PET Studies of Brain Glucose Metabolism and Blood Flow

by National Institute of Health

(Page 5 of 6)

Glucose Metabolism

To function properly, the brain needs a continuous supply of the sugar glucose, whose breakdown provides most of the energy the cells need for their diverse functions. Brain regions that are more active, including the cells of rapidly growing tumors, require more glucose. Similarly, lower-than-normal glucose metabolism suggests reduced brain activity indicative of neurological or cognitive problems. PET studies can help researchers identify brain regions that are active at any given time by administering radioactively labeled glucose and measuring its distribution in the brain. Brain glucose metabolism detectable with PET occurs mainly in the gray matter - the brain regions where the bodies of neurons are located. The amount of gray matter in the brain, however, can vary substantially among subjects. For example, chronic alcoholics frequently have smaller gray-matter volumes than nonalcoholics. Therefore, data regarding glucose metabolism must be expressed in terms of the gray-matter volume of a specific region, which can be determined by structural imaging techniques such as MRI.

PET studies have shown that glucose metabolism in alcoholics is decreased in the entire brain, with the most marked reductions in the frontal lobes and cerebellum. However, an assessment of the effects that reduced glucose metabolism may have on brain functioning in people with alcohol dependence is complicated by the alcohol-induced damage to other organs (the liver, stomach, or other vital organs) often found in those people. For example, people with liver cirrhosis resulting from chronic alcohol consumption exhibit decreased glucose utilization by gray matter in the frontal and temporal lobes as well as the basal ganglia. Thus, neurological and cognitive problems of alcoholics may not only be a consequence of reduced glucose metabolism but may reflect the effects of alcohol-induced liver, kidney, and heart dysfunction on the brain. Furthermore, glucose may play a different role in brain metabolism in alcoholics with clear neurological or cognitive problems than in healthy people. Further research is needed to clarify glucose metabolism in alcoholics with neurological and cognitive problems.

Regional Blood Flow

Glucose is brought to the brain via the bloodstream; accordingly, the rates of regional cerebral blood flow (rCBF) within various areas of the brain are regulated depending on the changing demands of these areas. This variability in blood flow depending on regional brain activity is the basis for using PET to measure rCBF. To detect changes in rCBF, investigators inject a radiotracer (typically radioactively labeled water, H2O) into the bloodstream and measure its deposition in the brain tissue, which is determined by the regional distribution of blood flow. 15O has a short half-life of 2 minutes and therefore can be injected repeatedly while the subjects perform various motor, sensory, or cognitive tasks under different conditions. Assessing the differences in blood flow between tasks enables investigators to identify the brain regions involved in each specific task. This approach can also be used to track the effects of acute alcohol ingestion on regional blood flow over a period of time.

Correlating Structural and Physiological Changes with Alcohol-Related Behaviors

Once PET and other studies have identified changes in brain structure and functioning of alcoholics, investigators must correlate these changes to alcohol-related behaviors in those patients. For example, studies have linked both shrinkage of the cerebellum and decreased blood flow in this region, as determined by imaging studies, to impaired balance and gait, which may cause falls, particularly in older alcoholics. Falls can result in head injuries and further deterioration in brain function. Other functional imaging studies have shown that decreases in blood flow and metabolism in the frontal lobes precede shrinkage of that brain region and major cognitive abnormalities.

Imaging studies also have demonstrated that cognitive functions and motor coordination may improve partially within 3 to 4 weeks of abstinence and that these improvements are accompanied by a partial reversal of brain shrinkage. Frontal lobe blood flow also increases with abstinence, returning to normal levels within 4 years, whereas a relapse to drinking leads to renewed brain shrinkage and blood flow reductions.

Finally, PET studies have helped researchers assess risk factors for alcoholism. In nonalcoholics, certain sedatives (benzodiazepines) produce a temporary impairment in coordination and cognition and a decrease in brain glucose metabolism similar to the effects of alcohol consumption. In alcoholics, however, some regions in the frontal lobe respond to benzodiazepines less strongly than they do in nonalcoholics. These results suggest that alcoholics may have a diminished capacity to dampen excessive neuronal activity and therefore may be less able to inhibit behavior.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.