Combined qualitative and quantitative MRI reveals short-term progression in facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by slowly progressive and heterogeneous muscle involvement; therefore, clinical measures show limited sensitivity to short-term change. Magnetic resonance imaging (MRI) provides useful biomarkers of muscle degeneration and disease activity. To investigate one-year longitudinal changes in lower leg muscles of patients with FSHD using qualitative (T1-weighted [T1w], STIR) and quantitative MRI (fat fraction [FF], water T2), and to assess their relationship with clinical function. Thirty-one patients with FSHD (21 men; age 44.2±17 years) and 30 matched controls underwent 3T MRI. Twenty-seven patients completed one-year follow-up. Semi-quantitative grading and quantitative measures were analyzed muscle-wise. Longitudinal changes and correlations with clinical scores were assessed. At baseline, T1w imaging showed marked inter- and intra-individual variability, with heterogeneous proximal–distal involvement in 22% of muscles and asymmetric involvement in 77% of patients. STIR hyperintensity was present in 25 patients. Over one-year, clinical decline was small (MRC: Δ=–0.26, p=0.018, SRM=-0.23; mobility: Δ=–0.41, p=0.031, SRM=-0.44). In contrast, quantitative MRI detected progression, with increases in FF (0.17±0.13 to 0.22±0.15, p<0.001, SRM=0.87), FF heterogeneity, and water T2 heterogeneity, while T1w scores and mean water T2 showed limited change. Progression was greatest in muscles with intermediate baseline FF (ΔFF/year: 0.049 vs 0.007, p<0.001). Baseline STIR and water T2 abnormalities predicted increases in FF but not T1w scores. FF correlated more strongly with clinical measures than T1w grading. Quantitative MRI is more sensitive than qualitative grading for detecting short-term disease progression in FSHD. Measures of heterogeneity and disease activity predict structural progression and represent promising biomarkers for clinical trials.