Simultaneous Assessment of Cardiac Inflammation and Extracellular Matrix Remodeling after Myocardial Infarction.

Background: Optimal healing of the myocardium following myocardial infarction (MI) requires a suitable degree of inflammation and its timely resolution, together with a well-orchestrated deposition and degradation of extracellular matrix (ECM) proteins.

Methods And Results: MI and SHAM-operated animals were imaged at 3,7,14 and 21 days with 3T magnetic resonance imaging (MRI) using a F/H surface coil. Mice were injected with F-perfluorocarbon (PFC) nanoparticles to study inflammatory cell recruitment, and with a gadolinium-based elastin-binding contrast agent (Gd-ESMA) to evaluate elastin content. F MRI signal co-localized with infarction areas, as confirmed by late-gadolinium enhancement, and was highest 7days post-MI, correlating with macrophage content (MAC-3 immunohistochemistry) (ρ=0.89,). F quantification with (MRI) and nuclear magnetic resonance (NMR) spectroscopy correlated linearly (ρ=0.58,). T mapping after Gd-ESMA injection showed increased relaxation rate (R) in the infarcted regions and was significantly higher at 21days compared with 7days post-MI (R[s]:21days=2.8 [IQR,2.69-3.30] vs 7days=2.3 [IQR,2.12-2.5], ), which agreed with an increased tropoelastin content (ρ=0.89, ). The predictive value of each contrast agent for beneficial remodeling was evaluated in a longitudinal proof-of-principle study. Neither R nor F at day 7 were significant predictors for beneficial remodeling (;). However, the combination of both measurements (R<2.34Hz and 0.55≤F≤1.85) resulted in an odds ratio of 30.0 (CI95%:1.41-638.15;) for favorable post-MI remodeling.

Conclusions: Multinuclear H/F MRI allows the simultaneous assessment of inflammation and elastin remodeling in a murine MI model. The interplay of these biological processes affects cardiac outcome and may have potential for improved diagnosis and personalized treatment.