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Am J Nucl Med Mol Imaging 2013;3(3):247-260
Original Article
Limitations of SRTM, Logan graphical method, and equilibrium analysis for
measuring transient dopamine release with [11C]raclopride PET
Jenna M Sullivan, Su Jin Kim, Kelly P Cosgrove, Evan D Morris
Yale PET Center, Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale
University, New Haven, CT, USA; Department of Diagnostic Radiology, Yale University School of Medicine, New Have, CT, USA;
Department of Biomedical Engineering, Yale University, New Haven, CT, USA
Received December 23, 2012; Accepted February 14, 2013; Epub April 9, 2013; Published April 15, 2013
Abstract: Conventional PET methods to estimate [11C]raclopride binding potential (BPND) assume that endogenous dopamine
concentration does not change during the scan time. However, this assumption is purposely violated in studies using
pharmacological or behavioral stimuli to invoke acute dopamine release. When the assumption of steady-state dopamine is
violated, conventional analysis methods may produce biased or even unusable estimates of BPND. To illustrate this problem, we
examined the effect of scan duration on ΔBPND estimated by three common analysis methods (simplified reference tissue model,
Logan graphical reference method, and equilibrium analysis) applied to simulated and experimental single-scan activation studies.
The activation – dopamine release – in both the simulated and experimental studies was brief. Simulations showed ΔBPND to be
highly dependent on the window of data used to determine BPND in the activation state. A similar pattern was seen in the data from
human smoking studies. No such pattern of ΔBPND dependence on the window of data used was apparent in simulations where
dopamine was held constant. The dependence of ΔBPND on the duration of data analyzed illustrates the inability of conventional
methods to reliably quantify short-lived increases in endogenous dopamine. (ajnmmi1212003).
Keywords: Binding potential (BPND), transient dopamine release, model selection, scan duration, smoking, time-invariant
Address correspondence to: Dr. Evan D Morris, Positron Emission Tomography (PET) Center, Yale University, 801 Howard Avenue,
PO Box 208048 New Haven, CT 06520-8048. Phone: 203-737-5752; Fax: 203-785-3107; E-mail: evan.morris@yale.edu
Original Article
Limitations of SRTM, Logan graphical method, and equilibrium analysis for
measuring transient dopamine release with [11C]raclopride PET
Jenna M Sullivan, Su Jin Kim, Kelly P Cosgrove, Evan D Morris
Yale PET Center, Department of Diagnostic Radiology, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale
University, New Haven, CT, USA; Department of Diagnostic Radiology, Yale University School of Medicine, New Have, CT, USA;
Department of Biomedical Engineering, Yale University, New Haven, CT, USA
Received December 23, 2012; Accepted February 14, 2013; Epub April 9, 2013; Published April 15, 2013
Abstract: Conventional PET methods to estimate [11C]raclopride binding potential (BPND) assume that endogenous dopamine
concentration does not change during the scan time. However, this assumption is purposely violated in studies using
pharmacological or behavioral stimuli to invoke acute dopamine release. When the assumption of steady-state dopamine is
violated, conventional analysis methods may produce biased or even unusable estimates of BPND. To illustrate this problem, we
examined the effect of scan duration on ΔBPND estimated by three common analysis methods (simplified reference tissue model,
Logan graphical reference method, and equilibrium analysis) applied to simulated and experimental single-scan activation studies.
The activation – dopamine release – in both the simulated and experimental studies was brief. Simulations showed ΔBPND to be
highly dependent on the window of data used to determine BPND in the activation state. A similar pattern was seen in the data from
human smoking studies. No such pattern of ΔBPND dependence on the window of data used was apparent in simulations where
dopamine was held constant. The dependence of ΔBPND on the duration of data analyzed illustrates the inability of conventional
methods to reliably quantify short-lived increases in endogenous dopamine. (ajnmmi1212003).
Keywords: Binding potential (BPND), transient dopamine release, model selection, scan duration, smoking, time-invariant
Address correspondence to: Dr. Evan D Morris, Positron Emission Tomography (PET) Center, Yale University, 801 Howard Avenue,
PO Box 208048 New Haven, CT 06520-8048. Phone: 203-737-5752; Fax: 203-785-3107; E-mail: evan.morris@yale.edu
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