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Published online before print April 10, 2008, 10.1148/radiol.2473070975
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(Radiology 2008;247:788-796.)
© RSNA, 2008

Molecular Imaging

Postinfarction Myocardial Scarring in Mice: Molecular MR Imaging with Use of a Collagen-targeting Contrast Agent1

Patrick A. Helm, PhD, Peter Caravan, PhD, Brent A. French, PhD, Vincent Jacques, PhD, Luhua Shen, MD, Yaqin Xu, MD, Ronald J. Beyers, PhD, R. Jack Roy, MS, Christopher M. Kramer, MD, and Frederick H. Epstein, PhD

1 From the Department of Radiology, University of Virginia, 409 Lane Rd, MR4 Bldg, Room 1186, Charlottesville, VA 22908 (P.A.H., B.A.F., Y.X., R.J.B., R.J.R. C.M.K., F.H.E.); and Epix Pharmaceuticals, Lexington, Mass (P.C., V.J., L.S.). Received June 5, 2007; revision requested August 6; revision received October 5; final version accepted October 29. Supported in part by National Institutes of Health grant RO1 EB 001763. F.H.E. supported by an American Heart Association Established Investigator award. P.A.H. supported by National Institutes of Health grant HL207284. Address correspondence to F.H.E. (e-mail: fredepstein{at}virginia.edu).

Purpose: To prospectively evaluate a gadolinium-based collagen-targeting contrast agent, EP-3533, for in vivo magnetic resonance (MR) imaging of myocardial fibrosis in a mouse model of healed myocardial infarction (MI).

Materials and Methods: All procedures were performed in accordance with protocols approved by the animal care and use committee. MI was induced in eight mice by means of occlusion of the left anterior descending coronary artery followed by reperfusion. Four MR examinations were performed in each animal: one examination before, one examination 1 day after, and two examinations 6 weeks after the MI. For the latter two examinations, electrocardiographically gated inversion-recovery gradient-echo MR images were acquired before and serially (every 5 minutes) after the intravenous injection of either gadopentetate dimeglumine or EP-3533. The image enhancement kinetic properties of the postinfarction scar, normal myocardium, and blood were compared.

Results: Dynamic T1-weighted MR imaging revealed the washout time constants for EP-3533 to be significantly longer than those for gadopentetate dimeglumine in regions of postinfarction scarring (mean, 194.8 minutes ±116.8 [standard deviation] vs 25.5 minutes ± 4.2; P < .05) and in normal myocardium (mean, 45.4 minutes ± 16.7 vs 25.1 minutes ± 9.7; P < .05). Findings on postmortem histologic sections stained for collagen correlated well with EP-3533–enhanced areas seen on inversion-recovery MR images. Fifty minutes after EP-3533 injection, the postinfarction scar tissue samples, as compared with the normal myocardium, had a twofold higher concentration of gadolinium.

Conclusion: Use of the gadolinium-based collagen-targeting contrast agent, EP-3533, enabled in vivo molecular MR imaging of fibrosis in a mouse model of healed postinfarction myocardial scarring.

© RSNA, 2008




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