Visual Read Protocols for Clinicians Analyzing 18F-PI-2620 tau PET/MRI Images

1531 Objectives: Abnormal tau protein is one of the primary pathologies associated with Alzheimer9s Disease (AD). Diagnosing tau pathology in vivo is crucial in disease diagnosis, clinical trial inclusion criteria, and therapy development. The goal of this study was to create and validate a clinical visual rating protocol for 18F-PI2620 and correlate with SUVR and disease. After thorough study of 18F-PI2620 PET/MR images by the authors, a visual read protocol was created with staging based on modified Braak stages. In Braak staging, neurofibrillary tau tangles are present primarily in the transentorhinal and entorhinal cortex in early stages (1e in our protocol), progress to the hippocampus (1h), then to the rest of the medial temporal cortex including lingual and fusiform gyrus (1m), spread to the remaining temporal cortex (2 in our protocol), and lastly impact the neocortex (3 in our protocol), Figure 1. For this work, 2 physicians were blinded to participant demographics, received training on this algorithm, independently viewed the fused non-normalized 18F-PI2620 PET/MR with MRIcron, and staged each participants’ scans according to the this clinical protocol. Tau staging was determined based on visual uptake greater than inferior cerebellar cortex. Participants were rated as positive or negative in each of the stages. Using this protocol for 18F-PI2620, concordance between raters varied from the upper limits of “fair” (Cohen’s k=0.35, p=5.3e-3 for 1h, hippocampal uptake) to “nearly perfect” (k=0.93, p= 1.1e-10 for stage 3, cortical uptake, Supplemental Figure). The raters’ visual categorization significantly correlated with SUVR for each relevant region of interest (p-value of 0.02 to 9e-13). Importantly for clinical trial inclusion/exclusion and disease diagnosis, none of the patients with a non-AD tauopathy disease were rated positively with this protocol by either rater. As tau tracers are being implemented in clinical trials, clinical evaluation is necessary. These tau PET tracers are promising candidates for subjectively quantifying disease burden in vivo clinically, using the modified Braak staging protocols developed here.