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

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 ( 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.

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

Keywords

humans
NAD/metabolism
magnetic resonance spectroscopy/methods
male
muscle, skeletal/metabolism
adults
female
age
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 ( 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. ",

keywords = "humans, NAD/metabolism, magnetic resonance spectroscopy/methods, male, muscle, skeletal/metabolism, adults, female, age, middle aged, adenosine triphosphate/metabolism, reproducibility of results, phantoms, imaging, magnetic resonance imaging/methods, phosphorus isotopes, mensen, NAD/metabolisme, magnetische resonantiespectroscopie/methoden, mannelijk, spieren, skelet/metabolisme, volwassenen, vrouwelijk, oud, middelbare leeftijd, adenosinetrifosfaat/metabolisme, reproduceerbaarheid van resultaten, fantomen, beeldvorming, magnetische resonantie beeldvorming/methoden, fosfor-isotopen",

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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year = "2024",

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doi = "10.1038/s41467-024-53292-4",

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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 ( 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.

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 ( 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.

KW - humans

KW - NAD/metabolism

KW - magnetic resonance spectroscopy/methods

KW - male

KW - muscle, skeletal/metabolism

KW - adults

KW - female

KW - age

KW - middle aged

KW - adenosine triphosphate/metabolism

KW - reproducibility of results

KW - phantoms, imaging

KW - magnetic resonance imaging/methods

KW - phosphorus isotopes

KW - mensen

KW - NAD/metabolisme

KW - magnetische resonantiespectroscopie/methoden

KW - mannelijk

KW - spieren, skelet/metabolisme

KW - volwassenen

KW - vrouwelijk

KW - oud

KW - middelbare leeftijd

KW - adenosinetrifosfaat/metabolisme

KW - reproduceerbaarheid van resultaten

KW - fantomen, beeldvorming

KW - magnetische resonantie beeldvorming/methoden

KW - fosfor-isotopen

U2 - 10.1038/s41467-024-53292-4

DO - 10.1038/s41467-024-53292-4

M3 - Article

C2 - 39443469

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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