{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:33:35Z","timestamp":1774935215049,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01NS099527"],"award-info":[{"award-number":["5R01NS099527"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["(RF)-2019-12370447"],"award-info":[{"award-number":["(RF)-2019-12370447"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sodium MRI can measure in vivo sodium concentrations in people with multiple sclerosis, but the extent to which these alterations reflect metabolic dysfunction in the absence of tissue damage or neuroaxonal loss remains uncertain. Increases in total sodium concentration and extracellular sodium concentration are believed to be indicative of tissue disruption and extracellular space expansion. Conversely, increase in intracellular sodium concentration may represent early and transient responses to neuronal insult, preceding overt tissue damage. Here, we explored the relationship between total sodium concentration, intracellular sodium concentration and intracellular sodium volume fraction, which reflects extracellular sodium concentration, against histology-validated microstructural metrics obtained using diffusion MRI. Fifty-two individuals with multiple sclerosis and 26 healthy controls underwent 1H\/23Na MRI. Microstructural parameters were derived using Diffusion Basis Spectrum Imaging and Neurite Orientation Dispersion and Density-Imaging models. A progressive worsening in total sodium concentration and intracellular sodium volume fraction was observed from HCs white matter to normal-appearing white matter and further into T2-hyperintense and T1-hypointense lesions. Both total sodium concentration and intracellular sodium volume fraction, but not intracellular sodium concentration, correlated with Neurite Orientation Dispersion and Density Imaging and Diffusion Basis Spectrum Imaging metrics within multiple sclerosis lesions. Our findings confirm the utility of total sodium concentration and extracellular sodium concentration as indicators of extracellular expansion and axonal loss and underscore intracellular sodium concentration as a valuable biomarker for metabolic dysfunction in multiple sclerosis.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae446","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T15:43:20Z","timestamp":1736178200000},"source":"Crossref","is-referenced-by-count":1,"title":["Relationship between sodium and diffusion MRI metrics in multiple sclerosis"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0304-0529","authenticated-orcid":false,"given":"Emilio","family":"Cipriano","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa , 16132 Genoa ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Boffa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa , 16132 Genoa ,","place":["Italy"]},{"name":"Department of Neurology, IRCCS Ospedale Policlinico San Martino , 16132 Genoa ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Graziano","sequence":"additional","affiliation":[{"name":"The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1825-8155","authenticated-orcid":false,"given":"Claire","family":"Wigley","sequence":"additional","affiliation":[{"name":"The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-2769","authenticated-orcid":false,"given":"Maria","family":"Petracca","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University of Rome , 00185 Rome ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Schiavi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa , 16132 Genoa ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Luigi","family":"Mancardi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa , 16132 Genoa ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Klineova","sequence":"additional","affiliation":[{"name":"The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Boada","sequence":"additional","affiliation":[{"name":"Radiological Sciences Laboratory, School of Medicine, Stanford University , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-0475","authenticated-orcid":false,"given":"Fred","family":"Lublin","sequence":"additional","affiliation":[{"name":"The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa , 16132 Genoa ,","place":["Italy"]},{"name":"Department of Neurology, IRCCS Ospedale Policlinico San Martino , 16132 Genoa ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lazar","family":"Fleysher","sequence":"additional","affiliation":[{"name":"Department of Radiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"issue":"10422","key":"2025010615275690600_fcae446-B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple 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imaging","volume":"4","author":"Madelin","year":"2014","journal-title":"Sci Rep"},{"issue":"3","key":"2025010615275690600_fcae446-B5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/ncpneuro0735","article-title":"Mechanisms of disease: Sodium channels and neuroprotection in multiple sclerosis\u2014Current status","volume":"4","author":"Waxman","year":"2008","journal-title":"Nat Clin Pract Neurol"},{"key":"2025010615275690600_fcae446-B6","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3389\/fneur.2019.00084","article-title":"Potential of sodium MRI as a biomarker for neurodegeneration and neuroinflammation in multiple sclerosis","volume":"10","author":"Huhn","year":"2019","journal-title":"Front Neurol"},{"issue":"7","key":"2025010615275690600_fcae446-B7","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/jnnp-2018-319634","article-title":"Cortical grey matter sodium accumulation is associated with disability and secondary progressive disease course in relapse-onset multiple sclerosis","volume":"90","author":"Brownlee","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"2025010615275690600_fcae446-B8","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/jmri.27201","article-title":"Sodium in the relapsing\u2013remitting multiple sclerosis spinal cord: Increased concentrations and associations with microstructural tissue anisotropy","volume":"52","author":"Solanky","year":"2020","journal-title":"J Magn Reson Imaging"},{"issue":"1","key":"2025010615275690600_fcae446-B9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/jmri.27832","article-title":"Longitudinal sodium MRI of multiple sclerosis lesions: Is there added value of sodium inversion recovery MRI","volume":"55","author":"Mennecke","year":"2022","journal-title":"J Magn Reson 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