Top

Magnetic Resonance Materials in Physics, Biology and Medicine

Published in:

01-02-2022 | Astrocytoma | Research Article

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

Authors: Dominik Juskanič, Jana Poláková Mištinová, Samuel Hollý, Monika Sekerešová, Kamil Koleják, Lukáš Pátrovič

Published in: Magnetic Resonance Materials in Physics, Biology and Medicine | Issue 1/2022

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.

Reitman ZJ, Jin G, Karoly ED et al (2011) Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc Natl Acad Sci 108:3270–3275. https://doi.org/10.1073/pnas.1019393108CrossRefPubMedPubMedCentral

Dang L, Yen K, Attar EC (2016) IDH mutations in cancer and progress toward development of targeted therapeutics. Ann Oncol 27:599–608. https://doi.org/10.1093/annonc/mdw013CrossRefPubMed

Liu X, Gong Y (2019) Isocitrate dehydrogenase inhibitors in acute myeloid leukemia. Biomark Res 7:22. https://doi.org/10.1186/s40364-019-0173-zCrossRefPubMedPubMedCentral

Amary MF, Bacsi K, Maggiani F et al (2011) IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathology 224:334–343. https://doi.org/10.1002/path.2913CrossRef

Salati M, Caputo F, Baldessari C et al (2020) IDH signalling pathway in cholangiocarcinoma: from biological rationale to therapeutic targeting. Cancers 12:3310. https://doi.org/10.3390/cancers12113310CrossRefPubMedCentral

Pansuriya TC, van Eijk R, d’Adamo P et al (2011) Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat Genet 43:1256–1261. https://doi.org/10.1038/ng.1004CrossRefPubMedPubMedCentral

Network TCGAR, Abeshouse A, Ahn J et al (2015) The molecular taxonomy of primary prostate cancer. Cell 163:1011–1025. https://doi.org/10.1016/j.cell.2015.10.025CrossRef

Raineri S, Mellor J (2018) IDH1: linking metabolism and epigenetics. Front Genet 9:493. https://doi.org/10.3389/fgene.2018.00493CrossRefPubMedPubMedCentral

Sulkowski PL, Corso CD, Robinson ND et al (2017) 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Sci Transl Med 9:eaal2463. https://doi.org/10.1126/scitranslmed.aal2463CrossRefPubMedPubMedCentral

10.

Tejera D, Kushnirsky M, Gultekin SH et al (2020) Ivosidenib, an IDH1 inhibitor, in a patient with recurrent, IDH1-mutant glioblastoma: a case report from a phase I study. CNS Oncol 9:CNS62. https://doi.org/10.2217/cns-2020-0014CrossRefPubMedPubMedCentral

11.

Wei S, Zhao J (2017) 2016 World health organization classification of tumors of the central nervous system: an interpretation. Chin J Neuromed 16:529–536. https://doi.org/10.3760/cma.j.issn.1671-8925.2017.05.018CrossRef

12.

Youssef G, Miller JJ (2020) Lower grade gliomas. Curr Neurol Neurosci 20:21. https://doi.org/10.1007/s11910-020-01040-8CrossRef

13.

Suh CH, Kim HS, Jung SC et al (2018) 2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma: a systemic review and meta-analysis using individual patient data. Neuro Oncol 20:1573–1583. https://doi.org/10.1093/neuonc/noy113CrossRefPubMedPubMedCentral

14.

Branzoli F, Stefano ALD, Capelle L et al (2017) Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy. Neuro Oncol 20:907–916. https://doi.org/10.1093/neuonc/nox214CrossRefPubMedCentral

15.

Kim H, Kim S, Lee HH, Heo H (2016) In-vivo proton magnetic resonance spectroscopy of 2-hydroxyglutarate in isocitrate dehydrogenase-mutated gliomas: a technical review for neuroradiologists. Korean J Radiol 17:620–632. https://doi.org/10.3348/kjr.2016.17.5.620CrossRefPubMedPubMedCentral

16.

Choi C, Ganji SK, DeBerardinis RJ et al (2012) 2-Hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med 18:624–629. https://doi.org/10.1038/nm.2682CrossRefPubMedPubMedCentral

17.

Starčuk Z, Starčuková J (2017) Quantum-mechanical simulations for in vivo MR spectroscopy: Principles and possibilities demonstrated with the program NMRScopeB. Anal Biochem 529:79–97. https://doi.org/10.1016/j.ab.2016.10.007CrossRefPubMed

18.

Naressi A, Couturier C, Devos JM et al (2001) Java-based graphical user interface for the MRUI quantitation package. Magn Reson Mater Phys Biol Med 12:141–152. https://doi.org/10.1016/s1352-8661(01)00111-9CrossRef

19.

