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(Circulation. 2005;112:1594-1600.)
© 2005 American Heart Association, Inc.

Imaging

Chronic Thrombus Detection With In Vivo Magnetic Resonance Imaging and a Fibrin-Targeted Contrast Agent

Marc Sirol, MD; Valentin Fuster, MD, PhD; Juan J. Badimon, PhD; John T. Fallon, MD, PhD; Pedro R. Moreno, MD; Jean-François Toussaint, MD, PhD; Zahi A. Fayad, PhD

From the Department of Cardiology (M.S.), Hôpital Lariboisière, Paris, France; the Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Cardiovascular Health Center (M.S., V.F., J.J.B., J.T.F., P.R.M., Z.A.F.); the Imaging Science Laboratories (M.S., Z.A.F.), Department of Radiology; the Cardiovascular Biology Research Laboratory (J.J.B.); and the Department of Pathology (J.T.F.), Mount Sinai School of Medicine, New York, NY; and the Department of Physiology and Radioisotopes (J.-F.T.), Hôpital Européen Georges Pompidou, Paris, France.

Correspondence to Z.A. Fayad, PhD, Imaging Science Laboratories, Mount Sinai School of Medicine, Box 1030, One Gustave L. Levy Place, New York, NY 10029-6574. E-mail Zahi.Fayad{at}mssm.edu

Received November 19, 2004; revision received June 2, 2005; accepted June 9, 2005.

Background— Arterial thrombosis plays a critical role in acute coronary syndromes and stroke. Therefore, the ability to detect thrombus in vivo has a significant clinical implication. Magnetic resonance imaging (MRI) has shown promise in noninvasive thrombus detection. However, thrombus characterization and age definition remain difficult. We sought to evaluate the use of a fibrin-targeted peptide (EP-2104R) for MR thrombus detection and to compare this modality with non–contrast-enhanced (NCE) MRI and with Gd-DTPA injection at various ages and time points after thrombus generation.

Methods and Results— Carotid artery thrombosis was induced by external injury and stasis in 18 rabbits. T1-weighted MRI was performed before and after contrast agent injection, within 6 hours of thrombus induction, at 48 hours, at 1 week, and every week up to 8 weeks after injury. Correlation with histopathology was performed. The fibrin-targeted contrast agent accurately detected all thrombi, regardless of their size, location, and age. Although thrombus signal intensity after injection decreased with thrombus age (P<0.001), enhancement at 8 weeks was still present. Gd-DTPA injection was not associated with an improvement of thrombus detection. EP-2104R was superior to both NCE and Gd-DTPA injection (P<0.001). Histopathologic examination showed thrombus organization over time. Fibrin was gradually replaced by fibrous tissue. A strong correlation was found between thrombus enhancement and collagen content of the organizing thrombus with time (R=–0.89; P<0.001).

Conclusions— In an experimental animal model of carotid thrombosis, we have demonstrated the superiority of a fibrin-targeted MR contrast agent for in vivo detection of chronic or organized thrombus, compared with NCE MRI and Gd-DTPA injection.

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