A comparison of 2‐hydroxyglutarate detection at 3 and 7 T with long‐TE semi‐LASER

Abnormally high levels of the ‘oncometabolite’ 2‐hydroxyglutarate (2‐HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2‐HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2‐HG detection. To combat this, several groups have proposed MRS methods at ultra‐high field (≥7 T) where theoretical increases in signal‐to‐noise ratio and spectral resolution could improve 2‐HG detection. Long echo time (long‐TE) semi‐localization by adiabatic selective refocusing (semi‐LASER) (TE = 110 ms) is a promising method for improved 2‐HG detection in vivo at either 3 or 7 T owing to the use of broad‐band adiabatic localization. Using previously published semi‐LASER methods at 3 and 7 T, this study directly compares the detectability of 2‐HG in phantoms and in vivo across nine patients. Cramér–Rao lower bounds (CRLBs) of 2‐HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild‐type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2‐HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ‐aminobutyric acid (GABA) and 2‐HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2‐HG detection using long‐TE acquisition at 7 T may allow for more rapid estimation of 2‐HG (within a few spectral averages) together with other associated metabolic markers in glioma.

[1]  W. Edelstein,et al.  The intrinsic signal‐to‐noise ratio in NMR imaging , 1986, Magnetic resonance in medicine.

[2]  P. Bottomley.  Spatial Localization in NMR Spectroscopy in Vivo , 1987, Annals of the New York Academy of Sciences.

[3]  J. Ingwall,et al.  Analysis of 23Na NMR spectra from isolated perfused hearts , 1991, Magnetic resonance in medicine.

[4]  S. Provencher.  Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[5]  R Gruetter,et al.  Automatic, localized in Vivo adjustment of all first‐and second‐order shim coils , 1993, Magnetic resonance in medicine.

[6]  T R Brown,et al.  Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study. , 1996, Journal of neurosurgery.

[7]  K. Uğurbil,et al.  Resolution improvements in in vivo 1H NMR spectra with increased magnetic field strength. , 1998, Journal of magnetic resonance.

[8]  M. Garwood,et al.  Simultaneous in vivo spectral editing and water suppression , 1998, NMR in biomedicine.

[9]  V. Govindaraju,et al.  Proton NMR chemical shifts and coupling constants for brain metabolites , 2000, NMR in biomedicine.

[10]  K Ugurbil,et al.  In vivo 1H NMR spectroscopy of the human brain at 7 T , 2001, Magnetic resonance in medicine.

[11]  R. Goebel,et al.  7T vs. 4T: RF power, homogeneity, and signal‐to‐noise comparison in head images , 2001, Magnetic resonance in medicine.

[12]  Peter Andersen,et al.  Proton T2 relaxation study of water, N‐acetylaspartate, and creatine in human brain using Hahn and Carr‐Purcell spin echoes at 4T and 7T , 2002, Magnetic resonance in medicine.

[13]  Akira Matsumura,et al.  Quantification of cerebral metabolites in glioma patients with proton MR spectroscopy using T2 relaxation time correction. , 2002, Magnetic resonance imaging.

[14]  R. Gruetter,et al.  Methodology of1H NMR spectroscopy of the human brain at very high magnetic fields , 2005, Applied magnetic resonance.

[15]  Mathias Hoehn,et al.  Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation , 2005, NMR in biomedicine.

[16]  Tommaso Scarabino,et al.  Proton MR spectroscopy of the brain at 3 T: an update , 2007, European Radiology.

[17]  Terence W Nixon,et al.  High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo , 2006, Magnetic resonance in medicine.

[18]  Arend Heerschap,et al.  Towards 1H-MRSI of the human brain at 7T with slice-selective adiabatic refocusing pulses , 2008, Magnetic Resonance Materials in Physics, Biology and Medicine.

[19]  D. Busam,et al.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2008, Science.

[20]  Dennis W J Klomp,et al.  Short echo time 1H‐MRSI of the human brain at 3T with minimal chemical shift displacement errors using adiabatic refocusing pulses , 2008, Magnetic resonance in medicine.

[21]  Andrey Korshunov,et al.  Analysis of the IDH1 codon 132 mutation in brain tumors , 2008, Acta Neuropathologica.

[22]  Wietske van der Zwaag,et al.  In vivo measurement of glycine with short echo-time 1H MRS in human brain at 7 T , 2009, Magnetic Resonance Materials in Physics, Biology and Medicine.

[23]  Ashish Jindal,et al.  Measurement of glycine in human prefrontal brain by point‐resolved spectroscopy at 7.0 tesla in vivo , 2009, Magnetic resonance in medicine.

