An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge

Yun Zhou, Ming Kai Chen, Christopher J. Endres, Weiguo Ye, James R. Brašić, Mohab Alexander, Andrew H. Crabb, Tomás R. Guilarte, Dean F. Wong

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background: Equilibrium analysis to quantify dynamic positron emission tomography (PET) with bolus followed by continuous tracer infusion and acute amphetamine challenge assumes that all tissue kinetics attain steady states during pre- and post-challenge phases. Violations of this assumption may result in unreliable estimation of the amphetamine-induced percent change in the binding potential (ΔBP%). Method: We derived an extended simplified reference tissue model (ESRTM) for modeling tracer kinetics in the pre- and post-challenge phases. Ninety-minute [11C]raclopride PET studies with bolus injection followed by continuous tracer infusion were performed on 18 monkeys and 2 baboons. Forty minutes after the bolus injection, a single acute intravenous amphetamine administration was given of 2.0 mg/kg to monkeys and of 0.05, 0.1, 0.5, and 1.5 mg/kg to baboons. Computer simulations further evaluated and characterized the ESRTM. Results: In monkey studies, the ΔBP% estimated by the ESRTM was 32 ± 11, whereas, the ΔBP% obtained using the equilibrium methods was 32% to 81% lower. In baboon studies, the ΔBP% values estimated with the ESRTM showed a linear relationship between the ΔBP% and the natural logarithm of amphetamine dose (R2 = 0.96), where the ΔBP% = 10.67Ln(dose) + 33.79 (0.05 ≤ dose in mg/kg ≤ 1.5). At 1.5 mg/kg amphetamine, the ΔBP% estimates from equilibrium methods were 18% to 40% lower than those estimated by the ESRTM. Results showed that the nonsteady state of tracer kinetics produced an underestimation of the ΔBP% from the equilibrium analysis. The accuracy of the ΔBP% estimates from the equilibrium analysis was significantly improved by the ESRTM. The ΔBP% estimated by the ESRTM in the study was consistent with that from previous [11C]raclopride PET with amphetamine challenge. Conclusion: In conclusion, the ESRTM is a robust kinetic modeling approach and is proposed for the quantification of dynamic PET with acute amphetamine stimulation.

Original languageEnglish
Pages (from-to)550-563
Number of pages14
JournalNeuroImage
Volume33
Issue number2
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

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    Zhou, Y., Chen, M. K., Endres, C. J., Ye, W., Brašić, J. R., Alexander, M., Crabb, A. H., Guilarte, T. R., & Wong, D. F. (2006). An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge. NeuroImage, 33(2), 550-563. https://doi.org/10.1016/j.neuroimage.2006.06.038