{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:12:21Z","timestamp":1790640741269,"version":"4.1.0"},"reference-count":37,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":267,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS112274, U01NS116776, and ZIANS003119"],"award-info":[{"award-number":["R01NS112274, U01NS116776, and ZIANS003119"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Medical Scientist Training Program","award":["T32 GM07170"],"award-info":[{"award-number":["T32 GM07170"]}]},{"name":"NIH Medical Research Scholars Program"},{"DOI":"10.13039\/100000910","name":"Conrad N. 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Existing diagnostic criteria incorporate presence of white matter lesions, but specificity can be improved using MS-specific imaging biomarkers, including paramagnetic rim lesions (PRLs) and central vein sign (CVS). However, manual segmentation of lesions, PRLs, and CVS is time-consuming and subjective. We propose a fully-automated joint segmentation method called Automated Lesion, PRL, and CVS Analysis (ALPaCA). We trained ALPaCA using subject-level cross-validation on 47 adults with MS and 50 adults with radiological MS mimics. ALPaCA uses a voxel-wise lesion segmentation method to propose a large set of lesion candidates. Lesion candidates are input into a multi-contrast, multi-label 3D convolutional neural network as 3D patches to produce lesion, PRL, and CVS predictions. When multiple lesions exist within a patch, an attention mechanism identifies which lesion candidate to classify. At the lesion level, ALPaCA achieves cross-validation areas under the receiver operating characteristic curve (AUROCs) of 0.95, 0.91, and 0.87 for lesion, PRL, and CVS classification, outperforming previous methods (all p &amp;lt; 0.001). Correlations between subject-level ALPaCA lesion and PRL scores with manual counts are higher than those of previous methods (p &amp;lt; 0.001; p = 0.03). Subject-level ALPaCA PRL and CVS scores are highly associated with MS in logistic regressions, when controlling for age and sex (p &amp;lt; 0.001). ALPaCA allows for fully-automated simultaneous segmentation of MS lesions, PRLs, and CVS using clinically-feasible scans. These segmentations outperform existing methods at the lesion and subject level.<\/jats:p>","DOI":"10.1162\/imag.a.932","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T20:01:36Z","timestamp":1758830496000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":4,"title":["Automated segmentation of multiple sclerosis lesions, paramagnetic rims, and central vein sign on MRI provides reliable diagnostic biomarkers"],"prefix":"10.1162","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1081-5038","authenticated-orcid":false,"given":"Fengling","family":"Hu","sequence":"first","affiliation":[{"name":"Penn Statistics in Imaging and Visualization Endeavor (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Penn Statistics in Imaging and Visualization Endeavor (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Penn Statistics in Imaging and Visualization Endeavor (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra M.","family":"Valcarcel","sequence":"additional","affiliation":[{"name":"Penn Statistics in Imaging and Visualization Endeavor (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"},{"name":"Genentech Inc. A Member of the Roche Group, South San Francisco, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Dworkin","sequence":"additional","affiliation":[{"name":"Penn Statistics in Imaging and Visualization Endeavor (PennSIVE), Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Renner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, United States"},{"name":"Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Daboul","sequence":"additional","affiliation":[{"name":"Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National 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Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Bar-Or","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Calabresi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leorah","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Neurology, 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