Quantitative MRI lower extremity muscle fat infiltration patterns in dystrophinopathy and calpainopathy across mobility levels

Topic:

Translational Research

Poster Number: P29

Author(s):

Kelly Rock, PT, DPT, PhD, University Of Florida, DJ Lott, PT, PhD, University of Florida, Rebecca J Willcocks, PhD, University of Florida, Sean C Forbes, PhD, University of Florida, AM Barnard, PT, DPT, PhD, University of Florida, Oneema Kamal, University Of Florida, Alexa Harris, University Of Florida, Julia Hinkle, University Of Florida, Claudia Senesac, University Of Florida, SH Subramony, MD, University of Florida, William D Rooney, PhD, Oregon Health and Science University, Glenn A Walter, PhD, University of Florida, Krista Vandenborne, PhD, University of Florida

Background: Becker (BMD), Duchenne (DMD), and limb-girdle type 2A (LGMD2A) muscular dystrophies result in fat replacement of muscle and impaired mobility. Yet, these diseases have varying clinical presentations and progressions. Quantitative MRI (qMRI) muscle fat fraction (FF) is a reliable biomarker of muscle deterioration showing promising use in clinical trials.
Objectives: We aimed to characterize and compare qMRI FF of lower extremity muscles in BMD, DMD, and LGMD2A.
Methods: 89 participants (46 BMD, 28 DMD, 15 LGMD2A) aged 7-62 years completed 3-point Dixon (chemical-shift) qMRI (TR: 10ms; TE: 1.1/2.5/3.9ms; 4mm slices) and were stratified by the Vignos Scale. Groups: (A) walks and climbs stairs unassisted (Vignos=1); (B) walks unassisted and climbs stairs with assistance or cannot climb stairs (Vignos=2-5); and (C) walks with assistance or cannot walk (Vignos=6-9). The average FF of the right gluteal muscles (GlutMax; GlutMinMed), thigh muscles (QUADS; HAMS), and calf muscles (SOL, TA, MG) and posterior-to-anterior muscle group ratios were calculated. Kruskal-Wallis tests were used to assess comparisons between mobility and diagnostic groups.
Results: Group A had average FF <20% in all muscles and diagnostic groups except for GlutMax and GlutMinMed in DMD. Compared to Group A, Group B had higher FF (+31-66%) in GlutMax, GlutMinMed, QUADS, and HAMS, and also in MG for BMD and LGMD2A, and SOL for LGMD2A. In Group B, HAMS and MG were lower in DMD, while SOL was higher in LGMD2A (p<0.05). Group C had average FF >70% in all muscles and diagnostic groups except the TA, and also SOL for BMD and LGMD2A, and MG for DMD. Posterior-anterior FF ratios of the calf were highest in LGMD2A, and thigh FF ratios were higher in BMD and LGMD2A compared to DMD.
Conclusions: These data support lower extremity muscle involvement in dystrophinopathy and calpainopathy in proximal-to-distal and posterior-to-anterior patterns. Stratifying by mobility level elucidates relevant muscle pathology as measured by qMRI FF. Despite differences in onset age and progression across BMD, DMD, and LGMD2A, the use of qMRI FF could help address challenges in clinical trial development and efficacy assessment.