Spatially constrained kinetic modeling with dual reference tissues improves 18F-flortaucipir PET in studies of Alzheimer disease

Tracer‐specific reference tissues selection improves detection of 18F‐FDG, 18F‐florbetapir, and 18F‐flortaucipir PET SUVR changes in Alzheimer's disease

“…For cross-sectional analysis, the presented d maps and covariates adjusted t maps showed that the cerebellum GM, centrum semiovale, and pons revealed similar performance in 18 F-flortaucipir, but the cerebellum GM was still the recommended reference tissue due to previous cerebral blood flow studies (Rubinski et al, 2021;Zhou et al, 2021). Our previous research has demonstrated that the centrum semiovale reference tissue-based DVR and SUVR at the late phase, as well as the cerebellum GM reference tissue-based R 1 and SUVR at the early phase, demonstrated higher Cohen's d effect size to detect tau deposition with improved quantification power for dynamic 18 F-flortaucipir PET quantifications (Zhou et al, 2021). Notice that the cerebellum GM was frequently used as reference tissue in full dynamic 18 Fflortaucipir PET studies (Baker et al, 2017;Barret et al, 2017;Devous Sr. et al, 2018;Golla et al, 2017).…”

“…To date, the cerebellum GM reference tissue, a region without relevant specific binding, has been suggested for the quantitation of amyloid and tau burden (Baker et al, 2017;Barret et al, 2017;Joachim, Morris, & Selkoe, 1989;Price et al, 2005;Yamaguchi, Hirai, Morimatsu, Shoji, & Nakazato, 1989), as well as for the quantification of the tracer perfusion (Bilgel et al, 2020;Weiner et al, 2013;Zhou et al, 2007Zhou et al, , 2021. For example, cerebellum GM was the suggested reference tissue to estimate relative transport rate R 1 for dynamic 18 F-flortaucipir PET studies (Zhou et al, 2021). Based on the cerebellum GM reference, the R 1 images derived from 11 C-PIB dynamic PET have been used to assess the cerebral blood flow decreases in AD studies (Bilgel et al, 2020).…”

“…A total of 18 ROIs including three reference tissues (cerebellum GM, centrum semiovale, and pons) and an additional 15 ROIs including the orbital frontal, prefrontal, superior frontal, medial temporal, inferior temporal, lateral temporal, parietal, posterior precuneus, anterior cingulate, posterior cingulate, occipital, entorhinal cortex, amygdala, hippocampus, and parahippocampal gyrus regions were manually delineated on the MRI template using the PMOD software program (PMOD 4.002, PMOD Technologies Ltd., Zürich, Switzerland) in standard MNI space. These ROI templates were previously developed in the Johns Hopkins Department of Radiology and have been validated in our former studies (Liu et al, 2019;Paranjpe et al, 2019;Yan et al, 2020Yan et al, , 2021Zhou et al, 2021).…”

“…All baseline scans were included for cross-sectional analysis and participants were classified as either CN (CDR = 0) or CI (CDR ≥ 0.5; Zhou et al, 2021). To investigate the sensitivity of the PET SUVR measurement in discriminating CN from CI, effects sizes were approximated using Cohen's d (Chand et al, 2020;Cohen, 1988;Lopresti et al, 2005;Sullivan & Feinn, 2012;Zhou et al, 2021) of CN and CI groups as follows:…”

“…Wu et al, 2012;Y. G. Wu, 2008), while the 18 F-florbetapir and 18 F-flortaucipir SUVRs can be used to approximate the tracer distribution volume ratio (DVR) of binding to Aβ and tau, respectively (Wong et al, 2010;Zhou et al, 2021;Zhou, Endres, Braši c, Huang, & Wong, 2003;Zhou, Sojkova, Resnick, & Wong, 2012).…”