Fibrin-targeted contrast agent for improvement of in vivo acute thrombus detection with magnetic resonance imaging

Objective : Plaque rupture leading to thrombosis and occlusion is a major source of acute coronary syndromes. Methods for accurate detection of thrombosis in veins or arteries may expand our capacity to predict clinical complications and guide therapeutic decisions. We sought to demonstrate the feasibility of in vivo acute thrombus detection using a fibrin-targeted gadolinium based magnetic resonance contrast agent (EP-1242). Methods : Carotid thrombosis was induced in 12 guinea pigs by external injury and blood stasis. MR images were obtained after thrombus formation pre- and post- EP-1242 injection, using a T1-weighted high-resolution fast spin-echo sequence. Results : An occlusive fibrin-rich thrombus was achieved in all animals. Correlation for thrombus location was excellent between MRI and histology (R = 0.94; P < 0.001). Contrast-enhanced MRI significantly improved thrombus detection when compared to non contrast-enhanced MRI (100% versus 41.6%; p < 0.001). In addition, thrombus signal intensity (SI) was significantly increased after injection (SI30 min-post = 4.39 ± 0.12 versus 1.0; p < 0.001). Contrast-to-noise ratio (CNR) was 43.8 ± 7.2, 30 min post-injection (P < 0.001). No enhancement was seen in the uninjured control arteries. Conclusions : We demonstrate the feasibility of in vivo MRI for carotid thrombus detection using a novel fibrin-targeted contrast agent. This technique significantly improves detection of small size thrombi in an animal model of occlusive fibrin-rich thrombosis.