In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent.
BACKGROUND
Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis.


RESULTS
Fifteen male New Zealand White rabbits (weight, approximately 3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell's viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as "hot spots" after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology.


CONCLUSIONS
We demonstrate the feasibility of in vivo "molecular" MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.
Botnar
René M
RM
Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA.
Perez
Alexandra S
AS
Witte
Sonia
S
Wiethoff
Andrea J
AJ
Laredo
James
J
Hamilton
James
J
Quist
William
W
Parsons
Edward C
EC
Vaidya
Anand
A
Kolodziej
Andrew
A
Barrett
John A
JA
Graham
Philip B
PB
Weisskoff
Robert M
RM
Manning
Warren J
WJ
Johnstone
Michael T
MT
D000208:Acute Disease; D000818:Animals; D001161:Arteriosclerosis / Q000150:complications / Q000473:pathology; D001667:Binding, Competitive; D003287:Contrast Media; D005337:Fibrin / Q000378:metabolism*; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010455:Peptides / Q000378:metabolism; D011817:Rabbits; D013927:Thrombosis / Q000175:diagnosis* / Q000209:etiology; D013997:Time Factors
D003287:Contrast Media; C490104:EP1873; D010455:Peptides; D005337:Fibrin; D019786:Gadolinium DTPA