{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:48:36Z","timestamp":1785160116292,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The choroid plexus (CP), a critical structure for cerebrospinal fluid (CSF) production, has been increasingly recognized for its involvement in Alzheimer\u2019s disease (AD). Accurate segmentation of CP from magnetic resonance imaging (MRI) remains challenging due to its irregular shape, variable MR signal, and proximity to the lateral ventricles. This study aimed to develop and evaluate a region-informed Gaussian Mixture Model (One-GMM) for automatic CP segmentation using anatomical priors derived from FreeSurfer (FS) software and compare it with manual, FS, and one previous GMM-based (Two-GMM) methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>T1-weighted (T1w) and T2-fluid-attenuated inversion recovery (FLAIR) MRI scans were acquired from 38 participants [19 cognitively normal (CN)], 11 with mild cognitive impairment (MCI), and 8 with AD. Manual segmentations served as ground truth. A GMM was applied within an anatomically constrained region combining the lateral ventricles and CP derived from FS reconstruction. The segmentation accuracy was assessed using the dice similarity coefficient (DSC), the 95th percentile Hausdorff distance (HD95), and volume difference percentage (VD%). Results were compared with those from FS and one previous GMM method-based segmentations across diagnostic groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The region-informed One-GMM achieved significantly higher accuracy compared to FS and Two-GMM, with a mean DSC of 0.82\u202f\u00b1\u202f0.05 for One-GMM versus 0.24\u202f\u00b1\u202f0.11 for FS (<jats:italic>p<\/jats:italic>\u202f\u202f&amp;lt;\u202f\u202f0.001), and 0.66\u202f\u00b1\u202f0.10 for Two-GMM (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), lower HD95 (One-GMM: 6.06\u202f\u00b1\u202f10.32\u202fmm vs. FS: 26.21\u202f\u00b1\u202f7.32\u202fmm vs. Two-GMM: 10.58\u202f\u00b1\u202f6.47\u202fmm), and comparable volume difference (One-GMM: 20.97\u202f\u00b1\u202f9.53% vs. FS: 24.32\u202f\u00b1\u202f28.13% vs. Two-GMM: 24.27\u202f\u00b1\u202f22.10, <jats:italic>p<\/jats:italic>\u202f=\u202f0.87). Segmentation accuracy of our proposed method was consistent across all diagnostic groups. Clinical analysis showed that there is no diagnostic group difference in CP volume obtained from manual, FS, Two-GMM, and our proposed One-GMM methods. In the whole cohort, there are also no age and sex effects of CP volume with all methods. Restricting to the CN group, CP volume from both manual (<jats:italic>p<\/jats:italic>\u202f=\u202f0.03), Two-GMM (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.01) and the proposed One-GMM (<jats:italic>p<\/jats:italic>\u202f=\u202f0.05), methods show an aging effect, but not for the FS segmented CP volume (<jats:italic>p<\/jats:italic>\u202f=\u202f0.22).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A region-informed One-GMM method significantly improved CP segmentation accuracy over FS, providing a practical and accessible tool for CP quantification in AD and other research studies. Within this small cohort, no diagnostic group difference in CP volume was observed. An aging effect of CP volume was found within the CN group.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1613320","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T05:37:33Z","timestamp":1753249053000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Region-informed machine learning model for choroid plexus segmentation in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Liangdong","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyuan H.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha A.","family":"Keil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Hani","family":"Hojjati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lissa","family":"Savard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firoza Z.","family":"Lussier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Rosa-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Glodzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mony J.","family":"de Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria C.","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/jmri.28759","article-title":"Current understanding of the anatomy, physiology, and magnetic resonance imaging of Neurofluids: update from the 2022 \u201cISMRM imaging Neurofluids study group\u201d workshop in Rome","volume":"59","author":"Agarwal","year":"2024","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"102926","DOI":"10.1016\/j.nicl.2021.102926","article-title":"Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression","volume":"33","author":"Althubaity","year":"2022","journal-title":"Neuroimage Clin."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e65341","DOI":"10.3791\/65341","article-title":"Manual segmentation of the human choroid plexus using brain MRI","volume":"202","author":"Bannai","year":"2023","journal-title":"J. Vis. Exp."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1177\/13524585241292965","article-title":"Imaging the choroid plexus","volume":"30","author":"Bergsland","year":"2024","journal-title":"Mult. Scler."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"01","DOI":"10.14336\/AD.2023.1226","article-title":"Association of plasma markers of Alzheimer\u2019s disease, neurodegeneration, and neuroinflammation with the choroid plexus integrity in aging","volume":"15","author":"Bouhrara","year":"2024","journal-title":"Aging Dis."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1007\/s00234-013-1290-2","article-title":"Measurement of choroid plexus perfusion using dynamic susceptibility MR imaging: capillary permeability and age-related changes","volume":"55","author":"Bouzerar","year":"2013","journal-title":"Neuroradiology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"776","DOI":"10.3174\/ajnr.A7903","article-title":"Choroid plexus calcification correlates with cortical microglial activation in humans: a multimodal PET, CT, MRI study","volume":"44","author":"Butler","year":"2023","journal-title":"AJNR Am. J. 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Alzheimers Dis."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3537","DOI":"10.1002\/alz.12970","article-title":"Pathogenesis of Alzheimer\u2019s disease: involvement of the choroid plexus","volume":"19","author":"\u010carna","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1148\/radiol.212400","article-title":"Choroid plexus volume and permeability at brain MRI within the Alzheimer disease clinical Spectrum","volume":"304","author":"Choi","year":"2022","journal-title":"Radiology"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1152\/physrev.1971.51.2.273","article-title":"Physiology of the choroid plexus","volume":"51","author":"Cserr","year":"1971","journal-title":"Physiol. 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Blood Flow Metab."