Dual-phase ¹⁸F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease

Background: This study investigated changes in brain perfusion and Aβ burden according to the progression of Alzheimer's disease (AD) by using a dual-phase ¹⁸F-florbetaben (FBB) PET protocol. Methods: Sixty subjects, including 12 with Aβ-negative normal cognition (Aβ⁻NC), 32 with Aβ-positive mild cognitive impairment (Aβ⁺MCI), and 16 with Aβ-positive AD (Aβ⁺AD), were enrolled. A dynamic PET scan was obtained in the early phase (0–10 min, eFBB) and delayed phase (90–110 min, dFBB), which were then averaged into a single frame, respectively. In addition to the averaged eFBB, an R1 parametric map was calculated from the eFBB scan based on a simplified reference tissue model (SRTM). Between-group regional and voxel-wise analyses of the images were performed. The associations between cognitive profiles and PET-derived parameters were investigated. Results: Both the R1 and eFBB perfusion reductions in the cortical regions were not significantly different between the Aβ⁻NC and Aβ⁺MCI groups, while they were significantly reduced from the Aβ⁺MCI to Aβ⁺AD groups in regional and voxel-wise analyses. However, cortical Aβ depositions on dFBB were not significantly different between the Aβ⁺MCI and Aβ⁺AD groups. There were strong positive correlations between the R1 and eFBB images in regional and voxel-wise analyses. Both perfusion components showed significant correlations with general and specific cognitive profiles. Conclusion: The results of this study demonstrated the feasibility of dual-phase ¹⁸F-FBB PET to evaluate different trajectories of dual biomarkers for neurodegeneration and Aβ burden over the course of AD. In addition, both eFBB and SRTM-based R1 can provide robust indices of brain perfusion.