Leg muscle MR biomarkers are responsive to disease progression after loss of ambulation and strongly correlate with upper extremity function


Clinical Trials

Poster Number: 117


Rebecca Willcocks, PhD, University of Florida, Sean C Forbes, PhD, University of Florida, William Rooney, PhD, Oregon Health & Science University, Alison Barnard, PhD, University of Florida, Donovan Lott, PT, PhD, CSCS, University of Florida, Eric Baetscher, Oregon Health and Science University, Prathyusha Bellam, PT, University of Florida, Erika Finanger, MD, Oregon Health & Science University, John Brandsema, MD, The Children's Hospital of Philadelphia, Claudia R Senesac, PT, PhD, University of Florida, Dah-Jyuu Wang, PhD, Children's Hospital of Philadelphia, Glenn Walter, PhD, University of Florida, Krista Vandenborne, PT, PhD, University of Florida

Magnetic resonance (MR) biomarkers are increasingly used in clinical trials in ambulatory individuals with DMD, and present even greater potential value for nonambulatory cohorts. However, MR measures of the arm have proven technically challenging and uncomfortable as patients experience contractures. We hypothesize that MR biomarkers in lower extremty muscles are both responsive to disease progression and clinically meaningful in nonambulatory individuals with DMD.

The ImagingDMD study includes longitudinal MR and function data in 180 individuals with DMD (749 study visits), including 56 nonambulatory individuals (140 visits). MR data includes fat fraction in thigh (vastus lateralis), calf (soleus), upper arm (biceps brachii) and shoulder (deltoid) muscles measured using MR spectroscopy, and MRI transverse relaxation time constant (T2) measures from 9 muscles (4 lower leg, 2 thigh, 3 upper extremity). In this investigation, we calculated the standardized response mean (SRM) over 1 year and evaluated the correlation with upper extremity muscle fat fraction (deltoid and biceps brachii) and function (Performance of Upper Limb (PUL)).

Upper and lower extremity muscle MR biomarkers are closely correlated with each other, with Spearman’s rho values between 0.70 and 0.88 . Leg muscle MR biomarkers are also significantly correlated with total PUL score (Spearman’s rho > 0.50 for all MR measurements; rho > 0.65 for fat fraction in the soleus and vastus lateralis). Lower extremity muscles also have strong responsiveness to disease progression after loss of ambulation, with SRM of 1.0 for soleus and 0.75 for vastus lateralis.

Leg muscle quantitative MRI measures are strongly correlated with both arm muscle MRI measures and upper extremity function. Leg muscle biomarkers are also responsive to disease progression in nonambulatory individuals with DMD. Leg muscle MR biomarkers are well characterized longitudinally, more reliably obtained than analogous upper extremity measures, and offer an attractive disease progression surrogate in nonambulatory DMD.