Quantitative whole-body MRI in FSHD: assessing systemic involvement and future directions

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive, highly variable disease marked by asymmetric and time-varying muscle degeneration. This review distills ten lessons learned from the evolution of magnetic resonance imaging (MRI) in FSHD, focusing primarily on quantitative whole-body MRI (WBMRI) using chemical-shift-based water-fat-separation imaging (Dixon) two-echo methods. A description of short tau inversion recovery (STIR) imaging results and brief discussion of other quantitative methods is included for additional biomarker context. Whereas early studies relied on qualitative ratings, single-slice measures, or sparse/aggregated muscle sampling for water/fat assessment, WBMRI analyses using Dixon methods can facilitate muscle-by-muscle quantification across the body, revealing new metrics and updated considerations that can advance functional modeling approaches. We then discuss implications of these individual quantitative measures for sensitively following muscle and task progression. Generally, the current use of one-size-fits-all functional endpoints can obscure change because task performance reflects not only muscle pathology but also musculoskeletal geometry and compensatory strategies. Building on these lessons, we emphasize the need for muscle-informed and patient-specific trial designs that identify and longitudinally track an individual's at-risk muscles alongside paired functional tasks to improve sensitivity and statistical power. Finally, we outline future directions, including integration with motion capture and biomechanics-informed models, finite element approaches, and complementary biomarkers. Together, these ten lessons support that this increasing complexity represents a path towards better understanding of disease expression, progression, and functional associations in FSHD.