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Abstract Rapid and accurate assessment of conditions characterized by altered blood flow, cardiac blood pooling, or internal bleeding is crucial for diagnosing and treating various clinical conditions. While widely used imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound offer unique diagnostic advantages, they fall short for specific indications due to limited penetration depth and prolonged acquisition times. Magnetic particle imaging (MPI), an emerging tracer‐based technique, holds promise for blood circulation assessments, potentially overcoming existing limitations with reduction in background signals and high temporal and spatial resolution, below the millimeter scale. Successful imaging of blood pooling and impaired flow necessitates tracers with diverse circulation half‐lives optimized for MPI signal generation. Recent MPI tracers show potential in imaging cardiovascular complications, vascular perforations, ischemia, and stroke. The impressive temporal resolution and penetration depth also position MPI as an excellent modality for real‐time vessel perfusion imaging via functional MPI (fMPI). This review summarizes advancements in optimized MPI tracers for imaging blood circulation and analyzes the current state of pre‐clinical applications. This work discusses perspectives on standardization required to transition MPI from a research endeavor to clinical implementation and explore additional clinical indications that may benefit from the unique capabilities of MPI. 

Magnetic particle imaging (MPI) is a novel biomedical imaging modality that allows non-invasive, tomographic, and quantitative tracking of the distribution of superparamagnetic iron oxide nanoparticle (SPION) tracers. While MPI possesses high sensitivity, detecting nanograms of iron, it does not provide anatomical information. Computed tomography (CT) is a widely used biomedical imaging modality that yields anatomical information at high resolution. A multimodal imaging agent combining the benefits of MPI and CT imaging would be of interest. Here we combine MPI-tailored SPIONs with CT-contrast hafnium oxide (hafnia) nanoparticles using flash nanoprecipitation to obtain dual-imaging MPI/CT agents. Co-encapsulation of iron oxide and hafnia in the composite nanoparticles was confirmed via transmission electron microscopy and elemental mapping. Equilibrium and dynamic magnetic characterization show a reduction in effective magnetic diameter and changes in dynamic magnetic susceptibility spectra at high oscillating field frequencies, suggesting magnetic interactions within the composite dual imaging tracers. The MPI performance of the dual imaging agent was evaluated and compared to the commercial tracer ferucarbotran. The dual-imaging agent has MPI sensitivity that is ∼3× better than this commercial tracer. However, worsening of MPI resolution was observed in the composite tracer when compared to individually coated SPIONs. This worsening resolution could result from magnetic dipolar interactions within the composite dual imaging tracer. The CT performance of the dual imaging agent was evaluated in a pre-clinical animal scanner and a clinical scanner, revealing better contrast compared to a commercial iodine-based contrast agent. We demonstrate that the dual imaging agent can be differentiated from the commercial iodine contrast agent using dual energy CT (DECT) imaging. Furthermore, the dual imaging agent displayed energy-dependent CT contrast arising from the combination of SPION and hafnia, making it potentially suitable for virtual monochromatic imaging of the contrast agent distribution using DECT.