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

• Published in: Nature communications Vol. 15; no. 1; pp. 9159 - 13
• Main Authors: Mevenkamp, Julian, Bruls, Yvonne M. H., Mancilla, Rodrigo, Grevendonk, Lotte, Wildberger, Joachim E., Brouwers, Kim, Hesselink, Matthijs K. C., Schrauwen, Patrick, Hoeks, Joris, Houtkooper, Riekelt H., Buitinga, Mijke, de Graaf, Robin A., Lindeboom, Lucas, Schrauwen-Hinderling, Vera B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.10.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 59; 59/57; 631/443/319/333/1465; 631/443/7; 639/166/985; 692/163/2743/393; Biopsy; Biosynthesis; Humanities and Social Sciences; Ischemia; Magnetic resonance imaging; Magnetic resonance spectroscopy; Metabolism; Metabolites; multidisciplinary; Muscles; NAD; NADH; Nicotinamide adenine dinucleotide; Older people; Physiological effects; Scanners; Science; Science (multidisciplinary); Skeletal muscle; Spectroscopy; Spectrum analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-53292-4

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 ( 31 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 + . 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 31 P-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. NADH and NAD+ act as electron donors and acceptors and NAD+ was shown to stimulate mitochondrial biogenesis and metabolic health. Here, the researchers developed and validated a non-invasive Phosphorous Magnetic Resonance Spectroscopy method to non-invasively quantify NAD+ and NADH in muscle on a clinical 3 T MRI scanner.