Quantitative muscle analysis in facioscapulohumeral muscular dystrophy using whole-body fat-referenced MRI: Protocol development, multicenter feasibility, and repeatability.

Functional performance tests are the gold standard to assess disease progression and treatment effects in neuromuscular disorders. These tests can be confounded by motivation, pain, fatigue, and learning effects, increasing variability and decreasing sensitivity to disease progression, limiting efficacy assessment in clinical trials with small sample sizes. We aimed to develop and validate a quantitative and objective method to measure skeletal muscle volume and fat content based on whole-body fat-referenced magnetic resonance imaging (MRI) for use in multisite clinical trials. Subjects aged 18 to 65 years, genetically confirmed facioscapulohumeral muscular dystrophy 1 (FSHD1), clinical severity 2 to 4 (Ricci's scale, range 0-5), were enrolled at six sites and imaged twice 4-12 weeks apart with T1-weighted two-point Dixon MRI covering the torso and upper and lower extremities. Thirty-six muscles were volumetrically segmented using semi-automatic multi-atlas-based segmentation. Muscle fat fraction (MFF), muscle fat infiltration (MFI), and lean muscle volume (LMV) were quantified for each muscle using fat-referenced quantification. Seventeen patients (mean age ± SD, 49.4 years ±13.02; 12 men) were enrolled. Within-patient SD ranged from 1.00% to 3.51% for MFF and 0.40% to 1.48% for MFI in individual muscles. For LMV, coefficients of variation ranged from 2.7% to 11.7%. For the composite score average of all muscles, observed SDs were 0.70% and 0.32% for MFF and MFI, respectively; composite LMV coefficient of variation was 2.0%. We developed and validated a method for measuring skeletal muscle volume and fat content for use in multisite clinical trials of neuromuscular disorders.

Widholm P ，Ahlgren A ，Karlsson M ，Romu T ，Tawil R ，Wagner KR ，Statland JM ，Wang LH ，Shieh PB ，van Engelen BGM ，Cadavid D ，Ronco L ，Odueyungbo AO ，Jiang JG ，Mellion ML ，Dahlqvist Leinhard O ... -  《-》

Quantitative Muscle Analysis in FSHD Using Whole-Body Fat-Referenced MRI: Composite Scores for Longitudinal and Cross-sectional Analysis.

Facioscapulohumeral muscular dystrophy (FSHD) is a rare, debilitating disease characterized by progressive muscle weakness. MRI is a sensitive assessment of disease severity and progression. We developed a quantitative whole-body (WB) musculoskeletal MRI (WB-MSK-MRI) protocol analyzing muscles in their entirety. This study aimed to assess WB-MSK-MRI as a potential imaging biomarker providing reliable measurements of muscle health that capture disease heterogeneity and clinically meaningful composite assessments correlating with severity and more responsive to change in clinical trials. Participants aged 18-65 years, with genetically confirmed FSHD1, clinical severity 2 to 4 (Ricci scale, range 0-5), and ≥1 short tau inversion recovery-positive lower extremity muscle eligible for needle biopsy, enrolled at 6 sites and were imaged twice 4-12 weeks apart. Volumetric analysis of muscle fat infiltration (MFI), muscle fat fraction (MFF), and lean muscle volume (LMV) in 18 (36 total) muscles from bilateral shoulder, proximal arm, trunk, and legs was performed after automated atlas-based segmentation, followed by manual verification. A WB composite score, including muscles at highest risk for progression, and functional cross-sectional composites for correlation with relevant functional outcomes including timed up and go (TUG), FSHD-TUG, and reachable workspace (RWS), were developed. Seventeen participants enrolled in this study; 16 follow-up MRIs were performed at 52 days (range 36-85 days). Functional cross-sectional composites (MFF and MFI) showed moderate to strong correlations: TUG (ρ = 0.71, ρ = 0.83), FSHD-TUG (ρ = 0.73, ρ = 0.73), and RWS (left arm: ρ = -0.71, ρ = -0.53; right arm: ρ = -0.61, ρ = -0.65). WB composite variability: LMVtot, coefficient of variation (CV) 1.9% and 3.4%; MFFtot, within-subject SD (Sw) 0.5% and 1.5%; and MFItot (Sw), 0.3% and 0.4% for normal and intermediate muscles, respectively. CV and Sw were higher in intermediate (MFI ≥0.10; MFF <0.50) than in normal (MFI <0.10, MFF <0.50) muscles. We developed a WB-MSK-MRI protocol and composite measures that capture disease heterogeneity and assess muscle involvement as it correlates with FSHD-relevant clinical endpoints. Functional composites robustly correlate with functional assessments. Stability of the WB composite shows that it could be an assessment of change in therapeutic clinical trials. This study provides Class II evidence that quantitative WB-MSK-MRI findings associate with FSHD1 severity measured using established functional assessments.

Mellion ML ，Widholm P ，Karlsson M ，Ahlgren A ，Tawil R ，Wagner KR ，Statland JM ，Wang L ，Shieh PB ，van Engelen BGM ，Kools J ，Ronco L ，Odueyungbo A ，Jiang J ，Han JJ ，Hatch M ，Towles J ，Leinhard OD ，Cadavid D ... -  《-》

MRI as outcome measure in facioscapulohumeral muscular dystrophy: 1-year follow-up of 45 patients.

Andersen G ，Dahlqvist JR ，Vissing CR ，Heje K ，Thomsen C ，Vissing J ... -  《-》

Muscle Quantitative MR Imaging and Clustering Analysis in Patients with Facioscapulohumeral Muscular Dystrophy Type 1.

Lareau-Trudel E ，Le Troter A ，Ghattas B ，Pouget J ，Attarian S ，Bendahan D ，Salort-Campana E ... -  《PLoS One》

Volumetric muscle composition analysis in sporadic inclusion body myositis using fat-referenced magnetic resonance imaging: Disease pattern, repeatability, and natural progression.

Heerfordt J ，Karlsson M ，Kusama M ，Ogata S ，Mukasa R ，Kiyosawa N ，Sato N ，Widholm P ，Dahlqvist Leinhard O ，Ahlgren A ，Mori-Yoshimura M ... -  《-》