Abstract 1724: MRI Enhanced with Magnetic Nanoparticles Measures Inflammatory Burden in Atherosclerosis In Vivo
Background: Inflammation contributes to the progression and acute complications of atherosclerosis. Imaging of macrophages in vivo may predict risk of subclinical lesions and identify individualized therapeutic targets.
Methods and Results: To test the hypothesis that nanoparticle-enhanced, high-resolution MRI can measure plaque macrophage accumulation in vivo, we employed a 3.0 Tesla magnet with clinically-approved, phagocyte-targeted super-paramagnetic iron oxide (MION47, 10 mgFe/kg, iv) in 6 cholesterol-fed New Zealand White rabbits 6 months after balloon injury. MRI visualized in vivo thickened abdominal aortas on T1 and T2-weighted spin echo (T1SE, 20 axial slices/animal; T2SE, 28 slices). Images 72 hours after MION47 injection exhibited signal reduction (darkening) in aortas on T2SE (signal intensity ratio: aortic wall/muscle; pre 1.44 ± 0.26 vs. post 0.95±0.22, 165 slices, p<0.01) while T1SE showed no significant effect. MRI also demonstrated ex vivo darkening of aortas on T2 weighted images in MION47-injected rabbits unlike control aortas (no injection). Histological assays further colocalized iron accumulation (Prussian blue staining) with immunoreactive macrophages in the intima, and correlated the magnitudes of T2 darkening in vivo with macrophage areas in situ (155 slices, r =0.77, P<0.01). Moreover, in vitro validation studies revealed a concentration-dependent MION47 uptake and shortened T2 relaxation time during differentiation of human primary macrophages.
Conclusion: MION47-enhanced MRI can detect plaque macrophages in vivo, offering the important information on inflammatory burden in atherosclerosis.