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

Abstract

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.

Non-Invasive Prediction of IDH Mutation in Patients with Glioma WHO II/III/IV Based on F-18-FET PET-Guided In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning

“…Numerous clinical trials predicting IDH mutation status using MRI/MRS/radiomics have been conducted with a summary sensitivity across all techniques of 86% (95% CI, 79-91%) and a summary specificity of 87% (95% CI, 91-100%), while pooled sensitivity and specificity for 2-HG MRS were 95% (95% CI, 85-98%) and 91% (95% CI, 83-96%), respectively [24]. Longer echo times (significant increased sensitivity and specificity in TE 97 ms compared to TE 30-35 ms) [30], ultra-high-field MRI (7T) [31,32], 2D correlation spectroscopy (COSY) at 3T [33] and 2D L-COSY at 7T [34] were used to improve detection of the 2-HG signal. Different post-processing techniques have also been applied in various settings, mostly in a limited number of patients (e.g., 38 patients in Reference [35]).…”

Methodological consensus on clinical proton MRS of the brain: Review and recommendations

“…Overall, we recommend the use of semi‐LASER due to its recent validation studies and increasing availability on clinical systems, as both research work‐in‐progress sequences and commercial product (Figure ). Furthermore, in our consensus survey, semi‐LASER was ranked as the most likely localization technique to improve clinical MRS. We also recommend the use of PRESS with VSS pulses if this is the only option available, but note this option lacks the partially suppressed J ‐coupling evolution and longer apparent T 2 relaxation when compared with semi‐LASER, and can inadvertently excite or refocus large signals (e.g., scalp lipids) that are difficult to suppress fully.…”

“…A further advantage of semi-LASER, compared with PRESS for the same TE, is longer apparent T 2 relaxation times and partially suppressed J-coupling evolution, due to the Carr-Purcell-Meiboom-Gill-like refocusing pulse train (and therefore enhanced detection of complex multiplets such as glutamate.) 79,83 Overall, we recommend the use of semi-LASER due to its recent validation studies [84][85][86][87][88][89] and increasing availability on clinical systems, as both research work-in-progress sequences and commercial product ( Figure 2). Furthermore, in our consensus survey, semi-LASER was ranked as the most likely localization technique to improve clinical MRS. We also recommend the use of PRESS with VSS pulses if this is the only option available, but note this option lacks the partially suppressed J-coupling evolution and longer apparent T 2 relaxation when compared with semi-LASER, and can inadvertently excite or refocus large signals (e.g., scalp lipids) that are difficult to suppress fully.…”

2-Hydroxyglutarate in Cancer Cells

“…Similar concentrations were found using long echo time MR spectroscopy with semi-localization by adiabatic selective refocusing. It was recognized that gliomas bearing IDH2 mutants accumulated more 2HG than those with IDH1 mutants (9,148).…”