Ethanol in human brain by magnetic resonance spectroscopy: Correlation with blood and breath levels, relaxation, and magnetization transfer

Background: proton magnetic resonance spectroscopy (H-1 MRS) allows measurement of alcohol in the human brain after alcohol consumption. However, the quantity of alcohol that can be detected in the brain by H-1 MRS pulse sequences has been controversial, with values ranging from about 24% to 94% of the temporally concordant blood alcohol concentrations. The quantitation of brain alcohol is critically affected by the kinetics of alcohol uptake and elimination, by the relaxation times of the protons that give rise to the brain alcohol signal, and by the specifics of both pulse sequence timing and radio frequency pulse applications. Methods: We investigated these factors in 20 light-drinking subjects after oral administration of approximately 0.85 g/kg body weight of alcohol by localized H-1 MRS and measurements of blood and breath alcohol concentrations obtained at the same time. Specifically, we measured transverse and longitudinal relaxation times of brain alcohol and its signal saturation on application of on- or off-resonance radio frequency pulses. All H-1 MRS measurements were performed at a time after brain and blood alcohol concentrations had equilibrated. Results: H-1 MRS measures of brain alcohol were correlated highly with both breath and blood alcohol concentrations after equilibration in brain tissue. The measured H-1 MRS relaxation times of brain alcohol were shorter than given in previous reports that were limited by smaller subject numbers, improper use of H-1 MRS methods, and estimates rather than measurements. The brain alcohol signal decreased by about 30% on application of on- or off-resonance saturation pulses. Conclusions: H-1 MRS allows direct measurement of brain alcohol, formerly only possible indirectly through inferences from breath alcohol levels. Quantitation of brain alcohol levels need to take into account measured relaxation times and alcohol signal attenuation due to presence and timing of standard radio frequency MRS pulses. Saturation experiments give evidence for the existence of more than one compartment of brain alcohol characterized by different molecular environments. They suggest that a fraction of brain alcohol is invisible to H-1 MRS.