Fibrin-targeted contrast agent for improvement of in vivo acute thrombus detection with magnetic resonance imaging

Sirol, Marc; Aguinaldo, Juan G.S.; Graham, Philip B.; Weisskoff, Robert; Lauffer, Randy; Mizsei, Gabor; Chereshnev, Igor; Fallon, John T.; Reis, Ernane; Fuster, Valentin; Toussaint, Jean-François; Fayad, Zahi A.

doi:10.1016/j.atherosclerosis.2005.02.013

« Previous Next »Atherosclerosis
Volume 182, Issue 1 , Pages 79-85, September 2005

Fibrin-targeted contrast agent for improvement of in vivo acute thrombus detection with magnetic resonance imaging☆

Marc Sirol
- Department of Cardiology, Hôpital Lariboisière, Paris, France
- Imaging Science Laboratories. Department of Radiology Mount Sinai School of Medicine, New York, NY, USA
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
Juan G.S. Aguinaldo
- Imaging Science Laboratories. Department of Radiology Mount Sinai School of Medicine, New York, NY, USA
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
Philip B. Graham
- Epix Pharmaceuticals, Cambridge, MA, USA
Robert Weisskoff
- Epix Pharmaceuticals, Cambridge, MA, USA
Randy Lauffer
- Epix Pharmaceuticals, Cambridge, MA, USA
Gabor Mizsei
- Imaging Science Laboratories. Department of Radiology Mount Sinai School of Medicine, New York, NY, USA
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
Igor Chereshnev
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
John T. Fallon
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
- Department of Pathology, Mount Sinai Medical Center, New York, NY, USA
Ernane Reis
- Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA
Valentin Fuster
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
Jean-François Toussaint
- Department of Radioisotopes, Hôpital Européen Georges Pompidou, Paris, France
Zahi A. Fayad
- Imaging Science Laboratories. Department of Radiology Mount Sinai School of Medicine, New York, NY, USA
- The Zena and Michael A. Wiener Cardiovascular Institute, The Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, Box 1030, One Gustave L. Place, New York, NY, USA
- Corresponding author. Tel.: +1 212 241 6858; fax: +1 212 534 2683.

Received 1 December 2004; received in revised form 28 January 2005; accepted 9 February 2005.

Abstract

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_30min-post=4.39±0.12 versus 1.0; p<0.001). Contrast-to-noise ratio (CNR) was 43.8±7.2, 30min 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.

Keywords: Contrast media, Fibrin-targeted, Magnetic resonance imaging, Thrombus