AUTHOR=Peretti Débora E. , Reesink Fransje E. , Doorduin Janine , de Jong Bauke M. , De Deyn Peter P. , Dierckx Rudi A. J. O. , Boellaard Ronald , Vállez García David TITLE=Optimization of the k2′ Parameter Estimation for the Pharmacokinetic Modeling of Dynamic PIB PET Scans Using SRTM2 JOURNAL=Frontiers in Physics VOLUME=7 YEAR=2019 URL=https://www.frontiersin.org/journals/physics/articles/10.3389/fphy.2019.00212 DOI=10.3389/fphy.2019.00212 ISSN=2296-424X ABSTRACT=

Background: This study explores different approaches to estimate the clearance rate of the reference tissue (k2′) parameter used for pharmacokinetic modeling, using the simplified reference tissue model 2 (SRMT2) and further explores the effect on the binding potential (BP_ND) of ¹¹C-labeled Pittsburgh Compound B (PIB) PET scans.

Methods: Thirty subjects underwent a dynamic PIB PET scan and were classified as PIB positive (+) or negative (–). Thirteen regions were defined from where to estimate k2′: the whole brain, eight anatomical region based on the Hammer's atlas, one region based on a SPM comparison between groups on a voxel level, and three regions using different BPNDSRTM thresholds.

Results: The different approaches resulted in distinct k2′ estimations per subject. The median value of the estimated k2′ across all subjects in the whole brain was 0.057. In general, PIB+ subjects presented smaller k2′ estimates than this median, and PIB–, larger. Furthermore, only threshold and white matter methods resulted in non-significant differences between groups. Moreover, threshold approaches yielded the best correlation between BPNDSRTM and BPNDSRTM2 for both groups (R² = 0.85 for PIB+, and R² = 0.88 for PIB–). Lastly, a sensitivity analysis showed that overestimating k2′ values resulted in less biased BPNDSRTM2 estimates.

Conclusion: Setting a threshold on BPNDSRTM might be the best method to estimate k2′ in voxel-based modeling approaches, while the use of a white matter region might be a better option for a volume of interest based analysis.