A non parametric method for the extraction of temporal information on neurotransmitter release from PET dynamic data
Abstract
Dynamic Positron Emission Tomography (PET) with radiolabeled receptor tracers such as [11C]raclopride has been used to detect the time-averaged effect of the release of endogenous dopamine (DA) in response to stimulation. Because the dynamics of drug-induced increases in DA may be associated with the rewarding properties of drugs of abuse there would be great value in being able to recover non-invasively the temporal pattern of DA increases in specific brain regions. We propose a non-parametric approach (non-parametric ntPET) to the analysis of dynamic PET data for extracting temporal characteristics of the free DA change (FDA ). A model-independent method is valuable because it alleviates the need to pre-assume a particular functional form for neurotransmitter release over time. An algebraic method based on singular value decomposition (SVD) is applied to simulated data under both rest (DA at baseline) and activated (transient DA release) conditions. We tested our method with simulated sets of realistic time activity curves representing uptake of [11C]raclopride, a DA receptor antagonist, in the brain. The timing of DA release was accurately recovered. We have applied our method to PET scans of 8 subjects. Each subject underwent two [11C]raclopride PET scans during which they either received iv alcohol or were shown visual cues related to alcohol. Each subject also received a rest scan. To support our findings, we devised and tested three hypotheses regarding the expected behavior of the FDA curves based on previous theoretical work that predicts the conventional change in binding potential as a function of FDA and tracer kinetics. The F DA curves recovered from our experiments in humans all conformed to our expectations. We have further extended non-parametric ntPET to a voxel-wise analysis of functional brain images from two PET acquisitions to create dynamic (4D) images of neurotransmitter (NT) level in the brain following a drug. As a result, we are able to present the first “movie” of DA release in the human brain during alcohol administration. Non-parametric ntPET promises a non-invasive and model-independent technique for determining the dynamics of the response of a neurotransmitter to cognitive or pharmacological stimuli at the regional or brain-wide level.
Degree
Ph.D.
Advisors
Bouman, Purdue University.
Subject Area
Biomedical research
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