{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:23:44Z","timestamp":1791433424480,"version":"4.3.3"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23NS126718"],"award-info":[{"award-number":["K23NS126718"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Program of the National Institute of Neurological Disorders and Stroke"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Paramagnetic rim lesions (PRLs) are an emerging biomarker for multiple sclerosis representing chronic, low-grade intraparenchymal brain inflammation. In addition to associating with greater disease severity, PRLs may be diagnostically supportive. Our aim in this study was to determine PRL specificity and sensitivity for discriminating multiple sclerosis from its diagnostic mimics using real-world clinical diagnostic and imaging data. This is a retrospective, cross-sectional analysis of a longitudinal cohort of patients with prospectively collected observational data. Patients were included if they underwent clinical evaluation in our academic neuroimmunology centre and had an available MRI scan from the same clinical 3-T magnet that included a T2*-weighted sequence with susceptibility post-processing (Susceptibility Weighted ANgiography protocol, General Electric). Susceptibility imaging-derived filtered phase maps and corresponding T2-fluid attenuated inversion recovery images were manually reviewed to determine PRLs. PRLs were categorized as \u2018definite\u2019, \u2018probable\u2019 or \u2018possible\u2019 based on modified, recent consensus criteria. We hypothesized that PRLs would convey a high specificity to discriminate multiple sclerosis from its MRI mimics. Five hundred seventy-four patients were evaluated in total: 473 with multiple sclerosis, 53 with non-inflammatory neurological disease and 48 with other inflammatory neurological disease. Identification of \u2018definite\u2019 or \u2018probable\u2019 PRL provided a specificity of 98% to discriminate multiple sclerosis from non-inflammatory neurological disease and other inflammatory neurological disease; sensitivity was 36%. Interrater agreement was almost perfect for definite\/probable identification at a subject level. PRLs convey high specificity for multiple sclerosis and can aid in the diagnostic evaluation. Modest sensitivity limits their use as single diagnostic indicators. Including lesions with lower confidence (\u2018possible\u2019) rapidly erodes specificity and should be interpreted with caution given the potential harms associated with misdiagnosis.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf211","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:43:40Z","timestamp":1748504620000},"source":"Crossref","is-referenced-by-count":11,"title":["Paramagnetic rim lesions are highly specific for multiple sclerosis in real-world data"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2408-4638","authenticated-orcid":false,"given":"Christopher C","family":"Hemond","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Massachusetts Memorial Medical Center, University of Massachusetts Chan Medical School , Worcester, MA 01655 ,","place":["USA"]},{"name":"Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish K","family":"Dundamadappa","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Massachusetts Memorial Medical Center, University of Massachusetts Chan Medical School , Worcester, MA 01655 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mugdha","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Massachusetts Memorial Medical Center, University of Massachusetts Chan Medical School , Worcester, MA 01655 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonggyu","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School , Worcester, MA 01655 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Robert H","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Massachusetts Memorial Medical Center, University of Massachusetts Chan Medical School , Worcester, MA 01655 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ionete","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Massachusetts Memorial Medical Center, University of Massachusetts Chan Medical School , Worcester, MA 01655 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2628-4334","authenticated-orcid":false,"given":"Daniel S","family":"Reich","sequence":"additional","affiliation":[{"name":"Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"2","key":"2025061005265564800_fcaf211-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"},{"issue":"1","key":"2025061005265564800_fcaf211-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ncl.2023.07.001","article-title":"Multiple sclerosis diagnostic delay and misdiagnosis","volume":"42","author":"Kaisey","year":"2024","journal-title":"Neurol Clin"},{"issue":"5","key":"2025061005265564800_fcaf211-B3","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/ana.25877","article-title":"Paramagnetic rim lesions are specific to multiple sclerosis: An international multicenter 3T MRI study","volume":"88","author":"Maggi","year":"2020","journal-title":"Ann