Abstract
We developed and evaluated an artificial intelligence (AI)-powered approach for easier quantification of tau PET uptake without requiring structural MR to aid earlier tracking of Alzheimer disease (AD). Methods: We implemented a deep neural network model that normalizes (18)F-AV1451 (tau) PET images to a standard template without requiring MR, using transfer learning from a model pretrained on amyloid PET. This model was integrated into an MR-free pipeline for tau PET quantification and validated on external dataset (Alzheimer Disease Neuroimaging Initiative). We examined correlations between model-derived tau uptake estimates and cognitive measures, including AD stage and episodic memory performance (n = 666). Longitudinal analyses were conducted to assess whether baseline tau deposition predicted future cognitive decline (n = 168). Results: The AI-powered pipeline achieved robust performance with intraclass correlation coefficients exceeding 0.97 for regional uptake estimation compared with MR-based ground truth. We also showed that the tau deposition in metatemporal regions was significantly correlated with Mini-Mental State Examination and Montreal Cognitive Assessment scores. Elevated tau PET uptake in the entorhinal cortex and inferior temporal gyrus predicted future cognitive decline. Conclusion: The proposed AI-powered pipeline enhances the clinical accessibility of tau PET by reducing scan costs and streamlining the uptake quantification, achieving high performance without requiring structural MR. We further demonstrated that the pipeline yields cognitively relevant outcome measures for early diagnosis and monitoring of AD progression to aid more personalized treatment strategies targeting AD biomarkers.