Heterogeneous Iron Oxide/Dysprosium Oxide Nanoparticles Target Liver for Precise Magnetic Resonance Imaging of Liver Fibrosis.

Abstract

Challenges remain in precisely diagnosing the progress of liver fibrosis in a noninvasive way. We here synthesized small (4 nm) heterogeneous iron oxide/dysprosium oxide nanoparticles (IO-DyO NPs) as a contrast agent (CA) for magnetic resonance imaging (MRI) to precisely diagnose liver fibrosis <i>in vivo</i> at both 7.0 and 9.4 T field strength. Our IO-DyO NPs can target the liver and show an increased <i>T</i>₂ relaxivity along with an increase of magnetic field strength. At a ultrahigh magnetic field, IO-DyO NPs can significantly improve spatial/temporal image resolution and signal-to-noise ratio of the liver and precisely distinguish the early and moderate liver fibrosis stages. Our IO-DyO NP-based MRI diagnosis can exactly match biopsy (a gold standard for liver fibrosis diagnosis in the clinic) but avoid the invasiveness of biopsy. Moreover, our IO-DyO NPs show satisfactory biosafety <i>in vitro</i> and <i>in vivo</i>. This work illustrates an advanced <i>T</i>₂ CA used in ultrahigh-field MRI (UHFMRI) for the precise diagnosis of liver fibrosis <i>via</i> a noninvasive means.