Upper and Lower Extremities in Duchenne Muscular Dystrophy Evaluated with Quantitative MRI and Proton MR Spectroscopy in a Multicenter Cohort

Abstract

Background Upper extremity MRI and proton MR spectroscopy are increasingly considered to be outcome measures in Duchenne muscular dystrophy (DMD) clinical trials. Purpose To demonstrate the feasibility of acquiring upper extremity MRI and proton (1H) MR spectroscopy measures of T2 and fat fraction in a large, multicenter cohort (ImagingDMD) of ambulatory and nonambulatory individuals with DMD; compare upper and lower extremity muscles by using MRI and 1H MR spectroscopy; and correlate upper extremity MRI and 1H MR spectroscopy measures to function. Materials and Methods In this prospective cross-sectional study, MRI and 1H MR spectroscopy and functional assessment data were acquired from participants with DMD and unaffected control participants at three centers (from January 28, 2016, to April 24, 2018). T2 maps of the shoulder, upper arm, forearm, thigh, and calf were generated from a spin-echo sequence (repetition time msec/echo time msec, 3000/20-320). Fat fraction maps were generated from chemical shift-encoded imaging (eight echo times). Fat fraction and 1H2O T2 in the deltoid and biceps brachii were measured from single-voxel 1H MR spectroscopy (9000/11-243). Groups were compared by using Mann-Whitney test, and relationships between MRI and 1H MR spectroscopy and arm function were assessed by using Spearman correlation. Results This study evaluated 119 male participants with DMD (mean age, 12 years ± 3 [standard deviation]) and 38 unaffected male control participants (mean age, 12 years ± 3). Deltoid and biceps brachii muscles were different in participants with DMD versus control participants in all age groups by using quantitative T2 MRI (P < .001) and 1H MR spectroscopy fat fraction (P < .05). The deltoid, biceps brachii, and triceps brachii were affected to the same extent (P > .05) as the soleus and medial gastrocnemius. Negative correlations were observed between arm function and MRI (T2: range among muscles, ρ = -0.53 to -0.73 [P < .01]; fat fraction, ρ = -0.49 to -0.70 [P < .01]) and 1H MR spectroscopy fat fraction (ρ = -0.64 to -0.71; P < .01). Conclusion This multicenter study demonstrated early and progressive involvement of upper extremity muscles in Duchenne muscular dystrophy (DMD) and showed the feasibility of MRI and 1H MR spectroscopy to track disease progression over a wide range of ages in participants with DMD. © RSNA, 2020 Online supplemental material is available for this article.

Figures

Graphical abstract

Figure 1:

Flowchart shows the recruitment of participants with Duchenne muscular dystrophy (DMD) and unaffected male control participants from the ImagingDMD cohort who had previously participated in lower extremity MRI and proton MR spectroscopy acquisitions. Reasons provided by the family for not participating in this study are included when available.

Figure 2a:

Example upper extremity MRI and proton (1H) MR spectroscopy (MRS) data acquired from the dominant (a) shoulder and (b) upper arm in control participants and participants with Duchenne muscular dystrophy (DMD) at different ages. Single voxel stimulated-echo acquisition mode 1H MR spectroscopy spectra were acquired at echo time of 27 msec from the deltoid (a) and biceps brachii (b).

Figure 2b:

Example upper extremity MRI and proton (1H) MR spectroscopy (MRS) data acquired from the dominant (a) shoulder and (b) upper arm in control participants and participants with Duchenne muscular dystrophy (DMD) at different ages. Single voxel stimulated-echo acquisition mode 1H MR spectroscopy spectra were acquired at echo time of 27 msec from the deltoid (a) and biceps brachii (b).

Figure 3:

Box and whisker plots show proton (1H) MR spectroscopy (MRS) 1H2O T2 (msec), MRI T2 (msec), MR spectroscopy fat fraction (MRS FF), and chemical shift-encoded imaging fat fraction (MRI FF) of the biceps brachii and deltoid in control participants and participants with Duchenne muscular dystrophy (DMD) in different age groups. Statistical significance was defined as a P value less than the Bonferroni-corrected P value. No differences were observed among age groups in control participants. Whisker bars represent 5th and 95th percentiles and dots are shown for outliers. * Significantly different than controls. # Significantly different between age groups in participants with DMD.

Figure 4:

Box and whisker plots of MRI T2 in upper and lower extremity muscles in different age groups. Whisker bars represent 5th and 95th percentiles and dots are shown for outliers. AF = anterior forearm, BB = biceps brachii, BFLH = biceps femoris long head, Del = deltoid, Gra = gracilis, MG = medial gastrocnemius, Per = peroneals, PF = posterior forearm, Sol = soleus, TA = tibialis anterior, TB = triceps brachii, TP = tibialis posterior, VL = vastus lateralis.

Figure 5:

Correlation scatterplots. A, Total performance of upper limb (PUL) and the composite upper extremity (UE) MRI T2 values were negatively correlated (ρ = −0.65; P < .001) in participants with Duchenne muscular dystrophy (DMD) and were negatively correlated in both ambulatory (ρ = −0.41; P = .003) and nonambulatory (ρ = −0.50; P = .01) participants with DMD when analyzed separately. B, Upper versus lower extremity (LE) MRI T2 composite measures were strongly positively correlated (ρ = 0.93; P < .001), including in both ambulatory (ρ = 0.88; P < .001) and nonambulatory (ρ = 0.97; P < .001) participants with DMD when analyzed separately.