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Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T

  • Julian Mevenkamp
  • , Yvonne M.H. Bruls
  • , Rodrigo Mancilla
  • , Lotte Grevendonk
  • , Joachim E. Wildberger
  • , Kim Brouwers
  • , Matthijs K.C. Hesselink
  • , Patrick Schrauwen
  • , Joris Hoeks
  • , Riekelt H. Houtkooper
  • , Mijke Buitinga
  • , Robin A. de Graaf
  • , Lucas Lindeboom
  • , Vera B. Schrauwen-Hinderling*
  • *Corresponding author for this work
  • Maastricht University
  • German Diabetes Center Düsseldorf
  • Leiden University
  • Amsterdam UMC
  • Yale University

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

NADH and NAD+ act as electron donors and acceptors and NAD+ was shown to stimulate mitochondrial biogenesis and metabolic health. We here develop a non-invasive Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) method to quantify these metabolites in human skeletal muscle on a clinical 3 T MRI scanner. This new MR-sequence enables NADH and NAD+ quantification by suppressing α-ATP signal, normally overlapping with NADH and NAD+. The sequence is based on a double spin echo in combination with a modified z-Filter achieving strong α-ATP suppression with little effect on NAD+ and NADH. Here we test and validate it in phantoms and in humans by measuring reproducibility and detecting a physiological decrease in NAD+ and increase in NADH induced by ischemia. Furthermore, the 31P-MRS outcomes are compared to analysis in biopsies. Additionally, we show higher NAD+ and lower NADH content in physically active older adults compared to sedentary individuals, reflecting increased metabolic health.

Original languageEnglish
Article number9159
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - 1 Dec 2024

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