LAUSR

Visual Abstract In tau PET, a reliable method to detect early tau accumulation in the brain is crucial. Noise, artifacts, and off-target uptake impede detection of subtle true-positive ligand binding. We hypothesize that identifying voxels with stable activity over time can enhance detection of true-positive tau. Methods: In total, 339 participants in the clinical spectrum ranging from clinically unimpaired to Alzheimer disease dementia underwent at least 2 serial tau PET scans with flortaucipir. The overlap index (OI) method was proposed to detect spatially identical, voxelwise SUV ratio (SUVR) elevation when seen sequentially in serial tau PET scans. The association of OI with tau accumulation, clinical diagnosis, and cognitive findings was evaluated. Results: OI showed good dynamic range in the low-SUVR window. Only OI was able to identify subgroups with increasing tau PET signal in low-SUVR meta–region-of-interest (ROI) groups. OI showed improved association with early clinical disease progression and cognitive scores versus meta-ROI SUVR measures. Conclusion: OI was more sensitive to tau signal elevation and longitudinal change than standard ROI measures, suggesting it is a more sensitive method for detecting early, subtle deposition of neurofibrillary tangles.