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We assessed the presence, frequency and pattern of MRI abnormalities in non-dystrophic myotonia patients. We reviewed T1-weighted and STIR (short-tau-inversion-recovery) 3T MRI sequences of lower limb muscles at thigh and calf level in 21 patients with genetically confirmed non-dystrophic myotonia: 11 with CLCN1 mutations and 10 with SCN4A mutations, and 19 healthy volunteers. The MRI examinations of all patients showed hyperintensity within muscles on either T1-weighted or STIR images. Mild extensive or marked T1-weighted changes were noted in 10/21 patients and no volunteers. Muscles in the thigh were equally likely to be affected but in the calf there was sparing of tibialis posterior. Oedema was common in calf musculature especially in the medial gastrocnemius with STIR hyperintensity observed in 18/21 patients. In 10/11 CLCN1 patients this included a previously unreported “central stripe”, also present in 3/10 SCN4A patients but no volunteers. Degree of fatty infiltration correlated with age (rho=0.46, p

Whilst spirometry is the most common test of pulmonary function in Duchenne muscular dystrophy (DMD), cine MRI of diaphragm motion may provide a more direct and sensitive measure of diaphragm dysfunction, especially in a setting of clinical trials. As part of an on-going, natural history study in non-ambulant DMD patients, cine MRI of diaphragm motion is investigated as a potential objective biomarker of disease severity. Cine MRI is acquired during several cycles of deep-breathing in non-ambulant DMD individuals and volunteers. Data taken in the sagittal plane is analysed to assess maximal change during the respiratory cycle in both 1D length measures (anterior, central, posterior, and diaphragm length) and 2D cross-sectional area using a semi-automated segmentation algorithm. Following initial pre-processing of the data, the algorithm uses a connected component analysis to extract an initial lung label, which is subsequently refined with active contouring and morphological operations (such as closing and region filling). The output data is used to assess the sensitivity of MRI as a measure of pulmonary function in DMD, particularly when compared to age, time to loss of ambulation, and the more commonly-used spirometry measures. The acquisition is repeated at 12, 24 and 48 weeks. To date, 16 non-ambulant DMD patients (mean age: 13.7; range 10,17) and 10 age-gender matched volunteers (mean age:14.6 years; range 13–17) have been imaged at baseline, and 9 DMD individuals at 24 months. The protocol was well-tolerated by all the subjects. The analysis of the data is currently on-going. This is the first study to explore the use of cine MRI of diaphragm motion as an outcome measure in clinical trials for non-ambulant DMD.

Outcome measures in Duchenne muscular dystrophy (DMD) currently rely on invasive or functional but not very sensitive tests. Muscle MRI could offer a valuable alternative. A reliable evaluation of the upper limb could permit inclusion of non-ambulant DMD individuals not able to perform functional tests such as the 6-min walk test. 16 DMD boys and 10 age gender and age matched controls were included in this on-going study. Fat–water quantification was used to compare fat-infiltration in the forearm muscles of non-ambulant DMD patients and healthy controls. DMD individuals underwent 3T 3-point Dixon imaging of the dominant forearm to measure muscle fat-fraction (f.f.). Ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. Patients also underwent physiotherapy evaluation: Performance of Upper Limb (PUL) module; wrist extension myometry; and EK2 performance of tasks in daily life interview. Time to loss of ambulation (LOA) was recorded. To date, 8 non-ambulant DMD patients (mean age: 13.6 years; mean duration of non-ambulation 20 months) and 10 volunteers (mean age:14.6 years) have been imaged. Overall mean f.f (±SD) in DMD was significantly higher than healthy controls: (13.4 ± 11% vs 0.8 ± 0.1%, p = 0.002). Total mean area was reduced in DMD (1735 ± 331 mm2) compared to healthy controls (2398 ± 821 mm2, p = 0.04). Overall f.f. correlated with LOA (Spearman r = 0.8, p = 0.02) and wrist extension myometry (r = 0.8, p = 0.004) and less strongly with PUL (r = −0.6, p = 0.09) and with EK2 (r = 0.6, p = 0.09). Final analysis will include longitudinal change at one-year follow up. Initial results support MRI fat quantification as a potential objective biomarker to monitor disease progression in the upper limb in DMD, showing significant correlation between putative MRI pathological indices and clinically meaningful endpoints.

MRI has an established role in aiding diagnosis of neuromuscular diseases1. Quantification of muscle atrophy and fat infiltration is a potential biomarker of disease progression2 but as the end stage pathological process, it won’t show early changes likely to be reversible with intervention. Changes in intra-muscle water distribution represent an earlier, more acute process potentially reversible with therapy.