Assessment of Diffuse Myocardial Fibrosis in Rats Using Small Animal Look-Locker Inversion Recovery (SALLI) T1 Mapping

Background It has been shown that the concentration of gadopentetate dimeglumine (GdDTPA) in myocardium and blood can be assessed from T1 measurements, and be used to calculate the extracellular volume (ECV) of the myocardium. We hypothesized that diffuse myocardial fibrosis in a small animal model could be quantitatively assessed by measuring myocardial ECV using small animal Look-Locker inversion recovery (SALLI) T1 mapping. Methods and Results Sprague-Dawley rats (n=10) were subjected to continuous angiotensin-2 (AT2) infusion for 2 weeks via a subcutaneously implanted minipump system. Magnetic resonance imaging (MRI) was performed both before and after AT2 infusion. The MRI protocol included multi-slice cine imaging as well as preand post-contrast SALLI T1 mapping and late gadolinium enhancement (LGE) imaging. Myocardial ECV was calculated from hematocrit and T1 values of blood and myocardium. During the course of AT2 infusion, systolic blood pressure raised from 122+/-10.9 to 152 +/-27.5 mmHg (mean+/-standard deviation, p=0.003). Normalized heart weight was significantly higher in AT2-treated animals than in control littermates (p=0.033). Cine MRI documented concentric leftventricular hypertrophy. Post-contrast myocardial T1 times were shortened after treatment (median [interquartile range] 712 [63] vs. 820 [131] ms, p=0.002). Myocardial ECV increased from 17.2 [4.3]% before to 23.0 [6.2]% after AT2 treatment (p=0.031), which was accompanied by perivascular fibrosis and micro scarring on myocardial histology. There was a moderate level of correlation between ECV and collagen volume fraction as assessed by histological analysis (r=0.69, p=0.013). Conclusions In a small animal model of left-ventricular hypertrophy, contrast-enhanced T1 mapping can be used to detect diffuse myocardial fibrosis by quantification of myocardial ECV.