Neurol"},{"issue":"14","key":"2025061005265564800_fcaf211-B4","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1177\/13524585221118677","article-title":"Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis","volume":"28","author":"Meaton","year":"2022","journal-title":"Mult Scler J"},{"issue":"12","key":"2025061005265564800_fcaf211-B5","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1001\/jamaneurol.2019.2399","article-title":"Association of chronic active multiple sclerosis lesions with disability in vivo","volume":"76","author":"Absinta","year":"2019","journal-title":"JAMA Neurol"},{"issue":"3","key":"2025061005265564800_fcaf211-B6","doi-asserted-by":"crossref","first-page":"fcab134","DOI":"10.1093\/braincomms\/fcab134","article-title":"Cortical and phase rim lesions on 7 T MRI as markers of multiple sclerosis disease progression","volume":"3","author":"Treaba","year":"2021","journal-title":"Brain Commun"},{"issue":"4\u20135","key":"2025061005265564800_fcaf211-B7","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":"30","author":"Reeves","year":"2024","journal-title":"Mult Scler J"},{"key":"2025061005265564800_fcaf211-B8","doi-asserted-by":"crossref","first-page":"104968","DOI":"10.1016\/j.msard.2023.104968","article-title":"Reliability of paramagnetic rim lesion classification on quantitative susceptibility mapping (QSM) in people with multiple sclerosis: Single-site experience and systematic review","volume":"79","author":"Reeves","year":"2023","journal-title":"Mult Scler Relat Disord"},{"issue":"9","key":"2025061005265564800_fcaf211-B9","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1093\/brain\/awae013","article-title":"Imaging chronic active lesions in multiple sclerosis: A consensus statement","volume":"147","author":"Bagnato","year":"2024","journal-title":"Brain"},{"issue":"7","key":"2025061005265564800_fcaf211-B10","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1212\/01.WNL.0000156155.19270.F8","article-title":"Multiple sclerosis severity score: Using disability and disease duration to rate disease severity","volume":"64","author":"Roxburgh","year":"2005","journal-title":"Neurology"},{"issue":"14","key":"2025061005265564800_fcaf211-B11","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1177\/1352458517690618","article-title":"Age related multiple sclerosis severity score: Disability ranked by age","volume":"23","author":"Manouchehrinia","year":"2017","journal-title":"Mult Scler J"},{"issue":"2","key":"2025061005265564800_fcaf211-B12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"issue":"8","key":"2025061005265564800_fcaf211-B13","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.1093\/brain\/awad073","article-title":"The radiologically isolated syndrome: Revised diagnostic criteria","volume":"146","author":"Lebrun-Fr\u00e9nay","year":"2023","journal-title":"Brain"},{"key":"2025061005265564800_fcaf211-B14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jneumeth.2016.03.001","article-title":"The first step for neuroimaging data analysis: DICOM to NIfTI conversion","volume":"264","author":"Li","year":"2016","journal-title":"J Neurosci Methods"},{"issue":"3","key":"2025061005265564800_fcaf211-B15","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuroimage.2006.01.015","article-title":"User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability","volume":"31","author":"Yushkevich","year":"2006","journal-title":"NeuroImage"},{"key":"2025061005265564800_fcaf211-B16","doi-asserted-by":"crossref","first-page":"101849","DOI":"10.1016\/j.nicl.2019.101849","article-title":"Automated segmentation of changes in FLAIR-hyperintense white matter lesions in multiple sclerosis on serial magnetic resonance imaging","volume":"23","author":"Schmidt","year":"2019","journal-title":"NeuroImage Clin"},{"key":"2025061005265564800_fcaf211-B17","doi-asserted-by":"crossref","first-page":"103611","DOI":"10.1016\/j.nicl.2024.103611","article-title":"LST-AI: A deep learning ensemble for accurate MS lesion segmentation","volume":"42","author":"Wiltgen","year":"2024","journal-title":"NeuroImage Clin"},{"issue":"43","key":"2025061005265564800_fcaf211-B18","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J Open Source Softw"},{"key":"2025061005265564800_fcaf211-B19","author":"Kuhn"},{"key":"2025061005265564800_fcaf211-B20","author":"Gamer"},{"issue":"4","key":"2025061005265564800_fcaf211-B21","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00401-018-1818-y","article-title":"Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: A retrospective autopsy cohort analysis","volume":"135","author":"Luchetti","year":"2018","journal-title":"Acta Neuropathol."