Magnetic Particle Imaging for Pulmonary Applications: Technological Advances, Biological Insights, and Clinical Translation

Background: Magnetic particle imaging (MPI) is an emerging, tracer-based modality that directly detects superparamagnetic iron oxide nanoparticles (SPIONs) with exceptional sensitivity, quantitative signal behavior, and full immunity to air–tissue susceptibility artifacts. These features make MPI particularly well-suited for pulmonary imaging, where traditional techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine-based ventilation/perfusion (V/Q) imaging are limited by radiation exposure, low contrast, and motion-related signal degradation. Objective: This review synthesizes the current state of MPI for lung imaging, with emphasis on its physical principles, tracer development, preclinical applications, and its potential role in assessing pulmonary perfusion, vascular integrity, inflammation, and therapeutic responses. Methods: A systematic evaluation of preclinical studies was performed across three major application domains: pulmonary perfusion mapping, cell tracking and therapeutic monitoring, and vascular injury and permeability assessment. Study designs, SPION formulations, MPI acquisition strategies, and validation methods, including histopathology, biodistribution, broncho-alveolar lavage fluid (BALF) analysis, and Evans Blue assays, were examined to characterize methodological consistency and imaging performance. Results: MPI consistently demonstrated high-contrast, quantitative visualization of pulmonary blood flow, endothelial barrier disruption, inflammatory signaling, and transplanted or inhaled cell populations. Tracer engineering played a critical role: macroaggregated albumin superparamagnetic iron oxide nanoparticles (MAA-SPIONs) enabled capillary-level perfusion mapping, LS-008 improved temporal resolution and vascular delineation, Synomag/Synomag-D allowed quantification of vascular leakage in acute and chronic lung injury, and vascular cell adhesion molecule-1 (VCAM-1)-targeted probes provided molecular-level assessment of inflammation. Hybrid MPI-CT and MPI-MRI approaches further enhanced anatomic localization and enabled accurate pulmonary blood volume (PBV) estimation. Across studies, MPI measurements showed strong agreement with established biological assays and remained free of the artifacts that limit CT and MRI in the lung. Conclusions: Preclinical evidence demonstrates that MPI is a robust, radiation-free, and quantitatively precise modality for functional and molecular lung imaging. Its ability to map perfusion, track therapeutic agents, and noninvasively quantify vascular permeability positions MPI as a promising future alternative or complement to CT, MRI, and nuclear medicine for pulmonary assessment. Continued tracer optimization, system scaling, and clinical validation are key steps toward translating MPI into routine clinical use.