Investigation of Atherosclerotic Plaques with MRI using Ultra-Small Iron Oxide Particles at 3T

Purpose: To investigate the uptake of an experimental USPIO contrast agent by atherosclerotic plaque in the aorta, using MRI at 3T. Previous studies have shown strong magnetic susceptibility effects in the bright vessel lumen, several days after injection of a comparable USPIO agent (Sinerem). Such studies are influenced by the choices of contrast agent, pulse sequence and field strength.

Methods and Materials: Four WHHL rabbits were injected with USPIOs (DDM43/34, Schering) at doses of 0.1, 0.25, 0.5 and 1.0 mmol/kg. Parasagittal MR angiography scans were acquired in a 3T clinical MRI scanner (Philips Medical Systems) using a head array coil, with a 3D gradient-echo sequence (TE/TR=2.1/5.6 ms, acquisition matrix 256×179×35, isotropic resolution 0.7mm, interpolated to 0.35mm, 12 NSA, scan time ~9 minutes).

Images were acquired before and immediately after USPIO administration, and again after 6 hours and at 1, 2 and 5 days. The blood signal, determined by competing T1 and T2* effects, is strong for only a small range of USPIO concentrations. For lower concentrations, at later time-points, additional MRA scans were acquired during gadopentate dimeglumine (Magnevist, Schering) infusion.

For histological comparison, two more animals were given doses of 0.1 and 1.0 mmol/kg, then scanned immediately and after 2 and 5 days. These animals were sacrificed; aortic slices were stained with HE and Prussian blue and RAM-11.

Results: Blood signal intensity changes suggest a (relatively fast) clearance of >~ 90% after 2 days. Widespread susceptibility artifacts demonstrated USPIO uptake in the lymphatic system, but surprisingly no such effects could be associated specifically with the vessel wall, despite some one-sided artifacts due to the nearby ribs and spine. Histologically, the two aortas contained plaques showing very little USPIO uptake, consistent with the MRI findings.

Conclusions: Despite the exciting potential of early plaque detection using USPIOs, some caution is advised, since a lack of susceptibility effects does not necessarily imply absence of plaque, even with the increased sensitivity to susceptibility offered by 3T. The choice of USPIO agent affects the clearance kinetics and thus uptake by plaques.