Research studies of brain metabolism and blood flow using positron emission tomography (PET) are proposed, with emphasis on studies of malignant gliomas of the brain. A project on malignant gliomas headed by the applicant will test hypotheses regarding the effects of corticosteroids on the blood-brain barrier, the relative advantage of carotid intra-arterial administration of the chemotherapeutic drug BCNU over intravenous administration, the effects of antineoplastic treatment on tumor glucose and oxygen metabolism, and the possible limitation in supply of glucose and oxygen as metabolic substrates in tumor. The applicant will collaborate with Dr. Sid Gilman on PET studies of abnormal motor function including studies of the metabolic correlates of abnormal posture following stroke, the barbiturate contrast method in stroke, and metabolism and blood flow in idiopathic dystonia and olivopontocerebellar atrophy. He will also collaborate with Dr. Bernard Agranoff on PET studies of normal aging and dementia including studies of the differential effects of sensory activation and barbiturate depression on glucose metabolism in aging and dementia, approaches to the measurement of brain protein synthesis, and application of protein synthesis measurement in aging and dementia. He will perform computer modeling studies to test a new algorithm proposed by the applicant for PET measurement of cerebral blood flow using oxygen 15-H2O and compare it to existing algorithms. He will test a hypothesis concerning compartmentation of oxygen 15-H2O in cerebral blood flow studies by computer analysis of PET data from normal subjects. In conjunction with his interest in brain tumor metabolism, he will participate in a clinical trial, headed by Dr. Harry Greenberg, of a new treatment regimen for malignant gliomas.
