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• Clinical Article •
Efficiency of 2-hydroxyglutarate quantification by long-echo proton magnetic resonance spectroscopy at 3.0 T in vitro and in vivo
YU Meimei  SHEN Huicong  SHEN Zhiwei  LIN Meiying  HOU Xinyi  CHEN Hongyan  CHEN Xuzhu  JI Nan 

Cite this article as: Yu MM, Shen HC, Shen ZW, et al. Efficiency of 2-hydroxyglutarate quantification by long-echo proton magnetic resonance spectroscopy at 3.0 T in vitro and in vivo. Chin J Magn Reson Imaging, 2020, 11(4): 275-280. DOI:10.12015/issn.1674-8034.2020.04.007.


[Abstract] Objective: Mutated isocitrate dehydrogenase (IDH) produce high accumulation levels of 2-hydroxyglutarate (2HG) that can be quantitatively detected by proton magnetic resonance spectroscopy (1H-MRS). Through in vitro and in vivo studies, the purpose of our study was to explore the efficacy of using long-echo (TE) point-resolved spectroscopy (PRESS) MRS to detect 2HG at 3.0 T in clinical setting.Materials and Methods: Two phantoms were set up, the first is a spherical phantom (diameter of about 6 cm plastic ball), which containing a range of known concentrations of 2HG 9 mmol/L, Glutamate (Glu) 12.5 mmol/L, Glutamine (Gln) 12.5 mmol/L, γ-Aminobutyric Acid (GABA) 2.0 mmol/L, N-acetylaspartate (NAA) 12.5 mmol/L, Creatine (Cr) 10.0 mmol/L, Choline (Cho) 3.0 mmol/L; The second includes six cylindrical gradient phantoms (both 60 mL plastic test tubes), and Glu 10 mmol/L, Cr 10 mmol/L, and 2HG 0.5, 1, 2, 4, 8, 16 mmol/L, respectively. Pointresolved spectroscopy (PRESS) sequence with long echo time (TE=97 ms, TE1=26 ms, TE2=71 ms) MRS was used to analyze for all the set phantoms. In addition, combined with T1WI and T1WI enhanced images, long TE PRESS MRS was performed on 4 subjects with suspected diagnosis of low-grade glioma in our study. IDH mutation status obtained by postoperative genetic testing was taken as the gold standard. The absolute concentration values of metabolites were acquired by LC model software fitting.Results: Phantoms results showed that 2HG could be detected effectively when the concentration of 2HG was 2-16 mmol/L. Compared with the real concentration of 2HG, the absolute concentration of 2HG obtained by LC model software was lower, while the concentration ratio of 2HG/Glu was close to the actual ratio. Three subjects were subsequently diagnosed histologically as gliomas, of which 2 were IDH mutant gliomas and 1 was IDH wild-type glioma. By long TE PRESS, the accumulation of 2HG was detected effectively in IDH mutant glioma, while there is no accumulation of 2HG in IDH wild-type glioma.Conclusions: The results of phantoms suggest that 2HG at low concentration can be masked and thus increase the false negative result. However, the ratio of 2HG/Glu is closer to the actual ratio, indicating that it may be more accurate to replace the absolute concentration value with the ratio. Combined with the results of scanning in vivo shows that it was feasible to use long TE PRESS sequence in the conventional glioma imaging protocol to detect 2HG accumulation and indirectly predict IDH mutation status. It is of great significance for the preoperative non-invasive diagnosis, guiding treatment strategy and prognosis evaluation of glioma.
[Keywords] 2-hydroxyglutarate；glioma；isocitrate dehydrogenase；magnetic resonance spectroscopy

YU Meimei Department of Radiology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

SHEN Huicong* Department of Radiology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

SHEN Zhiwei Department of Radiology, Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China

LIN Meiying Department of Radiology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

HOU Xinyi Department of Radiology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

CHEN Hongyan Department of Radiology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

CHEN Xuzhu Department of Radiology, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

JI Nan Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, China

*Correspondence to: Shen HC, E-mail: shenhuicong@126.com

Conflicts of interest   None.

ACKNOWLEDGMENTS  This work was part of National Key Research and Development Program No. 2018YFC0115604 National Natural Science Foundation of China No. 81772005
Received  2019-11-21
Accepted  2020-02-07
DOI: 10.12015/issn.1674-8034.2020.04.007
Cite this article as: Yu MM, Shen HC, Shen ZW, et al. Efficiency of 2-hydroxyglutarate quantification by long-echo proton magnetic resonance spectroscopy at 3.0 T in vitro and in vivo. Chin J Magn Reson Imaging, 2020, 11(4): 275-280. DOI:10.12015/issn.1674-8034.2020.04.007.

