P.62 Increased skeletal muscle extracellular volume fraction in patients with Becker muscular dystrophy assessed by quantitative magnetic resonance imaging

Abstract

Quantitative magnetic resonance imaging (MRI) is increasingly proposed in clinical trials related to dystrophinopathies, including Becker muscular dystrophy (BMD). Extracellular volume fraction (ECV) is a candidate variable to characterize muscle tissues microstructure. Previous studies have demonstrated that the myocardium of BMD patients presented increased ECV. Given that cardiac muscle shares important structural features with skeletal muscles, we hypothesize that ECV could also be a sensitive biomarker to monitor pathological alterations of the skeletal muscle structure in BMD patients. We established the sensitivity of ECV quantification using magnetic resonance fingerprinting with water and fat separation (MRF T1-FF) as an imaging biomarker of skeletal muscle tissue alterations in BMD, by comparison with fat fraction (FF) and water relaxation time quantification. Data from the thighs of 28 BMD patients and 8 healthy volunteers were acquired. The MRI exam comprised FF mapping, water T2 mapping and water T1 mapping before and after an intravenous injection of a gadolinium-based contrast agent using MRF T1-FF from which ECV was calculated. Mann-Whitney tests, Kruskal-Wallis tests, ROC curves analysis and Spearman-rank correlation tests were performed. ECV was higher in dystrophic patients than in controls (0.20 [0.16 – 0.28] vs 0.07 [0.06 – 0.07], p<.001). In muscles of BMD patients with normal FF, ECV was also higher than in muscles of healthy controls (0.11 [0.10 – 0.13] vs 0.07 [0.06 – 0.09], p<.001). ECV classified dystrophic muscles with high sensitivity and specificity (AUC, 0.98; 95%CI: 0.96-0.99, p <.001), and correlated significantly with FF (ρ = .62, p < .001), water T2 (ρ = .56, p = .002), Walton score (ρ = .58, p = .001) and serum cardiac troponin-T level (ρ = .63, p < .001). In conclusion, muscle ECV measured with MRF represents a promising imaging biomarker for the early detection of skeletal muscle involvement in patients with Becker muscular dystrophy.