Thesis

52 Chapter 3 18F-florbetaben) by visual assessment (23,24). The study protocol was approved by the Medical Ethics Review Committee of the Amsterdam UMC VU Medical center. All patients provided written informed consent before study participation. Imaging All subjects underwent 2 dynamic 18F-flortaucipir PET scans, acquired on a Philips Ingenuity TF-64 PET/CT scanner, with a time period of 2.16±0.3 y (SCD) or 2.26±0.3 y (AD) between both scanning sessions. For SCD subjects, each scanning session consisted of 2 dynamic PET scans of 60 and 50 min, respectively, with a 20-min break in between (14,25). For AD patients, each scanning session consisted of 2 dynamic PET scans of 30min and 20min, respectively, with a 50-min break in between (9). BPND, R1, and SUVr at 80–100 min were extracted in a priori–defined regions of interest (ROIs) in subject space using the Hammers and Svarer templates: Braak I/ II (entorhinal), Braak III/IV (limbic), and Braak V/VI (neocortical). These ROIs align with neuropathologically defined regions (26) and are informative for tau PET in AD (27–30). For each parameter and ROI, we calculated percentage change using the following formula (DVR [BPND + 1] or SUVr associated with the follow-up and baseline scans, respectively): Percentage change = (follow-up/baseline -1) X 100% We repeated all analyses with partial-volume–corrected data using the iterative deconvolution method, as described previously (31–33). Statistical Analyses To allow for direct comparison with SUVrs, DVR was used for all analyses. Paired t tests were performed to assess differences between parameters and time points. Pearson correlation coefficients were computed to assess the correlation between percentage change in SUVr and DVR (all ROIs combined). Bland–Altman analyses were performed to assess bias and agreement between percentage change in SUVr and DVR (all ROIs combined). Analyses were performed in R software, version 4.0.2, and GraphPad Prism, version 9.1.0. To explore whether the required sample size for (theoretic) future trials would differ when either quantitative or semiquantitative methods are used, sample sizes were calculated using GPower, version 3.1.9.7. For these analyses, we used a range of 0.5%–10% expected change in tracer retention over time, to inform on longitudinal study designs in the context of 18F-flortaucipir. Sample sizes were calculated for SUVr and DVR, for all 3 ROIs (Braak I/II, III/IV, and V/VI). The differences between 2 dependent means (matched pairs) was calculated, with an α (error probability) of 0.05 and a power (1 - βerror probability) of 0.80.

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