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Title
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Optimization of the parameter estimation for the pharmacokinetic modeling of dynamic PIB PET scans using SRTM2
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Author
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Abstract
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| 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 (BPND) of C-11-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 (R-2 = 0.85 for PIB+, and R-2 = 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. |
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Language
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English
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Source (journal)
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Frontiers in physics. - 2013, currens
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Publication
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2019
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ISSN
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2296-424X
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DOI
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10.3389/FPHY.2019.00212
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Volume/pages
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7
(2019)
, 11 p.
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Article Reference
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212
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ISI
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000504749800001
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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