Mark A. Mintun, M.D.

DEPARTMENT OF Radiology
Keywords: brain imaging, cerebral blood flow, depression, dopamine, positron emission tomography (PET)

Dr. Mintun’s research uses positron emission tomography (PET) in human subjects as a tool in the investigation of two distinct areas. The first area of research involves the study of the metabolic needs of the brain during neural work. While cerebral blood flow (CBF) augmentation is considered to be a hallmark of intensified neural activity, recent data from this laboratory have shown that in healthy human subjects the CBF response to physiological stimulation is not altered by stepped hypoglycemia or hypoxia and is driven by factors other than local requirements in glucose or oxygen. Theoretical modeling of oxygen delivery to human brain and actual measurements in healthy humans showed that adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Brain oxygen utilization increases during continuous physiological stimulation. The time course and magnitude of these changes suggest that the energy demands of neuronal activation are initially met predominantly by increased glycolysis, whereas continued neuronal activation eventually requires increased oxidative metabolism. The redox potential of the neural cells (NADH/NAD⁺ or lactate/pyruvate ratio) has been suggested to be an important sensor of blood flow need and this hypothesis was supported by the data obtained in animals and humans with CBF activation studies with lactate and pyruvate injections.

A second area of research involves the use of PET to study the biology of neuropsychiatric diseases. The current interest in the laboratory is the use of serotonergic measures to probe the changes in brain receptor function during treatment of depression with different antidepressant drugs. This research group has recently shown that, using the highly selective radioligand [¹⁸F]-altanserin to image serotonin-2A receptors in vivo, depressed patients have substantially decreased serotonin-2A receptors in the hippocampus compared to normal control subjects. The effect of antidepressant treatment on receptor density is being studied in order to study the responsiveness and down-regulation of this system. Other ongoing research has focused on the biology of addiction and involves the imaging of dopamine receptors in the basal ganglia, measuring the release of dopamine after pharmacologic challenges, and the measure of GABA-A receptors in different patient populations.