Relationship between quantitative MRI measures and future functional changes in boys with Duchenne muscular dystrophy (DMD)


Topic:

Clinical Trials

Poster Number: 108

Author(s):

Sarah Sherlock, PhD, Pfizer Inc, Cambridge, MA, Susan Hwang, PhD, Pfizer Inc, Cambridge, MA, Halah Aghamolaey, Quanticate, André Ahlgren, PhD, AMRA Medical AB, Linköping, Sweden, Per Widholm, MD, AMRA Medical AB, Linköping, Sweden, Olof Dahlqvist Leinhard, PhD, AMRA Medical AB, Linköping, Sweden, Markus Karlsson, PhD, AMRA Medical AB, Linköping, Sweden

Introduction: Magnetic resonance imaging (MRI) has been demonstrated to be an important non-invasive tool for monitoring disease progression in Duchenne muscular dystrophy (DMD). Several studies have also suggested the MRI measures can inform future functional changes and may serve as a biomarker for future clinical trials. Using MRI scans obtained as part of a Phase 2 study (NCT02310763, N=120) we conducted a post-hoc analysis to understand the relationship between muscle volume and fat measures to inform functional declines.

Methods: Muscle Fat Infiltration (MFI), Muscle Fat Fraction (MFF) and Lean Muscle Volume (LMV) measurements were derived from MRI scans of a single whole thigh of ambulatory boys (6-16 years of age) with DMD. Volumetric measures were derived for adductors, hamstrings and quadriceps at each timepoint. Relationship between the Change from baseline (CFB) in MRI measures after 49 weeks and the CFB in North Star Ambulatory Assessment Total Score (NSAA) measures after 97 weeks was assessed.

Results: Changes in MFF and MFI over 49 weeks were significantly correlated with NSAA scores after 97 weeks with all muscle groups showing negative correlations (Spearman rank correlation: -0.57≤ R ≤-0.70, p<0.001). LMV was positively correlated with NSAA in the adductors (R=0.65, p<0.001) and moderately correlated with quadriceps (R=0.51, p=0.002). MFI, MFF, and LMV measures in most regions were significantly correlated with the velocity of time to complete the 10m run/walk, also with the time to rise from floor velocity. Conclusion: These quantitative MRI observations provide additional evidence on the relationship between imaging and functional performance. LMV gains in the adductors and quadriceps would have the strongest benefit on improving NSAA scores, while MFI and MFF are important for all muscle regions. Additional relationships between muscle MRI progression and functional impacts will be presented.