Magnetic resonance imaging of the proximal upper extremity musculature in boys with Duchenne muscular dystrophy

Abstract

There is a pressing need for biomarkers and outcomes that can be used across disease stages in Duchenne muscular dystrophy (DMD), to facilitate the inclusion of a wider range of participants in clinical trials and to improve our understanding of the natural history of DMD. Quantitative magnetic resonance imaging (qMRI) and spectroscopy (MRS) biomarkers show considerable promise in both the legs and forearms of individuals with DMD, but have not yet been examined in functionally important proximal upper extremity muscles such as the biceps brachii and deltoid. The primary objective of this study was to examine the feasibility of implementing qMRI and MRS biomarkers in the proximal upper extremity musculature, and the secondary objective was to examine the relationship between MR measures of arm muscle pathology and upper extremity functional endpoints. Biomarkers included MRS and MRI measures of fat fraction and transverse relaxation time (T 2). The MR exam was well tolerated in both ambulatory and non-ambulatory boys. qMR biomarkers differentiated affected and unaffected participants and correlated strongly with upper extremity function (r = 0.91 for biceps brachii T 2 versus performance of upper limb score). These qMR outcome measures could be highly beneficial to the neuromuscular disease community, allowing measurement of the quality of functionally important muscles across disease stages to understand the natural history of DMD and particularly to broaden the opportunity for clinical trial participation.

Keywords: Biomarker; Magnetic resonance spectroscopy; Non-ambulatory; Transverse relaxation time.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1

Axial and coronal images of the upper arm in a CON subject and of the shoulder in a boy with DMD, demonstrating the voxel placement for MR spectroscopy.

Fig. 2

Fat fraction maps of the shoulder (a), upper arm (b), and forearm (c) from DMD subjects, and T2 maps from the shoulder (d), upper arm (e), and forearm (c) from the same subjects.

Fig. 3

MR images (water maps derived from chemical shift based imaging) from the arms of CON (a, b, and c) and DMD (d, e, and f, aged 12, 13, and 13 years) subjects, with muscles of interest labeled.

Fig. 4

MRI T2 measures were significantly elevated in DMD compared with CON in all proximal muscles. Error bars show standard error of the mean.

Fig. 5

MRI T2 (a) and MRI FF measures (b) in the proximal upper extremity muscles in CON, and young versus older boys with DMD. Error bars show standard error of the mean.

Fig. 6

(a) Example spectra from the BB demonstrated elevated FF in both ambulatory and nonambulatory boys with DMD. (b) FF measured using Dixon imaging correlated well with FF measured using MRS, the gold standard. (c) A strong correlation was also found between FF and MRI T2 measures