Abstract 1911: P947-enhanced MRI allows For In Vivo Monitoring of MMP activity and detection of Atherosclerotic Plaque Regression in Hypercholesterolemic Rabbits
Introduction. Matrix metalloproteinases (MMPs) are involved in atherosclerotic plaque growth and rupture. P947 (Guerbet) is a new MRI contrast agent with high affinity for MMPs.
Hypothesis. MMP activity and atherosclerotic plaque regression can be monitored in hypercholesterolemic rabbits with P947-enhanced MRI.
Methods. Atherosclerotic plaques were induced in the aorta of 8 New-Zealand White rabbits by double balloon injury (4 weeks apart) and 4 months hypercholesterolemic diet. At that time, a T1-weighted MRI of the aorta was acquired in 8 rabbits before and 90 minutes after intravenous injection of 50 μM Gd/kg of P947 and repeated after injection of 50 μM Gd/kg of a conventional MRI contrast agent (Gd-DOTA). After this first imaging session, 4 rabbits were maintained on a hypercholester-olemic diet (“progression” group) and 4 rabbits were switched to a chow diet (“regression” group). A second imaging session was performed 4 months later in both groups using the same protocol. On each MRI acquisition, signal intensities were measured in atherosclerotic plaques. In-situ zymography was performed on aortic sections to confirm differences in MMP activity in the different groups.
Results. On the first P947-enhanced MRI, signal intensities of atherosclerotic plaques increased similarly in rabbits from the “progression” group (36 ± 3 %) and from the “regression group” (41 ± 5 %). On the second P947-enhanced MRI, signal enhancement in atherosclerotic plaques from the “progression” group was similar to the first MRI (38 ± 2 %; p=NS vs. first MRI), while a significantly lower enhancement was found in the “regression group” (14 ± 3 %; p=0.05 vs. first MRI). No significant difference in signal intensity was found in atherosclerotic plaques on MRI after injection of Gd-DOTA. The differences detected in MRI correlated with decreased activity in the regression group compared to the progression group in the in-situ zymography studies.
Conclusion. P947-enhanced MRI allows the monitoring of MMP activity and plaque regression in the aorta of hypercholesterolemic rabbits.