In vivo magnetic resonance imaging of coronary thrombosis using a fibrin-binding molecular magnetic resonance contrast agent

• Published in: Circulation (New York, N.Y.) N.Y.), 2004-09, Vol.110 (11), p.1463-1466
• Main Authors: Botnar, René M, Buecker, Arno, Wiethoff, Andrea J, Parsons, Jr, Edward C, Katoh, Marcus, Katsimaglis, George, Weisskoff, Robert M, Lauffer, Randall B, Graham, Philip B, Gunther, Rolf W, Manning, Warren J, Spuentrup, Elmar
• Format: Article
• Language: English
• Subjects: Animals; Contrast Media - administration & dosage; Contrast Media - pharmacokinetics; Coronary Thrombosis - pathology; Coronary Vessels; Feasibility Studies; Female; Fibrin - metabolism; Fibrinogen - administration & dosage; Fibrinogen - analogs & derivatives; Fibrinogen - pharmacokinetics; Injections, Intra-Arterial; Magnetic Resonance Angiography; Pentetic Acid - administration & dosage; Pentetic Acid - analogs & derivatives; Pentetic Acid - pharmacokinetics; Sensitivity and Specificity; Stents; Sus scrofa
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000134960.31304.87

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. 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. 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.