{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:01:44Z","timestamp":1790449304805,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"APHM: Assistance Publique Hopitaux de Marseille","award":["AORC junior"],"award-info":[{"award-number":["AORC junior"]}]},{"DOI":"10.13039\/501100006510","name":"Association pour la Recherche sur la Scl\u00e9rose Lat\u00e9rale Amyotrophique et autres Maladies du Motoneurone","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006424","name":"F\u00e9d\u00e9ration pour la Recherche sur le Cerveau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006424","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by significant heterogeneity among patients. <jats:sup>23<\/jats:sup>Na MRI maps abnormal sodium homeostasis that reflects metabolic alterations and energetic failure contributing to the neurodegenerative process. In this study, we investigated disease severity at the individual level in ALS patients using brain <jats:sup>23<\/jats:sup>Na MRI.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p><jats:sup>1<\/jats:sup>H and <jats:sup>23<\/jats:sup>Na brain MRI were collected prospectively from 28 ALS patients. Individual map of abnormal total sodium concentration (TSC) was computed using voxel-based statistical mapping for each patient compared to a local database of 62 healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), ALSFRS-R slope, ALSFRS-R at 6-month and survival time.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Individual maps quantifying voxels with TSC increase evidenced a high heterogeneity between patients consistent with clinical presentation. The main areas involved were the corticospinal tracts. Half of patients showed abnormal TSC increase within more than 1% of whole brain voxels. Patients with TSC increase had worse clinical severity: higher ALSFRS-R slope (p = 0.02), lower ALSFRS-R at 6-month (p = 0.04), and shorter survival (p = 0.04). ALS patients with limited TSC increase had slower progression of disability or predominant lower motor neuron phenotype or shorter disease duration.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>This study mapping sodium homeostasis disturbances at the individual level in ALS patients through <jats:sup>23<\/jats:sup>Na MRI evidenced heterogeneity of TSC increase among patients associated with clinical presentation and disease severity. These findings suggest that TSC increase detected at the individual level by <jats:sup>23<\/jats:sup>Na MRI may be a useful marker of the clinical heterogeneity of ALS patients, a factor that is likely to greatly influence the results of therapeutic trials.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0316916","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:26:12Z","timestamp":1737570372000},"page":"e0316916","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["In vivo mapping of sodium homeostasis disturbances in individual ALS patients: A brain 23Na MRI study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-9374","authenticated-orcid":true,"given":"Aude-Marie","family":"Grapperon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Mounir","family":"El Mendili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Maarouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8073-102X","authenticated-orcid":true,"given":"Jean-Philippe","family":"Ranjeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4435-2257","authenticated-orcid":true,"given":"Maxime","family":"Guye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Verschueren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Attarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa","family":"Zaaraoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"pone.0316916.ref001","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(17)31287-4","article-title":"Amyotrophic lateral sclerosis","volume":"390","author":"MA van Es","year":"2017","journal-title":"Lancet"},{"key":"pone.0316916.ref002","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","article-title":"The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III)","volume":"169","author":"JM Cedarbaum","year":"1999","journal-title":"J Neurol Sci"},{"key":"pone.0316916.ref003","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S1474-4422(21)00465-8","article-title":"Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis","volume":"21","author":"SA Goutman","year":"2022","journal-title":"Lancet Neurol"},{"key":"pone.0316916.ref004","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1097\/WCO.0000000000000728","article-title":"Imaging in amyotrophic lateral sclerosis: MRI and PET","volume":"32","author":"J Kassubek","year":"2019","journal-title":"Curr Opin Neurol"},{"key":"pone.0316916.ref005","doi-asserted-by":"crossref","first-page":"784","DOI":"10.3389\/fnins.2018.00784","article-title":"Imaging