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12987-024-00525-9","article-title":"Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan","volume":"21","author":"Eisma","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.neuroimage.2012.01.021","article-title":"FreeSurfer","volume":"62","author":"Fischl","year":"2012","journal-title":"NeuroImage"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3390\/biomedicines10020224","article-title":"Choroid plexus in Alzheimer\u2019s disease\u2014the current state of knowledge","volume":"10","author":"Gi\u00e3o","year":"2022","journal-title":"Biomedicines"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s12987-024-00601-0","article-title":"Association between choroid plexus volume and cognitive function in community-dwelling older adults without dementia: a population-based cross-sectional analysis","volume":"21","author":"Hidaka","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1109\/34.232073","article-title":"Comparing images using the Hausdorff distance","volume":"15","author":"Huttenlocher","year":"1993","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A Paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"552","DOI":"10.14336\/AD.2024.0118","article-title":"Choroid plexus volume, amyloid burden, and cognition in the Alzheimer\u2019s disease continuum","volume":"16","author":"Jeong","year":"2025","journal-title":"Aging Dis."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13195-024-01520-w","article-title":"Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer\u2019s continuum","volume":"16","author":"Jiang","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.neuroimage.2011.06.080","article-title":"A comprehensive testing protocol for MRI neuroanatomical segmentation techniques: evaluation of a novel lateral ventricle segmentation method","volume":"58","author":"Kempton","year":"2011","journal-title":"NeuroImage"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12987-024-00554-4","article-title":"Associations between the choroid plexus and tau in Alzheimer\u2019s disease using an active learning segmentation pipeline","volume":"21","author":"Li","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12987-022-00318-y","article-title":"Decreased CSF clearance and increased brain amyloid in Alzheimer\u2019s disease","volume":"19","author":"Li","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e066276","DOI":"10.1002\/alz.066276","article-title":"Increased apparent blood flow and volume of the choroid plexus in the Alzheimer\u2019s disease patients","volume":"19","author":"Lu","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.neurobiolaging.2024.09.009","article-title":"Modeling the progression of neuropsychiatric symptoms in Alzheimer\u2019s disease with PET-based Braak staging","volume":"144","author":"Macedo","year":"2024","journal-title":"Neurobiol. Aging"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"12818","DOI":"10.1038\/s41598-025-97409-1","article-title":"Divergent neurodegeneration associations with choroid plexus volume and degree of calcification in cognitively normal APOE \u03b54 carriers and non-carriers","volume":"15","author":"Ozsahin","year":"2025","journal-title":"Sci. Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1038\/s41591-021-01456-w","article-title":"Microglial activation and tau propagate jointly across Braak stages","volume":"27","author":"Pascoal","year":"2021","journal-title":"Nat. Med."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/ima.20264","article-title":"The kinetics of 18f-fluorodeoxyglucose uptake in the choroid plexus","volume":"21","author":"Rmeily-Haddad","year":"2011","journal-title":"Int. J. Imaging Syst. Technol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1002\/jmri.28937","article-title":"A fully automatic method to segment choroid plexuses in multiple sclerosis using conventional MRI sequences","volume":"59","author":"Storelli","year":"2024","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s12987-024-00603-y","article-title":"Choroid plexus aging: structural and vascular insights from the HCP-aging dataset","volume":"21","author":"Sun","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3233\/JAD-190706","article-title":"Improving choroid plexus segmentation in the healthy and diseased brain: relevance for tau-PET imaging in dementia","volume":"74","author":"Tadayon","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.neurobiolaging.2020.01.005","article-title":"Choroid plexus volume is associated with levels of CSF proteins: relevance for Alzheimer\u2019s and Parkinson\u2019s disease","volume":"89","author":"Tadayon","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12880-015-0068-x","article-title":"Metrics for evaluating 3D medical image segmentation: analysis, selection, and tool","volume":"15","author":"Taha","year":"2015","journal-title":"BMC Med. Imaging"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1109\/TMI.2010.2046908","article-title":"N4ITK: improved N3 Bias correction","volume":"29","author":"Tustison","year":"2010","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"4946","DOI":"10.1016\/j.cell.2024.07.002","article-title":"The choroid plexus synergizes with immune cells during neuroinflammation","volume":"187","author":"Xu","year":"2024","journal-title":"Cell"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e70239","DOI":"10.1002\/alz.70239","article-title":"Choroid plexus free-water correlates with glymphatic function in Alzheimer\u2019s disease","volume":"21","author":"Xu","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"103368","DOI":"10.1016\/j.nicl.2023.103368","article-title":"Automatic segmentation of the choroid plexuses: method and validation in controls and patients with multiple sclerosis","author":"Yazdan Panah","year":"2023","journal-title":"Neuroimage Clin."},{"key":"ref40","author":"Zhao","year":"2020"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"101164","DOI":"10.1016\/j.neurad.2023.10.009","article-title":"Multimodal assessment of brain fluid clearance is associated with amyloid-beta deposition in humans","volume":"51","author":"Zhou","year":"2024","journal-title":"J. Neuroradiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1002\/alz.13659","article-title":"Parenchymal CSF fraction is a measure of brain glymphatic clearance and positively associated with amyloid beta deposition on PET","volume":"20","author":"Zhou","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/S1076-6332(03)00671-8","article-title":"Statistical validation of image segmentation quality based on a spatial overlap index","volume":"11","author":"Zou","year":"2004","journal-title":"Acad. Radiol."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1613320\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T05:37:34Z","timestamp":1753249054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1613320\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":43,"alternative-id":["10.3389\/fnagi.2025.1613320"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2025.1613320","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]},"article-number":"1613320"}}