4.0 T Water Proton T 1 Relaxation Times in Normal Human Brain and During Acute Ethanol Intoxication William D. Rooney, Jing-Huei Lee, Xin Li, Gene-Jack Wang, Dinko Franceschi, Charles S. Springer, Jr, and Nora D. Volkow Background: It has been reported that acute ethanol intoxication decreases the brain water proton magnetic resonance T 1 values, an effect that has been interpreted to indicate brain dehydration during this condition. Because water macromolecular interactions largely determine tissue water T 1 , another possible explanation for reduced brain water proton T 1 values is that the interaction between water and brain macromolecules is altered by ethanol. Methods: A 4.0 T magnetic resonance imaging (MRI) instrument was used to measure brain water proton T 1 relaxation times before, during, and after ethanol intoxication (dose, 0.75 mg/kg) in healthy controls. Results: The T 1 relaxation times as assessed with MRI were highly reproducible. The mean, paired ethanol-induced differences in T 1 were -0.004  0.007 sec (mean  standard deviation) for white matter and 0.010  0.015 sec for internal gray matter structures, neither of which was significant. Conclusions: This reasonably sensitive measurement does not support the view that tissue water content or water macromolecule interactions are significantly altered in the brain during acute alcohol intoxication in otherwise healthy subjects. Key Words: Brain Water, T 1 Relaxation Time, Magnetic Resonance Imaging, Acute Alcohol Intoxica- tion. T HE MECHANISMS OF ethanol intoxication have been investigated widely but are poorly understood. Theories that mechanisms invoke nonspecific membrane interactions largely have been replaced by proposals of direct interaction between ethanol and multiple receptor proteins (Faingold et al., 1998). Indirect mechanisms, how- ever, have not been supplanted completely. One hypothesis is that a nonspecific ethanol-induced membrane disruption alters receptor protein conformation (Melgaard, 1983; Tan and Weaver, 1997), whereas another suggests that ethanol displaces water from cellular macromolecules, which leads to conformation changes in membrane proteins (Isobe et al., 1994; Klemm, 1990). These proposals share the com- mon feature that the interaction dynamics between water and brain macromolecules may be altered when ethanol is present. The nuclear magnetic resonance (NMR) longitu- dinal relaxation time (T 1 ) of water protons is sensitive both to water fraction (Lynch, 1983) and to the molecular prop- erties of macromolecular sites (Venu et al., 1997). If either is sufficiently affected during ethanol intoxication, it could alter the relaxation time of the water proton NMR signal. In fact, several magnetic resonance studies have reported decreases in brain water proton T 1 values during acute ethanol intoxication (Besson et al., 1981; Hirakawa et al., 1994; Isobe et al., 1994; Mander et al., 1985) and have interpreted these findings to support the postulate of brain dehydration during this condition. Although these studies did not attempt to quantitate the proposed dehydration, it can be estimated. Using a linear relationship between brain water content and the inverse of the water proton relax- ation time, (T 1 ) -1 (Boisvert et al., 1990; Naruse et al., 1986; Rooney et al., 1996), we estimate that the reported 1% to 22% relative decrease in T 1 values (Besson et al., 1981; Hirakawa et al., 1994; Isobe et al., 1994; Mander et al., 1985) would correspond to a 0.4% to 9% decrease in brain water content. However, the relevance of these findings is limited for several reasons. First, the preclinical studies used ethanol doses that were much higher than those re- quired for intoxication in humans (Hirakawa et al., 1994; Isobe et al., 1994). Second, although a clinical study re- ported that water proton T 1 decreases during ethanol in- toxication, only alcoholic subjects were studied (Besson et al., 1981), so it is unclear the extent to which the T 1 decrease reflects acute versus chronic effects. To our knowledge only two studies have evaluated the effects on T 1 relaxation times of acute ethanol administration in hu- From the Chemistry (W.D.R., J-H.L, X.L., C.S.S.) and Medical (G-J.W., D.F., N.D.V.) Departments, Brookhaven National Laboratory, Upton, New York. Received for publication August 31, 1999; accepted March 3, 2000. This work was supported by Contracts DE-AC01–76CH00016 and DE- AC02–98CH10886 from the Department of Energy, Office of Biological and Environmental Research, and Grant AA 09481 from the National Institutes of Health. Reprint requests: William D. Rooney, Ph.D., Brookhaven National Lab- oratory, High-Field MRI Lab, Bldg. 560, P.O. Box 5000, Upton, NY 11973- 5000. Copyright © 2000 by the Research Society on Alcoholism. 0145-6008/00/2406-0830$03.00/0 ALCOHOLISM:CLINICAL AND EXPERIMENTAL RESEARCH Vol. 24, No. 6 June 2000 830 Alcohol Clin Exp Res, Vol 24, No 6, 2000: pp 830–836