Evaluation of a Sensitive Visual Read Algorithm for Assessing 3R/4R Tau PET Images

Developing and validating sensitive visual read algorithms for assessing Alzheimer disease-related tau in tau PET imaging is imperative, considering the implementation of the methodology in clinical practice and trials. Our aim was to compare 2 visual read algorithms for tau PET images to semiquantitative measurements and plasma phospho-tau 217 (p-tau217) status. <b>Methods:</b> In total, 1,654 participants were consecutively recruited from secondary memory clinics in southern Sweden as part of the prospective BioFINDER-2 cohort study (May 2017-September 2023). All participants underwent [¹⁸F]RO948 scans, and 37 participants underwent an additional [¹⁸F]flortaucipir scan. PET scans were read visually in accordance with the BioFINDER visual read (BF-VR) protocol and the established visual read method for [¹⁸F]flortaucipir (FTP-VR). Comparative analyses were conducted with semiquantitative SUV ratios (SUVRs) in the entorhinal cortex (ERC) and a temporal meta-region of interest and with plasma p-tau217 status. The primary endpoints of the study included the accuracy of visual read algorithms in detecting increases in semiquantitative SUVRs and p-tau217. Secondary outcomes included the intrarater and interrater reliabilities of the BF-VR. <b>Results:</b> Both visual read methods exhibited strong concordance with semiquantitative SUVRs. However, the BF-VR method demonstrated superior accuracy for tau in the ERC (93.9%; 95% CI, 92.6%-95.0%) compared with the FTP-VR method (89.9%; 95% CI, 88.3%-91.3%; <i>P</i> < 0.0001). The BF-VRs displayed lower accuracy when detecting tau in the temporal meta-region of interest (91.8%; 95% CI, 90.4%-93.1%) compared with the FTP-VRs (94.7%; 95% CI, 93.6%-95.8%; <i>P</i> = 0.002). Further, the BF-VRs exhibited similar accuracy (0.866; 95% CI, 0.847-0.884) to the FTP-VRs (0.857; 95% CI, 0.837-0.875; <i>P</i> = 0.54) for detection of p-tau217 abnormality. The interrater reliability of the BF-VR algorithm was excellent (weighted Cohen κ, 0.87; range, 0.82-0.93), and intrarater reliability was almost perfect (Cohen κ, 0.94; range, 0.89-0.98). The concordance of the BF-VR assessments of [¹⁸F]RO948 and [¹⁸F]flortaucipir images was excellent (Cohen κ, 0.94; range, 0.86-1.00). <b>Conclusion:</b> Visual reads offer a straightforward method for evaluating tau PET scans. The BF-VR algorithm provides a more accurate algorithm for detecting tau uptake in the ERC compared with the established FTP-VR algorithm and exhibits similar performance when using [¹⁸F]RO948 and [¹⁸F]flortaucipir images. The BF-VR algorithm further showed excellent interrater and intrarater reliabilities.