Lithium spectroscopic imaging of rat brain at therapeutic doses

Since the discovery that lithium (Li) is efficacious for the treatment of manic depressive illness, the brain Li distribution of mammals treated with lithium has been of interest. However, the spatial relationship of lithium in the brain regions to its function remains largely unknown. Knowledge of Li distribution in the brain is necessary to localize its action in the brain. Both the therapeutic and neurotoxic side effects of Li are centered mainly in the central nervous system and hence there is considerable interest in understanding the extent of lithium penetration into the central nervous system. The mechanism by which neurotoxic side effects are generated is not known and may, in part, be related to the particular distribution of lithium in the brain. The regional specificity in lithium's brain distribution could underlie important steps on its action. Li levels in various brain regions for autopsied rats and humans have been reported. However, many results are conflicting due to ion redistribution at death or during sample preparation. A direct nondestructive measurement of Li levels in the brain where the drug exerts its effects is certainly desirable. Because magnetic resonance technique can be used to observe Li, it can be an appropriate method to monitor and map the distribution in the brain. The application of MR technology to rat brain regions has provided information on lithium distribution in a non-invasive manner. The earlier development work at lower field strengths provided brain lithium information at high dose of Li administration. Here we demonstrate the feasibility of quantitative spectroscopic imaging on rat brain under therapeutic doses.