Our experimental study showed that, in WHHL rabbits, both D-and DM-USPIO particles were phagocytosed by macrophages embedded in atherosclerotic plaques. This leads to a susceptibility-induced signal reduction in the atherosclerotic vessel wall on T1-weighted 3D gradient echo (GRE) images. In the T1-weighted fast 3D GRE sequence, T1 shortening is a characteristic of lower USPIO concentration. This renders the signal bright, and produces a predominant T2/T2* shortening at higher concentrations, resulting in a completely dark signal. 33 Consequently, at the initial stage of USPIO administration, the signal of the aortic lumen is completely dark due to a high blood concentration of USPIO. According to Ruehm et al, 5 the uptake by the MPS of USPIO particles over a 4-to 5-day period creates an ideal situation for imaging the vascular wall. The iron concentration in inflammatory cells in plaques is sufficiently high for the production of dominant T2 and T2* effects, while its concentration in the blood pool is at levels at which T1 shortening effects predominate. In that study, iron particles were observed electron microscopically in actively phagocytosing cells, but not in inactive foam cells filled with fat vacuoles. These, and other observations, suggest that both D-and DM-USPIO are potential contrast agents for the diagnosis of atherosclerotic plaques -which exhibit high activity before the onset of luminal narrowing -and are potentially useful for the assessment of therapeutic effects of anti-atherosclerotic drugs, such as statins.