In Vivo 31P MRS Imaging of Intracellular NAD Contents and NAD+/NADH Redox States in Normal and Ischemic Brains

Xiao-Hong Zhu¹, Ming Lu¹, Yi Zhang¹, Wei Chen²

Nicotinamide adenine dinucleotide (NAD), as an important coenzyme and/or co-substrate in all living cells, plays vital roles in cellular metabolism and regulation. However, due to the technique limitation, it is very difficult to directly measure the NAD and its redox state (define as the ratio of oxidized and reduced forms: NAD⁺/NADH) in a live brain. We have developed an in vivo ³¹P MRS approach that is capable of quantitative and non-invasive imaging of the intracellular NAD levels and the NAD⁺/NADH ratio in intact organs, such as brain. In the present study, we applied this novel MRS approach to image the intracellular NAD contents, including the NAD⁺, NADH and total NAD concentrations, and the NAD⁺/NADH redox ratio in anesthetized cat brain under normal physiological condition, and in the rat brains under acute ischemia-recovery conditions. The results indicate that the NAD imaging approach can provide reliable measure of the cerebral NAD contents and redox state and is sensitive to detect their changes in response to physiopathological alteration in brain energy and metabolism; thus, has great values for basic biomedical research and potential for clinical translation.