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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.

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