Tau positron emission tomography harmonization using the CenTauR approach: General conversion equations, relevant cut‐points, and external validation
Alexis Moscoso Rial, Antoine Leuzy, Lars Lau Raket, Victor L. Villemagne, Gregory Klein, Matteo Tonietto, Emily Olafson, Ruben Smith, Christopher G. Schwarz, Suzanne Baker, Ziad S. Saad, Santiago Bullich, Brian Lopresti, Sandra Sanabria Bohorquez, Guilherme Domingues Kolinger, Olivia Lutz, Mercè Boada, Tobey J. Betthauser, Arnaud Charil, Emily C. Collins, Jessica A. Collins, Roger N. Gunn, Makoto Higuchi, Eric Hostetler, R. Matthew Hutchison, Leonardo Iaccarino, Philip S. Insel, Michael C. Irizarry, Clifford R. Jack, William J. Jagust, Keith A. Johnson, Sterling C. Johnson, Cécile Tissot, David Vállez García, Gemma Salvadó, Diane Stephenson, Marta Marquié, Sulantha Mathotaarachchi, Mark A. Mintun, Rik Ossenkoppele, Qi Huang, Xiaoxie Mao, Johannes Gnörich, Ioannis Pappas, Ronald C. Petersen, Konstantinos Chiotis, Gil D. Rabinovici, Pedro Rosa‐Neto, Andrew W. Stephens, Alex Whittington, Maria C. Carrillo, Michael J. Pontecorvo, Samantha Budd Haeberlein, Billy Dunn, Hartmuth C. Kolb, Nadine Tatton, Yashmin Karten, Matthias Brendel, Sid O'Bryant, Fang Xie, Christopher C. Rowe, Oskar Hansson, Vincent Doré, ,Abstract
INTRODUCTION
Tau positron emission tomography (PET) tracers differ in kinetics, binding properties, and quantification pipelines, complicating cross‐study comparisons. The CenTauR approach provides a unified framework for harmonizing tau PET quantification across tracers.
METHODS
We defined a tracer‐agnostic “Standard Method” using Statistical Parametric Mapping 12, standardized regions of interest, and harmonized acquisition parameters. Using data from five tau tracers—[ 18 F]flortaucipir, [ 18 F]MK‐6240, [ 18 F]PI‐2620, [ 18 F]RO948, and [ 18 F]GTP1—we applied the Joint Propagation Model to derive linear equations converting regional standardized uptake value ratios into the tracer‐independent CenTauR scale. Validation included independent cross‐sectional, longitudinal, and test–retest datasets across multiple cohorts.
RESULTS
The CenTauR scale yielded highly consistent regional values across tracers, with strong cross‐tracer agreement and robust performance in external validation cohorts. We also expressed clinically relevant cut‐points and staging boundaries on the CenTauR scale.
DISCUSSION
The CenTauR approach enables harmonized, tracer‐independent quantification of tau PET, supporting reproducibility across studies and improving interpretation in clinical research and multicenter trials.