Selection of the optimal intensity normalization region for FDG-PET studies of normal aging and Alzheimer’s disease

Abstract The primary method for measuring brain metabolism in humans is positron emission tomography (PET) imaging using the tracer 18F-fluorodeoxyglucose (FDG). Standardized uptake value ratios (SUVR) are commonly calculated from FDG-PET images to examine intra- and inter-subject effects. Various reference regions are used in the literature of FDG-PET studies of normal aging, making comparison between studies difficult. Our primary objective was to determine the optimal SUVR reference region in the context of healthy aging, using partial volume effect (PVE) and non-PVE corrected data. We calculated quantitative cerebral metabolic rates of glucose (CMRg) from PVE-corrected and non-corrected images from young and older adults. We also investigated regional atrophy using magnetic resonance (MR) images. FreeSurfer 6.0 atlases were used to explore possible reference regions of interest (ROI). Multiple regression was used to predict CMRg data, in each FreeSurfer ROI, with age and sex as predictors. Age had the least effect in predicting CMRg for PVE corrected data in the pons (r 2 = 2.83 × 10−3, p = 0.67). For non-PVE corrected data age also had the least effect in predicting CMRg in the pons (r 2 = 3.12 × 10−3, p = 0.67). We compared the effects of using the whole brain or the pons as a reference region in PVE corrected data in two regions susceptible to hypometabolism in Alzheimer’s disease, the posterior cingulate and precuneus. Using the whole brain as a reference region resulted in non-significant group differences in the posterior cingulate while there were significant differences between all three groups in the precuneus (all p < 0.004). When using the pons as a reference region there was significant differences between all groups for both the posterior cingulate and the precuneus (all p < 0.001). Therefore, the use of the pons as a reference region is more sensitive to hypometabism changes associated with Alzheimer’s disease than the whole brain