20 years of magnetic particle imaging - from patents to patients.

Magnetic Particle Imaging (MPI) has evolved over the past two decades from a conceptual imaging innovation to a promising modality ready for translation into clinical settings. MPI visualizes the distribution of superparamagnetic iron oxide nanoparticles (SPIONs) using time-varying magnetic fields and offers unique advantages such as high sensitivity, real-time 3D imaging, and the absence of ionizing radiation. This review traces key milestones in MPI's development across instrumentation, algorithmics, tracer systems, and medical applications. Advances in scanner technology include field-free point and field-free line architectures, with preclinical and now human-scale systems enabling imaging of extremities and the brain. Reconstruction methods in MPI have evolved along two complementary paths: system matrix-based reconstruction and x-space algorithms. Both approaches are well-established and offer distinct advantages in terms of image quality, computational efficiency, and application-specific flexibility. In parallel, nanoparticle design has advanced significantly, with novel tracers like SPION-loaded erythrocytes, magnetosomes, and SMART rhesins improving circulation time, specificity, or signal quality. MPI's sensitivity allows for diverse biomedical applications, including cardiovascular imaging, endovascular intervention guidance, stroke detection, perfusion monitoring, and cell tracking. The integration of MPI with other modalities such as MRI and CT further expands its diagnostic potential by adding an anatomical background. The recent reintroduction of a clinically approved tracer (Resotran) and the emergence of human-scale scanners mark important steps toward clinical implementation. As the field moves forward, the validation of clinical benefit through prospective trials remains a key challenge. Nevertheless, current momentum strongly suggests that MPI is ready to become a valuable tool in clinical diagnostics within the near future.