In vivo magnetic resonance imaging of coronary thrombosis using a fibrin-binding molecular magnetic resonance contrast agent.
BACKGROUND
The advent of fibrin-binding molecular magnetic resonance (MR) contrast agents and advances in coronary MRI techniques offers the potential for direct imaging of coronary thrombosis. We tested the feasibility of this approach using a gadolinium (Gd)-based fibrin-binding contrast agent, EP-2104R (EPIX Medical Inc), in a swine model of coronary thrombus and in-stent thrombosis.


RESULTS
Ex vivo and in vivo sensitivity of coronary MR thrombus imaging was tested by use of intracoronarily delivered Gd-DTPA-labeled fibrinogen thrombi (n=6). After successful demonstration, in-stent coronary thrombosis was induced by x-ray-guided placement of thrombogenic-coated, MR-lucent stents (n=5). After stent placement, 60 micromol of EP-2104R was injected via the left main coronary artery. Free-breathing, navigator-gated 3D coronary MR angiography and thrombus imaging were performed (1) before and after stent placement and (2) before and after EP-2104R. Thrombi were confirmed by x-ray angiography and autopsy. Fibrinogen thrombi: 5 of 6 intracoronarily delivered Gd-labeled fibrinogen clots (approximately 250 micromol/L Gd) were visible on MRI and subsequently confirmed by x-ray angiography. In-stent thrombi: in-stent thrombosis was observed in all stents after EP-2104R. Four of 5 thrombi were confirmed by x-ray angiography. Chemical analysis of 2 thrombi demonstrated 99 to 147 micromol/L Gd.


CONCLUSIONS
We demonstrate the feasibility of MRI of coronary thrombus and in-stent thrombosis using a novel fibrin-binding molecular MR contrast agent. Potential applications include detection of coronary in-stent thrombosis or thrombus burden in patients with acute coronary syndromes.
Botnar
René M
RM
Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA. rbotnar@bidmc.harvard.edu
Buecker
Arno
A
Wiethoff
Andrea J
AJ
Parsons
Edward C
EC
Katoh
Marcus
M
Katsimaglis
George
G
Weisskoff
Robert M
RM
Lauffer
Randall B
RB
Graham
Philip B
PB
Gunther
Rolf W
RW
Manning
Warren J
WJ
Spuentrup
Elmar
E
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003328:Coronary Thrombosis / Q000473:pathology*; D003331:Coronary Vessels; D005240:Feasibility Studies; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007269:Injections, Intra-Arterial; D018810:Magnetic Resonance Angiography; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D015607:Stents; D034421:Sus scrofa
D003287:Contrast Media; D004369:Pentetic Acid; D005337:Fibrin; D005340:Fibrinogen