Intracellular redox state revealed by in vivo (31) P MRS measurement of NAD(+) and NADH contents in brains.

PURPOSE

Nicotinamide adenine dinucleotide (NAD), in oxidized (NAD(+) ) or reduced (NADH) form, plays key roles in cellular metabolism. Intracellular NAD(+) /NADH ratio represents the cellular redox state; however, it is difficult to measure in vivo. We report here a novel in vivo (31) P MRS method for noninvasive measurement of intracellular NAD concentrations and NAD(+) /NADH ratio in the brain.

METHODS

It uses a theoretical model to describe the NAD spectral patterns at a given field for quantification. Standard NAD solutions and independent cat brain measurements at 9.4 T and 16.4 T were used to evaluate this method. We also measured T1 values of brain NAD.

RESULTS

Model simulation and studies of solutions and brains indicate that the proposed method can quantify submillimolar NAD concentrations with reasonable accuracy if adequate (31) P MRS signal-to-noise ratio and linewidth were obtained. The NAD concentrations and NAD(+) /NADH ratio of cat brains measured at 16.4 T and 9.4 T were consistent despite the significantly different T1 values and NAD spectra patterns at two fields.

CONCLUSION

This newly established (31) P MRS method makes it possible for the first time to noninvasively study the intracellular redox state and its roles in brain functions and diseases, and it can potentially be applied to other organs.