title: Postinfarction myocardial scarring in mice: molecular MR imaging with use of a collagen-targeting contrast agent.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, University of Virginia, 409 Lane Rd, MR4 Bldg, Room 1186, Charlottesville, VA 22908, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Helm
authors.forename: Peter
authors.initials: P
authors.lastname: Caravan
authors.forename: Brent A
authors.initials: BA
authors.lastname: French
authors.forename: Vincent
authors.initials: V
authors.lastname: Jacques
authors.forename: Luhua
authors.initials: L
authors.lastname: Shen
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Xu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Beyers
authors.forename: R Jack
authors.initials: RJ
authors.lastname: Roy
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kramer
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Epstein
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005355:Fibrosis / Q000473:pathology; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology*; D011446:Prospective Studies
chemical_list: D003287:Contrast Media; D003094:Collagen; D005682:Gadolinium; D019786:Gadolinium DTPA