Abstract 336: Iron Oxide Cellular MRI of Plaque Macrophages has Limited in vivo Uptake in Deep Foam Cells Despite Active Uptake in vitro
Objectives: The iron oxide agent, ferumoxtran-10 (FX), can be taken up by macrophages in atherosclerosis, but the distribution of uptake is not well understood. We evaluated superficial vs. deep macrophage uptake of FX in atherosclerotic lesions compared to in vitro uptake.
Methods: Twelve rabbits had atherosclerosis induced by aortic balloon injury and high-fat diet. Five days prior to sacrifice, 10 or 25 mgFe/kg of FX was given IV. The perfusion-fixed aorta was removed for ex vivo 1.5T MRI and histology. MRI signal intensity (SI) and SNR/CNR of the vessel wall were measured for the entire aorta. On histology, FX uptake was graded by Perl’s iron staining. Uptake in naïve vs. lipid-laden macrophages was compared in vitro using a macrophage cell line (RAW) after culture with or without oxidized LDL.
Results: FX uptake in plaque caused a decrease in SI and SNR/CNR of the vessel wall (Fig 1a⇓), which correlated with atherosclerosis severity as measured by wall area (r=-0.24~-0.38, all for p<0.001) and was associated with the degree of FX uptake on histology (p<0.05). The dose of 25 mgFe/kg caused greater signal loss compared to 10 mgFe/kg (p<0.005). The uptake of FX was much more prominent in the smaller macrophages near the lumen rather than the deep large foamy macrophages (Fig. 1b⇓). In contrast, in vitro macrophage uptake of FX was similar between lipid-laden and naive macrophages (p=0.7).
Conclusions: Quantitative MRI assessment of macrophage iron oxide uptake correlated with histology and the severity of atherosclerosis in a rabbit model. However, despite similar uptake in vitro, lipid-laden macrophages deep within the plaque had limited uptake in vivo, requiring further elucidation.