A ⁷Li NMR study of visibility, spin relaxation, and transport in normal human erythrocytes

Abstract

The behavior of the lithium (Li) ion in normal human erythrocytes has been studied by 7Li NMR. The uptake of Li into the cells was followed as a function of solution conditions, temperature, hematocrit, and blood age using dysprosium tripolyphosphate shift reagent. Under our conditions the uptake of Li increases with increasing hematocrit and blood age. For packed cells the extracellular 7Li spin-lattice relaxation time was only slightly longer than the intracellular relaxation time. Thus, T1 may not be useful for separate observation of intra- and extracellular Li in vivo. The intra- and extracellular T2s were substantially shorter than the corresponding T1s. Also, the intracellular T2 was considerably shorter than that for the extracellular compartment, suggesting that T2 may provide a noninvasive handle for observation of intracellular Li. Nuclear Overhauser enhancements could be observed for both extra- and intracellular 7Li, confirming that dipolar coupling to 1H is a contributing relaxation mechanism. The 7Li NMR visibility was essentially 100% at high Li concentrations, decreasing to about 84% at 1 mM Li. Based on time course studies of the invisibility, and a comparison of NMR and inductively coupled plasma results, it appears that the invisibility of the intra- and extracellular compartments for packed cells is the same. Although a 23Na double-quantum signal could be observed for red blood cells, no double-quantum signal was observed for 7Li.

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

“…Sodium-23 is 100% quadrupolar with a QCC of about 800 kHz for Na ϩ . In solution, 7 Li relaxes about 44% by a dipolar mechanism, and about 20% by a dipolar mechanism intracellularly in packed erythrocytes (23). It has much longer T 1 and T 2 than 23 Na under equivalent circumstances.…”

“…For a strongly quadrupolar, spin-3/2 nucleus like 23 Na, intrinsic biexponential transverse (T 2 ) spin relaxation is common in biological systems, even in a single compartment (16). Although 7 Li is also spin-3/2, its spin relaxation is only weakly quadrupolar (22).…”

“…Studies on cellular systems in vitro found monoexponential T 2 behavior intracellularly for 7 Li (23)(24)(25)(26)(27). Because of increased binding and the relatively restricted intracellular environment, cationic T 2 is expected and found to be lower intracellularly than extracellularly (23,26,28). Assuming the same holds true for Li in the brain in vivo, then biexponential behavior in a localized 7 Li MRS experiment, if observed, can be attributed to separate signals from the intra-and extracellular compartments.…”

“…Intrinsic biexponential T 2 relaxation has not been clearly observed for 7 Li in biological systems (13,15). Studies on cellular systems in vitro found monoexponential T 2 behavior intracellularly for 7 Li (23)(24)(25)(26)(27). Because of increased binding and the relatively restricted intracellular environment, cationic T 2 is expected and found to be lower intracellularly than extracellularly (23,26,28).…”

Biomedical applications of7Li NMR

“…Lithium-7 MRS has been shown to be feasible at 3.0 and 4.0 T. 17,48 More sensitive detection coils, isotopic enrichment, and novel postprocessing methods can further reduce the minimum detectable concentration in vivo, permitting more rapid measurements or better resolution in localized studies. It may be possible to increase in vivo sensitivity through a 7 Li-{ 1 H} nuclear Overhauser enhancement 52 or by dynamic nuclear polarization via water protons. 53 A potentially powerful feature of MRS is the ability to measure simultaneously the local tissue concentration of Li by 7 Li MRS and related changes in brain metabolism by 1 H or 31 P MRS. 54,55 Future 1 H or 31 P MRS studies of subjects on Li therapy would greatly benefit from the additional measurement of local Li concentration.…”