coverage, and matrix transformations to accelerate SM-based MPI reconstruction. In addition, the current phantoms and performance indicators used for SM-based reconstruction are listed. Finally, certain research suggestions for MPI reconstruction are proposed, expecting that this review will provide a certain reference for researchers in MPI reconstruction and will promote the future applications of MPI in clinical medicine.

Applications of magnetic particle imaging in the dementias.

This review discusses recent developments in the application of magnetic particle imaging (MPI) to dementia research. MPI is a tracer method that is currently in the preclinical development stage. It provides high sensitivity for the detection and localization of magnetic nanoparticles with very high spatial and temporal resolution and a similar application spectrum as PET. Unlike MRI, the MPI signal is not contaminated by background signal from tissues and is highly quantifiable in terms of local tracer concentrations. These properties make the technology ideally suited for localization of specific targets or quantification of vascular parameters. MPI uses magnetic nanoparticles which can be modified by various coatings, and by adding ligands (i.e. peptides or antibodies) for specific targeting. This makes MPI an attractive tool for the potential detection of abnormal protein deposits, such as Aβ plaques, with greater specificity than MRI. Neural stem cells can also be labelled with these nanoparticles ex vivo to monitor their migration in vivo. The capabilities of MPI opens the potential for several applications of MPI in neurocognitive disorders, including vascular imaging, detection of amyloid plaques and potentially other pathological hallmarks of Alzheimer's disease and stem-cell tracking.

The Applications of Magnetic Particle Imaging: From Cell to Body.

Magnetic particle imaging (MPI) is a cutting-edge imaging technique that is attracting increasing attention. This novel technique collects signals from superparamagnetic nanoparticles as its imaging tracer. It has characteristics such as linear quantitativity, positive contrast, unlimited penetration, no radiation, and no background signal from surrounding tissue. These characteristics enable various medical applications. In this paper, we first introduce the development and imaging principles of MPI. Then, we discuss the current major applications of MPI by dividing them into four categories: cell tracking, blood pool imaging, tumor imaging, and visualized magnetic hyperthermia. Even though research on MPI is still in its infancy, we hope this discussion will promote interest in the applications of MPI and encourage the design of tracers tailored for MPI.

Computational predictions of enhanced magnetic particle imaging performance by magnetic nanoparticle chains

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.