RT Journal Article T1 Ligand-Driven Optimization of Iron Oxide Nanoprobes forIn Vivo MRI Enhancement at Ultra-High Field A1 García Acevedo, Pelayo A1 Alonso Alonso, María Luz A1 Ortega Espina, Sara A1 Bañobre López, Manuel A1 Piñeiro Redondo, Yolanda A1 Iglesias Rey, Ramón A1 Rivas Rey, José K1 Contrast agents K1 Ligand exchange K1 Magnetic contrast agents K1 Magnetic resonance K1 Ultra high field-MRI AB Ultra-high-field magnetic resonance imaging (UHF-MRI, B0 > 7 T) combined with contrast enhancement (CE-MRI) offersunmatched spatial resolution, but high-field effects limit the performance of negative contrast agents. Here, we report a ligand-driven strategy to modulate the T2 relaxivity (r2 ) of monodisperse 12 nm iron oxide-based contrast agents synthesized by thermaldecomposition. Five surface chemistries–polyacrylic acid (PAA), poly(isobutylene-alt-maleic anhydride) (PMA), poly(maleicanhydride-alt-1-octadecene) (PMAO), citric acid (CA), and silica (SiO2 )─ were investigated under physiological conditions andin vivo using relaxometry (1.4 T), clinical (3 T), and UHF (9.4 T) MRI, achieving up to a 333 mm−1 s−1 increase in r2 . CA-coated T2contrast agents exhibited record-high r2 values (522 mm−1 s−1 at 3 T; 381 mm−1 s−1 at 9.4 T) in spherical iron oxide MNPs withinthe superparamagnetic size range (d < 20 nm). Correlations of r2 with hydrodynamic size, ζ-potential, and coating thicknessrevealed that ligand chemistry–specifically hydrophilicity and anionic surface charge–dominates over physical shell dimensionsin governing water accessibility and magnetic dephasing. This scalable ligand-exchange strategy enables precise T2 tuning at UHF,with phantom results reliably predicting in vivo UHF-MRI performance in rat brain models, advancing the design of neuroimaging nanoprobes. PB Wiley SN 1613-6810 YR 2026 FD 2026-02-03 LK https://hdl.handle.net/10347/46870 UL https://hdl.handle.net/10347/46870 LA eng NO García‐Acevedo, P., Alonso‐Alonso, M. L., Ortega‐Espina, S., Bañobre‐López, M., Piñeiro, Y., Iglesias‐Rey, R., & Rivas, J. (2026). Ligand‐driven optimization of iron oxide nanoprobes for in vivo MRI enhancement at ultra‐high field. Small Journal, 22. https://doi.org/10.1002/smll.202509792 NO This work was supported by CARTsol project (PLEC2022-009217 funded by MICINN/AEI /10.13039/ 501100011033 and NextGenerationEU/ PRTR). P. García-Acevedo thanks to Axencia Galega de Innovación (Spain) for his Posdoctoral Grant (Axudas de apoio á etapa de formación posdoutoral – IN606B-2024.1). R. Iglesias-Rey (CP22/00061) from the Miguel Servet Program of Instituto de Salud Carlos III and Co-financed by the EU. DS Minerva RD 9 may 2026