51 E ect of flow on longitudinal tau PET INTRODUCTION In vivo tau imaging allows for quantification of longitudinal changes in tau accumulation during the course of Alzheimer disease (AD) and can serve as a surrogate outcome measure in clinical trials. Several tau PET tracers are available for this purpose, of which 18F-flortaucipir is the only one approved by the Food and Drug Administration (1–5). 18F-flortaucipir PET images can be acquired using static or dynamic scanning protocols. Semiquantitative parameters such as SUV ratio (SUVr) can be derived from such a static PET scan. However, parameters derived from a dynamic PET scan, such as distribution volume ratio (DVR) or nondisplaceable binding potential (BPND), are fully quantitative and overall more accurate (6,7). Notwithstanding, dynamic protocols—because of the long scan duration—result in patient movement, lower patient comfort, and lower scanning efficiency. A compromise can be achieved by implementing a dual-time-window protocol in which overall scanning time is reduced by introducing a resting period during the scan while maintaining high quantitative accuracy (8–10). SUVr has the advantage of practical applicability and relative computational simplicity (2–5), while dynamic imaging studies provide more accurate measurements of specific binding and measure the relative tracer delivery (R1), a proxy for relative cerebral blood flow (“18F-flortaucipir R 1” section in the supplemental materials available at http://jnm.snmjournals.org) (7,11–15). R1 is important because blood flow changes can occur over time in AD because of disease progression or drug intervention. Longitudinal changes using SUVr may be biased by blood flow changes, whereas quantitative measures (BPND) are not (6,16). Currently, for 18F-flortaucipir the sensitivity of SUVr for changes in blood flow has not been investigated. Therefore, with this study we compared SUVr and DVR/BPND for 18F-flortaucipir PET in a 2-y follow-up observational study. Second, we used simulations to investigate how larger changes in R1 affect SUVr and DVR/BPND. MATERIALS AND METHODS Participants We included 62 subjects from the Amsterdam Dementia Cohort (17,18), of whom 38 were cognitively normal with subjective cognitive decline (SCD) and 24 cognitively impaired (i.e., mild cognitive impairment (MCI) due to AD (19) [n=4] or probable AD dementia (20) [n=20], grouped into 1 MCI/AD group). Twelve of 38 SCD subjects were classified as amyloid-β (Aβ) PET–positive (18F-florbetapir visual assessment (21)). All MCI/AD patients were classified as Aβ-positive by cerebrospinal fluid biomarkers (i.e., cerebrospinal fluid Aβ1-42 , 813 ng/L (22)) or a Aβ PET scan (11C-PiB or 3
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