Concordance Between [¹⁸F]Flortaucipir PET Visual Reads and CenTauR-Based Quantification

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.