Fe<sup>2+</sup>-Dominated Relaxometric Properties\nof Iron Oxide Nanoparticles as MRI Contrast Agents

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