209 Longitudinal change in ATN biomarkers This dual time point protocol was validated previously [12]. Forty-two individuals underwent a follow-up [18F]flortaucipir PET scan using the same procedure with a mean follow-up time of 2.1 ± 0.3 years. Baseline structural MRI images were obtained at five different systems (GE Discovery MR750 3T (n = 22), Philips PETMR 3T (n = 51), Signa 1.5T (n = 1), Titan 3T (n = 17), and external scan (n = 1)). The protocol included 3D T1-weighted images, 3D T2-weighted images, and 3D T2-weighted fluid-attenuated inversion-recovery (FLAIR) images [13]. T1-weighted images were used for co-registration to PET images and for determination of the N status. Follow-up MRI was available for 79 individuals with a mean follow-up time of 2.9 ± 0.9 years. Image analysis Data were reconstructed while using standard LOR RAMLA reconstruction algorithm with corrections for dead time, decay, attenuation, random coincidences, and scatter. Images were reconstructed with a matrix size of 128 × 128 × 90 and a voxel size of 2 × 2 × 2 mm3. For [18F]flortaucipir, both scan sessions (0–60 and 80–130min) 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. 3D T1-weighted MR images were co-registered to PET images using Vinci software (Max Planck Institute, Cologne, Germany). Next, regions of interest (ROIs) were defined on the co-registered MRI using the probabilistic Hammers brain atlas [14] in PVElab. Receptor parametric mapping (RPM) was used to generate parametric binding potential (BPND) images with cerebellar grey matter as a reference region using PPET [11, 15–17]. For [18F]florbetapir, we calculated (volume weighted) mean cortical BPND in a composite ROI consisting of orbitofrontal, temporal, parietal, anterior cingulate, posterior cingulate, and precuneus regions [6, 18]. Biomarkers: A, T, N Availability of biomarker status at two time points differed for each of the biomarkers (A: n = 92; T: n = 42; N: n = 79). For 39 individuals, a complete ATN profile over time could be constructed. The time difference with the [18F]florbetapir scan was 0.05 ± 0.15y for [18F]flortaucipir scans and 0.16 ± 0.62y for MRI scans. We used visual assessment of [18F]florbetapir PET scans to define A in the ATN classification. Since quantitative thresholdbased methods usually have a high degree of concordance with visual assessment [19, 20], we chose visual assessment to be consistent with methods used in clinical practice. In additional analyses, we used continuous mean cortical BPND in a composite ROI. We used [ 18F]flortaucipir PET scans as biomarker for T. We pragmatically used Gaussian mixture modeling as an unbiased, data-driven approach, to obtain a threshold. We first averaged values for the anterior part of the lateral temporal lobe for left and right sides. Since the focus of this study 8
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