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. Graaf, Lucas Lindeboom and Vera B. Schrauwen-Hinderling ()
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Julian Mevenkamp: Department of Radiology & Nuclear Medicine
Yvonne M. H. Bruls: Department of Radiology & Nuclear Medicine
Rodrigo Mancilla: Department of Nutrition & Movement Sciences (NUTRIM)
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
Joris Hoeks: Department of Nutrition & Movement Sciences (NUTRIM)
Riekelt H. Houtkooper: Gastroenterology Endocrinology Metabolism
Mijke Buitinga: Department of Radiology & Nuclear Medicine
Robin A. Graaf: Department of Radiology & Biomedical Imaging
Lucas Lindeboom: Department of Radiology & Nuclear Medicine
Vera B. Schrauwen-Hinderling: Department of Radiology & Nuclear Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53292-4

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