{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T12:24:45Z","timestamp":1787142285629,"version":"build-2736575974"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":174,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["737\/2021"],"award-info":[{"award-number":["737\/2021"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["01GI1601I"],"award-info":[{"award-number":["01GI1601I"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["RP-2017-08-ST2-004"],"award-info":[{"award-number":["RP-2017-08-ST2-004"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008721","name":"University College London Hospitals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018942","name":"Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018942","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The study of grey matter (GM) perfusion abnormalities in multiple sclerosis (MS) is gaining increasing interest, thanks to the recent developments in MRI techniques such as arterial spin labelling (ASL). Previous studies in small mixed cohorts have demonstrated reduced perfusion in different GM regions in patients with MS compared with controls, especially in the frontal\/parietal lobes and deep GM. In this multi-centre study, we aimed to investigate the relationship between ASL-perfusion patterns and GM atrophy in a large cohort of MS patients. We hypothesized that GM hypoperfusion is a phenomenon not wholly associated with the presence of structural atrophy. Therefore, we have evaluated whether GM perfusion changes are directly explained by underlying atrophy or occur in the absence of detectable GM tissue loss. Moreover, the relationship between clinical (physical and cognitive) measures and global GM perfusion level was assessed. Conventional structural and pseudo-continuous ASL data were acquired using 3T MRI scanners and a standardized protocol in four European MS centres. We included in the analysis 170 subjects [96 relapsing-remitting MS (RRMS), 41 primary-progressive MS (PPMS) and 33 healthy controls (HC)] that exhibited acceptable data quality and compatible acquisition schemes\/ASL maps. Global and regional cerebral blood flow (CBF) patterns were explored to identify group differences, statistically controlling for \u2018morphometric covariates\u2019 (i.e. total brain volume, cortical thickness or subcortical volume) along with age, sex, disease duration and total T2-lesion load in the analysis of covariance (\u2018basic covariates\u2019). Similarly, partial correlation analyses were performed to assess the association of global CBF with physical (Expanded Disability Status Scale) and cognitive (Symbol Digit Modalities Test) scores. Global GM CBF values were lower in RRMS (64.1 \u00b1 20.9\u2005mL\/100\u2005g\/min) and PPMS (52.9 \u00b1 16.1\u2005mL\/100\u2005g\/min) compared with HC (78.5 \u00b1 21.1\u2005mL\/100\u2005g\/min), with significant differences for both MS types compared with controls using both sets of covariates (pBonf\u22640.05). Moreover, regional perfusion reduction encompassing several cortical and subcortical GM regions were found in patients versus controls, even after the inclusion of the morphometric covariates, while there were no differences in GM perfusion levels between MS phenotypes. In all patients considered together, no significant associations between global GM CBF and physical disability\/cognitive tests scores were found when controlling for the confounding factors. These findings suggest that GM hypoperfusion is at least partially dissociated with atrophy. In this scenario, ASL-based perfusion may be a promising functional paraclinical tool to quantify GM neurovascular impairment in MS, aiding the understanding of the pathological mechanisms.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag225","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:38:13Z","timestamp":1782214693000},"source":"Crossref","is-referenced-by-count":0,"title":["Investigating the association between grey matter hypoperfusion and atrophy in multiple sclerosis using arterial spin labelling"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-3749","authenticated-orcid":false,"given":"Ilaria Boscolo","family":"Galazzo","sequence":"first","affiliation":[{"name":"Department of Engineering for Innovation Medicine, University of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1203-2670","authenticated-orcid":false,"given":"Marco","family":"Castellaro","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, University of Padova , 35131 Padova ,","place":["Italy"]},{"name":"Padova Neuroscience Center, University of Padova , 35131 Padova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Benedetta","family":"Pizzini","sequence":"additional","affiliation":[{"name":"Department of Engineering for Innovation Medicine, University of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-7774","authenticated-orcid":false,"given":"Francesco","family":"Crescenzo","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre-Neurology Unit, \u2018Mater Salutis\u2019 Hospital, Azienda ULSS 9 Scaligera , 37122 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Amann","sequence":"additional","affiliation":[{"name":"Medical Image Analysis Center (MIAC) AG , 4054 Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarmad","family":"Al-Araji","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bellenberg","sequence":"additional","affiliation":[{"name":"Ruhr University Bochum, St. Josef Hospital, Institute of Neuroradiology , 44791 Bochum ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-5818","authenticated-orcid":false,"given":"Alessia","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]},{"name":"Department of Radiology & Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit , 1081 Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]},{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena , 53100 Siena ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-7639","authenticated-orcid":false,"given":"Nicola","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena , 53100 Siena ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Enzinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz , 8036 Graz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Neurology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Vita-Salute San Raffaele University , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Gasperini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, S. Camillo