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  MR spectroscopy for in vivo assessment of the oncometabolite 2-hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T

Bisdas, S., Chadzynski, G., Braun, C., Schittenhelm, J., Skardelly, M., Hagberg, G., et al. (2016). MR spectroscopy for in vivo assessment of the oncometabolite 2-hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T. Journal of Magnetic Resonance Imaging, 44(4), 823-833. doi:10.1002/jmri.25221.

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Bisdas, S, Author
Chadzynski, GL1, Author           
Braun, C, Author
Schittenhelm, J, Author
Skardelly, M, Author
Hagberg, GE1, Author           
Ethofer, T, Author                 
Pohmann, R1, Author           
Shajan, G1, Author           
Engelmann, J1, Author           
Tabatabai, G, Author
Ziemann, U, Author
Ernemann, U, Author
Scheffler, K1, Author           
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              

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 Abstract: Purpose
To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T.
Materials and Methods
Spectra were acquired with a 9.4T whole-body scanner with the use of a custom-built head coil (16 channel transmit and 31 channel receive). A modified stimulated echo acquisition mode (STEAM) sequence was used for localization. Eighteen patients with brain tumors of probable glial origin participated in this study. The study was performed in accordance with the guidelines of the local Ethics Committee.
Results
The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20, P = 0.024), which probably reflects an attempt to replenish α-ketoglutarate lost by conversion to 2HG. We also observed significantly reduced glutathione (GSH) levels (39, P = 0.019), which could be similarly caused by depletion of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) during this conversion in IDH mutant gliomas.
Conclusion
We demonstrate that MRS at 9.4T provides a noninvasive measure of 2HG in vivo, which may be used for therapy planning and prognostication, and may provide insights into related pathophysiologic metabolic alterations associated with IDH mutations.

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 Dates: 2016-10
 Publication Status: Published in print
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 Identifiers: DOI: 10.1002/jmri.25221
BibTex Citekey: BisdasCBSSHEPSETZES2016
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Title: Journal of Magnetic Resonance Imaging
Source Genre: Journal
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Publ. Info: Chicago, IL : Society for Magnetic Resonance Imaging
Pages: - Volume / Issue: 44 (4) Sequence Number: - Start / End Page: 823 - 833 Identifier: ISSN: 1053-1807
CoNE: https://pure.mpg.de/cone/journals/resource/954925594512