Abstract
As a phosphorus-containing molecule, nicotinamide adenine dinucleotide is visible by phosphorus magnetic resonance spectroscopy (31P-MRS). However, the relatively low cellular levels of its oxidised (NAD+) and reduced (NADH) forms and a significant peak overlap hinder their evaluation in live tissues. This problem is critical when using 31P-MR spectroscopic imaging, where signals are localised from limited tissue volumes. We have reported improvements in spectral resolution of 31P-MRSI of human tissues in situ using a strict optimisation of the static magnetic field (B0 shimming) and 1H-irradiation during 31P acquisition. Given this, we aimed to demonstrate if these improvements allowed us to measure the in vivo intracellular levels of NAD+ and NADH at the relatively low magnetic field of 1.5 tesla (T). Our results show the feasibility of the in vivo determination of NAD+ and NADH from relatively small volumes of human tissues studied at 1.5 T. These results are clinically relevant as the currently available systems for human use mainly operate at 1.5 or 3.0.
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References
Goodman RP, Calvo SE, Mootha VK (2018) Spatiotemporal compartmentalization of hepatic NADH and NADPH metabolism. J Biol Chem 293(20):7508–7516. https://doi.org/10.1074/jbc.TM117.000258
Hassinen IE (2019) Signaling and regulation through the NAD(+) and NADP(+) networks. Antioxid Redox Signal 30(6):857–874. https://doi.org/10.1089/ars.2017.7479
Pina-Garza E, Garcia-Sainz A (1983) Chagoya de Sanchez V, Arias-Mendoza F. [ethanol: catabolism and metabolic effects. I. Introduction]. Gac Med Mex 119(1):1–14
Zhang Z, Xu HN, Li S, Chellappa K, Davis JG et al (2020) Rapamycin maintains NAD(+)/NADH redox homeostasis in muscle cells. Aging 12(18):17786–17799. https://doi.org/10.18632/aging.103954
Xu HN, Li LZ (2014) Quantitative redox imaging biomarkers for studying tissue metabolic state and its heterogeneity. J Innov Opt Heal Sci 7(2):1430002. https://doi.org/10.1142/S179354581430002X
Li LZ, Xu HN, Ranji M, Nioka S, Chance B (2009) Mitochondrial redox imaging for cancer diagnostic and therapeutic studies. J Innov Opt Heal Sci. 2:325–341. https://doi.org/10.1142/S1793545809000735
Lu M, Zhu XH, Zhang Y, Chen W (2014) Intracellular redox state revealed by in vivo (31) P MRS measurement of NAD(+) and NADH contents in brains. Magn Reson Med 71(6):1959–1972. https://doi.org/10.1002/mrm.24859
Zhu X-H, Lu M, Lee B-Y, Ugurbil K, Chen W (2015) In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci 112(9):2876–2881. https://doi.org/10.1073/pnas.1417921112
Kim SY, Cohen BM, Chen X, Lukas SE, Shinn AK, Yuksel AC et al (2017) Redox dysregulation in schizophrenia revealed by in vivo NAD+/NADH measurement. Schizophr Bull 43(1):197–204. https://doi.org/10.1093/schbul/sbw129
Conley KE, Ali AS, Flores B, Jubrias SA, Shankland EG (2016) Mitochondrial NAD(P)H in vivo: identifying natural indicators of oxidative phosphorylation in the (31)P magnetic resonance spectrum. Front Physiol 7:45. https://doi.org/10.3389/fphys.2016.00045
Arias-Mendoza F, Smith MR, Brown TR (2004) Predicting treatment response in non-Hodgkin's lymphoma from the pretreatment tumor content of phosphoethanolamine plus phosphocholine. Acad Radiol 11(4):368–376. https://doi.org/10.1016/s1076-6332(03)00721-9
Arias-Mendoza F, Payne GS, Zakian KL, Schwarz AJ, Stubbs M, Stoyanova R et al (2006) In vivo 31P MR spectral patterns and reproducibility in cancer patients studied in a multi-institutional trial. NMR Biomed 19(4):504–512. https://doi.org/10.1002/nbm.1057
Arias-Mendoza F, Zakian K, Schwartz A, Howe FA, Koutcher JA, Leach MO et al (2004) Methodological standardization for a multi-institutional in vivo trial of localized (31)P MR spectroscopy in human cancer research. In vitro and normal volunteer studies. NMR Biomed 17(6):382-391. https://doi.org/10.1002/nbm.915
Hu J, Javaid T, Arias-Mendoza F, Liu Z, McNamara R, Brown TR (1995) A fast, reliable, automatic shimming procedure using 1H chemical-shift-imaging spectroscopy. J Magn Reson B 108(3):213–219. https://doi.org/10.1006/jmrb.1995.1126
Brown TR (1992) Practical applications of chemical shift imaging. NMR Biomed. 5(5):238–243. https://doi.org/10.1002/nbm.1940050508
Brown TR, Kincaid BM, Ugurbil K (1982) NMR chemical shift imaging in three dimensions. Proc Natl Acad Sci U S A 79(11):3523–3526. https://doi.org/10.1073/pnas.79.11.3523
Nath K, Arias-Mendoza F, Xu HN, Gupta P, Li LZ (2022) Feasibility of noninvasive measurement of tumor NAD(H) by in vivo phosphorus-31 magnetic resonance spectroscopy. Adv Exp Med Biol
Acknowledgments
This work was supported by US NIH Grants R01CA118559 and R21CA152858 (PI: F. Arias-Mendoza) for the data acquisition and US NIH Grant R01CA191207 (PI: L. Z. Li) for the data analysis. The authors wish to thank the Cooperative Group of MRS in cancer (CoGMaC) for their participation acquiring the breast cancer data.
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Arias-Mendoza, F., Nath, K., Xu, H.N., Gupta, P.K., Li, L.Z. (2022). Assessment of Nicotinamide Adenine Dinucleotide in Human Tissues by In Vivo Phosphorus-31 Magnetic Resonance Spectroscopic Imaging at 1.5 Tesla. In: Scholkmann, F., LaManna, J., Wolf, U. (eds) Oxygen Transport to Tissue XLIII. Advances in Experimental Medicine and Biology, vol 1395. Springer, Cham. https://doi.org/10.1007/978-3-031-14190-4_52
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DOI: https://doi.org/10.1007/978-3-031-14190-4_52
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