TY - JOUR
T1 - An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge
AU - Zhou, Yun
AU - Chen, Ming Kai
AU - Endres, Christopher J.
AU - Ye, Weiguo
AU - Brašić, James R.
AU - Alexander, Mohab
AU - Crabb, Andrew H.
AU - Guilarte, Tomás R.
AU - Wong, Dean F.
N1 - Funding Information:
We thank the cyclotron and PET staff of the Johns Hopkins Medical Institutions. This study was funded by NIH grants ES10975, DA00412, DA11080, AA12839, NS38927, and HD2448. This work was partially presented at XXIInd International Symposium on Cerebral Blood Flow, Metabolism, and Function VIIth International Conference on Quantification of Brain Function with PET, Amsterdam, The Netherlands, June 7–11, 2005; and at The 52nd Society of Nuclear Medicine Annual Conference, June 18–22, 2005 in Toronto, Canada.
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuroimage.2006.06.038
DO - 10.1016/j.neuroimage.2006.06.038
M3 - Article
C2 - 16920365
AN - SCOPUS:33749266479
SN - 1053-8119
VL - 33
SP - 550
EP - 563
JO - NeuroImage
JF - NeuroImage
IS - 2
ER -