CenTauR: Towards a Universal Scale and Masks for Standardizing Tau Imaging Studies

INTRODUCTION Recently, an increasing number of tau tracers have become available. There is a need to standardize quantitative tau measures across tracers, supporting a universal scale. We developed several cortical tau masks and applied them to generate a tau imaging universal scale. METHOD 1045 participants underwent tau scans with either 18F-Flortaucipir, 18F-MK6240, 18F-PI2620, 18F-PM-PBB3, 18F-GTP1 or 18F-RO948. The mask was generated from cognitively unimpaired Aβ-subjects and AD patients with Aβ+. Four additional regional cortical masks were defined within the constraints of the global mask. A universal scale, the CenTauRz, was constructed. RESULTS None of the regions known to display off-target signal were included in the masks. The CenTauRz allows robustly discrimination between low and high levels of tau deposits. DISCUSSION We constructed several tau-specific cortical masks[*][1] for the AD continuum and a universal standard scale designed to capture the location and degree of abnormality that can be applied across tracers and across centres. Research in Context 1. Systematic review: The authors reviewed the literature using traditional (e.g., PubMed) sources and meeting abstracts and presentations. While the use of tau PET imaging rapidly increased in research and in clinical trials over the past few years, there is no standardization pipeline for the quantification of tau imaging across tau tracers and quantification software. 2. Interpretation: We built a global and several regional universal masks for the sampling of tau PET scans based on the most commonly used tau PET tracers. We then derived a universal scale across tracers, the CenTauRz, to measure the tau signal. 3. Future directions: Standardised quantification will facilitate the derivation of universal cut-off values, merging of large cohorts, and comparison of longitudinal changes across tracers and cohorts both in clinical studies and therapeutic trials. ### Competing Interest Statement Victor Villemagne has received research grants from NHMRC (GNT2001320), the Aging Mind Foundation (DAF2255207) and NIH 2P01AG025204-16) and is and has been a consultant or paid speaker at sponsored conference sessions for Eli Lilly, Life Molecular Imaging, ACE Barcelona, and IXICO. Sandra Sanabria Bohorquez and Robby Weimer are a full-time employee and stock owner of Roche. Santiago Bullich and Andrew Stephen are full-time employee of Life Molecular Imaging GmbH. Hitoshi Shimada and Makoto Higuchi hold patents on compounds related to the present report (JP 5422782/EP 12 884 742.3/CA2894994/HK1208672). Christopher C. Rowe has received research grants from NHMRC, Enigma Australia, Biogen, Eisai and Abbvie. He is on the scientific advisory board for Cerveau Technologies and consulted for Prothena, Eisai, Roche and Biogen Australia. Oskar Hansson has acquired research support (for the institution) from ADx, AVID Radiopharmaceuticals, Biogen, Eli Lilly, Eisai, Fujirebio, GE Healthcare, Pfizer, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Amylyx, Alzpath, BioArctic, Biogen, Cerveau, Eisai, Eli Lilly, Fujirebio, Genentech, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Siemens. The other authors did not report any conflict of interest. ### Funding Statement The research was supported by the Australian Federal Government through NHMRC grants APP1132604, APP1140853 and APP1152623 and by a grant from Enigma Australia. ### 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: Austin Health Human Research Ethics Committee gave ethical approval for this work 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: #fn-1