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Magnetic Particle Imaging
Magnetic nanoparticles (MNPs) have a wide range of applications; an area of particular interest is magnetic particle imaging (MPI). MPI is an imaging modality that utilizes superparamagnetic iron oxide particles (SPIONs) as tracer particles to produce highly sensitive and specific images in a broad range of applications, including cardiovascular, neuroimaging, tumor imaging, magnetic hyperthermia and cellular tracking.
MPI is a tracer-based, functional and tomographic imaging modality, which determines the spatial distribution of MNPs . MNPs are a widely diverse group of materials that have relevant and potentially ground-breaking applications in a wide variety of biomedical arenas including drug delivery, cell targeting, magnetic hyperthermia, and diagnostic imaging .
Magnetic particle imaging is an innovative imaging modality that is being developed to add strength and diversity to current imaging techniques such as MRI, CT, bioluminescence imaging (BLI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) . While each of these imaging techniques possess clinical utility, they are also accompanied by shortcomings. For example, MRI is a commonly utilized and powerful diagnostic tool in many clinical arenas, including cancer and cardiovascular imaging . Recently, the value has come into question, as limitations to MRI are recognized. Limitations include long scan times, lack of standards for quantitative measures for clinical usage, and inefficient recognition of false positive results prior to initiating treatment . Additionally, the various imaging techniques present a level of risk to patients, including radiation exposure during nuclear imaging procedures such as PET and CT scans , and gadolinium exposure during MRI, which can lead to systemic accumulation or nephrogenic systemic fibrosis in certain patients . With these limitations in mind, the desire for a safe, efficient, ultra-sensitive and specific, multipurpose imaging system that will produce quantifiable 3D images is obvious—and leads us to MPI.
Considering the described and perceived strengths of MNPs and MPI, the question arises regarding the lack of clinical use of this system. While there are many advantages to MPI and it undoubtedly has the potential to improve biomedical imaging, there are also many obstacles and challenges. These challenges include ideal MNP development, safety concerns and practical implementation .
2. Magnetic Nanoparticle Synthesis Methods
As the utility of MNPs across various applications becomes more widely accepted, new methods for MNP synthesis are being developed. Specifically, as SPIONs hold such strong promise in the field of MPI, there are many synthesis methods reported. The most common methods include co-precipitation, thermal decomposition, hydrothermal synthesis, microemulsion, electrochemical synthesis and bacterial synthesis .
Presently, producing a colloidally stable batch of iron oxide nanoparticles is dependent on particle size, surface chemistry, density, and aqueous conditions . Creating monodispersed iron oxide nanoparticles provides consistency, reproducible results, and predictable responses. This is critical, as limited reproducibility is a challenge in large-scale production and scalable production will be an important step to MPI becoming available for clinical use . Research has demonstrated that thermal decomposition techniques using nonpolar solvents produce highly monodispersed MNPs with specific surface coatings .
3. MPI Applications
3.1. Cancer Imaging
MPI research is pushing the boundaries of conventional oncology imaging, especially sensitivity and resolution, by utilizing the intrinsic characteristics of MNPs and SPIONS. Song et al.  explored this approach by creating Janus iron oxide particles coated with a semiconducting polymer. Those MNPs demonstrated 7-fold the intensity of commercial MRI tracers and 3-fold the intensity of commercial MPI tracers. The Janus MNPs properly imaged as few as 250 cancer cells in vivo. Compared to the clinical imaging capability of 109 cancer cells, 250 cells indicate a substantial significant difference in resolution and sensitivity.
Yu et al.  explored the possibility of in vivo cancer MPI imaging in a xenograft breast tumor rat model utilizing long circulating SPIO tracer (LS-008). Their work relied on the enhanced permeability and retention (EPR) effect that is understood to allow nanoparticles to preferentially accumulate in tumors due to the leaky vasculature of the tumor . They were able to demonstrate preferential accumulation of the particles within the tumors, with particles present within the tumor up to six days post injection, and a dose dependent increase in concentration of the tracer in blood. These findings provide confidence in the EPR effect and the quantitative abilities of MPI in vivo. This work led Yu et al.  to pose the question of MPI’s efficacy in less vascular tumors as well as metastatic tumors, given the heterogeneity of neoplasia, prior to suggesting clinical use of MPI for cancer imaging.
3.2. Cardiovascular Imaging
MPI offers benefits that are increasingly attractive for use in cardiovascular imaging . Magnetic nanoparticles can act as nano-probes and deliver significant information including anatomic and physiologic details of cardiovascular diseases . This behavior is largely a result of the size and physical characteristics of MNPs, as they are well suited for cellular imaging of myocardial and atherosclerotic anatomy and abnormalities . A main application of MPI for cardiovascular imaging is direct administration of MNPs into blood vessels to visualize blood flow. This is feasible due to the ability of MPI to image any depth of tissue  and is quite impactful, as visualizing blood flow can identify abnormalities in velocity or pattern of blood flow , which can indicate structural changes. Vaalma et al.  described the ability of MPI to investigate degree of stenosis within vasculature. It was found that at an appropriate clinical MNP concentration, an area of stenosis as small as 2 mm could be successfully imaged. MPI can also be used during cardiovascular interventions, such as catheter guidance in minimally invasive procedures .
3.4. Cell Tracking
3.5. Magnetic Hyperthermia
4. Safety and Toxicity
4.2. Toxicity Mechanisms
Accumulation and distribution of MNPs are a main cause for in vivo toxicity. It is well understood that the biodistribution of MNPs depends on the particle size, particle coating, and mass of particles administered .
Biodistribution of MNPs has been tracked via opsonization, a process where antibodies mark foreign pathogens (in this case MNPs) for elimination by phagocytes . It was determined that opsonized MNPs were removed from the bloodstream within a few minutes and were distributed as follows: 80–90% through the liver, 5–8% through the spleen, and 1–2% via the bone marrow . Additionally, interaction and toxicity of MNPs is highly dependent upon the particle surface. Therefore, investigation into ideal coatings for functional, excretable MNPs is necessary.
4.3. Methods for Limiting Toxicity
Desirable properties of MNPs to promote a healthy safety profile mainly include biocompatibility and an appropriate surface chemistry . Of these characteristics, a major technique to effectively reduce toxic effects of these MNPs is surface modification. Surface modifications can: decrease aggregation of MNPs, prevent changes in magnetic properties to maintain efficacy of the MNPs, and inhibit adhesion with plasma proteins to prevent major inflammatory responses in vivo.
5. Conclusions and Perspectives
Overall, MPI offers great promise for a wide range of applications, including but not limited to cancer, cardiovascular, pulmonary and neuroimaging, cellular tracking, and therapeutics such as magnetic hyperthermia. Currently, MPI remains a pre-clinical imaging modality and requires significant upscaling and safety profile development prior to being utilized clinically. However, over time and with extensive research and development, the field of magnetic particle imaging will no doubt revolutionize the accuracy, precision, and methodology in which innumerable diseases are diagnosed and monitored, and the therapy that is administered.
The entry is from 10.3390/ijms22147651
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