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

Author

Listed:
  • Julian Mevenkamp

    (Department of Radiology & Nuclear Medicine
    Department of Nutrition & Movement Sciences (NUTRIM))

  • Yvonne M. H. Bruls

    (Department of Radiology & Nuclear Medicine
    Department of Nutrition & Movement Sciences (NUTRIM))

  • Rodrigo Mancilla

    (Department of Nutrition & Movement Sciences (NUTRIM)
    Universidad Finis Terrae)

  • Lotte Grevendonk

    (Department of Nutrition & Movement Sciences (NUTRIM))

  • Joachim E. Wildberger

    (Department of Radiology & Nuclear Medicine)

  • Kim Brouwers

    (Department of Radiology & Nuclear Medicine)

  • Matthijs K. C. Hesselink

    (Department of Nutrition & Movement Sciences (NUTRIM))

  • Patrick Schrauwen

    (German Diabetes Center
    Clinical Epidemiology)

  • Joris Hoeks

    (Department of Nutrition & Movement Sciences (NUTRIM))

  • Riekelt H. Houtkooper

    (Gastroenterology Endocrinology Metabolism)

  • Mijke Buitinga

    (Department of Radiology & Nuclear Medicine
    Department of Nutrition & Movement Sciences (NUTRIM))

  • Robin A. Graaf

    (Department of Radiology & Biomedical Imaging)

  • Lucas Lindeboom

    (Department of Radiology & Nuclear Medicine
    Department of Nutrition & Movement Sciences (NUTRIM))

  • Vera B. Schrauwen-Hinderling

    (Department of Radiology & Nuclear Medicine
    Department of Nutrition & Movement Sciences (NUTRIM)
    German Diabetes Center)

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.

Suggested Citation

  • 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 , 2024. "Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53292-4
    DOI: 10.1038/s41467-024-53292-4
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    References listed on IDEAS

    as
    1. Thomas S. Blacker & Zoe F. Mann & Jonathan E. Gale & Mathias Ziegler & Angus J. Bain & Gyorgy Szabadkai & Michael R. Duchen, 2014. "Separating NADH and NADPH fluorescence in live cells and tissues using FLIM," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
    2. L. Grevendonk & N. J. Connell & C. McCrum & C. E. Fealy & L. Bilet & Y. M. H. Bruls & J. Mevenkamp & V. B. Schrauwen-Hinderling & J. A. Jörgensen & E. Moonen-Kornips & G. Schaart & B. Havekes & J. Vog, 2021. "Impact of aging and exercise on skeletal muscle mitochondrial capacity, energy metabolism, and physical function," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    3. Hassina Massudi & Ross Grant & Nady Braidy & Jade Guest & Bruce Farnsworth & Gilles J Guillemin, 2012. "Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-9, July.
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