Extracting Dopamine Transients from Dynamic PET Data: Application to Cigarette Smoking

Our overall goal is to extract brief neurochemical phenomena from dynamic PET (positron emission tomography) data acquired using tracers that target neuroreceptors. Conventional kinetic models of the uptake and retention of radiotracers which bind to receptors make the assumption that endogenous neurotransmitters (which compete with tracers) are not changing with time during the scan. In the case of fast-acting stimuli that cause only short-lived responses of the dopamine system, this assumption is not valid. We have introduced and validated a suite of kinetic models that can describe tracer uptake in the presence of short-lived neurotransmitter fluctuations induced by stimuli. Cigarette smoking is one such stimulus of interest. The calculated endpoint of our models is a dynamic series of dopamine levels at individual voxels, in the brain, that is, a “dopamine movie.” Dopamine movies reveal differences in spatio-temporal activation patterns in the brains of male and female smokers while they are smoking in the PET scanner. Findings may explain sex-differences in efficacy of treatments for smoking addiction.