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Abstract #3778

In Vivo 31 P MRS Study of Altered Intracellular NAD Content and NAD + /NADH Redox State in Hypoxic Brain

Ming Lu 1 , Xiao-Hong Zhu 1 , Yi Zhang 1 , and Wei Chen 1

1 Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, United States

Nicotinamide adenine dinucleotide (NAD) participates in various redox reactions in living organisms for supporting normal cellular functions and activities. The reduced (NADH) and oxidized (NAD + ) forms of NAD play key roles in cellular metabolism and regulation. The intracellular NAD + /NADH ratio, defined as intracellular redox state, reflects metabolic status and has been found to be associated with alterations in physiology and pathology. However, direct quantification of NAD and redox state in vivo is challenging. In this study, using our newly developed in vivo 31 P MRS approach for imaging NAD and its redox state in animal brains at 16.4 T, alterations of the NAD concentrations and redox state in rat brains from normoxia to hypoxia were studied. When reducing the oxygen supply from 30~40% (of O 2 and N 2 O mixture) to 5~6% level, the results indicated an increase of NADH contents (+25%), and decreases of [NAD + ] (-26%), NAD + /NADH ratio (-43%) and total [NAD] (-13%). Also, there were further increase of [NADH] and decreases of [NAD + ], NAD + /NADH ratio and total [NAD] in the postmortem brains. In summary, by using the novel 31 P MRS method, changes of cerebral redox state and the intracellular NAD contents can be robustly and non-invasively quantified under normal and hypoxic conditions. This simple and highly applicable MR imaging approach has a great potential for studying metabolic disorders in different organs of patients with hypoxic or ischemic syndrome.

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