57 E ect of flow on longitudinal tau PET Sample Size Calculations Large differences in required sample sizes were observed for small effect sizes, with the largest differences being between methods in the AD group (Supplementary Table 7). However, with larger effect sizes (in line with expectations in clinical trials), differences in required sample size between the 2 methods became negligible for both SCD and AD (Supplementary Table 7). Simulations Simulations with 5% coefficient of variance showed results similar to those for the simulated time–activity curves obtained with almost no noise (0.05% coefficient of variance). Therefore, to mimic real cohort data, only the results from time–activity curves with a 5% coefficient of variance were reported. Simulations revealed that under the SCD (almost no binding) and low-binding AD patient conditions, an inverse relation was observed; that is, with increasing flow, a decreasing bias for SUVr (with respect to true DVR) was observed (Figure 4). A similar behavior was also observed under the medium-binding AD patient condition, but to a lesser extent. In the high-binding condition for AD patients, however, a relatively smaller effect of flow was observed on SUVr, implying that SUVrs remained relatively constant irrespective of the change in flow. In the case of DVR, no effect of flow was observed with any of the conditions (Figure 4). On the basis of simulations, percentage bias in SUVr with respect to the true DVR varied with the choice of SUVr scanning interval and the underlying binding condition (Figure 5). In general, SUVr overestimated DVR for all simulated R1 conditions from 80 min after injection; however, the impact of the change in flow on the directionality of the bias seems also to vary with respect to the choice of SUVr scanning interval (Figure 5). 3
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