To compare the performances of two novel visual read-based methods for flortaucipir-PET in patients with Alzheimer’s Disease (AD) to identify high tau accumulation, defined as AD-signature weighted neocortical Standardized Uptake Value ratio (SUVr)>1.46.
Baseline flortaucipir-PET scans displaying advanced-AD tau-patterns (increased neocortical activity beyond posterior lateral temporal and occipital regions with bindings 1.65-times higher [1.65x-visual threshold] than cerebellar average) were utilized from the confirmatory phase of A05 study (N=78, NCT02016560). Four expert human-readers conducted reads using two novel visual read-based methods while being blinded to each other and all quantitative results. The first approach (SUVrmax-method) requires a reader to visually identify and hand-draw focal regions-of-interest on frontal areas with the highest bindings and calculate an SUVr between the identified frontal maximum and average cerebellum binding. The second approach (Enhanced Read-method) requires the reader to evaluate binding elevation compared to cerebellum with an enhanced visual threshold, either across gray matter (global, 3.795x-visual threshold) or only in the frontal lobe (2.805x-visual threshold), compared to the standard 1.65x-visual threshold specified in the FDA-approved Tauvid™ label. Methods were compared to the standard quantitative high tau determination as standard-of-truth.
Based on a previously found ROC-determined cut point using computer-generated SUVrmax values, the SUVrmax-method showed median 88% Positive Percent Agreement (PPA), 87% Negative Percent Agreement (NPA) and 87% overall accuracy across raters. The Enhanced Read-method showed median 75% PPA, 88% NPA and 85% overall accuracy and median 81% PPA, 91% NPA and 88% overall accuracy for global and frontal approaches, respectively.
Both novel flortaucipir-PET visual read-based methods showed comparable and promising performances in identifying AD with high tau, do not require computationally intensive approaches and can be implemented with different imaging software.