{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:38:15Z","timestamp":1791837495734,"version":"4.3.4"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Annette Funicello Research Fund for Neurological Diseases and internal resources of the Buffalo Neuroimaging Analysis Centre"},{"name":"Jacquemin Family Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) was originally proposed to quantify glymphatic functioning. Although a direct interpretation is now questioned, cross-sectional studies show associations with disability in people with multiple sclerosis (pwMS). Regardless, serial DTI-ALPS studies are largely lacking in MS. In a longitudinal study, we investigated DTI-ALPS with respect to confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) in people with relapsing-remitting MS (pwRRMS) and progressive MS (pwPMS). This study included 72 pwRRMS, 27 pwPMS, and 23 healthy controls (HC) imaged with 3T MRI and again after 5 years. The DTI-ALPS index was calculated using an automated pipeline using template-defined regions of interest (ROIs) in the superior longitudinal fasciculus and superior corona radiata. Areas corresponding to T2 hyperintensities were removed to avoid the influence of overt pathology. CDP and PIRA were assessed after 5 years and in 64 pwRRMS\/17 pwPMS after 10 years. Comparisons between those with and without follow-up CDP or PIRA were assessed using analysis of covariance and repeated including normal appearing white matter (NAWM) mean diffusivity (MD) as an additional covariate. Multivariable binary logistic regression was used to explore whether DTI-ALPS offers independent value beyond general disease burden. Although significantly lower in pwMS compared with HCs (1.347 \u00b1 0.178 versus 1.437 \u00b1 0.132, P = 0.034, partial \u03b72 = 0.021), the difference was no longer so after controlling for NAWM MD (P = 0.094, partial \u03b72 = 0.024). DTI-ALPS decreases over 5 years were similar between HC and pwMS (P = 0.188, partial \u03b72 = 0.021). In pwRRMS, baseline DTI-ALPS was lower in those who developed CDP or PIRA at 5- and 10 years of follow-up (all P \u2264 0.019, partial \u03b72 &amp;gt; 0.080, except for PIRA at 5 years, P = 0.051, partial \u03b72 = 0.055). When controlling for NAWM MD, results were in line with original findings. Baseline T2-LV was the only retained imaging predictor of CDP and PIRA over 5 years while only baseline DTI-ALPS was selected for in 10 year models. No associations were found in the pwPMS group. Changes in DTI-ALPS over 5 years did not relate to CDP nor PIRA in neither group. In conclusion, although DTI-ALPS values were not significantly different compared with HCs after considering NAWM MD, decreased baseline DTI-ALPS is associated with disability progression in pwRRMS. The lack of associations in pwPMS suggests that DTI-ALPS may be less informative with more advanced disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag002","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:47:00Z","timestamp":1767790020000},"source":"Crossref","is-referenced-by-count":6,"title":["Diffusion tensor imaging along the perivascular space and disease progression in people with multiple sclerosis: a 5-year longitudinal MRI study"],"prefix":"10.1093","volume":"8","author":[{"given":"Ashley","family":"Tranquille","sequence":"first","affiliation":[{"name":"Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zivadinov","sequence":"additional","affiliation":[{"name":"Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York , Buffalo, NY 14203 ,","place":["USA"]},{"name":"Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Weinstock-Guttman","sequence":"additional","affiliation":[{"name":"Department of Neurology, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana P","family":"Eckert","sequence":"additional","affiliation":[{"name":"Department of Neurology, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hojnacki","sequence":"additional","affiliation":[{"name":"Department of Neurology, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-4658","authenticated-orcid":false,"given":"Michael G","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7792-0433","authenticated-orcid":false,"given":"Niels","family":"Bergsland","sequence":"additional","affiliation":[{"name":"Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York , Buffalo, NY 14203 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"9","key":"2026012106164665000_fcag002-B1","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1007\/s11604-022-01275-0","article-title":"Diffusion-weighted image analysis along the perivascular space (DWI-ALPS) for evaluating interstitial fluid status: Age dependence in normal subjects","volume":"40","author":"Taoka","year":"2022","journal-title":"Jpn J Radiol"},{"issue":"5","key":"2026012106164665000_fcag002-B2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1177\/1073858417691030","article-title":"The glymphatic pathway: Waste removal from the CNS via cerebrospinal fluid transport","volume":"23","author":"Benveniste","year":"2017","journal-title":"Neuroscientist"},{"issue":"3","key":"2026012106164665000_fcag002-B3","doi-asserted-by":"crossref","first-page":"268","DOI":"10.2463\/mrms.rev.2023-0175","article-title":"Diffusion tensor image analysis ALong the perivascular space (DTI-ALPS): Revisiting the meaning and significance of the method","volume":"23","author":"Taoka","year":"2024","journal-title":"Magn Reson Med Sci"},{"issue":"2","key":"2026012106164665000_fcag002-B4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00234-023-03270-2","article-title":"Glymphatic imaging: A critical look at the DTI-ALPS index","volume":"66","author":"Ringstad","year":"2024","journal-title":"Neuroradiology"},{"issue":"4","key":"2026012106164665000_fcag002-B5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","article-title":"Evaluation of glymphatic system activity with the diffusion MR technique: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases","volume":"35","author":"Taoka","year":"2017","journal-title":"Jpn J Radiol"},{"key":"2026012106164665000_fcag002-B6","doi-asserted-by":"crossref","first-page":"105767","DOI":"10.1016\/j.parkreldis.2023.105767","article-title":"Glymphatic function assessment in Parkinson's disease using diffusion tensor image analysis along the perivascular space","volume":"114","author":"Bae","year":"2023","journal-title":"Parkinsonism Relat Disord"},{"issue":"12","key":"2026012106164665000_fcag002-B7","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1093\/brain\/awae288","article-title":"Longitudinal analysis of glymphatic function in amyotrophic lateral sclerosis and primary lateral sclerosis","volume":"147","author":"Sharkey","year":"2024","journal-title":"Brain"},{"issue":"8","key":"2026012106164665000_fcag002-B8","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1093\/brain\/awab454","article-title":"Glymphatic system impairment in multiple sclerosis: Relation with brain damage and disability","volume":"145","author":"Carotenuto","year":"2022","journal-title":"Brain"},{"key":"2026012106164665000_fcag002-B9","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1177\/13524585241280842","article-title":"Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability","volume":"30","author":"Bayoumi","year":"2024","journal-title":"Mult Scler"},{"issue":"5","key":"2026012106164665000_fcag002-B10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/ana.25463","article-title":"Silent progression in disease activity-free relapsing multiple sclerosis","volume":"85","author":"University of California SFMSET","year":"2019","journal-title":"Ann Neurol"},{"issue":"10422","key":"2026012106164665000_fcag002-B11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"issue":"7","key":"2026012106164665000_fcag002-B12","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1001\/jamaneurol.2022.1025","article-title":"Association of brain atrophy with disease progression independent of relapse activity in patients with relapsing multiple sclerosis","volume":"79","author":"Cagol","year":"2022","journal-title":"JAMA Neurol"},{"issue":"5","key":"2026012106164665000_fcag002-B13","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/ana.22521","article-title":"Multiple sclerosis normal-appearing white matter: Pathology-imaging correlations","volume":"70","author":"Moll","year":"2011","journal-title":"Ann Neurol"},{"issue":"14","key":"2026012106164665000_fcag002-B14","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1177\/1352458515576985","article-title":"Corticospinal tract integrity is related to primary motor cortex thinning in relapsing-remitting multiple sclerosis","volume":"21","author":"Bergsland","year":"2015","journal-title":"Mult Scler"},{"issue":"1","key":"2026012106164665000_fcag002-B15","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/ene.13769","article-title":"Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: A 5-year longitudinal study","volume":"26","author":"Jakimovski","year":"2019","journal-title":"Eur J Neurol"},{"issue":"11","key":"2026012106164665000_fcag002-B16","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology"},{"key":"2026012106164665000_fcag002-B17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1177\/13524585241229956","article-title":"Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years","volume":"20","author":"Reeves","year":"2024;","journal-title":"Mult Scler."},{"issue":"7","key":"2026012106164665000_fcag002-B18","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1177\/1352458517709619","article-title":"Greater sensitivity to multiple sclerosis disability worsening and progression events using a roving versus a fixed reference value in a prospective cohort study","volume":"24","author":"Kappos","year":"2018","journal-title":"Mult Scler"},{"issue":"9","key":"2026012106164665000_fcag002-B19","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"},{"issue":"7","key":"2026012106164665000_fcag002-B20","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1212\/WNL.57.7.1239","article-title":"Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS","volume":"57","author":"Zivadinov","year":"2001","journal-title":"Neurology"},{"issue":"12","key":"2026012106164665000_fcag002-B21","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1002\/hbm.21402","article-title":"The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis","volume":"33","author":"Gelineau-Morel","year":"2012","journal-title":"Hum Brain Mapp"},{"issue":"1","key":"2026012106164665000_fcag002-B22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1006\/nimg.2002.1040","article-title":"Accurate, robust, and automated longitudinal and cross-sectional brain change analysis","volume":"17","author":"Smith","year":"2002","journal-title":"Neuroimage"},{"issue":"4","key":"2026012106164665000_fcag002-B23","first-page":"1885","article-title":"Cross-vendor test-retest validation of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating glymphatic system function","volume":"15","author":"Liu","year":"2024","journal-title":"Aging Dis"},{"key":"2026012106164665000_fcag002-B24","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.mri.2019.05.008","article-title":"Synthesized b0 for diffusion distortion correction (Synb0-DisCo)","volume":"64","author":"Schilling","year":"2019","journal-title":"Magn Reson Imaging"},{"issue":"2","key":"2026012106164665000_fcag002-B25","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S1053-8119(03)00336-7","article-title":"How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging","volume":"20","author":"Andersson","year":"2003","journal-title":"Neuroimage"},{"key":"2026012106164665000_fcag002-B26","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.neuroimage.2015.10.019","article-title":"An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging","volume":"125","author":"Andersson","year":"2016","journal-title":"Neuroimage"},{"issue":"3","key":"2026012106164665000_fcag002-B27","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.neuroimage.2008.12.037","article-title":"Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration","volume":"46","author":"Klein","year":"2009","journal-title":"Neuroimage"},{"issue":"8","key":"2026012106164665000_fcag002-B28","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1212\/WNL.52.8.1626","article-title":"Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis","volume":"52","author":"Werring","year":"1999","journal-title":"Neurology"},{"issue":"3","key":"2026012106164665000_fcag002-B29","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1148\/radiol.2021203784","article-title":"Contrast-enhanced MRI T1 mapping for quantitative evaluation of putative dynamic glymphatic activity in the human brain in sleep-wake states","volume":"300","author":"Lee","year":"2021","journal-title":"Radiology"},{"key":"2026012106164665000_fcag002-B30","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.neuroimage.2018.12.026","article-title":"Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: An aquaporin-4 study","volume":"188","author":"Ohene","year":"2019","journal-title":"Neuroimage"},{"issue":"1","key":"2026012106164665000_fcag002-B31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12987-023-00415-6","article-title":"Usefulness of intravoxel incoherent motion MRI for visualizing slow cerebrospinal fluid motion","volume":"20","author":"Yamada","year":"2023","journal-title":"Fluids Barriers CNS"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcag002\/66312735\/fcag002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/1\/fcag002\/66312735\/fcag002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/1\/fcag002\/66312735\/fcag002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:19:05Z","timestamp":1768994345000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcag002\/8417525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,2]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcag002","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"fcag002"}}