In Vivo Assessment of Intracellular NAD + /NADH Redox State in Human Brain at 4 Tesla

NAD ⁺ and NADH play key roles in cellular respiration. Intracellular redox state defined by the NAD ⁺ /NADH ratio (RX) reflects the cellular metabolic and physiopathological status. By taking the advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo ³¹ P MRS based NAD assay for noninvasive measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T, respectively. To explore its potential for clinical translation, in this study, we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a relatively lower field of 4 T by incorporating ¹ H-decoupling technique with the ³¹ P NAD assay. The use of ¹ H-decoupling significantly narrowed the linewidths of NAD and -ATP resonances, resulting in higher sensitivity and better-resolved resonance signals as compare to the ¹ H-coupled spectrum. These improvements made it possible for reliably quantifying cerebral RX and NAD concentrations, which are consistent with previously reported results obtained at 7 T in similar aged human subjects. In summary, this work demonstrates the capability and utility of the ¹ H-decoupled ³¹ P MRS-based NAD assay at lower field strength, which indicates potential opportunities for studying NAD metabolism and redox state in human brain at clinical setting.

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