Biomarkers for the Diagnosis and Prognosis of Neurodegenerative Diseases. The Example of Amyotrophic Lateral Sclerosis","volume":"12","author":"M Maz\u00f3n","year":"2018","journal-title":"Front Neurosci"},{"key":"pone.0316916.ref006","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/14737175.2018.1464912","article-title":"Implications of structural and functional brain changes in amyotrophic lateral sclerosis","volume":"18","author":"T Dharmadasa","year":"2018","journal-title":"Expert Rev Neurother"},{"key":"pone.0316916.ref007","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/14737175.2018.1463160","article-title":"Neuroimaging in amyotrophic lateral sclerosis: current and emerging uses","volume":"18","author":"F Agosta","year":"2018","journal-title":"Expert Rev Neurother"},{"key":"pone.0316916.ref008","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/s41582-023-00891-2","article-title":"Biomarkers in amyotrophic lateral sclerosis: current status and future prospects","volume":"19","author":"R McMackin","year":"2023","journal-title":"Nat Rev Neurol"},{"key":"pone.0316916.ref009","first-page":"1","article-title":"Graph theory network analysis reveals widespread white matter damage in brains of patients with classic ALS","author":"V Rajagopalan","year":"2024","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"pone.0316916.ref010","doi-asserted-by":"crossref","first-page":"e231630","DOI":"10.1148\/radiol.231630","article-title":"The Lateral Corticospinal Tract Sign: An MRI Marker for Amyotrophic Lateral Sclerosis","volume":"312","author":"MJ Wendebourg","year":"2024","journal-title":"Radiology"},{"key":"pone.0316916.ref011","doi-asserted-by":"crossref","first-page":"e209623","DOI":"10.1212\/WNL.0000000000209623","article-title":"Progressive Cerebrocerebellar Uncoupling in Sporadic and Genetic Forms of Amyotrophic Lateral Sclerosis","volume":"103","author":"M Tahedl","year":"2024","journal-title":"Neurology"},{"key":"pone.0316916.ref012","doi-asserted-by":"crossref","first-page":"103633","DOI":"10.1016\/j.nicl.2024.103633","article-title":"Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study","volume":"43","author":"H-P M\u00fcller","year":"2024","journal-title":"Neuroimage Clin"},{"key":"pone.0316916.ref013","doi-asserted-by":"crossref","first-page":"e207946","DOI":"10.1212\/WNL.0000000000207946","article-title":"Structural and Functional Brain Network Connectivity at Different King\u2019s Stages in Patients With Amyotrophic Lateral Sclerosis","volume":"102","author":"EG Spinelli","year":"2024","journal-title":"Neurology"},{"key":"pone.0316916.ref014","doi-asserted-by":"crossref","first-page":"e2552","DOI":"10.1212\/WNL.0000000000010731","article-title":"Structural and functional brain connectome in motor neuron diseases: A multicenter MRI study","volume":"95","author":"S Basaia","year":"2020","journal-title":"Neurology"},{"key":"pone.0316916.ref015","doi-asserted-by":"crossref","first-page":"118968","DOI":"10.1016\/j.neuroimage.2022.118968","article-title":"Modeling seeding and neuroanatomic spread of pathology in amyotrophic lateral sclerosis","volume":"251","author":"S Pandya","year":"2022","journal-title":"Neuroimage"},{"key":"pone.0316916.ref016","doi-asserted-by":"crossref","first-page":"494","DOI":"10.3174\/ajnr.A8154","article-title":"Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis","volume":"45","author":"P Tilsley","year":"2024","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0316916.ref017","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/ana.26488","article-title":"MRI Clustering Reveals Three ALS Subtypes With Unique Neurodegeneration Patterns","volume":"92","author":"HHG Tan","year":"2022","journal-title":"Ann Neurol"},{"key":"pone.0316916.ref018","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.1007\/s00415-022-11081-3","article-title":"Clusters of anatomical disease-burden patterns in ALS: a data-driven approach confirms radiological subtypes","volume":"269","author":"P Bede","year":"2022","journal-title":"J Neurol"},{"key":"pone.0316916.ref019","doi-asserted-by":"crossref","first-page":"fcae222","DOI":"10.1093\/braincomms\/fcae222","article-title":"Different patterns of structural network impairments in two amyotrophic lateral sclerosis subtypes driven by 18F-fluorodeoxyglucose positron emission tomography\/magnetic resonance hybrid imaging","volume":"6","author":"F Feng","year":"2024","journal-title":"Brain Commun"},{"key":"pone.0316916.ref020","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3174\/ajnr.A7823","article-title":"Clinical Profiles and Patterns of Neurodegeneration in Amyotrophic Lateral Sclerosis: A Cluster-Based Approach Based on MR Imaging Metrics","volume":"44","author":"G