Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T
NADH and NAD<sup>+</sup> act as electron donors and acceptors and NAD<sup>+</sup> was shown to stimulate mitochondrial biogenesis and metabolic health. We here develop a non-invasive Phosphorous Magnetic Resonance Spectroscopy (<sup>31</sup>P-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<sup>+</sup>. 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<sup>+</sup> and NADH. Here we test and validate it in phantoms and in humans by measuring reproducibility and detecting a physiological decrease in NAD<sup>+</sup> and increase in NADH induced by ischemia. Furthermore, the <sup>31</sup>P-MRS outcomes are compared to analysis in biopsies. Additionally, we show higher NAD<sup>+</sup> and lower NADH content in physically active older adults compared to sedentary individuals, reflecting increased metabolic health.
Authors
- Riekelt H. Houtkooper (ORCID: https://orcid.org/0000-0001-9961-0842)
- Lucas Lindeboom (ORCID: https://orcid.org/0000-0002-3857-5024)
- Lotte Grevendonk (ORCID: https://orcid.org/0000-0001-9540-1832)
- Joachim Ernst Wildberger (ORCID: https://orcid.org/0000-0002-4810-6854)
- Joris Hoeks (ORCID: https://orcid.org/0000-0002-0265-0870)
- Kim Brouwers
- Julian Mevenkamp
- Robin A. de Graaf (ORCID: https://orcid.org/0000-0002-6570-7010)
- Mijke Buitinga (ORCID: https://orcid.org/0000-0002-4202-2473)
- Vera B. Schrauwen‐Hinderling (ORCID: https://orcid.org/0000-0001-7795-584X)
- Yvonne M. H. Bruls (ORCID: https://orcid.org/0000-0002-0945-1030)
- Rodrigo Mancilla (ORCID: https://orcid.org/0000-0002-2143-6386)
- Patrick Schrauwen (ORCID: https://orcid.org/0000-0002-0973-847X)
- Matthijs K. C. Hesselink (ORCID: https://orcid.org/0000-0003-3084-0687)
Institutions
- Leiden University Medical Center (NL)
- Maastricht University Medical Centre (NL)
- Yale University (US)
- Maastricht University (NL)
- Finis Terrae University (CL)
- Amsterdam University Medical Centers (NL)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- University of Amsterdam (NL)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-24
- DOI
- https://doi.org/10.1038/s41467-024-53292-4
- Citations
- 9
- Primary Topic
- Metabolism and Genetic Disorders
- Type
- article
- Field-Weighted Citation Impact
- 3.43