39 Shortening the scan duration DISCUSSION The current study demonstrated that for [18F]flortaucipir expanding the break in the dual-time-window protocol with just a 50-min overall scanning time (early interval of 0–30 min, than a coffee break, followed by a late interval of 80–100 min) had minimal effect on the quantitative accuracy. The optimal shortened dual-time-window protocol (0–30/80–100 min) allows sufficiently accurate estimation of BPND while reducing patient burden and enables interleaved scanning, where other patients could use the camera during breaks within the scan period. An excellent correlation was observed between the shortened acquisition protocol (0–30/80–100 min) and the original dual-time-window (0–60/80–130 min) protocol. Four different interpolation methods were used to interpolate the missing data between the two time windows for the reference region TAC (cerebellum grey matter). According to our results, POP-IP_2T4k_VB interpolation, which uses a population-averaged plasma input function, showed a good correspondence of the estimated kinetic parameters to that obtained from the original scan protocol, and the lowest under/over-estimation(s) compared to other interpolation methods. Heeman et al. [29] showed that POP-IP_2T4k_VB interpolation method also works well to interpolate the missing data points in a dual-time-window protocol for [18F]flutemetamol and [18F]florbetaben. They concluded that the introduction of a gap with a maximum of 60 min in a dual-time-window protocol (early interval of 0–30 min followed by a late interval of 90–110 min) does not affect quantitative accuracy for [18F]flutemetamol and [18F]florbetaben. As such, POP-IP_2T4k_V B interpolation does not only work well for [18F]flortaucipir but also for [18F]flutemetamol and [18F]florbetaben, possibly because the model describes the in vivo kinetics of the tracers best and is therefore ideal for estimating the missing reference region data points accurately. The correlations for all interpolation methods were comparable (Table 2). This was not expected, since linear and exponential interpolation did not follow the course of tracer as can be observed in Figure 1. A possible explanation could be that the gap between the dual-time-windows was not substantially large enough to see significant differences in correlations between the interpolation methods. However, a substantial underestimation (at times up to 20 % or even more) was observed in AD patients for the shortened SRTM BPND values obtained with linear and exponential interpolation methods when compared to plasma input DVR-1 and SRTM BPND obtained with the original scan duration. This indicates that these interpolation methods are not suitable for quantitatively accurate kinetic parameter estimation for [18F]flortaucipir. For SRTM BP ND values obtained with POP-IP _2T4k_VB interpolation, the biases remained within~ 10 % for the same comparisons 2
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