Operationalising the Centiloid Scale for [18F]florbetapir PET Studies on PET/MR

Purpose The Centiloid scale provides a systematic means of harmonising amyloid-β PET measures across different acquisition and processing methodologies. This work explores the Centiloid transformation of [18F]florbetapir PET data acquired on a combined PET/MR scanner and processed with methods that differ from the standard Centiloid pipeline. Methods The Standard PiB and Florbetapir Calibration datasets were processed using a standardised uptake value ratio (SUVR) pipeline with MRI parcellations from the Geodesic Information Flow (GIF) algorithm in native PET space. We generated SUVRs using whole cerebellum (GIF_WCSUVR) and eroded white matter (GIF_WMSUVR) reference regions, with and without partial volume correction (PVC). Linear regression was used to calibrate these processing pipelines to the standard Centiloid approach. We then applied the resulting transformation to 432 florbetapir scans from the Insight 46 study of mostly cognitively normal individuals aged ∼70 years, and defined Centiloid cutpoints for amyloid-β positivity using Gaussian-mixture modelling. Results GIF-based SUVR processing pipelines were suitable for conversion according to Centiloid criteria. For GIF_WCSUVR, cutpoints translated to 14.2 Centiloids, or 11.8 with PVC. There was a differential relationship between florbetapir uptake in WM and WC regions in Florbetapir Calibration and Insight 46 datasets, causing implausibly low Centiloid values for GIF_WMSUVR. Linear adjustment to account for this difference resulted in Centiloid cutpoints of 18.1 for GIF_WMSUVR (17.0 with PVC). Conclusion Our results show florbetapir SUVRs acquired on PET/MR scanners can be reliably converted to Centiloids. Acquisition or biological factors can have large effects on Centiloid values from different datasets, we propose a correction to account for these effects. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is principally funded by grants from Alzheimer's Research UK (ARUK-PG2014-1946, ARUK-PG2017-1946), the Medical Research Council Dementias Platform UK (CSUB19166), and the Wolfson Foundation (PR/ylr/18575). Florbetapir amyloid tracer is provided by AVID Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), which had no part in the design, conduct, analysis of the study. The National Survey of Health and Development is funded by the Medical Research Council (MC\_UU\_12019/1, MC\_UU\_12019/3).AK was supported by a Wolfson Clinical Research Fellowship and a Weston Brain Institute and Selfridges Group Foundation award (UB17005). TDP was supported by a Wellcome Trust Clinical Research Fellowship (200109/Z/15/Z). The NSHD, MR and AW are funded by the Medical Research Council (MC\_UU\_00019/1, MC\_UU\_00019/3, and additionally MC\_UU\_12019/3 for MR). NCF is supported by UK Dementia Research Institute at University College London, Medical Research Council, National Institute for Health Research (Senior Investigator award), and Engineering and Physical Sciences Research Council. JMS is supported by University College London Hospitals Biomedical Research Centre, Engineering and Physical Sciences Research Council (EP/J020990/1), British Heart Foundation (PG/17/90/33415), and EU Horizon 2020 research and innovation programme (666992). NCF and JMS are supported by the National Institute for Health Research Queen Square Dementia Biomedical Research Unit and the Leonard Wolfson Experimental Neurology Centre. NCF research group has received payment for consultancy or for conducting studies from Biogen, Eli Lilly Research Laboratories, GE Healthcare, and Roche. NCF receives no personal compensation for the aforementioned activities. JMS has received research funding from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly), has consulted for Roche Pharmaceuticals, Biogen, Merck, and Eli Lilly, given educational lectures sponsored by GE Healthcare, Eli Lilly, and Biogen, and serves on a Data Safety Monitoring Committee for Axon Neuroscience SE. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted by the National Research Ethics Service (NRES) Committee London (REC reference 14/LO/1173). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data and scripts in the present study are available upon reasonable request to the authors or from publicly available datasets.