Forlanini, Hospital Rome , 00152 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Granziera","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine, Translational Imaging in Neurology (ThINk) Basel, University Hospital Basel and University of Basel , 4123 Basel ,","place":["Switzerland"]},{"name":"Department of Neurology, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel , 4031 Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine, Translational Imaging in Neurology (ThINk) Basel, University Hospital Basel and University of Basel , 4123 Basel ,","place":["Switzerland"]},{"name":"Department of Neurology, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel , 4031 Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Lukas","sequence":"additional","affiliation":[{"name":"Ruhr University Bochum, St. Josef Hospital, Institute of Neuroradiology , 44791 Bochum ,","place":["Germany"]},{"name":"Ruhr University Bochum, St. Josef Hospital, Department of Neurology , 44791 Bochum ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Menegaz","sequence":"additional","affiliation":[{"name":"Department of Engineering for Innovation Medicine, University of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Palace","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford , OX39DU Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8093-4548","authenticated-orcid":false,"given":"Marco","family":"Pitteri","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]},{"name":"Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, UCLH , WC1N3BG London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-4320","authenticated-orcid":false,"given":"Maria A","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Neurology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Vita-Salute San Raffaele University , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-6750","authenticated-orcid":false,"given":"Alex","family":"Rovira","sequence":"additional","affiliation":[{"name":"Department of Radiology, Section of Neuroradiology, Hospital Universitari Vall d'Hebron, Universitat Aut\u00f2noma de Barcelona , 08035 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1589-2254","authenticated-orcid":false,"given":"Jaume","family":"Sastre-Garriga","sequence":"additional","affiliation":[{"name":"Centre d'Esclerosi M\u00faltiple de Catalunya (Cemcat), Servei de Neurologia, Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron , 08035 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Tamanti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Biomedicine and Movement, The Multiple Sclerosis Center of University Hospital of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Vrenken","sequence":"additional","affiliation":[{"name":"Department of Radiology & Nuclear Medicine, Amsterdam University Medical Center, Vrije Universiteit , 1081 Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-1414","authenticated-orcid":false,"given":"Matthias","family":"Weigel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Medicine, Translational Imaging in Neurology (ThINk) Basel, University Hospital Basel and University of Basel , 4123 Basel ,","place":["Switzerland"]},{"name":"Department of Neurology, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Division of Radiological Physics, Department of Radiology, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios C","family":"Yiannakas","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Yousry","sequence":"additional","affiliation":[{"name":"Neuradiolological Academic Unit, BRR, UCL , WC1N3BG London ,","place":["UK"]},{"name":"Lysholm Department of Neuroradiology, UCLH , WC1N3GB London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-1367","authenticated-orcid":false,"given":"Olga","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Faculty of Brain Sciences, Queen Square MS Centre, UCL Queen Square Institute of Neurology, University College London , WC1N3BG London ,","place":["UK"]},{"name":"National Institute for Health Research (NIHR), UCLH Biomedical Research Centre , NW12DA London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Biomedicine and Movement, The Multiple Sclerosis Center of University Hospital of Verona , 37134 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"issue":"2","key":"2026081907311500900_fcag225-B1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N Engl J Med."},{"key":"2026081907311500900_fcag225-B2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/brain\/awy088","article-title":"Progression of regional grey matter atrophy in multiple 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oxime","volume":"33","author":"Lycke","year":"1993","journal-title":"Eur Neurol"},{"key":"2026081907311500900_fcag225-B6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/brain\/awh007","article-title":"Changes in cerebral perfusion precede plaque formation in multiple sclerosis: A longitudinal perfusion MRI study","volume":"127","author":"Wuerfel","year":"2004","journal-title":"Brain"},{"key":"2026081907311500900_fcag225-B7","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1093\/brain\/awab029","article-title":"Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis","volume":"144","author":"Granziera","year":"2021","journal-title":"Brain"},{"key":"2026081907311500900_fcag225-B8","doi-asserted-by":"crossref","first-page":"994","DOI":"10.3174\/ajnr.A5504","article-title":"What have we learned from perfusion MRI in multiple sclerosis?","volume":"39","author":"Lapointe","year":"2018","journal-title":"AJNR Am J 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Evidence for a multifactorial approach to assess neurodegeneration","volume":"15","author":"Lagana","year":"2018","journal-title":"Curr Neurovasc Res"},{"key":"2026081907311500900_fcag225-B27","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fneur.2018.00305","article-title":"Cerebral blood flow changes in multiple sclerosis and neuromyelitis optica and their correlations with clinical disability","volume":"9","author":"Zhang","year":"2018","journal-title":"Front Neurol"},{"key":"2026081907311500900_fcag225-B28","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1111\/ene.15289","article-title":"Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function","volume":"29","author":"Testud","year":"2022","journal-title":"Eur J 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