Estimating intracellular lithium in brain in vivo by localized 7Li magnetic resonance spectroscopy

The therapeutic mechanism of action of lithium (Li) in bipolar disorder is unknown. While Li is presumed to work intracellularly in the brain, the fraction of intracellular Li in the brain in vivo is not known. It has not yet been possible to determine, directly and noninvasively, the intra- to extracellular distribution of Li in human brain in vivo. Lithium-7 ((7)Li) MR is the only technique available for measuring noninvasively the concentration of Li in the brain in vivo. Here the individual components of biexponential (7)Li transverse (T(2)) relaxation in rat brain in vivo are identified with intra- and extracellular Li, and used to estimate its compartmental distribution. Intracellular T(2) was 14.6 +/- 6.9 ms, while extracellular T(2) was 160 +/- 52 ms in nine rats. The fraction of intracellular brain Li ranged from 37% to 75% (mean: 63 +/- 11%). Further, the biexponential T(2) results provided the basis for estimating Li compartmental distribution from monoexponential T(2) decays using a simple linear approximation. The fraction of intracellular Li estimated from monoexponential T(2) decays agreed with the corresponding biexponential estimates in most cases.