{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:29:20Z","timestamp":1786566560057,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41EB017183"],"award-info":[{"award-number":["P41EB017183"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R01EB027075"],"award-info":[{"award-number":["R01EB027075"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Magnetic Resonance Imaging"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Assessment of cerebrovascular reactivity (CVR) has been reported using acetazolamide\u2010augmented blood oxygenation level\u2010dependent (BOLD) MRI; however, wide intersubject baseline variability can complicate interpretation.<\/jats:p>\n <\/jats:sec>\n \n Purpose<\/jats:title>\n \n To develop an\n integrated normalization<\/jats:italic>\n framework combining machine learning\u2010guided identification of healthy voxels for subject\u2010specific baseline rescaling with atlas\u2010based assessment.\n <\/jats:p>\n <\/jats:sec>\n \n Study Type<\/jats:title>\n Retrospective.<\/jats:p>\n <\/jats:sec>\n \n Population<\/jats:title>\n 26 subjects (age 51\u2009\u00b1\u200913 at first scan, 50% women, 34 exams) with unilateral steno\u2010occlusive disease (SOD) and 9 subjects with bilateral disease (age 55\u2009\u00b1\u200912, 4\/9 women) underwent acetazolamide\u2010augmented BOLD\u2010MRI.<\/jats:p>\n <\/jats:sec>\n \n Field Strength\/Sequence<\/jats:title>\n T1\u2010weighted MPRAGE (1\u2009mm isotropic) and gradient\u2010echo EPI at 3\u2009T.<\/jats:p>\n <\/jats:sec>\n \n Assessment<\/jats:title>\n \n Machine learning models (random forest, XGBoost, LightGBM, and neural networks) were trained to identify healthy candidate voxels using a previously reported pipeline based on baseline resting\u2010state BOLD temporal shift features derived from 32 arterial territories. A healthy reference CVR atlas was constructed from unaffected hemispheres. Individual CVR maps were rescaled using predicted healthy voxels and converted to\n Z<\/jats:italic>\n \u2010scores and risk index maps using the reference atlas.\n <\/jats:p>\n <\/jats:sec>\n \n Statistical Tests<\/jats:title>\n \n Coefficient of variation (CV) within normal hemispheres, lesion contrast\u2010to\u2010noise ratio (CNR), Lesion ROC AUC, asymmetry index (AI) in unilateral patients, and chi\u2010square distance between thresholded normal and abnormal CVR distributions across all patients were compared between atlas\u2010based\n group normalization<\/jats:italic>\n alone and the proposed\n integrated normalization<\/jats:italic>\n using paired\n t<\/jats:italic>\n \u2010tests. (cutoff\n p<\/jats:italic>\n \u2009=\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CV within normal hemispheres significantly decreased (1.07\u2009\u00b1\u20090.15 vs. 0.45\u2009\u00b1\u20090.09), indicating improved inter\u2010subject stability. Lesion CNR and ROC AUC improved across all impairment thresholds (CNR: 0.73\u20131.12 vs. 0.79\u20131.19; AUC: 0.76\u20130.89 vs. 0.81\u20130.90). AI increased significantly at higher risk thresholds (\u2265\u20090.78), with no significant difference at the lowest threshold (\n p<\/jats:italic>\n \u2009=\u20090.181). Chi\u2010square analysis demonstrated significantly increased separation between CVR distributions at intermediate thresholds.\n <\/jats:p>\n <\/jats:sec>\n \n Data Conclusion<\/jats:title>\n \n The proposed\n integrated normalization<\/jats:italic>\n improves the stability, discriminability, and interpretability of acetazolamide\u2010augmented BOLD\u2010CVR for detection of cerebrovascular impairment.\n <\/jats:p>\n <\/jats:sec>\n \n Evidence Level<\/jats:title>\n 3.<\/jats:p>\n <\/jats:sec>\n \n Technical Efficacy<\/jats:title>\n Stage 2.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jmri.70388","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:00:37Z","timestamp":1780488037000},"page":"804-812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Data\u2010Driven Normalization Framework for Subject\u2010Specific Cerebrovascular Reactivity Assessment in Cerebrovascular Disease"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3987-6624","authenticated-orcid":false,"given":"Yihui","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Radiology Stanford University School of Medicine Palo Alto California USA"},{"name":"Department of Radiology New York University Grossman School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-7849","authenticated-orcid":false,"given":"Siddhant","family":"Dogra","sequence":"additional","affiliation":[{"name":"Department of Radiology New York University Grossman School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology Weill Cornell Medical College New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Polimeni","sequence":"additional","affiliation":[{"name":"Department of Radiology Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-1094","authenticated-orcid":false,"given":"Seena","family":"Dehkharghani","sequence":"additional","affiliation":[{"name":"Department of Radiology Stanford University School of Medicine Palo Alto California USA"},{"name":"Department of Radiology New York University Grossman School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.24.1.35"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000113732"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.643468"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.11.018"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0730-725X(01)00227-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1538"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyw108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.30481"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.194"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116365"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A9267"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28648"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-020-00821-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.221473"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4973"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27410"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.184"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A8813"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-022-01923-0"},{"key":"e_1_2_8_23_1","unstructured":"B. d B.Frederick T.Salo D. 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