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Thirty\u2010two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n RR selection and RR type impact CL the most, particularly in amyloid\u2010negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below\u00a0\u00b1\u00a03.95 CL for amyloid beta positivity cutoffs (CL\u00a0<\u00a024).<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n We developed a framework for evaluating Centiloid (CL) variability to different factors.<\/jats:p>\n <\/jats:list-item>\n \n Reference region selection and delineation had the highest impact on CL values.<\/jats:p>\n <\/jats:list-item>\n \n Whole cerebellum (WCB) and whole cerebellum plus brainstem (WCB+BSTM) as reference regions yielded consistent results across tracers.<\/jats:p>\n <\/jats:list-item>\n \n The standard CL pipeline is robust against atrophy and image resolution variation.<\/jats:p>\n <\/jats:list-item>\n \n Estimated within\u2010 and between\u2010pipeline variability (95% confidence interval) in absolute CL units.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.13883","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T03:48:50Z","timestamp":1720064930000},"page":"5102-5113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-6768","authenticated-orcid":false,"given":"Mahnaz","family":"Shekari","sequence":"first","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center (BBRC) Pasqual Maragall Foundation Barcelona Spain"},{"name":"IMIM (Hospital del Mar Medical Research Institute) Barcelona Spain"},{"name":"Universitat Pompeu Fabra Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3308-3167","authenticated-orcid":false,"given":"David","family":"V\u00e1llez Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6263-1762","authenticated-orcid":false,"given":"Lyduine E.","family":"Collij","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam Netherlands"},{"name":"Clinical Memory Research Unit Clinical Sciences Malm\u00f6 Lund University Malm\u00f6 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8419-6423","authenticated-orcid":false,"given":"Hugh","family":"Pemberton","sequence":"additional","affiliation":[{"name":"GE Healthcare Life Sciences Amersham UK"},{"name":"Institute of Neurology and Centre for Medical Image Computing University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Ro\u00e9 Vellv\u00e9","sequence":"additional","affiliation":[{"name":"Life Molecular Imaging GmbH Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Bullich","sequence":"additional","affiliation":[{"name":"Life Molecular Imaging GmbH Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Buckley","sequence":"additional","affiliation":[{"name":"GE Healthcare Life Sciences Amersham 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