Stefan D, Cesare FD, Andrasescu A et al (2009) Quantitation of magnetic resonance spectroscopy signals: the jMRUI software package. Meas Sci Technol 20:104035. https://doi.org/10.1088/0957-0233/20/10/104035CrossRef

20.

Govindaraju V, Young K, Maudsley AA (2000) Proton NMR chemical shifts and coupling constants for brain metabolites. Nmr Biomed 13:129–153. https://doi.org/10.1002/1099-1492(200005)13:3%3c129::aid-nbm619%3e3.0.co;2-vCrossRefPubMed

21.

Kaiser LG, Marjańska M, Matson GB et al (2010) 1H MRS detection of glycine residue of reduced glutathione in vivo. J Magn Reson 202:259–266. https://doi.org/10.1016/j.jmr.2009.11.013CrossRefPubMed

22.

Wilson M (2021) spant: an R package for magnetic resonance spectroscopy analysis. J Open Source Softw 6:3646. https://doi.org/10.21105/joss.03646CrossRef

23.

Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679. https://doi.org/10.1002/mrm.1910300604CrossRefPubMed

24.

Choi C, Raisanen JM, Ganji SK et al (2016) 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 34:4030–4039. https://doi.org/10.1200/jco.2016.67.1222CrossRefPubMedPubMedCentral

25.

Nagashima H, Tanaka K, Sasayama T et al (2016) Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. Neuro Oncol 18:1559–1568. https://doi.org/10.1093/neuonc/now090CrossRefPubMedPubMedCentral

26.

de la Fuente MI, Young RJ, Rubel J et al (2016) Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma. Neuro Oncol 18:283–290. https://doi.org/10.1093/neuonc/nov307CrossRefPubMed

27.

Costanzo AD, Trojsi F, Popolizio T et al (2006) High field brain MRI. Use Clin Pract. https://doi.org/10.1007/3-540-31776-7_18CrossRef

28.

Andronesi OC, Kim GS, Gerstner E et al (2012) Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci Transl Med 4:116ra4. https://doi.org/10.1126/scitranslmed.3002693CrossRefPubMedPubMedCentral

29.

Crisi G, Filice S, Michiara M et al (2018) 2-Hydroxyglutarate detection by short echo time magnetic resonance spectroscopy in routine imaging study of brain glioma at 3.0 T. J Comput Assist Tomogr 42:469–474. https://doi.org/10.1097/rct.0000000000000705CrossRefPubMed

30.

Tietze A, Choi C, Mickey B et al (2018) Non-invasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting. J Neurosurg 128:391–398. https://doi.org/10.3171/2016.10.jns161793CrossRefPubMed

31.

Zhou M, Zhou Y, Liao H et al (2018) Diagnostic accuracy of 2-hydroxyglutarate magnetic resonance spectroscopy in newly diagnosed brain mass and suspected recurrent gliomas. Neuro Oncol 20:1262–1271. https://doi.org/10.1093/neuonc/noy022CrossRefPubMedPubMedCentral

32.

Liu A, Hou C, Chen H et al (2016) Genetics and epigenetics of glioblastoma: applications and overall incidence of IDH1 mutation. Front Oncol 6:16. https://doi.org/10.3389/fonc.2016.00016CrossRefPubMedPubMedCentral

33.

Liao Y, Oros-Peusquens A-M, Lindemeyer J et al (2019) An MR technique for simultaneous quantitative imaging of water content, conductivity and susceptibility, with application to brain tumours using a 3T hybrid MR-PET scanner. Sci Rep UK 9:88. https://doi.org/10.1038/s41598-018-36435-8CrossRef

34.

Gu W, Fang S, Hou X et al (2021) Exploring diagnostic performance of T2 mapping in diffuse glioma grading. Quant Imaging Med Surg 11:2942954–2943954. https://doi.org/10.21037/qims-20-916CrossRef

35.

Kern M, Auer TA, Picht T et al (2020) T2 mapping of molecular subtypes of WHO grade II/III gliomas. Bmc Neurol 20:8. https://doi.org/10.1186/s12883-019-1590-1CrossRefPubMedPubMedCentral

Title: Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment
Authors: Dominik Juskanič
Jana Poláková Mištinová
Samuel Hollý
Monika Sekerešová
Kamil Koleják
Lukáš Pátrovič
Publication date: 01-02-2022
Publisher: Springer International Publishing
Keywords: Astrocytoma
Glioma
Glioma
Astrocytoma
Astrocytoma
Glioma
Published in: Magnetic Resonance Materials in Physics, Biology and Medicine / Issue 1/2022
Print ISSN: 0968-5243
Electronic ISSN: 1352-8661
DOI: https://doi.org/10.1007/s10334-021-00989-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2022

Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

Overestimation of grey matter atrophy in glioblastoma patients following radio(chemo)therapy

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

What do we know about dynamic glucose-enhanced (DGE) MRI and how close is it to the clinics? Horizon 2020 GLINT consortium report

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue