Multi-parametric MR in Becker muscular dystrophy patients

Abstract

Quantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to be highly associated with functional tests in BMD. However, the muscle strength per unit of contractile cross-sectional area is lower in patients with BMD compared with healthy controls. This suggests that the quality of the non-fat-replaced (NFR) muscle tissue is lower than in healthy controls. Consequently, a measure that reflects changes in muscle tissue itself is needed. Here, we explore the potential of water T₂ relaxation times, diffusion parameters and phosphorus metabolic indices as early disease markers in patients with BMD. For this purpose, we examined these measures in fat-replaced (FR) and NFR lower leg muscles in patients with BMD and compared these values with those in healthy controls. Quantitative proton MRI (three-point Dixon, multi-spin-echo and diffusion-weighted spin-echo echo planar imaging) and 2D chemical shift imaging ³¹ P MRS data were acquired in 24 patients with BMD (age 18.8-66.2 years) and 13 healthy controls (age 21.3-63.6 years). Muscle fat fractions, phosphorus metabolic indices, and averages and standard deviations (SDs) of the water T₂ relaxation times and diffusion tensor imaging (DTI) parameters were assessed in six individual leg muscles. Phosphodiester levels were increased in the NFR and FR tibialis anterior, FR peroneus and FR gastrocnemius lateralis muscles. No clear pattern was visible for the other metabolic indices. Increased T₂ SD was found in the majority of FR muscles compared with NFR and healthy control muscles. No differences in average water T₂ relaxation times or DTI indices were found between groups. Overall, our results indicate that primarily muscles that are further along in the disease process showed increases in T₂ heterogeneity and changes in some metabolic indices. No clear differences were found for the DTI indices between groups.

Keywords: Becker muscular dystrophy; phosphorus MRS; quantitative MRI; skeletal muscle.

FIGURE 1

Flow diagram describing the exclusion of datasets

FIGURE 2

Multi‐parametric axial images of the lower leg of a patient with BMD: A, first echo of a multi‐SE image with ROIs for the six lower leg muscles—GCM, GCL, SOL, TA, PER and TP; B, reconstructed T ₂ map using the EPG algorithm; C, SE‐EPI images with diffusion weighting (b = 450 s/mm²); D, offline reconstructed water map of the Dixon scan using six‐fat‐peak model; E, scatter dot plots of the mean fat fraction (%fat) with the 95% confidence interval in all patients with BMD for the GCM, GCL, PER, SOL, TA and TP muscles. The cut‐off fat fractions for the individual muscles used to divide the patients with BMD into groups are reported on the graph

FIGURE 3

Scatter dot plots of the MD, FA and the three eigenvalues with the 95% confidence interval in healthy controls (HC), NFR BMD muscles and FR BMD muscles for the TA muscle. Significant differences between groups are indicated with asterisks (*). The other analyzed lower leg muscles showed similar findings

FIGURE 4

Multi‐SE images, reconstructed T ₂ maps using EPG fit, T ₂ maps without pixels with %fat > 50% and error maps of the residual of the EPG fit are shown for the middle slice in a healthy control, a mildly affected patient with BMD and a severely affected patient with BMD. Fat fractions for the individual leg muscles in the mildly/severely affected patient with BMD were as follows: GCL 6.4/51.7%; GCM 7.7/46.9%; SOL 5.3/51.2%; PER 10.2/66.9%; TA 4.8/42.2%; TP 4.5/6.9%. Note the increase in error of the residuals near the arteries

FIGURE 5

Scatter dot plots of the average water T ₂ relaxation times (water T ₂ (ms)) with the 95% confidence interval in healthy controls and NFR BMD muscles and FR BMD muscles for the GCM, GCL, PER, SOL, TA and TP muscles. Significant differences between groups are indicated with an asterisk (*)

FIGURE 6

Scatter dot plots of the SD of the water T ₂ relaxation times (T ₂SD) with the 95% confidence interval in healthy controls and NFR BMD muscles and FR BMD muscles for the GCM, GCL, PER, SOL, TA and TP muscles. Significant differences between groups are indicated with an asterisk (*). Note the lack of change in the TP muscle, which is also the muscle with the lowest increase in %fat (see Figure 2)

FIGURE 7

Representative ³¹P spectrum for a muscle from a healthy control subject, an NFR muscle of a patient with BMD and an FR muscle of a patient with BMD. Note the reduction in SNR in the phosphorus spectrum of the FR BMD muscle. The spectra are scaled according to the PCr peak

FIGURE 8

Mean values ± SDs for P_i/ATP, P_i/PCr, PCr/ATP, PDE/ATP and intracellular tissue pH in healthy control muscles, NFR BMD muscles and FR BMD muscles for each muscle. Significant differences between NFR and FR BMD muscles and controls are marked with an asterisk (*)