Quantitative muscle MRI captures early muscle degeneration in calpainopathy

Abstract

To evaluate differences in qMRI parameters of muscle diffusion tensor imaging (mDTI), fat-fraction (FF) and water T2 time in leg muscles of calpainopathy patients (LGMD R1/D4) compared to healthy controls, to correlate those findings to clinical parameters and to evaluate if qMRI parameters show muscle degeneration in not-yet fatty infiltrated muscles. We evaluated eight thigh and seven calf muscles of 19 calpainopathy patients and 19 healthy matched controls. MRI scans were performed on a 3T MRI including a mDTI, T2 mapping and mDixonquant sequence. Clinical assessment was done with manual muscle testing, patient questionnaires (ACTIVLIM, NSS) as well as gait analysis. Average FF was significantly different in all muscles compared to controls (p < 0.001). In muscles with less than 8% FF a significant increase of FA (p < 0.005) and decrease of RD (p < 0.004) was found in high-risk muscles of calpainopathy patients. Water T2 times were increased within the low- and intermediate-risk muscles (p ≤ 0.045) but not in high-risk muscles (p = 0.062). Clinical assessments correlated significantly with qMRI values: QMFM vs. FF: r = - 0.881, p < 0.001; QMFM versus FA: r = - 0.747, p < 0.001; QMFM versus MD: r = 0.942, p < 0.001. A good correlation of FF and diffusion metrics to clinical assessments was found. Diffusion metrics and T2 values are promising candidates to serve as sensitive early and non-invasive methods to capture early muscle degeneration in non-fat-infiltrated muscles in calpainopathies.

Figure 1

Example images of the applied MRI sequences. mDixon fat fraction (FF), fractional anisotropy (FA), mean diffusivity (MD) and T2 maps for thigh and calf muscles of two representative LGMD patients, and a healthy control (HC).

Figure 2

Overview of fat infiltration and mutations in calpainopathy patients. VL vastus lateralis, VM vastus medialis, RF rectus femoris, SM semimembranosus, ST semitendinosus, BF biceps femoris, SAR Sartorius, GR gracilis, GM gastrocnemius medialis, GL gastrocnemius lateralis, SOL soleus, TA tibialis anterior, PER peroneal group, EDL extensor digitorum longus, TP tibialis posterior.

Figure 3

qMRI data in low-fat muscles. Overview of mean fat fractions of all LGMD patients in thigh and calf muscles (a). High-risk muscles are coloured in yellow and orange, intermediate-risk muscles are coloured in green and low-risk muscles are coloured in blue. Muscle groups with significant differences of FA and MD in muscles with FF < 8% and SNR > 10 and T2 in muscle groups with FF < 8% between study groups are coloured in red (b) (increase/decrease in patient group: burgundy / pink).

Figure 4

qMRI data and QMFM correlations. Spearman rank correlation coefficients (r) of qMRI values fat fraction (FF), fractional anisotropy (FA), mean diffusivity (MD), and T2 time of all thigh muscles to Quick Motor Function Measure (QMFM). Regression lines are coloured in red, 95%-confidence intervals are coloured in black.