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



Verma, Gaurav, Mohan, Suyash, Nasrallah, MacLean P, Brem, Steven, Lee, John YK, Chawla, Sanjeev, Wang, Sumei, Nagarajan, Rajakumar, Thomas, M Albert and Poptani, Harish ORCID: 0000-0002-0593-3235
(2016) Non-invasive detection of 2-hydroxyglutarate in IDH-mutated gliomas using two-dimensional localized correlation spectroscopy (2D L-COSY) at 7 Tesla. JOURNAL OF TRANSLATIONAL MEDICINE, 14 (1). 274-.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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 3.0 ppm 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.<h4>Results</h4>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).<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: 2-Hydroxyglutarate, Isocitrate dehydrogenase, Phosphocholine, Correlation spectroscopy, Brain tumor
Depositing User: Symplectic Admin
Date Deposited: 21 Nov 2016 09:45
Last Modified: 03 Mar 2023 10:01
DOI: 10.1186/s12967-016-1035-1
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3004134