Most people know about the standard methods used to measure alcohol concentrations in breath and blood, even if they haven’t personally experienced apprehension for driving while impaired (DWI). A study in the August issue of Alcoholism: Clinical & Experimental Research has refined this ability even further, using proton (1H) magnetic resonance spectroscopy (MRS) to directly measure alcohol concentrations throughout the brain. While this new capability won’t be applied any time soon to suspect DWI offenders, it will help researchers who seek to understand the biological basis for alcohol abuse.
"The scientific community is still uncertain about how exactly alcohol causes intoxication, tolerance, and dependence," said Marc J. Kaufman, assistant professor of psychiatry at Harvard Medical School and associate research pharmacologist at McLean Hospital. He explained that researchers believe that alcohol’s effects are produced by its interaction with brain membranes. Membranes contain protein elements called "receptors" that communicate neuronal activity, allowing us to move, feel, think, and remember. In order to function correctly, receptors must be correctly positioned in membranes. Alcohol appears to adhere to or stick to membranes, thereby disrupting receptor positioning, which leads to altered brain function, intoxication, tolerance, and the development of alcohol problems.
"For the first time," said Kaufman, "this study documents in the living human brain this adherence phenomenon, called the ‘magnetization transfer’ effect. By providing new data on the physical interactions between alcohol and the human brain, this study takes an important step toward clarifying the mechanisms that cause alcohol problems."
Dieter J. Meyerhoff, associate professor of radiology at the University of California - San Francisco and lead author of the study, expanded on the complexities of alcohol’s effects on the brain, and the challenges of measuring these effects.
"When you pour a red aqueous liquid in a glass of water," he said, " you can see that it is not distributed evenly throughout the glass right away. You have to wait a while until all of the water in the glass has the same light-red color. This mechanism of distribution is called diffusion or, more generally, equilibration. It takes about an hour for the alcohol that has been ingested to distribute throughout different tissues and regions of the brain. After this equilibration period, the brain alcohol signal strength is linearly related to the breath and blood alcohol concentrations." Scientists can use this co-linearity in breath, blood, and brain measurements to ‘map’ alcohol’s effects on the brain, to a degree.
"Alcohol likely exists in more than one molecular environment in tissue," Meyerhoff explained. "One, it exists in intra- and extra-cellular fluid, just as it would exist in a glass of water, and we call this ‘free’ alcohol. Two, it exists in a molecular state where it interacts with or adheres to cell membranes, and this fraction we call ‘bound’ alcohol. 1H MRS technology allows direct measurement of free alcohol, but not of bound alcohol. Therefore, bound alcohol is also called ‘MRS-invisible.’" Yet, as Kaufman noted earlier, it is this bound, MRS-invisible alcohol that is believed responsible for altered brain function. So, scientists find themselves trying to determine the amount of the invisible fraction of brain alcohol in order to calculate the total concentration of alcohol in the brain.
"The exact concentration of alcohol in the brain is the sum of both free and bound alcohol," continued Meyerhoff. "If we can detect in the brain 90% of what is found in the blood and breath, that means that 10% must be bound. If we measure 50%, that means that the other 50% must be bound. That is a big difference and, considering that the bound alcohol is probably responsible for the effects of alcohol on brain and function, it is critical to know the exact proportions that are involved."
Alcohol may also have different effects on different parts of the brain, which again may be detectable by 1H MRS technology. For example, said Meyerhoff, it is assumed that brain alcohol concentration is proportional to the concentration of water in the brain. That is, the distribution of alcohol depends solely on the concentration of water in brain tissue. White matter is about 70 percent water, and gray matter about 85 percent water.
"Therefore," he explained, "there should be more alcohol in gray matter than in white matter. Yet different regions of the brain contain different amounts of white and gray matter, so it is thought that they also contain different amounts of alcohol. It is known that some brain regions are affected to different degrees by the chronic presence of alcohol. For example, the frontal brain regions shrink preferentially due to long-term heavy drinking. It is also known that alcohol affects brain function, which may be due to the actual amount of alcohol in the brain region that subserves these functions. So, one of the questions we could ask is if region-specific brain shrinkage or specific brain dysfunction due to chronic alcohol abuse may be due to different concentrations of alcohol in the brain. 1H MRS technology can potentially answer this question."
Although excited about the research, Kaufman said "it is unlikely that the measurement of human brain alcohol with magnetic resonance spectroscopy, as described by this study, will be used widely. Certainly there are easier and more cost-efficient ways to do this. In fact, brain alcohol levels can be reasonably estimated from an arterial blood sample." As well, noted Meyerhoff, changes in brain alcohol concentrations are generally well reflected by changes in breath alcohol concentrations. Then why the fuss? Both scientists noted that the true value of this study involves the future applications of what has been uncovered.
"These findings are undeniably valuable for researchers who study the physical interactions of alcohol and brain membranes," explained Kaufman. "Some researchers, for example, have proposed that alcohol adheres to membranes differently in heavy drinkers who have developed alcohol tolerance. This is important because alcohol tolerance is thought to predispose people to develop alcohol problems or become alcoholics. Future studies in this area will characterize the biophysics of alcohol/neuronal membrane interactions that will likely result in alcohol intoxication, tolerance, and dependence. In short, a better understanding of the molecular interactions that are associated with these behavioral states should lead to the development of treatment options."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Fein, G., & Meyerhoff, D.J. (2000, August). Ethanol in human brain by magnetic resonance spectroscopy: Correlation with blood and breath levels, relaxation, and magnetization transfer. Alcoholism: Clinical and Experimental Research, 24(8), 1227-1235.
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