We propose to establish a facility at University of Michigan for the development of a new, non-invasive approach to human brain research utilizing positron emitting metabolic and pharmacologic probes. A dedicated medical cyclotron, a """"""""head only"""""""" positron-emission tomographic scanner, and expanded radiochemical/radiopharmaceutical facilities will complement an existing nuclear medicine facility. Proposed studies have involved the use of established positron-emitting probes, 13N-ammonia, 11C or 18F-2-deoxyglucose, and 11C-valine, to study metabolic correlates of Huntington's disease, seizure disorders, inner ear disease, and strokes resulting from sickle cell anemia. We will also investigate the hypotonic and hypertonic phases of paralysis associated with stroke. New positron-emitting radiopharmaceuticals will also be synthesized. 18F-valine and related amino acids will be used initially for the evaluation of brain protein synthesis in phenylketonuria and then will be extended to the study of other conditions associated with this project. Inert halogenated hydrocarbons will be employed to visualize brain white matter in associated feasibility studies from multiple sclerosis and patients with white matter infarctions. Probes of cholinergic and dopaminergic receptors, 11C-quinuclidinyl benzilate, 11C-spiroperidol, and related analogs, are proposed in connection with the studies on Huntington's disease.
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