Abstract
2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumor cell isocitrate dehydrogenase mutations that may enable the differential diagnosis of patients with glioma. At 3 T, detection of 2-HG with magnetic resonance spectroscopy is challenging because of metabolite signal overlap and spectral pattern modulation by slice selection and chemical shift displacement. Using density matrix simulations and phantom experiments, an optimized semi-LASER scheme (echo time = 110 milliseconds) considerably improves localization of the 2-HG spin system compared with that of an existing point-resolved spectroscopy sequence. This results in a visible 2-HG peak in the in vivo spectra at 1.9 ppm in the majority of isocitrate dehydrogenase-mutated tumors. Detected concentrations of 2-HG were similar using both sequences, although the use of semi-LASER generated narrower confidence intervals. Signal overlap with glutamate and glutamine, as measured by pairwise fitting correlation, was reduced. Lactate was readily detectable across patients with glioma using the method presented here (mean Cramér–Rao lower bound: 10% ± 2%). Together with more robust 2-HG detection, long-echo time semi-LASER offers the potential to investigate tumor metabolism and stratify patients in vivo at 3 T.
Highlights
The Promise of 2-HG status is key for presurgical diagnosis and subsequent monitoring of treatment efficacy and relapse.Personalized medication in the treatment of cancer requires the discovery of reliable biomarkers and the development of tools capable of differential diagnosis according to genetic subtypes
Accumulation of the “oncometabolite” D-2-hydroxyglutarate (2-HG) in the majority (ϳ80%) of grades 2–3 gliomas and secondary glioblastomas [1, 2] is potentially such a biomarker. 2-HG is produced as a metabolic product of somatic mutations in genes encoding for isocitrate dehydrogenase (IDH) [2], IDH1 and IDH2, which encode for enzymes located in the cytosol and mitochondria, respectively
2-HG as a Detectable Molecule 2-HG is detectable in brain tumors using magnetic resonance spectroscopy (MRS), initially using ex vivo high-resolution magic-angle spinning [7], thereby enabling the possibility of IDH identification without the need for invasive surgical biopsy
Summary
The Promise of 2-HG status is key for presurgical diagnosis and subsequent monitoring of treatment efficacy and relapse.Personalized medication in the treatment of cancer requires the discovery of reliable biomarkers and the development of tools capable of differential diagnosis according to genetic subtypes. The Promise of 2-HG status is key for presurgical diagnosis and subsequent monitoring of treatment efficacy and relapse. 2-HG as a Detectable Molecule 2-HG is detectable in brain tumors using magnetic resonance spectroscopy (MRS), initially using ex vivo high-resolution magic-angle spinning [7], thereby enabling the possibility of IDH identification without the need for invasive surgical biopsy. In their initial work, used a short-echo time (TE ϭ 30 milliseconds) proton MRS pointresolved spectroscopy (PRESS) [9, 10] sequence at 3 T to demonstrate 2-HG detection in vivo [11]. Even at 9.4 T (where spectral resolution is ϳ3 times greater), accurate short-TE detection of 2-HG
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
