Abstract 1049: Noninvasive Detection of Macrophage-dense Atherosclerotic Plaque in Hyperlipidemic Rabbits using ‘Positive Contrast’ Magnetic Resonance Imaging.
Purpose: To identify macrophage-dense atherosclerotic plaques after the systemic administration of superparamagnetic nanoparticles with magnetic resonance imaging (MRI) using a positive contrast off-resonance imaging sequence (Inversion Recovery with ON-resonant water suppression, “IRON”).
Methods and Results: Using a clinical 3T MRI scanner, IRON MRI was performed on 7 heritable hyperlipidemic and 4 control rabbits prior to injection and at days 1, 3, and 6 post-injection of monocrystalline iron oxide nanoparticles, (MION-47, 500μmol Fe/kg total dose I.V.). The MRI signal enhancement was correlated with histological evaluation of plaques and macrophage density. Signal enhancement was localized in areas of plaque in hyperlipidemic rabbits after MION-47 injection (b, solid arrows) compared to baseline (a), but not in control rabbits (c, hatched arrows). This positive signal corresponded to iron deposition (stained blue) in macrophage-dense (stained red) plaques on histology (d-e) in hyperlidemic rabbits. No evidence of plaque was found in control rabbits (f). MRI enhancement was highly correlated to the number of histologically detected macrophages (r=0.71, p<0.001). Macrophage-dense plaque were detected by MRI with a high accuracy (AUC=0.92, SE=0.04, 95% CI=0.84 – 0.96, p<0.001). No significant enhancement was measured in remote areas without histological evidence of plaque or in control rabbits without atherosclerosis.
Conclusion: IRON MRI in conjunction with superparamagnetic nanoparticles may be a useful approach for the noninvasive, serial evaluation of inflammatory-rich, vulnerable plaques.