title: Assessment of myocardial infarction and postinfarction scar remodeling with an elastin-specific magnetic resonance agent.
abstract: BACKGROUND
  To prospectively evaluate an elastin-specific MR contrast agent (ESMA) for in vivo targeting of elastic fibers in myocardial infarction (MI) and postinfarction scar remodeling.
  
  
  RESULTS
  MI was induced in C57BL/6J mice (n=40) by permanent ligation of the left anterior descending coronary artery. MRI was performed at 7 and 21 days after MI. The merits of gadolinium-based ESMA (Gd-ESMA) were compared with gadopentetic acid (Gd-DTPA) for infarct size determination, contrast-to-noise ratio (CNR), and enhancement kinetics. Specific binding in vivo was evaluated by blocking the molecular target using nonparamagnetic lanthanum-ESMA. In vivo imaging results were confirmed by postmortem triphenyltetrazolium chloride staining, elastica van Gieson staining, and Western blotting. Delayed enhancement MRI revealed prolonged enhancement of Gd-ESMA in the postischemic scar compared with Gd-DTPA. Infarct size measurements showed good agreement between Gd-ESMA and Gd-DTPA and were confirmed by ex vivo triphenyltetrazolium chloride staining. Preinjection of the blocking lanthanum-ESMA resulted in significantly lower CNR of Gd-ESMA at the infarct site (P=0.0019). Although no significant differences in CNR were observed between delayed enhancement imaging and Gd-DTPA between days 7 and 21 (1.8± versus 3.8; P=ns), Gd-ESMA showed markedly higher CNR on day 21 after MI (14.1 versus 4.9; P=0.0032), which correlated with increased synthesis of tropoelastin detected by Western blot analysis and histology. Higher CNR values for Gd-ESMA further correlated with improved ejection fraction of the mice on day 21 after MI.
  
  
  CONCLUSIONS
  Gd-ESMA enables targeting of elastin within the infarct scar in a mouse model of MI. The imaging properties of Gd-ESMA allow quantification of intrascar elastin content in vivo and thereby provide potential for noninvasive characterization of postinfarction scar remodeling.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Wildgruber
authors.forename: Isabella
authors.initials: I
authors.lastname: Bielicki
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.forename: Katja
authors.initials: K
authors.lastname: Kosanke
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.forename: Marcus
authors.initials: M
authors.lastname: Settles
authors.forename: David C
authors.initials: DC
authors.lastname: Onthank
authors.forename: Richard R
authors.initials: RR
authors.lastname: Cesati
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
authors.forename: Armin M
authors.initials: AM
authors.lastname: Huber
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Rummeny
authors.forename: Axel K
authors.initials: AK
authors.lastname: Walch
authors.forename: René M
authors.initials: RM
authors.lastname: Botnar
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000175:diagnosis* / Q000209:etiology; D003287:Contrast Media; D003331:Coronary Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology*; D004549:Elastin; D005260:Female; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis*; D009206:Myocardium / Q000473:pathology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D003287:Contrast Media; D004549:Elastin; D019786:Gadolinium DTPA
keywords: magnetic resonance imaging; molecular imaging; myocardial infarction; ventricular remodeling