Ultra-high-field magnetic resonance imaging (UHF-MRI, B > 7 T) combined with contrast enhancement (CE-MRI) offers unmatched spatial resolution, but high-field effects limit the performance of negative contrast agents. Here, we report a ligand-driven strategy to modulate the T relaxivity (r) of monodisperse 12 nm iron oxide-based contrast agents synthesized by thermal decomposition. Five surface chemistries-polyacrylic acid (PAA), poly(isobutylene-alt-maleic anhydride) (PMA), poly(maleic anhydride-alt-1-octadecene) (PMAO), citric acid (CA), and silica (SiO)─ were investigated under physiological conditions and in vivo using relaxometry (1.4 T), clinical (3 T), and UHF (9.4 T) MRI, achieving up to a 333 mm s increase in r. CA-coated T contrast agents exhibited record-high r values (522 mm s at 3 T; 381 mm s at 9.4 T) in spherical iron oxide MNPs within the superparamagnetic size range (d < 20 nm). Correlations of r with hydrodynamic size, ζ-potential, and coating thickness revealed that ligand chemistry-specifically hydrophilicity and anionic surface charge-dominates over physical shell dimensions in governing water accessibility and magnetic dephasing. This scalable ligand-exchange strategy enables precise T tuning at UHF, with phantom results reliably predicting in vivo UHF-MRI performance in rat brain models, advancing the design of neuroimaging nanoprobes.
Keywords: contrast agents, ligand exchange, magnetic contrast agents, magnetic resonance, ultra high field‐MRI
Small (Weinheim an der Bergstrasse, Germany)
Journal Article
English
41631453
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