Non-invasive detection of 2-hydroxyglutarate in IDH-mutated gliomas using two-dimensional localized correlation spectroscopy (2D L-COSY) at 7 Tesla

Gaurav Verma, Suyash Mohan, MacLean L.P. Nasrallah, Steven Brem, John Y.K. Lee, Sanjeev Chawla, Sumei Wang, Rajakumar Nagarajan, M. Albert Thomas, Harish Poptani

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background: Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the "oncometabolite" 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism. This study aims to assess tumor metabolism using 2D L-COSY at 7T for the detection of 2HG in IDH-mutant gliomas. Methods: Nine treatment-naïve patients with suspected intracranial neoplasms were scanned at 7T MRI/MRS scanner using the 2D L-COSY technique. 2D-spectral processing and analyses were performed using a MATLAB-based reconstruction algorithm. Cross and diagonal peak volumes were quantified in the 2D L-COSY spectra and normalized with respect to the creatine peak at 3.0ppm and quantified data were compared with previously-published data from six normal subjects. Detection of 2HG was validated using findings from immunohistochemical (IHC) staining in patients who subsequently underwent surgical resection. Results: 2HG was detected in both of the IDH-mutated gliomas (grade III Anaplastic Astrocytoma and grade II Diffuse Astrocytoma) and was absent in IDH wild-type gliomas and in a patient with breast cancer metastases. 2D L-COSY was also able to resolve complex and overlapping resonances including phosphocholine (PC) from glycerophosphocholine (GPC), lactate (Lac) from lipids and glutamate (Glu) from glutamine (Gln). Conclusions: This study demonstrates the ability of 2D L-COSY to unambiguously detect 2HG in addition to other neuro metabolites. These findings may aid in establishing 2HG as a biomarker of malignant progression as well as for disease monitoring in IDH-mutated gliomas.

Original languageEnglish
Article number274
JournalJournal of Translational Medicine
Volume14
Issue number1
DOIs
StatePublished - 22 Sep 2016
Externally publishedYes

Keywords

  • 2-Hydroxyglutarate
  • Brain tumor
  • Correlation spectroscopy
  • Isocitrate dehydrogenase
  • Phosphocholine

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