Quantitative and statistical analyses of PET imaging studies of amyloid deposition in humans

Abstract

In vivo amyloid imaging could aid in earlier detection of Alzheimer's disease (AD) and anti-amyloid therapy development. We compared quantitative region-of-interest (ROI) and voxel-based statistical analyses of positron emission tomography (PET) studies of the /sup 11/C-labeled amyloid-imaging agent, PIB. High specific activity PIB PET studies were performed in 5 AD and 5 control subjects (ECAT HR+, 10-15 mCi, arterial input, 90 min). Magnetic resonance (MR) imaging was performed (ROI delineation). Quantitative analyses yielded regional PIB retention values (i.e., DVratio (DVR): radiotracer distribution volume (DV) normalized to the cerebellar reference DV). Statistical parametric mapping (SPM) and partial least squares (PLS) analyses were applied to PIB DVR images (arterial based) that were spatially normalized to an elderly MR template (55-90 years, n=268). The regional tissue response functions (fast and slow kinetic components) were consistent with the DVR values. The ROI, SPM (p<.025, 50 voxel extent, false discovery correction), and PLS (saliences) analyses yielded marked PIB retention in areas of AD brain that were consistent with known areas of amyloid deposition in AD, as compared to reference retention in areas unaffected by amyloid in AD (white matter, cerebellum, control brain). Voxel-based analyses of PIB PET data will likely prove valid and robust for mapping amyloid deposition on a cross-sectional and longitudinal basis in AD.