OBJECTIVE: To provide evidence for quantitative magnetic resonance (qMR) 
biomarkers in Duchenne muscular dystrophy by investigating the relationship 
between qMR measures of lower extremity muscle pathology and functional 
endpoints in a large ambulatory cohort using a multicenter study design.
METHODS: MR spectroscopy and quantitative imaging were implemented to measure 
intramuscular fat fraction and the transverse magnetization relaxation time 
constant (T2) in lower extremity muscles of 136 participants with Duchenne 
muscular dystrophy. Measures were collected at 554 visits over 48 months at one 
of three imaging sites. Fat fraction was measured in the soleus and vastus 
lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower 
extremity muscles. Ambulatory function was measured using the 10m walk/run, 
climb four stairs, supine to stand, and six minute walk tests.
RESULTS: Significant correlations were found between all qMR and functional 
measures. Vastus lateralis qMR measures correlated most strongly to functional 
endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing 
muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 
0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were 
excellent indicators of loss of functional ability and correlated with 
qualitative measures of function. A VL FF of 0.40 was an approximate lower 
threshold of muscle pathology associated with loss of ambulation.
DISCUSSION: Lower extremity qMR biomarkers have a robust relationship to 
clinically meaningful measures of ambulatory function in Duchenne muscular 
dystrophy. These results provide strong supporting evidence for qMR biomarkers 
and set the stage for their potential use as surrogate outcomes in clinical 
trials.