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Wildgruber, M.* ; Bielicki, I.* ; Aichler, M. ; Kosanke, K.* ; Feuchtinger, A. ; Settles, M.* ; Onthank, D.C.* ; Cesati, R.R.* ; Robinson, S.P.* ; Huber, A.M.* ; Rummeny, E.J.* ; Walch, A.K. ; Botnar, R.M.*

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

Circ.-Cardiovasc. Imaging 7, 321-329 (2014)

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BACKGROUND: -To prospectively evaluate an elastin-specific magnetic resonance contrast agent (ESMA) for in-vivo targeting of elastic fibers in myocardial infarction and post-infarction scar remodeling. METHODS AND RESULTS: -Myocardial infarction (MI) was induced in C57BL/6J mice (n=40) by permanent ligation of the left anterior descending coronary artery (LAD). Magnetic Resonance Imaging (MRI) was performed at 7 and 21 days post MI. The merits of gadolinium-based ESMA (Gd-ESMA) were compared to Gd-DTPA in terms of infarct-size determination, contrast-to-noise ratio (CNR) and enhancement kinetics. Specific binding in-vivo was evaluated by blocking the molecular target using non-paramagnetic Lanthanum-ESMA (La-ESMA). In-vivo imaging results were confirmed by post-mortem triphenyltetrazoliumcholride (TTC) staining, Elastica-Van-Gieson (EvG) staining and Western Blotting. Delayed enhancement MRI revealed prolonged enhancement of Gd-ESMA in the post-ischemic scar compared to Gd-DTPA. Infarct size measurements showed good agreement between Gd-ESMA and Gd-DTPA and were confirmed by ex-vivo TTC staining. Pre-injection of the blocking La-ESMA resulted in significantly lower CNR of Gd-ESMA at the infarct site (p=0.0019). While no significant differences in CNR were observed between delayed-enhancement imaging with Gd-DTPA between day 7 and 21 (1.8 ± vs 3.8, p=ns), Gd-ESMA showed markedly higher CNR on day 21 post MI (14.1 vs 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 myocardial infarction. The imaging properties of Gd-ESMA allow quantification of intra-scar elastin content in-vivo and thereby provides potential for non-invasive characterization of post-infarction scar remodeling.

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