Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.

<h4>Background and objectives</h4>Limb-girdle muscular dystrophy R9 (LGMD-R9) is a rare neuromuscular disease with no curative treatment. Sensitive non-invasive biomarkers are necessary to monitor disease progression and evaluate the efficacy of novel therapies. Here, we investigated sev...

Full description

Saved in:
Bibliographic Details
Main Authors: Susanne S Rauh, Pierre-Yves Baudin, Tanya Stojkovic, Simone Birnbaum, Valérie Decostre, Rachida-Lydie Zanfongnon, Yves Fromes, Melissa T Hooijmans, Gustav J Strijkers, Jean-Yves Hogrel, Sophie Olivier, Benjamin Marty, Harmen Reyngoudt
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0321463
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849315581965107200
author Susanne S Rauh
Pierre-Yves Baudin
Tanya Stojkovic
Simone Birnbaum
Valérie Decostre
Rachida-Lydie Zanfongnon
Yves Fromes
Melissa T Hooijmans
Gustav J Strijkers
Jean-Yves Hogrel
Sophie Olivier
Benjamin Marty
Harmen Reyngoudt
author_facet Susanne S Rauh
Pierre-Yves Baudin
Tanya Stojkovic
Simone Birnbaum
Valérie Decostre
Rachida-Lydie Zanfongnon
Yves Fromes
Melissa T Hooijmans
Gustav J Strijkers
Jean-Yves Hogrel
Sophie Olivier
Benjamin Marty
Harmen Reyngoudt
author_sort Susanne S Rauh
collection DOAJ
description <h4>Background and objectives</h4>Limb-girdle muscular dystrophy R9 (LGMD-R9) is a rare neuromuscular disease with no curative treatment. Sensitive non-invasive biomarkers are necessary to monitor disease progression and evaluate the efficacy of novel therapies. Here, we investigated several quantitative MRI parameters as suitable biomarkers for evaluating disease progression in LGMD-R9.<h4>Methods</h4>Bilateral quantitative MRI of the lower limbs was performed in individuals with LGMD-R9 and healthy controls. Quantitative thigh and leg muscle MRI, functional tests (including time-up-and-go (TUG) and time-to-climb-4-stairs (4S climb)), and muscle strength tests were performed in individuals with LGMD-R9 at baseline, 1-year, and 2-years. qMRI included assessment of muscle fat fraction (FF), water T2, water T1, intramuscular pH from 1H MR spectroscopy, and diffusion tensor imaging (DTI) parameters. Differences between LGMD-R9 and controls, over time, and the relationship between baseline water T1 and water T2 parameters and disease progression (FF, functional and strength parameters) were assessed by linear mixed models and correlation analyses.<h4>Results</h4>18 individuals with LGMD-R9 and 13 controls were enrolled. At baseline, elevated FF, water T2, water T1, and pH were observed in LGMD-R9 (p < 0.05). No differences between controls and LGMD-R9 were found in the DTI parameters. An overall tendency to an increase in FF and a decrease in functional measures were observed over 2 years. However, the changes did not reach significance (p = 0.057-0.752). Baseline water T1 and baseline water T2 correlated with the increase in FF (ΔFF) and change in TUG (ΔTUG) and 4S climb (Δ4S climb) over 2 years (correlation coefficient ≥  0.6, p < 0.05). No correlation with the strength measures was found.<h4>Conclusion</h4>Our findings suggest that FF, water T2, water T1, and pH are effective biomarkers for LGMD-R9. The correlation of water T2 and water T1 with ΔFF, ΔTUG, and Δ4S climb suggests their potential in predicting disease progression.
format Article
id doaj-art-25b5051f94264aba9d8f2e6b532a95df
institution Kabale University
issn 1932-6203
language English
publishDate 2025-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-25b5051f94264aba9d8f2e6b532a95df2025-08-20T03:52:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01204e032146310.1371/journal.pone.0321463Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.Susanne S RauhPierre-Yves BaudinTanya StojkovicSimone BirnbaumValérie DecostreRachida-Lydie ZanfongnonYves FromesMelissa T HooijmansGustav J StrijkersJean-Yves HogrelSophie OlivierBenjamin MartyHarmen Reyngoudt<h4>Background and objectives</h4>Limb-girdle muscular dystrophy R9 (LGMD-R9) is a rare neuromuscular disease with no curative treatment. Sensitive non-invasive biomarkers are necessary to monitor disease progression and evaluate the efficacy of novel therapies. Here, we investigated several quantitative MRI parameters as suitable biomarkers for evaluating disease progression in LGMD-R9.<h4>Methods</h4>Bilateral quantitative MRI of the lower limbs was performed in individuals with LGMD-R9 and healthy controls. Quantitative thigh and leg muscle MRI, functional tests (including time-up-and-go (TUG) and time-to-climb-4-stairs (4S climb)), and muscle strength tests were performed in individuals with LGMD-R9 at baseline, 1-year, and 2-years. qMRI included assessment of muscle fat fraction (FF), water T2, water T1, intramuscular pH from 1H MR spectroscopy, and diffusion tensor imaging (DTI) parameters. Differences between LGMD-R9 and controls, over time, and the relationship between baseline water T1 and water T2 parameters and disease progression (FF, functional and strength parameters) were assessed by linear mixed models and correlation analyses.<h4>Results</h4>18 individuals with LGMD-R9 and 13 controls were enrolled. At baseline, elevated FF, water T2, water T1, and pH were observed in LGMD-R9 (p < 0.05). No differences between controls and LGMD-R9 were found in the DTI parameters. An overall tendency to an increase in FF and a decrease in functional measures were observed over 2 years. However, the changes did not reach significance (p = 0.057-0.752). Baseline water T1 and baseline water T2 correlated with the increase in FF (ΔFF) and change in TUG (ΔTUG) and 4S climb (Δ4S climb) over 2 years (correlation coefficient ≥  0.6, p < 0.05). No correlation with the strength measures was found.<h4>Conclusion</h4>Our findings suggest that FF, water T2, water T1, and pH are effective biomarkers for LGMD-R9. The correlation of water T2 and water T1 with ΔFF, ΔTUG, and Δ4S climb suggests their potential in predicting disease progression.https://doi.org/10.1371/journal.pone.0321463
spellingShingle Susanne S Rauh
Pierre-Yves Baudin
Tanya Stojkovic
Simone Birnbaum
Valérie Decostre
Rachida-Lydie Zanfongnon
Yves Fromes
Melissa T Hooijmans
Gustav J Strijkers
Jean-Yves Hogrel
Sophie Olivier
Benjamin Marty
Harmen Reyngoudt
Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.
PLoS ONE
title Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.
title_full Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.
title_fullStr Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.
title_full_unstemmed Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.
title_short Multi-parametric quantitative MRI of the lower limb muscles in a longitudinal study of limb-girdle muscular dystrophy R9.
title_sort multi parametric quantitative mri of the lower limb muscles in a longitudinal study of limb girdle muscular dystrophy r9
url https://doi.org/10.1371/journal.pone.0321463
work_keys_str_mv AT susannesrauh multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT pierreyvesbaudin multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT tanyastojkovic multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT simonebirnbaum multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT valeriedecostre multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT rachidalydiezanfongnon multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT yvesfromes multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT melissathooijmans multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT gustavjstrijkers multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT jeanyveshogrel multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT sophieolivier multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT benjaminmarty multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9
AT harmenreyngoudt multiparametricquantitativemriofthelowerlimbmusclesinalongitudinalstudyoflimbgirdlemusculardystrophyr9