Correlation between whole body muscle MRI and functional measures in paediatric patients with facioscapulohumeral muscular dystrophy.

Symptoms and severity of facioscapulohumeral muscular dystrophy (FSHD) can vary greatly, even within the same family. Clinical trial readiness requires accurate and reliable methods of assessing disease stage and progression. MRI has not previously been assessed as a disease biomarker in paediatric FSHD. Eleven patients with FSHD1 underwent whole body muscle MRI. Pre-selected muscles were analysed by a paediatric radiologist using the semi-quantitative Mercuri/Kim method. Within each domain (oedema, fat replacement, atrophy) scores for each muscle were then summated to give each participant three cumulative domain scores. The same participants had functional measures scored: FSHD-CSS (Ricci), FSHD-CS (Lamperti), FSHD-COM, PUL2.0, MFM-32, 6MWT, myometry and manual muscle testing. Pearson coefficient was calculated to determine strength of correlation. The scores for atrophy and fat replacement showed strong correlation with functional outcome measures, particularly FSHD-CSS, FSHD-CS and FSHD-COM. In contrast, muscle oedema correlated poorly with all functional outcome measures, with no relationship seen to the 6MWT. This study of eleven children suggests that semi-quantitative visual Mercuri score utilising fat replacement or atrophy on whole body muscle MRI correlates strongly with disease-specific functional measures and may be a useful measure of disease severity in paediatric FSHD.

Woodcock IR ，de Valle K ，Varma N ，Kean M ，Ryan MM ... -  《-》

Five-year follow-up study on quantitative muscle magnetic resonance imaging in facioscapulohumeral muscular dystrophy: The link to clinical outcome.

It is unclear how changes in quantitative muscle magnetic resonance imaging (MRI) relate to changes in clinical outcome in facioscapulohumeral muscular dystrophy (FSHD), although this information is crucial for optimal use of MRI as imaging biomarker in trials. We therefore assessed muscle MRI and clinical outcome measures in a large longitudinal prospective cohort study. All patients were assessed by MRI at baseline and at 5-year follow-up, employing 2pt-Dixon and turbo inversion recovery magnitude (TIRM) sequences, after which fat fraction and TIRM positivity of 19 leg muscles were determined bilaterally. The MRI compound score (CoS) was defined as the mean fat fraction of all muscles weighted for cross-sectional area. Clinical outcome measures included the Ricci-score, FSHD clinical score (FSHD-CS), MRC sumscore (MRC-SS), and motor-function-measure (MFM). We included 105 FSHD patients [mean age 54 ± 14 years, median Ricci-score 7 (range 0-10)]. The median change over 5 years' time in the MRI-CoS was 2.0% (range -4.6 to +12.1; P < 0.001). The median change over 5 years' time in clinical outcome measures was small in all measures, with z-scores ranging from 5.0 to 7.2 (P < 0.001). The change in MRI-CoS correlated with change in FSHD-CS and Ricci-score (ρ = 0.25, respectively; ρ = 0.23, P < 0.05). The largest median increase in MRI-CoS was seen in baseline subgroups with an MRI-CoS 20-40% (6.1%), with ≥2 TIRM positive muscles (3.5%) or with an FSHD-CS 5-10 (3.1%). This 5-year study showed significant changes in MRI and clinical outcome measures and a significant correlation between changes in MRI-CoS and changes in clinical outcome measures. In addition, we identified subgroups of patients that are most prone to radiological disease progression. This knowledge further establishes quantitative MRI parameters as prognostic biomarkers in FSHD and as efficacy biomarkers in upcoming clinical trials.

Vincenten SCC ，Mul K ，van As D ，Jansen JJ ，Heskamp L ，Heerschap A ，van Engelen BGM ，Voermans NC ... -  《-》

Muscle MRI findings in facioscapulohumeral muscular dystrophy.

Gerevini S ，Scarlato M ，Maggi L ，Cava M ，Caliendo G ，Pasanisi B ，Falini A ，Previtali SC ，Morandi L ... -  《-》

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 ... -  《-》

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 ... -  《-》