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 19F/1H surface coil. Mice were injected with 19F-perfluorocarbon (PFC) nanoparticles to study inflammatory cell recruitment, and with a gadolinium-based elastin-binding contrast agent (Gd-ESMA) to evaluate elastin content. 19F 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,P<0.0001). 19F quantification with in vivo (MRI) and ex vivo nuclear magnetic resonance (NMR) spectroscopy correlated linearly (ρ=0.58,P=0.020). T1 mapping after Gd-ESMA injection showed increased relaxation rate (R1) in the infarcted regions and was significantly higher at 21days compared with 7days post-MI (R1[s-1]:21days=2.8 [IQR,2.69-3.30] vs 7days=2.3 [IQR,2.12-2.5], P<0.05), which agreed with an increased tropoelastin content (ρ=0.89, P<0.0001). The predictive value of each contrast agent for beneficial remodeling was evaluated in a longitudinal proof-of-principle study. Neither R1 nor 19F at day 7 were significant predictors for beneficial remodeling (P=0.68;P=0.062). However, the combination of both measurements (R1<2.34Hz and 0.55≤19F≤1.85) resulted in an odds ratio of 30.0 (CI95%:1.41-638.15;P=0.029) for favorable post-MI remodeling. Conclusions: Multinuclear 1H/19F 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.

Improved segmented modified Look-Locker inversion recovery T1 mapping sequence in mice.

OBJECT: To develop and evaluate a 2D modified Look-Locker (MOLLI) for high-resolution T1 mapping in mice using a 3T MRI scanner. MATERIALS AND METHODS: To allow high-resolution T1 mapping in mice at high heart rates a multi-shot ECG-triggered 2D MOLLI sequence was developed. In the proposed T1 mapping sequence the optimal number of sampling points and pause cardiac cycles following an initial adiabatic inversion pulse was investigated in a phantom. Seven native control and eight mice, 3 days post myocardial infarction (MI) after administration of gadolinium were scanned. Two experienced readers graded the visual T1 map quality. RESULTS: In T1 phantoms, there were no significant differences (<0.4% error) between 12, 15 and 20 pause cardiac cycles (p = 0.1, 0.2 and 0.6 respectively) for 8 acquisition cardiac cycles for 600bpm in comparison to the conventional inversion recovery spin echo T1 mapping sequence for short T1's (<600 ms). Subsequently, all in-vivo scans were performed with 8 data acquisitions and 12 pause cardiac cycles to minimize scan time. The mean native T1 value of myocardium in control animal was 820.5±52 ms. The post-contrast T1 measured 3 days after MI in scar was 264±59 ms and in healthy myocardium was 512±62 ms. The Bland-Altman analysis revealed mean difference of only -1.06% of infarct size percentage between T1 maps and LGE. CONCLUSIONS: A multi-shot 2D MOLLI sequence has been presented that allows reliable measurement of high spatial resolution T1 maps in mice for heart rates up to 600bpm.