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 o...

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Main Authors: Mary A. Neal, Carla F. Bolano‐Diaz, Mark Richardson, Jassi Michell‐Sodhi, Robert Muni‐Lofra, Meredith K. James, Kieren G. Hollingsworth, Heather Hilsden, Ian Wilson, Andrew M. Blamire, Volker Straub, Peter E. Thelwall, Jordi Diaz‐Manera
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Journal of Cachexia, Sarcopenia and Muscle
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Online Access:https://doi.org/10.1002/jcsm.13709
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author Mary A. Neal
Carla F. Bolano‐Diaz
Mark Richardson
Jassi Michell‐Sodhi
Robert Muni‐Lofra
Meredith K. James
Kieren G. Hollingsworth
Heather Hilsden
Ian Wilson
Andrew M. Blamire
Volker Straub
Peter E. Thelwall
Jordi Diaz‐Manera
author_facet Mary A. Neal
Carla F. Bolano‐Diaz
Mark Richardson
Jassi Michell‐Sodhi
Robert Muni‐Lofra
Meredith K. James
Kieren G. Hollingsworth
Heather Hilsden
Ian Wilson
Andrew M. Blamire
Volker Straub
Peter E. Thelwall
Jordi Diaz‐Manera
author_sort Mary A. Neal
collection DOAJ
description 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 T2 DP [SD] = 33.8 [2.7] ms, 1H T2 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.
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spelling doaj-art-e5dd1bceb36d443fa685bbec5528cb4c2025-08-20T02:57:35ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-02-01161n/an/a10.1002/jcsm.13709Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy ControlsMary A. Neal0Carla F. Bolano‐Diaz1Mark Richardson2Jassi Michell‐Sodhi3Robert Muni‐Lofra4Meredith K. James5Kieren G. Hollingsworth6Heather Hilsden7Ian Wilson8Andrew M. Blamire9Volker Straub10Peter E. Thelwall11Jordi Diaz‐Manera12Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKTranslational and Clinical Research Institute Newcastle University Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKTranslational and Clinical Research Institute Newcastle University Newcastle upon Tyne UKTranslational and Clinical Research Institute Newcastle University Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKTranslational and Clinical Research Institute Newcastle University Newcastle upon Tyne UKThe John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne UKABSTRACT 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 T2 DP [SD] = 33.8 [2.7] ms, 1H T2 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.https://doi.org/10.1002/jcsm.13709biomarkersdysferlinopathyimagingmuscle MRImuscular dystrophysodium MRI
spellingShingle Mary A. Neal
Carla F. Bolano‐Diaz
Mark Richardson
Jassi Michell‐Sodhi
Robert Muni‐Lofra
Meredith K. James
Kieren G. Hollingsworth
Heather Hilsden
Ian Wilson
Andrew M. Blamire
Volker Straub
Peter E. Thelwall
Jordi Diaz‐Manera
Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy Controls
Journal of Cachexia, Sarcopenia and Muscle
biomarkers
dysferlinopathy
imaging
muscle MRI
muscular dystrophy
sodium MRI
title Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy Controls
title_full Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy Controls
title_fullStr Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy Controls
title_full_unstemmed Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy Controls
title_short Rapid Quantitative Assessment of Muscle Sodium Dynamics After Exercise Using 23Na‐MRI in Dysferlinopathy and Healthy Controls
title_sort rapid quantitative assessment of muscle sodium dynamics after exercise using 23na mri in dysferlinopathy and healthy controls
topic biomarkers
dysferlinopathy
imaging
muscle MRI
muscular dystrophy
sodium MRI
url https://doi.org/10.1002/jcsm.13709
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