TY - JOUR
T1 - Optimization of the k'2 Parameter Estimation for the Pharmacokinetic Modeling of Dynamic PIB PET Scans Using SRTM2
AU - Peretti, D. bora E.
AU - Reesink, Fransje E.
AU - Doorduin, Janine
AU - de Jong, Bauke M.
AU - de Deyn, Peter P.
AU - Dierckx, Rudi A. J. O.
AU - Boellaard, Ronald
AU - Vállez García, David
PY - 2019/12/12
Y1 - 2019/12/12
N2 - Background: This study explores different approaches to estimate the clearance rate of the reference tissue (k'2) parameter used for pharmacokinetic modeling, using the simplified reference tissue model 2 (SRMT2) and further explores the effect on the binding potential (BPND) 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 k'2 : 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 BPSRTMND thresholds. Results: The different approaches resulted in distinct k'2 estimations per subject. The median value of the estimated k'2 across all subjects in the whole brain was 0.057. In general, PIB+ subjects presented smaller k'2 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 BPSRTMND and BPSRTM2ND for both groups (R2 = 0.85 for PIB+, and R2 = 0.88 for PIB–). Lastly, a sensitivity analysis showed that overestimating k'2 values resulted in less biased BPSRTM2ND estimates. Conclusion: Setting a threshold on BPSRTMND might be the best method to estimate k'2 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.
AB - Background: This study explores different approaches to estimate the clearance rate of the reference tissue (k'2) parameter used for pharmacokinetic modeling, using the simplified reference tissue model 2 (SRMT2) and further explores the effect on the binding potential (BPND) 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 k'2 : 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 BPSRTMND thresholds. Results: The different approaches resulted in distinct k'2 estimations per subject. The median value of the estimated k'2 across all subjects in the whole brain was 0.057. In general, PIB+ subjects presented smaller k'2 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 BPSRTMND and BPSRTM2ND for both groups (R2 = 0.85 for PIB+, and R2 = 0.88 for PIB–). Lastly, a sensitivity analysis showed that overestimating k'2 values resulted in less biased BPSRTM2ND estimates. Conclusion: Setting a threshold on BPSRTMND might be the best method to estimate k'2 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85077287766&origin=inward
U2 - https://doi.org/10.3389/fphy.2019.00212
DO - https://doi.org/10.3389/fphy.2019.00212
M3 - Article
SN - 2296-424X
VL - 7
JO - Frontiers in Physics
JF - Frontiers in Physics
M1 - 212
ER -