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. 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), pp. 823-833. (doi:10.1002/jmri.25221) (PMID:26970248)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gunamony, Dr Shajan
Authors: Bisdas, S., Chadzynski, G. L., Braun, C., Schittenhelm, J., Skardelly, M., Hagberg, G. E., Ethofer, T., Pohmann, R., Shajan, G., Engelmann, J., Tabatabai, G., Ziemann, U., Ernemann, U., and Scheffler, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Journal of Magnetic Resonance Imaging
Publisher:Wiley
ISSN:1053-1807
ISSN (Online):1522-2586
Published Online:11 March 2016

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