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Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment

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Abstract

Objective

Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. Detecting 2HG by MR spectroscopy (MRS) has been proven viable in the last decade but has not entirely found its way into the clinical routine. This study aimed to explore the adoption of 2HG MRS while acknowledging factors that influence its performance in the clinical environment.

Methods

Thirty-nine MR spectra were acquired and reported prospectively in patients with suspected glioma using a 3 T system with Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) sequence utilizing averaged free induction decay (FID) signals. Postprocessing and evaluation of spectra were performed with jMRUI and LCModel. 2HG concentration estimates, 2HG/Cr ratio, together with quality measures, including Cramér–Rao lower bounds (CRLBs), full-width at half-maximum (FWHM) values, and signal-to-noise ratio (SNR) were calculated using LCModel. Immunohistochemistry and genomic analysis results used as a ground truth were available for 15 patients.

Results

The threshold for test positivity was set according to the ROC curve at 1 mM. Calculated sensitivity was 57.14% (95% CI 0.20–0.88), specificity 87.5% (95% CI 0.46–0.99), positive predictive value 80%, and negative predictive value 70%. Overall diagnostic accuracy was 73.33% (95% CI 0.45–0.92). The 2HG/Cr ratio with the cutoff value 0.085 significantly improved sensitivity and overall diagnostic accuracy [85.71%, 95% CI 0.42–1.00 and 86.67%, (95% CI 0.60–0.98), respectively].

Conclusion

Multiple factors compromising spectral quality in the clinical adoption of edited 2HG MRS resulted in diminished sensitivity but clinically acceptable specificity. Furthermore, the 2HG/Cr ratio performs better than the sole 2HG concentration estimate in the pre-operative setting.

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Acknowledgements

The MRS package was developed by Edward J. Auerbach and Małgorzata Marjańska and provided by the University of Minnesota under a C2P agreement. The authors would like to thank Małgorzata Marjańska and Marek Chmelík for guidance in data acquisition and helpful discussions.

Funding

No funding was received for conducting this study. The authors have no relevant financial or non-financial interests to disclose.

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Authors and Affiliations

  1. JESSENIUS-Diagnostic Center, Nitra, Slovakia

    Dominik Juskanič, Samuel Hollý & Lukáš Pátrovič

  2. Medical Faculty, Comenius University in Bratislava, Bratislava, Slovakia

    Dominik Juskanič & Jana Poláková Mištinová

  3. Faculty Hospital, Nitra, Slovakia

    Dominik Juskanič, Monika Sekerešová & Kamil Koleják

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  1. Dominik Juskanič
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Contributions

DJ: study conception and design, analysis and interpretation of data, and drafting of the manuscript. JPM: study conception and design, and drafting of the manuscript. SH: acquisition of data, analysis, and interpretation of data. LP: analysis and interpretation of data, and critical revision. KK: resection of tumors. MS: ex vivo tissue analysis.

Corresponding author

Correspondence to Dominik Juskanič.

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Ethical standards

This study was approved by the Ethical Committee of Faculty Hospital in Nitra, which complies with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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Juskanič, D., Mištinová, J.P., Hollý, S. et al. Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment. Magn Reson Mater Phy 35, 45–52 (2022). https://doi.org/10.1007/s10334-021-00989-y

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  • DOI: https://doi.org/10.1007/s10334-021-00989-y

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