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 (SI(30 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.
Sirol
Marc
M
Department of Cardiology, Hôpital Lariboisière, Paris, France.
Aguinaldo
Juan G S
JG
Graham
Philip B
PB
Weisskoff
Robert
R
Lauffer
Randy
R
Mizsei
Gabor
G
Chereshnev
Igor
I
Fallon
John T
JT
Reis
Ernane
E
Fuster
Valentin
V
Toussaint
Jean-François
JF
Fayad
Zahi A
ZA
D000208:Acute Disease; D000818:Animals; D002341:Carotid Artery Thrombosis / Q000175:diagnosis*; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D005337:Fibrin; D006168:Guinea Pigs; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*
D003287:Contrast Media; C506893:EP-1242; D010456:Peptides, Cyclic; D005337:Fibrin