Assessment of myocardial infarction and postinfarction scar remodeling with an elastin-specific magnetic resonance agent

Moritz Wildgruber, Isabella Bielicki, Michaela Aichler, Katja Kosanke, Annette Feuchtinger, Marcus Settles, David C. Onthank, Richard R. Cesati, Simon P. Robinson, Armin M. Huber, Ernst J. Rummeny, Axel K. Walch, Reń M. Botnar

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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. Methods and 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.

Original languageEnglish
Pages (from-to)321-329
Number of pages9
JournalCirculation: Cardiovascular Imaging
Volume7
Issue number2
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Magnetic Resonance Imaging
  • Molecular Imaging
  • Myocardial Infarction
  • Ventricular Remodeling

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