Milella","year":"2023","journal-title":"AJNR Am J Neuroradiol"},{"key":"pone.0316916.ref021","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/WCO.0000000000001295","article-title":"Pathological insights derived from neuroimaging in amyotrophic lateral sclerosis: emerging clinical applications","volume":"37","author":"S Tu","year":"2024","journal-title":"Curr Opin Neurol"},{"key":"pone.0316916.ref022","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1007\/s00415-020-10368-7","article-title":"Cortical progression patterns in individual ALS patients across multiple timepoints: a mosaic-based approach for clinical use","volume":"268","author":"M Tahedl","year":"2021","journal-title":"J Neurol"},{"key":"pone.0316916.ref023","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/ana.25706","article-title":"Connectome-Based Propagation Model in Amyotrophic Lateral Sclerosis","volume":"87","author":"JM Meier","year":"2020","journal-title":"Ann Neurol"},{"key":"pone.0316916.ref024","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1093\/brain\/awad351","article-title":"Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis","volume":"147","author":"A Northall","year":"2024","journal-title":"Brain"},{"key":"pone.0316916.ref025","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1148\/radiol.2019182276","article-title":"Quantitative Brain Sodium MRI Depicts Corticospinal Impairment in Amyotrophic Lateral Sclerosis","volume":"292","author":"A-M Grapperon","year":"2019","journal-title":"Radiology"},{"key":"pone.0316916.ref026","first-page":"204062232211094","article-title":"Relaxation-weighted 23 Na magnetic resonance imaging maps regional patterns of abnormal sodium concentrations in amyotrophic lateral sclerosis","volume":"13","author":"H-P M\u00fcller","year":"2022","journal-title":"Therapeutic Advances in Chronic Disease"},{"key":"pone.0316916.ref027","doi-asserted-by":"crossref","first-page":"984","DOI":"10.3174\/ajnr.A7559","article-title":"Alterations of Microstructure and Sodium Homeostasis in Fast Amyotrophic Lateral Sclerosis Progressors: A Brain DTI and Sodium MRI Study","volume":"43","author":"MME Mendili","year":"2022","journal-title":"American Journal of Neuroradiology"},{"key":"pone.0316916.ref028","unstructured":"Grapperon A-M, El Mendili MM, Maarouf A, Ranjeva JP, Guye, Verschueren A, et al. In vivo mapping of sodium homeostasis disturbances in individual ALS patients: a brain 23Na MRI study. ISMRM proceedings. Singapore; 2024."},{"key":"pone.0316916.ref029","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1136\/jnnp-2016-314661","article-title":"What does the ALSFRS-R really measure? A longitudinal and survival analysis of functional dimension subscores in amyotrophic lateral sclerosis","volume":"88","author":"J Rooney","year":"2017","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0316916.ref030","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1212\/01.wnl.0000194316.91908.8a","article-title":"Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS","volume":"66","author":"F Kimura","year":"2006","journal-title":"Neurology"},{"key":"pone.0316916.ref031","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1007\/s00415-015-7731-6","article-title":"Predicting prognosis in amyotrophic lateral sclerosis: a simple algorithm","volume":"262","author":"M Elamin","year":"2015","journal-title":"J Neurol"},{"key":"pone.0316916.ref032","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1148\/radiol.12112680","article-title":"Distribution of brain sodium accumulation correlates with disability in multiple sclerosis: a cross-sectional 23Na MR imaging study","volume":"264","author":"W Zaaraoui","year":"2012","journal-title":"Radiology"},{"key":"pone.0316916.ref033","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1109\/TMI.2010.2046908","article-title":"N4ITK: Improved N3 Bias Correction","volume":"29","author":"NJ Tustison","year":"2010","journal-title":"IEEE Trans Med Imaging"},{"key":"pone.0316916.ref034","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/jon.12521","article-title":"Cortical Thickness Estimations of FreeSurfer and the CAT12 Toolbox in Patients with Alzheimer\u2019s Disease and Healthy Controls","volume":"28","author":"R Seiger","year":"2018","journal-title":"J Neuroimaging"},{"key":"pone.0316916.ref035","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1177\/13524585221102587","article-title":"Grey-matter sodium concentration as an individual marker of multiple sclerosis severity","volume":"28","author":"A Maarouf","year":"2022","journal-title":"Mult Scler"},{"key":"pone.0316916.ref036","doi-asserted-by":"crossref","first-page":"e24969","DOI":"10.1371\/journal.pone.0024969","article-title":"Prevalence of Grey Matter Pathology in Early Multiple Sclerosis Assessed by Magnetization