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

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 ( 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 a-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 a-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 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.