27 Shortening the scan duration For the full kinetic model cohort, continuous arterial blood sampling, using an online detection, [23] was collected during 60-min p.i. PET acquisition. Furthermore, manual arterial samples were collected at set time points (5, 10, 15, 20, 40, 60, 80, 105 and 130 min p.i.) to measure plasma metabolite fractions and plasma-to-wholeblood ratios. Using the aforementioned information, the continuous online blood sampler data was calibrated and corrected for metabolites, plasma-to-whole-blood ratios and delay, providing a metabolite-corrected arterial plasma input function. In addition, whole-blood input function was obtained for blood volume correction. Image Processing PET scans were reconstructed with a matrix size of 128 × 128 × 90 and a final voxel size of 2 × 2 × 2 mm3. All standard corrections were applied. During processing of the PET scans, first part and second part of the scan were checked for motion, separately. Thereafter, both the PET scan sessions were co-registered into a single dataset of 29 frames (1 × 15, 3 × 5, 3 × 10, 4 × 60, 2 × 150, 2 × 300, 4 × 600 and 10 × 300 s) using Vinci software (Max Plank Institute, Cologne, Germany). The last 10 frames belonged to the second PET session. Structural 3D T1-weighted MRI images were co-registered to the PET images also using Vinci software (Max Plank Institute, Cologne, Germany). The Hammers template [24], which is incorporated in PVElab [25], was used to delineate regions of interest (ROIs) on the co-registered MR scan and superimposed onto the dynamic PET scan to obtain regional time activity curves (TACs). All 68 cortical and subcortical regions from the Hammer template were included. Regional TACs extracted from the PET scans were analyzed using a reversible 2-tissue compartment model with blood volume correction (2T4k_VB) and simplified reference tissue model (SRTM) [26]. Receptor parametric mapping (RPM) [27] and standardized uptake value ratios (SUVr) were used to obtain parametric images. Cerebellum grey matter (obtained from PVElab) was used as the reference region. Shortening the Second Part of the Scan (80–130 Min P.I.) In these analyses, the first part of the scan remained 0–60 min p.i. The second part of the scan was shortened; three shorter time intervals were explored: 80–120 min, 80–110 min and 80–100 min. For each subject, shortened PET scans were acquired by removing 2 to 6 frames to reach the specified scan intervals. Reference region TACs were extracted from these shortened PET scans to estimate kinetic parameters. BPND and R1 values were estimated using RPM from the three different scan durations (0–60/80–100, 0–60/80–110 and 0–60/80–120 min). RPM-derived regional BPND and R1 values were compared to the corresponding non-linear regression (NLR)-based SRTM-derived BPND and R1, and plasma input–derived distribution volume 2
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