Thesis

183 Longitudinal tau PET and atrophy grouped based on amyloid status (negative and positive) for analyses. The study is 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. Written informed consent was obtained from all participants prior to participation. Image acquisition All 61 individuals from the follow-up sample underwent dynamic [18F]flortaucipir PET and MRI scans at baseline and two year follow-up. Dynamic [18F]flortaucipir PET scans were acquired on a PET-CT scanner (Philips Medical Systems, Best, The Netherlands) at the Amsterdam UMC VU Medical Center. Individual doses of [18F]flortaucipir were synthesized on site, using a previously described protocol [31]. All individuals at baseline participated in an initial scanning protocol of 130 minutes, consisting of a 60 minutes dynamic emission scan, a 20 minutes break and another dynamic emission scan between 80 to 130 minutes post-injection [31]. In order to lower the burden associated with a long scanning protocol, especially for AD patients, our research group recently validated a quantitatively accurate shortened scanning protocol of 100 minutes [32]. Subsequently, all CI AD patients participating in follow-up PET scans for our ongoing longitudinal cohort study participated in the recently validated scanning protocol of 100 minutes, consisting of a 30 minutes dynamic emission scan, a 50 minutes break and a second dynamic emission scan between 80 to 100 minutes post-injection. In order to correct for this adjusted scanning protocol at follow-up, the 130 minutes baseline scans of these individuals were analyzed as biphasic 100 minutes scans (n = 26). Scanning protocols were initiated with a low-dose CT for attenuation correction, followed by simultaneously injecting ~240±10 MBq [18F]flortaucipir (bolus) and starting the first dynamic emission scan. After a break and a second low-dose CT for attenuation correction, another dynamic emission scan was performed. During scan procedures, head movements were restricted by a headband and head positioning was regularly checked using laser beams. PET scans were reconstructed with a matrix size of 128 x 128 x 90 and a voxel size of 2 x 2 x 2 mm3, including standard corrections for attenuation, dead time, randoms, decay and scatter. For each scan protocol, the later dynamic PET scan was coregistered to the first dynamic PET scan into a single dataset. Furthermore, all individuals underwent a structural whole-brain MRI scan on a 3.0 Tesla (3 T) MRI scanner at baseline and follow-up (Ingenuity Time-of-Flight (Phillips medical systems, Best, The Netherlands)). The scanning protocol for the Ingenuity Time-of-Flight scanner included an isotropic structural 3D T1-weighted image using a sagittal turbo gradient-echo sequence (1.00 m3 isotropic voxels, repetition time= 7.9 ms, echo times= 4.5 ms and flip angle= 8°) and a 3D fluid-atten7

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