Longitudinal Evaluation of Muscle Composition Using Magnetic Resonance in 4 Boys With Duchenne Muscular Dystrophy: Case Series

Abstract

Background: Duchenne muscular dystrophy (DMD), an inherited recessive X chromosome-linked disease, is the most severe childhood form of muscular dystrophy. Boys with DMD experience muscle loss, with infiltration of intramuscular fat into muscles.

Objectives: This case series describes the progression of DMD in boys using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Magnetic resonance results are then compared with an established functional timed test.

Methods: Four boys with DMD and 4 healthy age-matched controls were chosen from a larger cohort. Boys with DMD were assessed at 4 time points over 2 years, with controls assessed at baseline only. Progression of the disease was documented by assessing the plantar flexors using MRI and MRS techniques and by assessing ambulation using the 30-Foot Fast Walk Test.

Results: Transverse relaxation time (T2) values were elevated in all boys with DMD at baseline. The lipid ratio increased rapidly as the disease progressed in 2 boys. Discrete changes in T2 in the other 2 boys with DMD indicated a slower disease progression. Magnetic resonance imaging and MRS allowed monitoring of the disease over all time periods regardless of ambulation status.

Limitations: The magnetic resonance data were collected with 2 different magnets at 2 different field strengths (1.5 and 3.0 T). Although we corrected for this difference, care must be taken in interpreting data when different image collection systems are used. This was a case series of 4 boys with DMD taken from a larger cohort study.

Conclusions: Magnetic resonance imaging and MRS are objective, noninvasive techniques for measuring muscle pathology and can be used to detect discrete changes in both people who are ambulatory and those who are nonambulatory. These techniques should be considered when monitoring DMD progression and assessing efficacy of therapeutic interventions.

© 2015 American Physical Therapy Association.

Figures

Figure 1.

Participant DMD 8A: (A) T2 (transverse relaxation time), a marker of muscle damage and inflammation; (B) CSAmax (maximal cross-sectional area); (C) lipid fraction presented as total percentage of muscle infiltrated with lipid; and (D) 30-Foot Fast Walk Test. These measurements are represented with different patterned columns for the baseline measure of the healthy age-matched control and participant with Duchenne muscular dystrophy (DMD) for baseline, 6, 12, and 24 months (except for the 30-Foot Fast Walk Test, which had only the baseline measure prior to becoming nonambulatory). This participant demonstrated a rapid disease progression over time across all measurements.

Figure 2.

Example of lipid changes over 2 years in the soleus muscle of participant DMD 8A compared with age-matched control at baseline. T1 fat-suppressed images with voxel placement and associated magnetic resonance spectroscopy for corresponding time points were used to demonstrate changes. Note the water peak decreased and the lipid peak increased over time in this individual, demonstrating the replacement of muscle by fat. The y-axis units of the spectra represent arbitrary units, and the values were quantified as a ratio lipid/(lipid+water) for comparisons. DMD=Duchenne muscular dystrophy.

Figure 3.

Participant DMD 8B: (A) T2 (transverse relaxation time), a marker of muscle damage and inflammation; (B) CSAmax (maximal cross-sectional area); (C) lipid fraction presented as total percentage of muscle infiltrated with lipid; and (D) 30-Foot Fast Walk Test. These measurements are represented with different patterned columns for the baseline measure of the healthy matched control and participant with Duchenne muscular dystrophy (DMD) for baseline, 6, 12, and 24 months. Note that the lipid fraction and CSAmax demonstrated a gradual increase over the 2-year time period. However, the T2 values and 30-Foot Fast Walk Test remain fairly stable over this same time period.

Figure 4.

Participant DMD 11: (A) T2 (transverse relaxation time), a marker of muscle damage and inflammation; (B) CSAmax (maximal cross-sectional area), (C) lipid fraction presented as total percentage of muscle infiltrated with lipid; and (D) 30-Foot Fast Walk Test. These measurements are represented with different patterned columns for the baseline measure of the healthy matched control and participant with Duchenne muscular dystrophy (DMD) for baseline, 6, 12, and 24 months. Note that this individual remained stable across time periods except for an increase in CSAmax, demonstrating a slower progression of this disease.

Figure 5.

Participant DMD 13: (A) T2 (transverse relaxation time), a marker of muscle damage and inflammation; (B) CSAmax (maximal cross-sectional area); (C) lipid fraction presented as total percentage of muscle infiltrated with lipid; and (D) 30-Foot Fast Walk Test. These measurements are represented with different patterned columns for the baseline measure of the healthy matched control and participant with Duchenne muscular dystrophy (DMD) for baseline, 6, 12, and 24 months (except for the 30-Foot Fast Walk Test; 24 months, the participant was nonambulatory). Note the progressive nature of the lipid fraction and increase in time to perform the 30-Foot Fast Walk Test over the 2-year period. T2 and CSAmax remained relatively stable across time periods.

Figure 6.

T1–weighted magnetic resonance images with fat suppression at the 2-year time point for all participants with Duchenne muscular dystrophy (DMD) were used for visual inspection, and the control image was taken at baseline. The individual muscles of the lower leg are indicated in the control image: F=fibularis muscles (fibularis longus and brevis), TA=tibialis anterior muscle, TP=tibialis posterior muscle, LG=lateral gastrocnemius muscle, and MG=medial gastrocnemius muscle. Note the general pattern of hypointensity with fibularis muscles most affected, soleus and gastrocnemius muscles intermediate, and tibialis posterior and tibialis anterior muscles least affected. These findings are indicative of the disease progression.