[1]
Balss J, Meyer J, Mueller W, et al. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol, 2008, 116(6): 597-602.
[2]
De Carli E, Wang X, Puget S. IDH1 and IDH2 Mutations in Gliomas. N Engl J Med, 2009, 360(21): 2248-2249.
[3]
Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature, 2009, 462(7274): 739-744.
[4]
王汝佳，沈桂权，高波．脑胶质瘤IDH-1突变的影像学研究进展．磁共振成像, 2016, 7(9): 711-715.
[5]
Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell, 2011, 19(1): 17-30.
[6]
Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature, 2012, 483(7390): 474-478.
[7]
Zhao S, Lin Y, Xu W, et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1. Science, 2009, 324(5924): 261-265.
[8]
Andronesi OC, Kim GS, Gerstner E, et al. Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci Transl Med, 2012, 4(116): 116.
[9]
Choi C, Raisanen JM, Ganji SK, et al. Prospective longitudinal analysis of 2-hydroxyglutarate magnetic resonance spectroscopy identifies broad clinical utility for the management of patients with IDH-mutant glioma. J Clin Oncol, 2016, 34(33): 4030-4039.
[10]
Tietze A, Choi C, Mickey B, et al. Noninvasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting. J Neurosurg, 2018, 128(2): 391-398.
[11]
Zhou M, Zhou Y, Liao H, et al. Diagnostic accuracy of 2-hydroxyglutarate magnetic resonance spectroscopy in newly diagnosed brain mass and suspected recurrent gliomas. Neuro-Oncology, 2018, 20(9): 1262-1271.
[12]
Choi C, Ganji SK, DeBerardinis RJ, et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med, 2012, 18(4): 624-629.
[13]
Suh CH, Kim HS, Paik W, et al. False-positive measurement at 2-hydroxyglutarate MR spectroscopy in isocitrate dehydrogenase wild-type glioblastoma: A multifactorial analysis. Radiology, 2019, 291(3): 752-762.
[14]
de la Fuente MI, Young RJ, Rubel J, et al. Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenasemutant glioma. Neuro-Oncology, 2016,18(2): 283-290.
[15]
Natsumeda M, Motohashi K, Igarashi H, et al. Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. Neurosurg Rev, 2018, 41(2): 641-647.
[16]
Nagashima H, Tanaka K, Sasayama T, et al. Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. Neuro-Oncology, 2016, 18: 1559-1568.
[17]
Pope WB, Prins RM, Albert Thomas M, et al. Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J Neurooncol, 2012, 107(1): 197-205.
[18]
Branzoli F, Di Stefano AL, Capelle L, et al. Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy. Neuro-Oncology, 2018, 20(7): 907-916. DOI: 10.1093/neuonc/nox214.
[19]
Natsumeda M, Igarashi H, Nomura T, et al. Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy. Acta Neuropathol Commun, 2014, 2(1): 158.
[20]
Crisi G, Filice S, Michiara M, et al. 2-hydroxyglutarate detection by short echo time magnetic resonance spectroscopy in routine imaging study of brain glioma at 3.0 T. J Computer Assist Tomogr, 2018, 42(3): 469-474.
[21]
Verma G, Mohan S, Nasrallah MP, et al. Non-invasive detection of 2-hydroxyglutarate in IDH-mutated gliomas using two-dimensional localized correlation spectroscopy (2D L-COSY) at 7 Tesla. J Transl Med, 2016, 14(1): 274.
[22]
Provencher SW. Estimation of metabolite concentrations from localizedin vivo proton NMR spectra. Magne Reson Med, 1993, 30(6): 672-679.
[23]
林坤，次旦旺久，王晓明．多模态磁共振成像技术在胶质瘤细胞增殖诊断中的应用．磁共振成像, 2017, 8(6): 470-474.
[24]
Suh CH, Kim HS, Jung SC, et al. 2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: a systemic review and meta-analysis using individual patient data. Neuro-Oncology, 2018, 20(12): 1573-1583.
[25]
Beiko J, Suki D, Hess KR, et al. IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro-Oncology, 2014, 16(1): 81-91.
[26]
Andronesi OC, Arrillaga-Romany IC, Ly KI, et al. Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate. Nat Commun, 2018, 9(1): 1474.
[27]
Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science, 2013, 340(6132): 626-630.
[28]
Turcan S, Fabius AW, Borodovsky A, et al. Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT inhibitor decitabine. Oncotarget, 2013, 4(10): 1729-1736.
[29]
Schumacher T, Bunse L, Pusch S, et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature, 2014, 512(7514): 324-327.
[30]
Bertolino N, Marchionni C, Ghielmetti F, et al. Accuracy of 2-hydroxyglutarate quantification by short-echo proton-MRS at 3 T: A phantom study. Phys Med, 2014, 30(6): 702-707. DOI: 10.1016/j.ejmp.2014.03.002.
[31]
Berrington A, Voets NL, Plaha P, et al. Improved Localization for 2-hydroxyglutarate detection at 3 T using long-TE semi-LASER. Tomography, 2016, 2(2): 94-105.
[32]
Choi C, Ganji S, Hulsey K, et al. A comparative study of short- and long-TE 1H MRS at 3 T for in vivo detection of 2-hydroxyglutarate in brain tumors: MRS detectability of 2-hydroxyglutarate. NMR Biomed, 2013, 26(10): 1242-1250.

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