Iron Oxide Nanoparticle Uptake in Mouse Brachiocephalic Artery Atherosclerotic Plaque Quantified by T₂-Mapping MRI

The purpose of our study was to monitor the iron oxide contrast agent uptake in mouse brachiocephalic artery (BCA) atherosclerotic plaques in vivo by quantitative T₂-mapping magnetic resonance imaging (MRI). Female ApoE^-/- mice (n = 32) on a 15-week Western-type diet developed advanced plaques in the BCA and were injected with ultra-small superparamagnetic iron oxides (USPIOs). Quantitative in vivo MRI at 9.4 T was performed with a Malcolm-Levitt (MLEV) prepared T₂-mapping sequence to monitor the nanoparticle uptake in the atherosclerotic plaque. Ex vivo histology and particle electron paramagnetic resonance (pEPR) were used for validation. Longitudinal high-resolution in vivo T₂-value maps were acquired with consistent quality. Average T₂ values in the plaque decreased from a baseline value of 34.5 ± 0.6 ms to 24.0 ± 0.4 ms one day after injection and partially recovered to an average T₂ of 27 ± 0.5 ms after two days. T₂ values were inversely related to iron levels in the plaque as determined by ex vivo particle electron paramagnetic resonance (pEPR). We concluded that MRI T₂ mapping facilitates a robust quantitative readout for USPIO uptake in atherosclerotic plaques in arteries near the mouse heart.