In vivo 31P MRS assessment of intracellular NAD metabolites and NAD+/NADH redox state in human brain at 4 T

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Abstract

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 advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo 31P MRS-based NAD assay for noninvasive and quantitative measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T. To explore its potential for clinical application, in this study we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a lower field of 4 T by incorporating the 1H-decoupling technique with the in vivo 31P NAD assay. The use of 1H decoupling significantly narrowed the linewidths of NAD and α-ATP resonances, resulting in higher sensitivity and better spectral resolution as compared with the 1H-coupled 31P spectrum. These improvements made it possible to reliably quantify cerebral NAD concentrations and RX, consistent with previously reported results obtained from similar age human subjects at 7 T. In summary, this work demonstrates the capability and utility of the 1H-decoupled 31P MRS-based NAD assay at lower field strength; thus, it opens new opportunities for studying intracellular NAD metabolism and redox state in human brain at clinical settings. This conclusion is supported by the simulation results, indicating that similar performance and reliability as observed at 4T can be achieved at 3 T with the same signal-to-noise ratio.

Original languageEnglish (US)
Pages (from-to)1010-1017
Number of pages8
JournalNMR in biomedicine
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2016

Bibliographical note

Publisher Copyright:
Copyright © 2016 John Wiley & Sons, Ltd.

Keywords

  • H decoupling
  • NAD and NADH
  • human brain
  • in vivo P MRS
  • intracellular redox state

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