Journal Article Ahead of print
PubMed: 42562606 DOI: 10.2967/jnumed.126.272722
Concordance Between [ 18F]Flortaucipir PET Visual Reads and CenTauR-Based Quantification.
J Nucl Med
Authors: Stamatia Karagianni, Alexis Moscoso, Sheelakumari Raghavan, Martijn van Essen, Ismini Mainta, Valle Camacho, Omar Rodríguez-Fonseca, Jesús Silva-Rodríguez, Andrés Perissinotti, Yuna Gu, Jihwan Yun, Nicolai Franzmeier, Michel J Grothe, Sang Won Seo, Giovanni B Frisoni, Valentina Garibotto, Christopher G Schwarz, Ronald C Petersen, Clifford R Jack, Prashanthi Vemuri, Michael Schöll
Affiliations
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Nuclear Medicine Department and Molecular Imaging Group, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
- Department of Radiology, Mayo Clinic, Rochester, Minnesota.
- Department of Clinical Physiology/Nuclear Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
- Division of Nuclear Medicine, Geneva University Hospitals, Geneva, Switzerland.
- Department of Nuclear Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
- Nuclear Medicine Department, Lucus Augusti University Hospital, Lugo, Spain.
- Reina Sofía Foundation Alzheimer's Centre, CIEN Foundation, ISCIII, Madrid, Spain.
- Nuclear Medicine Department, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain.
- Biomedical Research Networking Centre of Bioengineering, Biomaterials and Nanomedicine, ISCIII, Barcelona, Spain.
- Samsung Alzheimer Research Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.
- Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.
- Institute for Stroke and Dementia Research, LMU University Hospital, LMU Munich, Munich, Germany.
- Munich Cluster for Systems Neurology, Munich, Germany.
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Korea.
- Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Korea.
- Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
- Laboratory of Neuroimaging of Aging, University of Geneva, Geneva, Switzerland.
- Faculty of Medicine, University of Geneva and Center for Biomedical Imaging, Switzerland.
- Department of Neurology, Mayo Clinic, Rochester, Minnesota; and.
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden;.
- Department of Neuropsychiatry, Sahlgrenska University Hospital, Mölndal, Sweden.
Abstract
Tau PET imaging with [ 18F]flortaucipir allows for the visualization and mapping of aggregated tau deposits, a key neuropathologic feature of Alzheimer disease (AD). A visual interpretation method for [ 18F]flortaucipir was approved by the Food and Drug Administration and European Medicines Agency and has been implemented for a standardized, clinically usable definition of tau PET positivity. The CenTauR z method, on the other hand, offers the possibility to harmonize the definition of tau PET positivity across different radiotracers using quantitative metrics, but its concordance with clinically relevant [ 18F]flortaucipir visual reads remains unclear. Methods: A convenience sample of 3991 participants, including cognitively unimpaired (CU) and cognitively impaired (CI) individuals (i.e., those with mild cognitive impairment or AD dementia), underwent [ 18F]flortaucipir PET imaging. Each [ 18F]flortaucipir scan was assessed by 3 trained readers using the approved visual interpretation method and quantified using the CenTauR z quantification pipeline in different regions of interest (ROIs). Concordance between positive visual reads and CenTauR z-defined positivity (i.e., >2 on the CenTauR z scale) was assessed using Cohen κ. Receiver-operating-characteristic (ROC) analysis evaluated the discriminative power of continuous CenTauR z values in distinguishing between negative and positive visual reads. Generalized additive models examined clinical progression on the basis of visual and CenTauR z-based assessments of tau PET positivity. Results: Concordance between visual reads and CenTauR z-based assessments of tau PET positivity was moderate, particularly in CU individuals (κ = 0.23-0.55 for CU participants, κ = 0.57-0.82 for CI participants, depending on the ROI). ROC analysis revealed that the agreement remained moderate, independent of the CenTauR z cut point used (area under the ROC curve, 0.72-0.87 vs. 0.87-0.97 for CU and CI individuals, respectively). Among discordant cases, participants with visually positive/CenTauR z-negative tau PET scans were more frequently amyloid-positive and exhibited faster clinical progression compared with visually negative/CenTauR z-positive individuals. Conclusion: Our findings highlight the relatively limited agreement between the visual assessment of [ 18F]flortaucipir PET images and CenTauR z-based quantification, particularly in CU individuals. Participants with visually positive/CenTauR z-negative tau PET scans showed a high frequency of amyloid positivity and faster clinical progression, suggesting that visual reads are more sensitive to heterogeneous, clinically relevant tau accumulation patterns not captured by ROI-based methods. These findings underscore the need for new quantification approaches to better capture the complex patterns of tau deposition, important for early AD detection and monitoring.
MeSH
Positron-Emission Tomography, Cognitive Dysfunction, Nuclear Medicine, Amyloid, Roc Curve