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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.

Original publication

DOI

10.1002/nbm.3886

Type

Journal article

Journal

NMR Biomed

Publication Date

03/2018

Volume

31

Keywords

2-HG, detection, glioma, ultra-high field, Adult, Brain Neoplasms, Choline, Creatine, Female, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Magnetic Resonance Spectroscopy, Male, Middle Aged, Young Adult