Effects of Motion and White Matter Hyperintensities on Reference Region Based ¹⁸F-Synvest-1 PET Quantification in Alzheimer’s Disease and Healthy Volunteers

18F-SynVesT-1 is a PET tracer targeting synaptic vesicle protein 2A, a surrogate marker of synaptic density. Simplified quantification using pseudo-reference regions such as the centrum semiovale (CSO) or whole cerebellum (CER) has previously been validated in healthy volunteers and Alzheimer’s disease. This study assessed how motion correction and white-matter hyperintensities (WMH) affect 18F-SynVesT-1 quantification. We reconstructed 18F-SynVesT-1 images for 40 healthy volunteers and 31 patients with Alzheimer’s disease 60-90 minutes post-injection with 3 motion handling methods: no motion correction; 5 minute frame-based post-reconstruction coregistration and averaging, and a high-temporal-resolution data-driven motion correction applied during reconstruction. WMH were segmented from T2-FLAIR images and excluded from the CSO to generate lesion-corrected CSO regions. A region-based voxelwise partial volume correction was applied. SUV and SUVRCSO/CER were compared across motion- and lesion-handling methods and the effects on group differentiation were explored. Data-driven motion correction during reconstruction improved visual image sharpness and increased SUV in high-binding cortical regions (median +0.3-1.0