We propose to test hypotheses important to the understanding of several cerebral disorders which are characterized by regional dysfunctions involving altered cerebral perfusion, metabolism, amino acid utilization, or neurotransmitter processes. To accomplish this positron emission tomography (PET) will be applied to quantify these local cerebral measures. New PET markers will be introduced, in addition to those already available, to permit in vivo determination of neurotransmitter processes associated with dopaminergic, noradrenergic, serotonergic, cholinergic, glutaminergic, and GABAergic systems. This will be accomplished by a cohesive development process for selection of new radiotracers, preparation in positron-emitter labeled form, evaluation in small animals and then in primates, development of mathematical models, and assessment of radiotracer pharmacokinetics in human PET studies. Clinical research projects are supported by scientific cores responsible for cyclotron, chemistry, tomography, data analysis and administrative functions. It is expected that these efforts will enhance understanding and improve diagnosis and management of patients with disorders of motor function, Huntington's disease, Parkinson's disease, brain tumors, and epilepsy.
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