Magnetic resonance imaging and spectroscopy assessment of lower extremity skeletal muscles in boys with Duchenne muscular dystrophy: a multicenter cross sectional study

Abstract

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that (1)H2O T2 derived using (1)H-MRS and MRI-T2 will be sensitive to muscle involvement at a young age (5-7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls.

Methods: MR data were acquired from 123 boys with DMD (ages 5-14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children's Hospital of Philadelphia). T2-weighted multi-slice spin echo (SE) axial images and single voxel 1H-MRS were acquired from the lower leg and thigh to measure lipid fraction and (1)H2O T2.

Results: MRI-T2, (1)H2O T2, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T2, (1)H2O T2 and lipid fraction and vastus lateralis MRI-T2 and (1)H2O T2. In the boys with DMD, MRI-T2 and lipid fraction were greater (p<0.05) in the oldest age group (11-14 years) than the youngest age group (5-6.9 years), while 1H2O T2 was lower in the oldest age group compared to the young age group.

Discussion: Overall, MR measures of T2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys.

Conflict of interest statement

Competing Interests: R.S.F. Financial activities related to the present article: None to disclose. Financial activities not related to the present article: institution received a grant from PTC Therapeutics for a study of ataluren in DMD for which R.S.F. was the primary investigator (some of the subjects in that study also participated in the current study, but no financial conflict is identified). Other relationships: unpaid advisor to Muscular Dystrophy Association and Parent Project Muscular Dystrophy. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Example upper leg axial spin echo (SE) images (TE 60 ms) with single voxel 1H-MRS spectra (TE 108 ms) from the vastus lateralis of a control and boys with DMD at different ages.

Figure 2. MRS 1H2O T2 (ms), MRI-T2 (ms), and lipid fraction [lipid/(lipid+water)] in the soleus (A) and vastus lateralis (B) of control and DMD age groups.

DMD were significantly different (

Figure 3. Scatterplot displaying the relationship between 1H2O T2 and lipid/(lipid+water) in the soleus of controls and boys with DMD.

Red dotted lines denote 95% confidence interval of MRS 1H2O T2 in controls (A). In those with low lipid/(lipid+water) levels (i.e., less than 5%), the 1H2O T2 was longer in DMD (n = 34) than controls (n = 29) (B). * denotes significantly different (<0.05) than controls. Bars represent mean (SEM).

Figure 4. Comparison of tibialis anterior (TA), tibialis posterior (TP), peroneus brevis and longus (Per), and medial gastrocnemius (MG) of the lower leg (A) and the gracilis (Gra) and biceps femoris long head (BFLH) of the thigh (B).

In all muscles and age groups DMD was greater than controls, except in Gra in the 5–6.9 and 7–8.9 age groups. # indicates differences (