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Here we characterize an automated LC segmentation approach (referred to as the funnel\u2010tip [FT] method) in healthy individuals and individuals with LC degeneration in the context of Alzheimer's disease (AD, confirmed with tau\u2010PET imaging using [18F]MK6240). The first sample included <jats:italic>n<\/jats:italic>\u2009=\u2009190 individuals across the AD spectrum from cognitively normal to moderate AD. LC signal assayed with FT segmentation showed excellent agreement with manual segmentation (intraclass correlation coefficient [ICC]\u2009=\u20090.91). Compared to other methods, the FT method showed numerically higher correlation to AD status (defined by presence of tau: Cohen's <jats:italic>d<\/jats:italic>\u2009=\u20090.64) and AD severity (Braak stage: Pearson <jats:italic>R<\/jats:italic>\u2009=\u2009\u2212.35, cognitive function: <jats:italic>R<\/jats:italic>\u2009=\u2009.25). In a separate sample of <jats:italic>n<\/jats:italic>\u2009=\u200912 control participants, the FT method showed excellent scan\u2013rescan reliability (ICC\u2009=\u20090.82). In another sample of <jats:italic>n<\/jats:italic>\u2009=\u200930 control participants, we found that the structure of the LC defined by FT segmentation approximated its expected shape as a contiguous line: &lt;5% of LC voxels strayed &gt;1 voxel (0.69\u2009mm) from this line. The FT LC segmentation shows high agreement with manual segmentation and captures LC degeneration in AD. This practical method may facilitate larger research studies of the human LC\u2010norepinephrine system and has potential to support future use of neuromelanin\u2010sensitive MRI as a clinical biomarker.<\/jats:p>","DOI":"10.1002\/hbm.26324","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T18:08:32Z","timestamp":1682964512000},"page":"3913-3925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characterization of an automated method to segment the human locus coeruleus"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-6176","authenticated-orcid":false,"given":"Ahmad","family":"Sibahi","sequence":"first","affiliation":[{"name":"Institute of Mental Health Research at the Royal University of Ottawa  Ottawa Ontario 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Chamoun","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging, McGill University  Montreal Quebec Canada"},{"name":"Douglas Research Institute, Le Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux (CIUSSS) de l'Ouest\u2010de\u2010l'\u00cele\u2010de\u2010Montr\u00e9al, McGill University  Montreal Quebec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Quebec Canada"},{"name":"Department of Psychiatry McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krysta","family":"Boutin\u2010Miller","sequence":"additional","affiliation":[{"name":"Institute of Mental Health Research at the Royal University of Ottawa  Ottawa Ontario 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