OBJECTIVE: To quantify disease progression in individuals with Duchenne muscular 
dystrophy (DMD) using magnetic resonance biomarkers of leg muscles.
METHODS: MRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired 
from 104 participants with DMD and 51 healthy controls using a prospective 
observational study design with patients with DMD followed up yearly for up to 6 
years. Fat fractions (FFs) in vastus lateralis and soleus muscles were 
determined with 1H MRS. MRI quantitative T2 (qT2) values were measured for 3 
muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in 
biomarkers were modeled with a cumulative distribution function using a 
nonlinear mixed-effects approach.
RESULTS: MRS FF and MRI qT2 increased with DMD disease duration, with the 
progression time constants differing markedly between individuals and across 
muscles. The average age at half-maximal muscle involvement (μ) occurred 4.8 
years earlier in vastus lateralis than soleus, and these measures were strongly 
associated with loss-of-ambulation age. Corticosteroid treatment was found to 
delay μ by 2.5 years on average across muscles, although there were marked 
differences between muscles with more slowly progressing muscles showing larger 
delay.
CONCLUSIONS: MRS FF and MRI qT2 provide sensitive noninvasive measures of DMD 
progression. Modeling changes in these biomarkers across multiple muscles can be 
used to detect and monitor the therapeutic effects of corticosteroids on disease 
progression and to provide prognostic information on functional outcomes. This 
modeling approach provides a method to transform these MRI biomarkers into 
well-understood metrics, allowing concise summaries of DMD disease progression 
at individual and population levels.
CLINICALTRIALSGOV IDENTIFIER: NCT01484678.