Deuterium magnetic resonance spectroscopy for assessing glucose metabolism in healthy and in neurooncology diseased brain. Review

Aim: to present a new method for assessing glucose catabolism in brain tissues of healthy volunteers and neurooncology patients. This method is MR spectroscopy with resonance frequency of deuterium (hydrogen isotope) called deuterium metabolic imaging - DMI.

Material and methods. We searched scientific papers in PubMed and Google Scholar indexing systems for 2017–2022 publicatioin years. Keywords used: deuterium spectroscopy, DMI, DMV, PET, non-proton spectroscopy, brain tumor metabolism, Warburg effect in brain tumor, glucose/glucolytic flux/metabolism.

Results. 474 articles were analyzed, 21 of which were used for this review. The references list additionaly includes 9 articles for 1924–2014 pyublication years. The review covers the history of proton and multinuclear MR spectroscopy (phosphorus, carbon, deuterium) development of and PET diagnostics. We described DMI applicability in visual and quantitative assessment of tissue metabolism disorders in brain tumors and discussed its future use in clinical practice.

Conclusion. Compared to fluorodeoxyglucose (FDG) PET, the DMI method provides additional information on metabolic disorders during anaerobic glycolysis in a tumor. DMI can be implemented and performed on clinical MRI scanners.

1. Kornienko V.N., Pronin I.N. Diagnostic Neuroradiology. In 3 vol. Moscow: IE “TM Andreeva”, 2008–2009. (In Russian)

2. Magnetic resonance spectroscopy / Eds Trufanov G.E., Tyutin L.A. SPb: “ELBI-SPb”, 2008. 239 p. (In Russian)

3. Maudsley A.A., Andronesi O.C., Barker P.B. et al. Advanced magnetic resonance spectroscopic neuroimaging: Experts' consensus recommendations. NMR Biomed. 2021; 34 (5): e4309. https://doi.org/10.1002/nbm.4309

4. Zakharova N.E., Pronin I.N., Batalov A.I. Shul'ts E.I., Tyurina A.N., Baev A.A., Fadeeva L.M. Modern standards for magnetic resonance imaging of the brain tumors. Burdenko's Journal of Neurosurgery = Zhurnal “Voprosy neirokhirurgii” imeni N.N. Burdenko. 2020; 84 (3): 102–112. https://doi.org/10.17116/neiro202084031102 (In Russian)

5. Stagg C., Rothman D. Magnetic Resonance Spectroscopy: Tools for Neuroscience Research and Emerging Clinical Applications. Elsevier, 2014. 398 p. Hardback ISBN: 9780124016880. eBook ISBN: 9780124016972

6. Tyurina A.N., Pronin I.N., Fadeeva L.M., Batalov A.I., Zakharova N.E., Podoprigora A.E., Shults E.I., Kornienko V.N. Proton 3D MR spectroscopy in the diagnosis of glial brain tumors. Medical Visualization. 2019; 23 (3): 8–18. https://doi.org/10.24835/1607-0763-2019-3-8-18 (In Russian)

7. Semenova N.A., Manzhurtsev A.V., Menshchikov P.E., Ublinskiy M.V., Akhadov T.A. Magnetic resonance spectroscopy: non-invasive studiesof human brain metabolism in normal and pathological conditions. Progress in Physiological Science. 2019; 50 (1): 58–74. https://doi.org/10.1134/S0301179819010107 (In Russian)

8. Jones P.J., Leatherdale S.T. Stable isotopes in clinical research: safety reaffirmed. Clin. Sci. (Lond.). 1991; 80 (4): 277–280. https://doi.org/10.1042/cs0800277

9. Pronin I.N., Zakharova N.E., Podoprigora A.E., Batalov A.I., Tyurina A.N., Mertsalova M.P., Fadeeva L.M., Golanov A.V., Postnov A.A., Rodionov P.V., Potapov A.A. Phosphorus (P) magnetic resonance spectroscopy for evaluation of brain tissue metabolism and measuring non-invasive pH. A study involving 23 volunteers. Part I. Burdenko's Journal of Neurosurgery = Zhurnal “Voprosy neirokhirurgii” imeni N.N. Burdenko. 2019; 83 (2): 5–10. https://doi.org/10.17116/neiro2019830215 (In Russian)

10. Wang Z.J., Ohliger M.A., Larson P.E.Z. et al. Hyper-polarized 13 C MRI: State of the Art and Future Directions. Radiology. 2019; 291 (2): 273–284. https://doi.org/10.1148/radiol.2019182391

11. Lu M., Zhu X.H., Zhang Y. et al. Quantitative assessment of brain glucose metabolic rates using in vivo deuterium magnetic resonance spectroscopy. J. Cereb. Blood. Flow. Metab. 2017; 37 (11): 3518–3530. https://doi.org/10.1177/0271678X17706444

