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Background: A potential source of error in quantifying longitudinal changes in amyloid and tau imaging is the spatial resolution of PET. Partial volume correction (PVC) methods have been developed to account for this, but there remains a lack of consensus in the Alzheimer's field on their use due to a lack of method evaluation relative to ground truth. The aim of this work was to evaluate various reconstruction and image‐based PVC techniques using an anatomically accurate 3D‐printed PET phantom with physiologically relevant radiotracer distributions. Methods: A lateral temporal phantom (Figure 1) with six fillable, thin‐walled (1.0 mm) chambers corresponding to inferior, middle, and superior temporal gray matter (GM) and white matter (WM) regions was constructed via 3D‐printing (Formlabs Form 3) using the FreeSurfer v5.3 segmented sample subject "bert" as a pattern. Inferior and superior temporal GM regions were filled with a 3.0 kBq/cc concentration of F‐18 solution and WM regions with 1.5 kBq/cc, simulating a high amyloid‐burden subject with a GM‐to‐WM radioactivity ratio of 2:1. The phantom was scanned on a Siemens Biograph mCT and reconstructed using three techniques: FBP; OSEM; and TrueX, an iterative method with system matrix modeling using a spatially variant point spread function. Image‐based geometric transfer matrix (GTM) PVC was applied to the FBP and OSEM images. Regional uncorrected and PVC radioactivity concentrations were compared to known ground truth. Results: FBP, OSEM, and TrueX PET images are presented in Figure 2. Inferior and superior temporal GM and WM radioactivity concentrations for each of the reconstructions, uncorrected and PVC, are presented in Figure 3. Conclusion: GTM PVC resulted in more accurate regional quantification relative to uncorrected data, regardless of reconstruction method. TrueX, which accounts for the system resolution during reconstruction, did not result in improved quantitative accuracy despite apparent differences in image quality. Optimization of TrueX parameters may result in improved quantitation accuracy. This study adhered to one fundamental assumption of the GTM technique: radioactivity uniformity within a region. This assumption may be violated in human imaging. Future studies will address this and will examine varying levels of amyloid and tau burden and cortical atrophy. [ABSTRACT FROM AUTHOR]

Background: The AT(N) model of Alzheimer's disease (AD) posits a temporal evolution of β‐amyloid (Aβ) accumulation followed by tau then neurodegeneration. We investigated whether longitudinal relationships of these pathologies varied by sex and cerebral small vessel disease burden (cSVD), hypothesizing stronger associations in women and those with high baseline cSVD. Method: Participants included 37 non‐demented older adults (mean 74 y/o at inclusion; 59% female; 89% white; 29% APOE4+). Tau was measured once at time 0 using 18F‐AV‐1451 in an AD composite region of interest. Global amyloid and cerebral metabolism in lateral temporal lobe (neurodegeneration) were measured at repeated annual visits (8 years before tau‐PET to 2 years after), using 11C‐PiB and 18F‐fluorodeoxyglucose (FDG)‐PET. cSVD at study inclusion was characterized by high or low white matter hyperintensity (WMH) volume on MRI. We calculated individual slopes of Aβ and cerebral metabolism up to the tau‐PET visit (time ‐8 to 0) using linear mixed effects models. Using age‐adjusted linear regression models, we examined associations of Aβ slope, tau, and cerebral metabolism slope or metabolism at the final visit (time≥0). We tested effect modification by sex and WMH using interaction terms and stratified analyses when interaction p<0.10. Result: Associations of Aβ slope with tau varied by sex (p‐interaction=0.007) but not WMH. Greater increase in Aβ slope was associated with greater tau in women (β=3.5, p=0.004), but not men (β= ‐1.2, p=0.34). Tau did not predict cerebral metabolism at the final FDG visit (β=0.10, p=0.67), but increasing Aβ slope predicted hypometabolism at the final FDG visit (β= ‐2.1, p=0.01). Neither of these relationships varied by sex or WMH. Associations of cerebral metabolism slope with tau varied by sex (p‐interaction=0.08), but not WMH. Decreasing cerebral metabolism slope was associated with greater tau in women (β= ‐16.3, p=0.05), but not men (β=4.7, p=0.59). Further adjustment for APOE4 (N=31) did not appreciably alter results. Conclusion: In non‐demented older adults, we found that associations of Aβ and cerebral hypometabolism with later increased tau were stronger in women than men; cSVD did not modify these associations. Tau did not predict later cerebral metabolism, while Aβ did. [ABSTRACT FROM AUTHOR]