Reduced Magnetic Coupling in Ultrasmall Iron Oxide T1 MRI Contrast Agents

Contrast agents for magnetic resonance imaging (MRI) are essential for evidential visualization of soft tissues pathologies. Contrast-enhanced MRI can be carried out with T1- and T2-weighted sequences that require as contrast agents paramagnetic and superparamagnetic materials, respectively. The T1-weighted imaging is frequently preferred over T2-, as it induces a bright contrast for sharper image analysis and allows more rapid image acquisition. Commonly used and FDA-approved T1 contrast agents, however, were shown to be associated with nephrogenic systematic fibrosis due to Gd3+ release from the injected complexes. Here, ultrasmall iron oxide nanocrystals are produced by scalable flame aerosol technology and investigated as T1 MRI contrast agents by focusing on structure–function relationships and cytocompatibility. The optimized nanocrystals are shown to be a promising cytocompatible alternative to commercial Gd-complexes as they attain comparable relaxivities with no apparent cytotoxicity at clinically relevant concentrations tested in vitro against four different cell types (PC3, HepG2, THP-1, and red blood cells). By using SiO2 as a spacing material, the contrast enhancement could be finely tuned by decreasing the effective magnetic size of iron oxide resulting in significant T1 contrast enhancement due to reduced magnetic coupling