Skeletal muscles of ambulant children with Duchenne muscular dystrophy: validation of multicenter study of evaluation with MR imaging and MR spectroscopy

Abstract

Purpose: To validate a multicenter protocol that examines lower extremity skeletal muscles of children with Duchenne muscular dystrophy (DMD) by using magnetic resonance (MR) imaging and MR spectroscopy in terms of reproducibility of these measurements within and across centers.

Materials and methods: This HIPAA-compliant study was approved by the institutional review boards of all participating centers, and informed consent was obtained from each participant or a guardian. Standardized procedures with MR operator training and quality assurance assessments were implemented, and data were acquired at three centers by using different 3-T MR imaging instruments. Measures of maximal cross-sectional area (CSAmax), transverse relaxation time constant (T2), and lipid fraction were compared among centers in two-compartment coaxial phantoms and in two unaffected adult subjects who visited each center. Also, repeat MR measures were acquired twice on separate days in 30 boys with DMD (10 per center) and 10 unaffected boys. Coefficients of variation (CVs) were computed to examine the repeated-measure variabilities within and across centers.

Results: CSAmax, T2 from MR imaging and MR spectroscopy, and lipid fraction were consistent across centers in the phantom (CV, <3%) and in the adult subjects who traveled to each site (CV, 2%-7%). High day-to-day reproducibility in MR measures was observed in boys with DMD (CSAmax, CV = 3.7% [25th percentile, 1.3%; 75th percentile, 5.1%]; contractile area, CV = 4.2% [25th percentile, 0.8%; 75th percentile, 4.9%]; MR imaging T2, CV = 3.1% [25th percentile, 1.2%; 75th percentile, 4.7%]; MR spectroscopy T2, CV = 3.9% [25th percentile, 1.5%; 75th percentile, 5.1%]; and lipid fraction, CV = 4.7% [25th percentile, 1.0%; 75th percentile, 5.3%]).

Conclusion: The MR protocol implemented in this multicenter study achieved highly reproducible measures of lower extremity muscles across centers and from day to day in ambulatory boys with DMD.

© RSNA, 2013.

Figures

Figure 1a:

Graphs show interrater reliability of CSAmax in lower leg muscles in subjects with DMD as measured by (a) Pearson correlation (r = 0.997) and (b) CV. Per = PL and PB muscles, Sol = soleus muscle.

Figure 1b:

Graphs show interrater reliability of CSAmax in lower leg muscles in subjects with DMD as measured by (a) Pearson correlation (r = 0.997) and (b) CV. Per = PL and PB muscles, Sol = soleus muscle.

Figure 2a:

Representative gradient-echo axial MR images (lower leg: repetition time msec/echo time msec, 12/2.2; flip angle, 20°; thigh: 12/2.3; flip angle, 20°) acquired on separate days (day 1: a and c; day 2: b and d) in (a, b) lower right leg and (c, d) upper right leg in 11.6-year-old boy with DMD. MR imaging analysis of the TA, PL and PB (Per), MG, soleus (Sol), VL, LHBF (BFI), gracilis (Gra), and ST muscles was performed.

Figure 2b:

Representative gradient-echo axial MR images (lower leg: repetition time msec/echo time msec, 12/2.2; flip angle, 20°; thigh: 12/2.3; flip angle, 20°) acquired on separate days (day 1: a and c; day 2: b and d) in (a, b) lower right leg and (c, d) upper right leg in 11.6-year-old boy with DMD. MR imaging analysis of the TA, PL and PB (Per), MG, soleus (Sol), VL, LHBF (BFI), gracilis (Gra), and ST muscles was performed.

Figure 2c:

Representative gradient-echo axial MR images (lower leg: repetition time msec/echo time msec, 12/2.2; flip angle, 20°; thigh: 12/2.3; flip angle, 20°) acquired on separate days (day 1: a and c; day 2: b and d) in (a, b) lower right leg and (c, d) upper right leg in 11.6-year-old boy with DMD. MR imaging analysis of the TA, PL and PB (Per), MG, soleus (Sol), VL, LHBF (BFI), gracilis (Gra), and ST muscles was performed.

Figure 2d:

Representative gradient-echo axial MR images (lower leg: repetition time msec/echo time msec, 12/2.2; flip angle, 20°; thigh: 12/2.3; flip angle, 20°) acquired on separate days (day 1: a and c; day 2: b and d) in (a, b) lower right leg and (c, d) upper right leg in 11.6-year-old boy with DMD. MR imaging analysis of the TA, PL and PB (Per), MG, soleus (Sol), VL, LHBF (BFI), gracilis (Gra), and ST muscles was performed.

Figure 3a:

(a) Bar graph shows day-to-day variability of MR imaging T2 measures in the soleus for boys with DMD and control subjects. (b) Box plot shows median within-subject day-to-day CV and 10th, 25th, 75th, and 90th percentiles for the soleus (Sol), MG, PL and PB (Per), TA, gracilis (Gra), ST, and VL muscles in boys with DMD. (c) Box plot shows CVs of the three centers. Within-subject CV was calculated by dividing the standard deviation by the mean and multiplying the result by 100%.

Figure 3b:

(a) Bar graph shows day-to-day variability of MR imaging T2 measures in the soleus for boys with DMD and control subjects. (b) Box plot shows median within-subject day-to-day CV and 10th, 25th, 75th, and 90th percentiles for the soleus (Sol), MG, PL and PB (Per), TA, gracilis (Gra), ST, and VL muscles in boys with DMD. (c) Box plot shows CVs of the three centers. Within-subject CV was calculated by dividing the standard deviation by the mean and multiplying the result by 100%.

Figure 3c:

(a) Bar graph shows day-to-day variability of MR imaging T2 measures in the soleus for boys with DMD and control subjects. (b) Box plot shows median within-subject day-to-day CV and 10th, 25th, 75th, and 90th percentiles for the soleus (Sol), MG, PL and PB (Per), TA, gracilis (Gra), ST, and VL muscles in boys with DMD. (c) Box plot shows CVs of the three centers. Within-subject CV was calculated by dividing the standard deviation by the mean and multiplying the result by 100%.

Figure 4a:

(a) Bar graph shows day-to-day variability of lipid fraction in the soleus in boys with DMD and control boys. (b) Box plot shows median within-subject CV with 10th, 25th, 75th, and 90th percentiles for the soleus (Sol) and VL muscles in boys with DMD. (c) Box plot shows the day-to-day CV of the three centers.

Figure 4b:

(a) Bar graph shows day-to-day variability of lipid fraction in the soleus in boys with DMD and control boys. (b) Box plot shows median within-subject CV with 10th, 25th, 75th, and 90th percentiles for the soleus (Sol) and VL muscles in boys with DMD. (c) Box plot shows the day-to-day CV of the three centers.

Figure 4c:

(a) Bar graph shows day-to-day variability of lipid fraction in the soleus in boys with DMD and control boys. (b) Box plot shows median within-subject CV with 10th, 25th, 75th, and 90th percentiles for the soleus (Sol) and VL muscles in boys with DMD. (c) Box plot shows the day-to-day CV of the three centers.