Fe2+-Dominated Relaxometric Properties of Iron Oxide Nanoparticles as MRI Contrast Agents

Iron oxide nanoparticles (IONPs) have garnered significant interest as magnetic resonance imaging (MRI) contrast agents due to their exceptional magnetic properties and biocompatibility. Toward more precise diagnosis of diseases, the relaxometric properties of IONPs have become a key research focus. Despite extensive studies on structural factors such as size, morphology, surface modification, crystalline phase, and aggregation state, the correlation between the intrinsic structure and relaxometric behavior remains unclear, particularly for ultrasmall IONPs. To address this issue, we carefully compared IONPs with identical size, shape, and surface modification and found out strong correlations among the content of Fe 2+ ions, oxygen vacancies, and the relaxometric properties. By optimizing the reaction system, ultrasmall IONPs showing outstanding relaxometric performance, with longitudinal relaxivity up to 9.0 mM –1 s –1 and transverse relaxivity up to 28.5 mM –1 s –1, were successfully obtained. These results underscore the pivotal role of Fe 2+ in the relaxometric properties of IONP-based MRI contrast agents.