Precision estimates of relative and absolute cerebral blood flow in Alzheimer's disease and cognitively normal individuals

Alzheimer's disease is characterized by regional reductions in cerebral blood flow (CBF). Although the gold standard for measuring CBF is [O-15]H2O PET, proxies of relative CBF, derived from the early distribution phase of amyloid and tau tracers, have gained attention. The present study assessed precision of [O-15]H2O derived relative and absolute CBF, and compared precision of these measures with that of (relative) CBF proxies. Dynamic [O-15]H2O, [F-18]florbetapir and [F-18]flortaucipir PET test-retest (TrT) datasets with eleven, nine and fourteen subjects, respectively, were included. Analyses were performed using an arterial input model and/or a simplified reference tissue model, depending on the data available. Relative CBF values (i.e. K-1/K-1 ' and/or R-1) were obtained using cerebellar cortex as reference tissue and TrT repeatability (i.e. precision) was calculated and compared between tracers, parameters and clinical groups. Relative CBF had significantly better TrT repeatability than absolute CBF derived from [O-15]H2O (r = -0.53), while best TrT repeatability was observed for [F-18]florbetapir and [F-18]flortaucipir R-1 (r = -0.23, r = -0.33). Furthermore, only R-1 showed, better TrT repeatability for cognitively normal individuals. High precision of CBF proxies could be due to a compensatory effect of the extraction fraction, although changes in extraction fraction could also bias these proxies, but not the gold standard.