12. De Feyter H.M., Behar K.L. Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo. Sci. Adv. 2018; 4 (8): eaat7314. https://doi.org/10.1126/sciadv.aat7314

13. Kreis F., Wright A.J., Hesse F. et al. Measuring tumor glycolytic flux in vivo by using fast deuterium MRI. Radiology. 2020; 294: 289–296. https://doi.org/10.1148/radiol.2019191242

14. De Feyter H.M., de Graaf R.A. Deuterium metabolic imaging – Back to the future. J. Magn. Reson. 2021; 326: 106932. https://doi.org/10.1016/j.jmr.2021.106932

15. Hesse F., Somai V., Kreis F. et al. Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging. Proc. Natl. Acad. Sci. U.S.A. 2021; 118 (12): e2014631118. https://doi.org/10.1073/pnas.2014631118

16. Ruhm L., Avdievich N., Ziegs T. et al. Deuterium metabolic imaging in the human brain at 9.4 Tesla with high spatial and temporal resolution. Neuroimage. 2021; 244: 118639. https://doi.org/10.1016/j.neuroimage.2021.118639

17. Straathof M., Meerwaldt A.E., De Feyter H.M. et al. Deuterium Metabolic Imaging of the Healthy and Diseased Brain. Neuroscience. 2021; 474: 94–99. https://doi.org/10.1016/j.neuroscience.2021.01.023

18. Ouwerkerk R. Deuterium MR spectroscopy: a new way to image glycolytic flux rates. Radiology. 2020; 294 (2): 297–298. https://doi.org/10.1148/radiol.2019192024

19. Simões R.V., Henriques R.N., Cardoso B.M. et al. Glucose fluxes in glycolytic and oxidative pathways detected in vivo by deuterium magnetic resonance spectroscopy reflect proliferation in mouse glioblastoma. Neuroimage Clin. 2022; 33: 102932. https://doi.org/10.1016/j.nicl.2021.102932

20. Urey H.C., Brickwedde F.G., Murphy G.M. A Hydrogen Isotope of Mass 2. Physical Review. 1932; 39 (1): 164–165. https://doi.org/10.1103/PhysRev.39.164

21. Schoenheimer R., Rittenberg D. Deuterium as an indicator in the study of intermediary metabolism. Science. 1935; 82 (2120): 156–157. https://doi.org/10.1126/science.82.2120.156

22. Ackerman J.J., Ewy C.S., Kim S.G., Shalwitz R.A. Deuterium magnetic resonance in vivo: the measurement of blood flow and tissue perfusion. Ann. N.Y. Acad. Sci. 1987; 508: 89–98. https://doi.org/10.1111/j.1749-6632.1987.tb32897.x

23. Detre J.A., Subramanian V.H., Mitchell M.D. et al. Measurement of regional cerebral blood flow in cat brain using intracarotid 2H2O and 2H NMR imaging. Magn. Reson. Med. 1990; 14 (2): 389–395. https://doi.org/10.1002/mrm.1910140223

24. Warburg O., Posener K., Negelein E. Über den stoffwechsel der carcinomzelle. Naturwissenschaften. 1924; 12 (50): 1131–1137. https://doi.org/10.1007/BF01504608

25. de Graaf R.A., Hendriks A.D., Klomp D.W.J. et al. On the magnetic field dependence of deuterium metabolic imaging. NMR Biomed. 2020; 33 (3): e4235. https://doi.org/10.1002/nbm.4235

26. De Feyter H.M., Behar K.L., Corbin Z.A. et al. Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo. Sci. Adv. 2018; 4 (8): eaat7314. https://doi.org/10.1126/sciadv.aat7314

27. Hartmann B., Müller M., Seyler L. et al. Feasibility of deuterium magnetic resonance spectroscopy of 3-O-Methylglucose at 7 Tesla. PLoS One. 2021; 16 (6): e0252935. https://doi.org/10.1371/journal.pone.0252935

28. Ananieva E.A., Wilkinson A.C. Branched-chain amino acid metabolism in cancer. Curr. Opin. Clin. Nutr. Metab. Care. 2018; 21 (1): 64–70. https://doi.org/10.1097/MCO.0000000000000430

29. Tsuji A.B., Sugyo A., Sudo H. et al. Preclinical assessment of early tumor response after irradiation by positron emission tomography with 2-amino-[3-11C]isobutyric acid. Oncol. Rep. 2015; 33 (5): 2361–2367. https://doi.org/10.3892/or.2015.3868

30. Tönjes M., Barbus S., Park Y.J. et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat. Med. 2013; 19 (7): 901–908. https://doi.org/10.1038/nm.3217