EVIDENCE OF MULTIPLE ETHANOL POOLS IN THE BRAIN - AN IN-VIVO PROTON MAGNETIZATION-TRANSFER STUDY

Studies of isolated cell membranes and animal brain extracts have show n that ethanol (EtOH) partitions into cell membranes. We tested the hy pothesis that EtOH in the living brain after EtOH administration exist s in two or more pools: a free, mobile pool of EtOH and one or more Et OH pools that are restricted in their molecular mobility, possibly bec ause of association with membranes. In vivo brain proton magnetic reso nance spectroscopy (H-1 MRS) routinely detects the methyl protons of t he mobile EtOH pool but does not detect motionally restricted EtOH. We used in vivo brain H-1 MRS in rat brain (n = 11) after intraperitonea l EtOH administration to measure the signal intensity of methyl EtOH p rotons in the presence and absence of off-resonance saturation. Off-re sonance saturation resulted in a 33 +/- 4% decrease of the EtOH methyl proton signal. We interpret this signal reduction as a magnetization transfer effect It is consistent with the existence of an MRS-invisibl e EtOH pool with restricted molecular mobility, which is in exchange w ith the free EtOH pool. Off-resonance saturation at the water frequenc y resulted in an even larger decrease of the EtOH methyl signal, consi stent with water molecules being in close proximity to EtOH molecules at the restricted motion site(s). These results provide support for th e hypothesis that partial MRS-invisibility of brain EtOH is at least t o some extent caused by the presence of a (MRS-invisible) pool of moti onally restricted EtOH. They also strongly suggest that water suppress ion, routinely used in in vive H-1 MRS, may reduce the observable EtOH methyl signal intensity through a magnetization transfer mechanism. T hese studies may provide both a mechanism of, and a means to investiga te the alterations of EtOH MRS visibility observed in heavy drinkers.