Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na-MRI in Dysferlinopathy and Healthy Controls

Abstract

Background

Dysferlin plays a key role in cell membrane repair; its absence or malfunction in patients with dysferlin-deficient limb girdle muscular dystrophy leads to muscle fibre death. Muscle magnetic resonance (MR) imaging allows non-invasive and repeatable measurements that can report on pathological changes observed in dysferlinopathy patients (DP). We aimed to demonstrate the feasibility of utilising volume-localised ²³Na spectroscopy as a novel approach to characterise muscle Na⁺ content and biexponential T₂* at rest, and dynamically post-exercise, in patients with dysferlinopathy and in matched healthy controls.

Methods

Adult DP and age and sex matched healthy volunteers (HV) were recruited and scanned on a 3 T clinical MR scanner. Following baseline scans, participants performed physiotherapist-guided isometric dorsiflexion contractions until tibialis anterior (TA) muscle exhaustion. Dynamic volume-localised sodium-23 (²³Na)- and proton (¹H)-MR scans were acquired serially for 35 min post-exercise. MR data were analysed to determine TA lipid content, change in TA sodium content, biexponential sodium T₂* properties and TA water ¹H T₂.

Results

Ten DP (mean age ± standard deviation [SD]: 38.0 ± 10.8 years; 80% female) and 10 HV (mean age ± SD: 38.9 ± 11.5 years) were scanned. Baseline muscle water ¹H T₂ and sodium concentration were significantly higher in DP compared to matched controls (¹H T_{2 DP} [SD] = 33.8 [2.7] ms, ¹H T_{2 HV} = 29.3 [1.1] ms, p < 0.001; [²³Na]_DP = 36.2 [11.4] mM, [²³Na]_HV = 19.6 [3.1] mM, p < 0.001). ¹H T₂ and sodium content in healthy controls showed significant post-exercise elevation with a slower time-to-peak for sodium content compared to ¹H T₂. ¹H T₂ and sodium content change post-exercise was highly variable in the DP group. Notably, ²³Na dynamics in one DP with normal muscle fat fraction were similar to HV. Biexponential ²³Na T₂* was measured at baseline in HV (T₂*_slow = 13.4 [2.3] ms, T₂*_fast = 2.2 [1.3] ms), and DP (T₂*_slow = 14.0 [1.5] ms and T₂*_fast = 1.0 [0.5] m). Equivalent measurements post-exercise revealed an increase in the fraction of the slow-relaxing component in HV (p < 0.05), consistent with oedematous changes.

Conclusions

Assessment of TA muscle fat fraction, ¹H T₂, sodium content and sodium T₂* relaxation properties revealed differences at baseline and in post-exercise dynamics between patients with dysferlinopathy and matched controls. Post-exercise ²³Na recovery dynamics followed a well-defined time course in HV. Heterogeneous alterations in sodium content and MR relaxation properties in DP may reflect altered ion homeostasis associated with chronic muscle damage.