ntPET: PET Analysis Methods for Tracking Temporal (Phasic) Fluctuations in Neurotransmitter Levels. Validation Experiments and Future Uses.
PET imaging with receptor ligands (e.g., [11C]raclopride) have been used routinely to detect average (tonic) changes in neurotransmitter (e.g., dopamine) levels in response to pharmacological or cognitive stimuli. But conventional analysis of PET data via change in binding potential retains no information regarding the timing of the change. That is, large but short-lived changes in dopamine levels (as would be expected after iv cocaine) may be indistinguishable from moderate but gradual, and long-lived changes (as would be expected with oral methylphenidate). Recently, we have pioneered a suite of analysis tools (models, data-based methods, etc) to extract stimulus-induced temporal patterns of neurotransmitter change contained within dynamic PET data. We have performed preliminary validations of these methods in humans and in animals. These studies have lead to a new type of image data that can be best visualized as parametric maps of time-of-peak-dopamine or as ‘dopamine movies’. The methods will be introduced and the validations presented. We believe that ntPET adds a new dimension to potential PET studies of the brain for which phasic dopamine changes are of import. We have begun to formulate plans for applying our analysis methods to the study of drug abuse and medications for addictions as well as to understanding the long-term side effects of treatments for Parkinson’s disease. A rationale for such applications and future plans will be discussed.