Next-Generation Magnetic Particle Imaging: Innovations In System Architectures, Tracer Engineering, and Clinical Translation.

Magnetic Particle Imaging (MPI) is an emerging tracer-based imaging modality that enables real-time, quantitative visualization with zero tissue background, high sensitivity, and depth-independent signal detection. Unlike conventional imaging methods that rely on intrinsic tissue contrast or radioactive decay, MPI image formation is governed by the nonlinear magnetization dynamics of superparamagnetic iron oxide nanoparticles, making imaging performance fundamentally dependent on nanoparticle properties and magnetic field generation. This review presents a system- and materials-oriented overview of MPI. We first summarize the physical principles of MPI, including nonlinear magnetization, relaxation dynamics, and field-free-region-based spatial encoding. We then review representative MPI system architectures, ranging from closed-bore preclinical scanners to open, single-sided, hand-held, and hybrid platforms, and discuss how scaling, power consumption, and accessibility influence system performance in preclinical and human-scale settings. We further highlight rational tracer engineering using a "Core-Shell-Function" framework, emphasizing how magnetic core design, surface modification, and functionalization together determine signal generation, in vivo behavior, and imaging performance. Finally, we summarize key biomedical applications, including cell tracking, angiography, tumor imaging, and intraoperative guidance, and discuss remaining challenges for clinical translation. This review provides an integrated framework for advancing MPI toward functional imaging and precision medicine.