Proton T2 measurement and quantification of lactate in brain tumors by MRS at 3 Tesla in vivo.

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-echo time (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.

In vivo detection of citrate in brain tumors by 1H magnetic resonance spectroscopy at 3T.

PURPOSE: To test whether citrate is elevated in adult patients with gliomas using (1)H magnetic resonance spectroscopy (MRS) at 3T in vivo. METHODS: Thirty-four adult patients were enrolled in the study, including six subjects with glioblastomas, eight subjects with astrocytomas (World Health Organization grade 3, n = 5; grade 2, n = 3), and 20 subjects with oligodendrogliomas (grade 3, n = 5; grade 2, n = 15). Five healthy volunteers were studied for baseline citrate data. Single-voxel localized spectra were collected with point-resolved spectroscopy (PRESS) echo times of 35 and 97 ms and were analyzed with LCModel software using numerically calculated basis spectra that included the effects of the PRESS radiofrequency and gradient pulses. RESULTS: Citrate was not measurable by MRS in healthy brain but was detected in tumor patients at both echo times. The citrate concentration was estimated to be as high as 1.8 mM with reference to water at 42 M, with Cramér-Rao lower bounds (CRLB) as low as 5%. The mean citrate level was 0.7 ± 0.4 mM (mean ± SD, n = 32) with a median CRLB of ∼12%. No correlation was identified between citrate concentration and tumor grade or histological type. CONCLUSION: Citrate was increased in the majority of gliomas in adult patients. The elevated citrate in our data indicates an altered metabolic state of tumor relative to healthy brain.

Measurement of regional variation of GABA in the human brain by optimized point-resolved spectroscopy at 7 T in vivo.

The (1)H resonances of γ-aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short-TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point-resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE2) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T1 -weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N-acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J-coupled spin metabolites in human brain at 7 T.

A comparative study of short- and long-TE ¹H MRS at 3 T for in vivo detection of 2-hydroxyglutarate in brain tumors.

2-Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The (1) H resonances of the J-coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point-resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25-ppm resonance. The performance of the methods is evaluated using data from phantoms, seven 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 radiofrequency and gradient pulses.

Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma.

Purpose 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 Methods 2HG 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. Results Quantitative 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 ± 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. Conclusion 2HG 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.