82 Chapter 4 < 813 pg/mL [17] and/or abnormal Aβ PET (on visual read)). According to the NIAAA Research Framework [18], all subjects are considered in the AD pathophysiological continuum. Subjects were excluded if they had severe traumatic brain injury, abnormalities on MRI likely to interfere with segmentation of tau PET and participation in drug trial with a tau or Aβ-targeting agent. All procedures were in accordance with the ethical standards of the Medical Ethics Review Committee of the Amsterdam UMC VU Medical Center and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Image acquisition All participants underwent a single dynamic [18F]flortaucipir PET scan at the Amsterdam UMC VU Medical Center on an Ingenuity TF PET-CT scanner (Philips Medical Systems, Best, The Netherlands) within 1 year from their neuropsychological examination. [18F]Flortaucipir was synthesized at the Amsterdam UMC VU Medical Center, using a protocol described in detail previously [19]. The scan protocol started with a low-dose CT for attenuation correction, followed by a 234 ± 14 MBq [18F]flortaucipir bolus injection (injected mass 1 ± 1 μg). Simultaneously with tracer injection, a 60-min dynamic emission scan was initiated. After a 20-min break and following a second low-dose CT for attenuation correction, an additional dynamic emission scan was performed during the interval 80–130 min post-injection. During scanning, head movements were restricted by a head holder with band and head position was regularly checked. PET scans were reconstructed using a matrix size of 128 × 128 × 90 and a final voxel size of 2 × 2 × 2 mm3. All standard corrections for dead time, decay, attenuation, randoms and scatter were performed. Both 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), in which the last 10 frames belonged to the second PET session. In addition, all subjects underwent structural MRI on a 3.0 Tesla (3 T) Philips medical systems’ Ingenuity TF PET-MRI. The protocol included an isotropic structural 3D T1-weighted image using a sagittal turbo gradient-echo sequence (1.00 mm3 isotropic voxels, repetition time = 7.9 ms, echo time = 4.5 ms, and flip angle = 8°), and a 3D fluid-attenuated inversion recovery (FLAIR) image (1.04 × 1.04 × 1.12 mm voxels, repetition time = 4800 ms, echo time = 278.8 ms, flip angle 90°). PET and MR analyses Using Vinci software (Max Plank Institute, Cologne, Germany), T1-weighted MR images were co-registered to their individual PET scans in native space. To delineate
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