Proton magnetic resonance spectroscopy (MRS) of the brain can detect 2-hydroxyglutarate (2HG), the oncometabolite produced in neoplasms harboring a mutation in the gene coding for isocitrate dehydrogenase (IDH ). We conducted a prospective longitudinal imaging study to determine whether quantitative assessment of 2HG by MRS could serve as a noninvasive clinical imaging biomarker for IDH-mutated gliomas. Patients and Methods2HG MRS was performed in 136 patients using point-resolved spectroscopy at 3 T in parallel with standard clinical magnetic resonance imaging and assessment. Data were analyzed in patient cohorts representing the major phases of the glioma clinical course and were further subgrouped by histology and treatment type to evaluate 2HG. Histologic correlations were performed. ResultsQuantitative 2HG MRS was technically and biologically reproducible. 2HG concentration . 1 mM could be reliably detected with high confidence. During the period of indolent disease, 2HG concentration varied by less than 6 1 mM, and it increased sharply with tumor progression. 2HG concentration was positively correlated with tumor cellularity and significantly differed between high-and lower-grade gliomas. In response to cytotoxic therapy, 2HG concentration decreased rapidly in 1p/19q codeleted oligodendrogliomas and with a slower time course in astrocytomas and mixed gliomas. The magnitude and time course of the decrease in 2HG concentration and magnitude of the decrease in tumor volume did not differ between oligodendrogliomas treated with temozolomide or carmustine. Criteria for 2HG MRS were established to make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a surgical procedure. Conclusion2HG concentration as measured by MRS was reproducible and reliably reflected the disease state. These data provide a basis for incorporating 2HG MRS into clinical management of IDH-mutated gliomas.

2-hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenases (IDH) 1 and 2. The 1H resonances of the J-coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here we report a comparative study at 3T of the utility of the PRESS (point-resolved spectroscopy) sequence with a standard short TE (35 ms) and a long TE (97 ms) which had been theoretically designed for detecting the 2HG 2.25 ppm resonance. The performance of the methods is evaluated using data from phantoms, 7 healthy volunteers, and 22 subjects with IDH-mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radio-frequency and gradient pulses.

Purpose To evaluate the T2 relaxation time of lactate (Lac) in brain tumors and the correlation of the T2 and concentration with tumor grades. Methods Eight pairs of the subecho time sets of point-resolved spectroscopy were selected between 58 and 268 ms, with numerical and phantom analyses, for Lac T2 measurement. In-vivo spectra were acquired from 24 subjects with gliomas (13 low grade and 11 high grade) and analyzed with LCModel using numerically-calculated basis spectra. The metabolite T2 relaxation time was obtained from monoexponential fitting of the multi-TE signal estimates versus TE. The metabolite concentration was estimated from the zero-TE extrapolation of the T2 fits. Results The Lac T2 was estimated to be approximately 240 ms, without a significant difference between low and high grade tumors. The Lac concentration was estimated to be 4.1±3.4 and 7.0±4.7 mM for low and high grades respectively, but the difference was not significant. Conclusion The Lac T2 was similar among gliomas regardless of their tumor grades. This suggests that the T2 value from this study may be applicable to obtain the T2 relaxation-free estimates of Lac in a subset of brain tumors.