{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:41:50Z","timestamp":1790725310641,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Foundation grant #159910"],"award-info":[{"award-number":["Foundation grant #159910"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u201082744"],"award-info":[{"award-number":["MOP\u201082744"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009663","name":"University Health Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015150","name":"St. Michael's Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006127","name":"Queen's University Faculty of Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006127","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014405","name":"Centre for Addiction and Mental Health Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    White matter hyperintensities (WMHs) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI\u2010based segmentation methods are often sensitive to acquisition protocols, scanners, noise\u2010level, and image contrast, failing to generalize to other populations and out\u2010of\u2010distribution datasets. Given these concerns, we propose a novel Bayesian 3D convolutional neural network with a U\u2010Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control, and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. Four hundred thirty\u2010two subjects were recruited to train the CNNs from four multisite imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multisite study. We compared our model to two established state\u2010of\u2010the\u2010art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U\u2010Net achieved the highest Dice similarity coefficient of 0.89\u2009\u00b1\u20090.08 and the lowest modified Hausdorff distance of 2.98\u2009\u00b1\u20094.40\u2009mm. We further validated our models highlighting their robustness on \u201cclinical adversarial cases\u201d simulating data with low signal\u2010to\u2010noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/hypermapp3r.readthedocs.io\/\">https:\/\/hypermapp3r.readthedocs.io<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/hbm.25784","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T05:35:16Z","timestamp":1643348116000},"page":"2089-2108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation"],"prefix":"10.1002","volume":"43","author":[{"given":"Parisa","family":"Mojiri Forooshani","sequence":"first","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Biparva","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel E.","family":"Ntiri","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndon","family":"Boone","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa F.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Adamo","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miracle","family":"Ozzoude","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J. M.","family":"Scott","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dar","family":"Dowlatshahi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Ottawa Brain and Mind Institute, The Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane M.","family":"Lawrence\u2010Dewar","sequence":"additional","affiliation":[{"name":"Thunder Bay Regional Health Research Institute  Thunder Bay Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Health York University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[{"name":"The Edmond J. Safra Program in Parkinson's Disease Toronto Western Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Marcotte","sequence":"additional","affiliation":[{"name":"School of Speech Pathology and Audiology University of Montreal  Montreal Quebec Canada"},{"name":"Centre int\u00e9gr\u00e9\u2002universitaire de sant\u00e9\u2002et de services sociaux du Nord\u2010de\u2010l\u2019\u00eele\u2010de\u2010Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Leonard","sequence":"additional","affiliation":[{"name":"Audiology and Speech\u2010Language Pathology Program, School of Rehabilitation Sciences University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Speech\u2010Language Pathology and the Rehabilitation Sciences Institute University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Rochon","sequence":"additional","affiliation":[{"name":"Department of Speech\u2010Language Pathology and the Rehabilitation Sciences Institute University of Toronto  Toronto Ontario Canada"},{"name":"KITE Research Institute, Toronto Rehab, University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Heyn","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Department of Medical Imaging University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bartha","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Strother","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics Rotman Research Institute, Baycrest, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Claude","family":"Tardif","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute, University of Montreal  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Symons","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology Division) Sunnybrook HSC and University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Swartz","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology Division) Sunnybrook HSC and University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Moody","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Black","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"},{"name":"Department of Medicine (Neurology Division) Sunnybrook HSC and University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5880-0818","authenticated-orcid":false,"given":"Maged","family":"Goubran","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Research Program Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"},{"name":"Heart and Stroke Foundation, Canadian Partnership for Stroke Recovery  Toronto Ontario Canada"},{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1613","volume-title":"Proceedings of the 32nd international conference on machine learning","author":"Blundell C.","year":"2015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.284"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-46723-8_49"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23894"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c3666"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2016.415"},{"key":"e_1_2_9_8_1","first-page":"1050","article-title":"Dropout as a Bayesian approximation: Representing model uncertainty in deep learning","volume":"48","author":"Gal Y.","year":"2016","journal-title":"Proceedings of the 33rd International Conference on Machine Learning"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24811"},{"key":"e_1_2_9_10_1","first-page":"2348","volume-title":"Advances in neural information processing systems","author":"Graves A.","year":"2011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.07.018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910340618"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.12.022"},{"key":"e_1_2_9_14_1","first-page":"770","article-title":"Deep residual learning for image recognition","author":"He K.","year":"2016","journal-title":"Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.124651"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2005.070193"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2019.105065"},{"key":"e_1_2_9_18_1","first-page":"448","article-title":"Batch normalization: Accelerating deep network training by reducing internal covariate shift","volume":"37","author":"Ioffe S.","year":"2015","journal-title":"ICML'15: Proceedings of the 32nd International Conference on International Conference on Machine Learning"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ima.20277"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.026170"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2016.10.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlx009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.5244\/c.31.57"},{"key":"e_1_2_9_24_1","first-page":"5574","volume-title":"Advances in neural information processing systems 30","author":"Kendall A.","year":"2017"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.041286"},{"key":"e_1_2_9_26_1","volume-title":"The 3rd International Conference for Learning Representations","author":"Kingma D. P.","year":"2015"},{"key":"e_1_2_9_27_1","volume-title":"31st Conference on Neural Information Processing Systems","author":"Lakshminarayanan B.","year":"2017"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14539"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24647"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e3181d71a13"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.07.005"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000456710"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1109\/3DV.2016.79"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2019.00083"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-0745-0"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12021-021-09510-1"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-00928-1_56"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspl.1895.0041"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.10"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.09.013"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3791\/50887"},{"key":"e_1_2_9_42_1","article-title":"Evaluating the impact of intensity normalization on MR image synthesis","author":"Reinhold J. C.","year":"2019","journal-title":"Proceedings of SPIE\u2010\u2010the International Society for Optical Engineering"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24574-4_28"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1109\/WACV.2018.00093"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2007.23"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116056"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.06.029"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2010.2046908"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3612"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neucom.2019.01.103"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.02.034"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.114.001140"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1109\/access.2019.2948476"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-014-1322-6"},{"key":"e_1_2_9_55_1","article-title":"Multi\u2010scale context aggregation by dilated convolutions","author":"Yu F.","year":"2016","journal-title":"CoRR"},{"key":"e_1_2_9_56_1","article-title":"Brain atlas guided attention U\u2010net for white matter Hyperintensity segmentation","author":"Zhang Z.","year":"2020","journal-title":"ArXiv"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcp.2018.04.018"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25784","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hbm.25784","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25784","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T14:10:50Z","timestamp":1692972650000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.25784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":56,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/hbm.25784"],"URL":"https:\/\/doi.org\/10.1002\/hbm.25784","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.18.456666","asserted-by":"object"}]},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"value":"1065-9471","type":"print"},{"value":"1097-0193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]},"assertion":[{"value":"2021-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}