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 de Graaf; Lucas Lindeboom; Vera B Schrauwen-Hinderling

doi:10.1038/s41467-024-53292-4

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 de Graaf, Lucas Lindeboom, Vera B Schrauwen-Hinderling^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 ( 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.

Original language	English
Article number	9159
Number of pages	13
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-53292-4
Publication status	Published - 24 Oct 2024

Keywords

Humans
NAD/metabolism
Magnetic Resonance Spectroscopy/methods
Male
Muscle, Skeletal/metabolism diagnostic imaging
Adult
Female
Aged
Middle Aged
Adenosine Triphosphate/metabolism
Reproducibility of Results
Phantoms, Imaging
Magnetic Resonance Imaging/methods
Phosphorus Isotopes

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Mevenkamp, J., Bruls, Y. M. H., Mancilla, R., Grevendonk, L., Wildberger, J. E., Brouwers, K., Hesselink, M. K. C., Schrauwen, P., Hoeks, J., Houtkooper, R. H., Buitinga, M., de Graaf, R. A., Lindeboom, L., & Schrauwen-Hinderling, V. B. (2024). Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T. Nature Communications, 15(1), Article 9159. https://doi.org/10.1038/s41467-024-53292-4

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

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 ( 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.",

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author = "Julian Mevenkamp and Bruls, {Yvonne M H} and Rodrigo Mancilla and Lotte Grevendonk and Wildberger, {Joachim E} and Kim Brouwers and Hesselink, {Matthijs K C} and Patrick Schrauwen and Joris Hoeks and Houtkooper, {Riekelt H} and Mijke Buitinga and {de Graaf}, {Robin A} and Lucas Lindeboom and Schrauwen-Hinderling, {Vera B}",

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Mevenkamp, J , Bruls, YMH, Mancilla, R, Grevendonk, L , Wildberger, JE, Brouwers, K, Hesselink, MKC, Schrauwen, P, Hoeks, J, Houtkooper, RH, Buitinga, M, de Graaf, RA, Lindeboom, L & Schrauwen-Hinderling, VB 2024, 'Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T', Nature Communications, vol. 15, no. 1, 9159. https://doi.org/10.1038/s41467-024-53292-4

TY - JOUR

T1 - Development of a 31P magnetic resonance spectroscopy technique to quantify NADH and NAD+ at 3 T

AU - Mevenkamp, Julian

AU - Bruls, Yvonne M H

AU - Mancilla, Rodrigo

AU - Grevendonk, Lotte

AU - Wildberger, Joachim E

AU - Brouwers, Kim

AU - Hesselink, Matthijs K C

AU - Schrauwen, Patrick

AU - Hoeks, Joris

AU - Houtkooper, Riekelt H

AU - Buitinga, Mijke

AU - de Graaf, Robin A

AU - Lindeboom, Lucas

AU - Schrauwen-Hinderling, Vera B

PY - 2024/10/24

Y1 - 2024/10/24

N2 - 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.

AB - 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.

KW - Humans

KW - NAD/metabolism

KW - Magnetic Resonance Spectroscopy/methods

KW - Male

KW - Muscle, Skeletal/metabolism diagnostic imaging

KW - Adult

KW - Female

KW - Aged

KW - Middle Aged

KW - Adenosine Triphosphate/metabolism

KW - Reproducibility of Results

KW - Phantoms, Imaging

KW - Magnetic Resonance Imaging/methods

KW - Phosphorus Isotopes

U2 - 10.1038/s41467-024-53292-4

DO - 10.1038/s41467-024-53292-4

M3 - Article

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 9159

ER -

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

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Keywords

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