Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model

Author:

Leuzy Antoine123,Raket Lars Lau14,Villemagne Victor L.567,Klein Gregory8,Tonietto Matteo8,Olafson Emily9,Baker Suzanne10,Saad Ziad S.11,Bullich Santiago12,Lopresti Brian13,Bohorquez Sandra Sanabria9,Boada Mercè1415,Betthauser Tobey J.161718,Charil Arnaud19,Collins Emily C.4,Collins Jessica A.20,Cullen Nicholas2,Gunn Roger N.2122,Higuchi Makoto23,Hostetler Eric24,Hutchison R. Matthew20,Iaccarino Leonardo4,Insel Philip S.25,Irizarry Michael C.16,Jack Clifford R.26,Jagust William J.27,Johnson Keith A.2829,Johnson Sterling C.161718,Karten Yashmin2,Marquié Marta1718,Mathotaarachchi Sulantha3,Mintun Mark A.4,Ossenkoppele Rik130,Pappas Ioannis3132,Petersen Ronald C.33,Rabinovici Gil D.3435,Rosa‐Neto Pedro3637,Schwarz Christopher G.26,Smith Ruben138,Stephens Andrew W.12,Whittington Alex21,Carrillo Maria C.39,Pontecorvo Michael J.4,Haeberlein Samantha Budd3,Dunn Billy40,Kolb Hartmuth C.3,Sivakumaran Sudhir2,Rowe Christopher C.6741,Hansson Oskar142,Doré Vincent743

Affiliation:

1. Clinical Memory Research Unit Department of Clinical Sciences Lund University Lund Sweden

2. Critical Path for Alzheimer's Disease (CPAD) Consortium Critical Path Institute Tucson Arizona USA

3. Enigma Biomedical Group Knoxville Tennessee USA

4. Eli Lilly and Company Indianapolis Indiana USA

5. Department of Neurology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

6. Florey Department of Neuroscience University of Melbourne Parkville Victoria Australia

7. Department of Molecular Imaging & Therapy Austin Health Heidelberg Victoria Australia

8. F. Hoffmann‐La Roche Ltd Basel Switzerland

9. Clinical Imaging Group Genentech, Inc. South San Francisco California USA

10. Lawrence Berkeley National Laboratory Berkeley California USA

11. Janssen Research & Development Merryfield Row San Diego California USA

12. Life Molecular Imaging GmbH Berlin Germany

13. Department of Radiology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

14. Ace Alzheimer Center Barcelona Universitat Internacional de Catalunya Barcelona Spain

15. Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III Av. de Monforte de Lemos Madrid Spain

16. Wisconsin Alzheimer's Disease Research Center University of Wisconsin‐Madison School of Medicine and Public Health Madison Wisconsin USA

17. Department of Medicine Division of Geriatrics University of Wisconsin‐Madison School of Medicine and Public Health Madison Wisconsin USA

18. Department of Medical Physics, University of Wisconsin‐Madison School of Medicine and Public Health Madison Wisconsin USA

19. Eisai, Inc. Nutley New Jersey USA

20. Biogen Cambridge Massachusetts USA

21. Invicro Hammersmith Hospital London UK

22. Brain Sciences Imperial College London Hammersmith Hospital London UK

23. Department of Functional Brain Imaging Institute for Quantum Medical Science National Institutes for Quantum Science and Technology Inage‐ku Chiba‐shi Chiba Japan

24. Merck & Co., Inc West Point Pennsylvania USA

25. Department of Psychiatry and Behavioral Sciences University of California San Francisco California USA

26. Department of Neurology Mayo Clinic Rochester Minnesota USA

27. University of California Berkeley Lawrence Berkeley National Laboratory Berkeley California USA

28. Harvard Medical School Department of Radiology Boston Minnesota USA

29. Gordon Center for Medical Imaging Massachusetts General Hospital Boston Minnesota USA

30. Amsterdam University Medical Center, Neuroscience Campus Amsterdam Alzheimercenter HZ Amsterdam the Netherlands

31. Department of Psychology Helen Wills Neuroscience Institute University of California Berkeley California USA

32. Department of Neurology VA Northern California Health Care System Martinez California USA

33. Department of Radiology Mayo Clinic Rochester Minnesota USA

34. Department of Neurology Memory and Aging Center Weill Institute for Neurosciences University of California San Francisco California USA

35. Department of Radiology & Biomedical Imaging University of California San Francisco California USA

36. Translational Neuroimaging Laboratory Department of Neurology and Neurosurgery, Faculty of Medicine, The McGill University Research Centre for Studies in Aging McGill University Verdun Quebec Canada

37. Montreal Neurological Institute McGill University Montréal Québec Canada

38. Department of Neurology Skåne University Hospital Lund Sweden

39. Alzheimer's Association Chicago Illinois USA

40. Senior advisor to CPAD Consortium Critical Path Institute Tucson Arizona USA

41. The Australian Dementia Network (ADNeT) The University of Melbourne Parkville Victoria Australia

42. Memory Clinic Skåne University Hospital Malmö Sweden

43. Health and Biosecurity Flagship, The Australian eHealth Research Centre CSIRO Parkville Victoria Australia

Abstract

AbstractINTRODUCTIONTau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.METHODSUsing head‐to‐head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed “CenTauR” [CTR]). JPM is a statistical model that simultaneously models the relationships between head‐to‐head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale.RESULTSA strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach.DISCUSSIONPreliminary findings using the JPM support the development and adoption of a universal scale for tau‐PET quantification.Highlights Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed “CenTauRs”. Tested a Centiloid‐like linear regression approach. Using five cohorts with head‐to‐head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Funder

Vetenskapsrådet

Hjärnfonden

Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse

Alzheimer's Association

American College of Radiology

Rainwater Charitable Foundation

Publisher

Wiley

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