Transfer Ratio Imaging","volume":"6","author":"L Crespy","year":"2011","journal-title":"PLoS ONE"},{"key":"pone.0316916.ref037","doi-asserted-by":"crossref","DOI":"10.1016\/j.jns.2021.117584","article-title":"Evaluation and categorisation of individual patients based on white matter profiles: Single-patient diffusion data interpretation in neurodegeneration","volume":"428","author":"M Tahedl","year":"2021","journal-title":"Journal of the Neurological Sciences"},{"key":"pone.0316916.ref038","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s13311-016-0484-9","article-title":"Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis","volume":"14","author":"RAL Menke","year":"2017","journal-title":"Neurotherapeutics"},{"key":"pone.0316916.ref039","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3389\/fneur.2019.00229","article-title":"Tracking a Fast-Moving Disease: Longitudinal Markers, Monitoring, and Clinical Trial Endpoints in ALS","volume":"10","author":"RH Chipika","year":"2019","journal-title":"Front Neurol"},{"key":"pone.0316916.ref040","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3109\/21678421.2015.1051989","article-title":"Mind the gap: the mismatch between clinical and imaging metrics in ALS","volume":"16","author":"attendees of the 4th NiSALS meeting","year":"2015","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"pone.0316916.ref041","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nn.3584","article-title":"State of play in amyotrophic lateral sclerosis genetics","volume":"17","author":"AE Renton","year":"2014","journal-title":"Nat Neurosci"},{"key":"pone.0316916.ref042","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.3389\/fneur.2018.01063","article-title":"Biomarkers for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated With Hexanucleotide Expansion Mutations in C9orf72","volume":"9","author":"MK Floeter","year":"2018","journal-title":"Front Neurol"},{"key":"pone.0316916.ref043","doi-asserted-by":"crossref","first-page":"103505","DOI":"10.1016\/j.nicl.2023.103505","article-title":"Structural and microstructural neuroimaging signature of C9orf72-associated ALS: A multiparametric MRI study","volume":"39","author":"M Wiesenfarth","year":"2023","journal-title":"Neuroimage Clin"},{"key":"pone.0316916.ref044","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1007\/s00415-023-11764-5","article-title":"Presymptomatic grey matter alterations in ALS kindreds: a computational neuroimaging study of asymptomatic C9orf72 and SOD1 mutation carriers","volume":"270","author":"P Bede","year":"2023","journal-title":"J Neurol"},{"key":"pone.0316916.ref045","doi-asserted-by":"crossref","first-page":"103400","DOI":"10.1016\/j.nicl.2023.103400","article-title":"C9orf72 ALS mutation carriers show extensive cortical and subcortical damage compared to matched wild-type ALS patients","volume":"38","author":"A Nigri","year":"2023","journal-title":"Neuroimage Clin"},{"key":"pone.0316916.ref046","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/nbm.3389","article-title":"Imaging of sodium in the brain: a brief review","volume":"29","author":"NJ Shah","year":"2016","journal-title":"NMR Biomed"},{"key":"pone.0316916.ref047","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.3389\/fneur.2021.715618","article-title":"Increased Sodium Concentration in Substantia Nigra in Early Parkinson\u2019s Disease: A Preliminary Study With Ultra-High Field (7T) MRI","volume":"12","author":"S Grimaldi","year":"2021","journal-title":"Frontiers in Neurology"},{"key":"pone.0316916.ref048","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.neuroimage.2012.07.009","article-title":"Increased brain tissue sodium concentration in Huntington\u2019s Disease\u2014A sodium imaging study at 4 T","volume":"63","author":"K Reetz","year":"2012","journal-title":"NeuroImage"},{"key":"pone.0316916.ref049","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10334-013-0396-1","article-title":"Topography of brain sodium accumulation in progressive multiple sclerosis","volume":"27","author":"A Maarouf","year":"2014","journal-title":"Magn Reson Mater Phy"},{"key":"pone.0316916.ref050","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1093\/brain\/awt149","article-title":"Sodium accumulation is associated with disability and a progressive course in multiple sclerosis","volume":"136","author":"D Paling","year":"2013","journal-title":"Brain"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316916","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:26:28Z","timestamp":1737570388000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316916"}},"subtitle":[],"editor":[{"given":"Belgin","family":"Sever","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0316916","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]}}}