[24]  F. Ducray,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.

[25]  Franklyn A Howe,et al.  Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers , 2010, Molecular Cancer.

[26]  L. Liau,et al.  Cancer-associated IDH1 mutations produce 2-hydroxyglutarate , 2009, Nature.

[27]  P. Kleihues,et al.  IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. , 2009, The American journal of pathology.

[28]  S. Mueller,et al.  (1)H MRS detection of glycine residue of reduced glutathione in vivo. , 2010, Journal of magnetic resonance.

[29]  Gülin Öz,et al.  Short‐echo, single‐shot, full‐intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: Validation in the cerebellum and brainstem , 2011, Magnetic resonance in medicine.

[30]  D. Dubowitz,et al.  Clinical pitfalls related to short and long echo times in cerebral MR spectroscopy. , 2011, Journal of neuroradiology. Journal de neuroradiologie.

[31]  Hong Wu,et al.  Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy , 2012, Journal of Neuro-Oncology.

[32]  R. Deberardinis,et al.  Measurement of glycine in the human brain in vivo by 1H‐MRS at 3 T: application in brain tumors , 2011, Magnetic resonance in medicine.

[33]  Michael Garwood,et al.  Localized 1H NMR spectroscopy in different regions of human brain in vivo at 7 T: T2 relaxation times and concentrations of cerebral metabolites , 2012, NMR in biomedicine.

[34]  W. Teeuwisse,et al.  Simulations of high permittivity materials for 7 T neuroimaging and evaluation of a new barium titanate‐based dielectric , 2012, Magnetic resonance in medicine.

[35]  Ovidiu C. Andronesi,et al.  Detection of 2-Hydroxyglutarate in IDH-Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy , 2012, Science Translational Medicine.

[36]  Gülin Öz,et al.  Regional neurochemical profiles in the human brain measured by 1H MRS at 7 T using local B1 shimming , 2012, NMR in biomedicine.

[37]  Yan Li,et al.  T1 and T2 Metabolite Relaxation Times in Normal Brain at 3T and 7T , 2013 .

[38]  Craig Malloy,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 , 2013, NMR in biomedicine.

[39]  T. Soga,et al.  Quantitative metabolome analysis profiles activation of glutaminolysis in glioma with IDH1 mutation , 2014, Tumor Biology.

[40]  Pierre-Gilles Henry,et al.  Improved quantification precision of human brain short echo‐time 1H magnetic resonance spectroscopy at high magnetic field: A simulation study , 2014, Magnetic resonance in medicine.

[41]  Jens Frahm,et al.  Clinical proton MR spectroscopy in central nervous system disorders. , 2013, Radiology.

[42]  K. Choe,et al.  Proton T2 measurement and quantification of lactate in brain tumors by MRS at 3 Tesla in vivo , 2015, Magnetic resonance in medicine.

[43]  T. Uchihara,et al.  Propagation of Aβ, tau and α-synuclein pathology between experimental models and human reality: prions, propagons and propaganda , 2015, Acta Neuropathologica.

[44]  D. Giavarina.  Understanding Bland Altman analysis , 2015, Biochemia medica.

[45]  Roland Kreis,et al.  The trouble with quality filtering based on relative Cramér‐Rao lower bounds , 2016, Magnetic resonance in medicine.

[46]  G. Reifenberger,et al.  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary , 2016, Acta Neuropathologica.

[47]  Klaus Scheffler,et al.  MR spectroscopy for in vivo assessment of the oncometabolite 2‐hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T , 2016, Journal of magnetic resonance imaging : JMRI.

[48]  Peter Jezzard,et al.  Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations. , 2016, Cancer research.

[49]  Wen Jun Xu,et al.  On the Utility of Short Echo Time (TE) Single Voxel 1H–MRS in Non–Invasive Detection of 2–Hydroxyglutarate (2HG); Challenges and Potential Improvement Illustrated with Animal Models Using MRUI and LCModel , 2016, PloS one.

[50]  H. Urbach,et al.  Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme , 2016, Scientific Reports.

[51]  N. Voets,et al.  Improved Localization for 2-Hydroxyglutarate Detection at 3 T Using Long-TE Semi-LASER , 2016, Tomography.

[52]  Edward Pan,et al.  In vivo detection of 2‐hydroxyglutarate in brain tumors by optimized point‐resolved spectroscopy (PRESS) at 7T , 2017, Magnetic resonance in medicine.

[53]  E. Maher,et al.  Detection of 2‐hydroxyglutarate in brain tumors by triple‐refocusing MR spectroscopy at 3T in vivo , 2017, Magnetic resonance in medicine.