},{"issue":"7878","key":"2025061005265564800_fcaf211-B22","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s41586-021-03892-7","article-title":"A lymphocyte\u2013microglia\u2013astrocyte axis in chronic active multiple sclerosis","volume":"597","author":"Absinta","year":"2021","journal-title":"Nature"},{"issue":"6","key":"2025061005265564800_fcaf211-B23","first-page":"987","article-title":"Quantitative susceptibility mapping of time-dependent susceptibility changes in multiple sclerosis lesions","volume":"40","author":"Zhang","year":"2019","journal-title":"AJNR Am J Neuroradiol"},{"issue":"12","key":"2025061005265564800_fcaf211-B24","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1002\/acn3.52220","article-title":"Clinical relevance of paramagnetic rim lesion heterogeneity in multiple sclerosis","volume":"11","author":"St\u00f6lting","year":"2024","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"2025061005265564800_fcaf211-B25","doi-asserted-by":"crossref","first-page":"120","DOI":"10.2214\/AJR.21.26777","article-title":"Paramagnetic rim lesions in multiple sclerosis: Comparison of visualization at 1.5-T and 3-T MRI","volume":"219","author":"Hemond","year":"2022","journal-title":"AJR Am J Roentgenol"},{"issue":"2","key":"2025061005265564800_fcaf211-B26","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/acn3.52256","article-title":"Brain lesion characteristics in Chinese multiple sclerosis patients: A 7-T MRI cohort study","volume":"12","author":"Su","year":"2025","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"2025061005265564800_fcaf211-B27","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/jmri.23603","article-title":"Iron deposition in multiple sclerosis lesions measured by susceptibility-weighted imaging filtered phase: A case control study","volume":"36","author":"Hagemeier","year":"2012","journal-title":"J Magn Reson Imaging"},{"issue":"4","key":"2025061005265564800_fcaf211-B28","doi-asserted-by":"crossref","first-page":"e200253","DOI":"10.1212\/NXI.0000000000200253","article-title":"Central vein sign, cortical lesions, and paramagnetic rim lesions for the diagnostic and prognostic workup of multiple sclerosis","volume":"11","author":"Borrelli","year":"2024","journal-title":"Neurol Neuroimmunol Neuroinflammation"},{"issue":"11","key":"2025061005265564800_fcaf211-B29","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1177\/1352458512441270","article-title":"Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis","volume":"18","author":"Wuerfel","year":"2012","journal-title":"Mult Scler J"},{"key":"2025061005265564800_fcaf211-B30","doi-asserted-by":"crossref","first-page":"102412","DOI":"10.1016\/j.nicl.2020.102412","article-title":"RimNet: A deep 3D multimodal MRI architecture for paramagnetic rim lesion assessment in multiple sclerosis","volume":"28","author":"Barquero","year":"2020","journal-title":"NeuroImage Clin"},{"key":"2025061005265564800_fcaf211-B31","doi-asserted-by":"crossref","first-page":"103205","DOI":"10.1016\/j.nicl.2022.103205","article-title":"Cortical lesions, central vein sign, and paramagnetic rim lesions in multiple sclerosis: Emerging machine learning techniques and future avenues","volume":"36","author":"La Rosa","year":"2022","journal-title":"NeuroImage Clin"},{"key":"2025061005265564800_fcaf211-B32","doi-asserted-by":"crossref","first-page":"102796","DOI":"10.1016\/j.nicl.2021.102796","article-title":"Fully automated detection of paramagnetic rims in multiple sclerosis lesions on 3T susceptibility-based MR imaging","volume":"32","author":"Lou","year":"2021","journal-title":"NeuroImage Clin"},{"issue":"12","key":"2025061005265564800_fcaf211-B33","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrneurol.2016.166","article-title":"The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: A consensus statement from the North American Imaging in Multiple Sclerosis Cooperative","volume":"12","author":"Sati","year":"2016","journal-title":"Nat Rev Neurol"},{"issue":"7","key":"2025061005265564800_fcaf211-B34","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1093\/brain\/awz144","article-title":"Assessment of lesions on magnetic resonance imaging in multiple sclerosis: Practical guidelines","volume":"142","author":"Filippi","year":"2019","journal-title":"Brain"},{"issue":"3","key":"2025061005265564800_fcaf211-B35","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/13524585221141964","article-title":"Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis","volume":"29","author":"Calvi","year":"2023","journal-title":"Mult Scler J"},{"issue":"6","key":"2025061005265564800_fcaf211-B36","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1177\/13524585231162262","article-title":"Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis","volume":"29","author":"Elliott","year":"2023","journal-title":"Mult Scler J"},{"issue":"1","key":"2025061005265564800_fcaf211-B37","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/brain\/awy296","article-title":"Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions","volume":"142","author":"Kaunzner","year":"2019","journal-title":"Brain"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcaf211\/63400417\/fcaf211.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/3\/fcaf211\/63400417\/fcaf211.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/3\/fcaf211\/63400417\/fcaf211.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T05:27:07Z","timestamp":1749533227000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaf211\/8152946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaf211","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.08.14.24312000","asserted-by":"object"}]},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"fcaf211"}}