Multi-slice MRI reveals heterogeneity in disease distribution along the length of muscle in Duchenne muscular dystrophy

Abstract

Background: Duchenne muscular dystrophy (DMD) causes progressive pathologic changes to muscle secondary to a cascade of inflammation, lipid deposition, and fibrosis. Clinically, this manifests as progressive weakness, functional loss, and premature mortality. Though insult to whole muscle groups is well established, less is known about the relationship between intramuscular pathology and function.

Objective: Differences of intramuscular heterogeneity across muscle length were assessed using an ordinal MRI grading scale in lower leg muscles of boys with DMD and correlated to patient's functional status.

Methods: Cross sectional T1 weighted MRI images with fat suppression were obtained from ambulatory boys with DMD. Six muscles (tibialis anterior, extensor digitorum longus, peroneus, soleus, medial and lateral gastrocnemii) were graded using an ordinal grading scale over 5 slice sections along the lower leg length. The scores from each slice were combined and results were compared to global motor function and age.

Results: Statistically greater differences of involvement were observed at the proximal ends of muscle compared to the midbellies. Multi-slice assessment correlated significantly to age and the Vignos functional scale, whereas single-slice assessment correlated to the Vignos functional scale only. Lastly, differential disease involvement of whole muscle groups and intramuscular heterogeneity were observed amongst similar age subjects.

Conclusion: A multi-slice ordinal MRI grading scale revealed that muscles are not uniformly affected, with more advanced disease visible near the tendons in a primarily ambulatory population with DMD. A geographically comprehensive evaluation of the heterogeneously affected muscle in boys with DMD may more accurately assess disease involvement.

Keywords: Duchenne Muscular Dystrophy; magnetic resonance imaging; myotendinous junction.

Figures

Figure 1.

Schematic representation of slice selections along the length of the lower leg. Representation of the slice positions based the percentage distance along the tibia (starting at the tibial plateau) along the longitudinal axis: proximal (P): ~10-12%, mid-proximal (MP): ~17-21%, middle (M): 25-28%, mid-distal (MD): 33-37%, distal (D): 41-45% inferior of the tibial plateau.

Figure 2.

Descriptions of the ordinal MRI scores to describe disease involvement of muscle.

Figure 3.

Representative transverse T1-weighted MR images with fat suppression of the lower leg of a control subject (top row) and subject with DMD (bottom row). MR imaging evaluation of the TA, EDL, Per, Sol, MG, and LG (labeled on the middle control image) was performed on all muscle groups in a manner described in Figure 2. Note the differences in the Per (dashed arrow) and TA (solid arrow) muscles at the proximal and distal compared to the middle slices in the DMD patient.

Figure 4.

Ordinal MRI Scores from two representative DMD patients (A = 10.0 years, B = 10.7 years) demonstrating differences in involvement along the length of six lower leg muscle groups. X axes are labeled with P (proximal), MP (mid-proximal), M (middle), MD (mid-distal), and D (distal).

Figure 5.

Frequency of involvement of six muscles in lower legs of boys with DMD. Shown are A: Peroneus, B: Extensor Digitorum Longus, C: Tibialis Anterior, D: Soleus, E: Medial Gastrocnemius, F: Lateral Gastrocnemius with differing MRI scores based on slice location. MRI scores of 0 were considered to be “not affected,” scores of 1 and 2 were considered to be “moderately affected,” and scores of 3-5 were considered to be “severely affected”.

Figure 6.

Age and function are compared to MRI scores. The sum of the scores of the multi-slice (Fig. 6a; rho = 0.69, p