Gore, John C.

ABSTRACTSurgical biopsy of brainstem tumors carries a risk of neurological injury. We performed magnetic resonance spectroscopy (MRS) of 2‐hydroxyglutarate (2HG) and glycine in patients with brainstem tumors to assess the feasibility of detecting and quantifying 2HG in the brainstem to obviate the need for a diagnostic biopsy and to establish the clinical significance of glycine MRS in brainstem tumors in vivo. Twenty adult patients with radiographically identified presumed brainstem gliomas were prospectively enrolled in the study. Proton MRS was obtained at 3T with a protocol tailored for detection of 2HG and glycine (TE 97‐ms PRESS). Spectra were fit using LCModel software and in‐house basis signals of metabolites and lipids. The metabolite concentrations were quantified with reference to water and examined with respect to clinical outcomes, including postgadolinium MRI and overall survival time. MRS data from 19 patients were included in subsequent analysis, excluding suboptimal data from one patient. Tumors with elevated 2HG (> 1.9 mM, N = 8) and undetectable 2HG (< 0.3 mM, N = 11) were clearly distinguishable. Tumors with elevated glycine (> 1.5 mM, N = 4) showed rapid progression. Kaplan–Meier survival analyses with metabolite measures demonstrated that tumors with 2HG higher than 1.0 mM were significantly associated with a favorable prognosis (p = 0.01). In contrast, tumors with glycine higher than 2.5 mM showed a strong association with poor survival (p = 0.0005). The data confirm detection of 2HG in brainstem tumors at a concentration that is consistent with an IDH mutation and expected good prognosis, whereas elevated glycine in brainstem tumors portends rapid tumor progression and a worse prognosis.

PurposeThe need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J‐difference editing of lactate, threonine can be co‐edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow‐band editing 180° pulses (E180) in MEGA‐PRESS acquisitions to resolve separately the 1.3‐ppm resonances of lactate and threonine.MethodsTwo 45.3‐ms rectangular E180 pulses, which had negligible effects 0.15‐ppm away from the carrier frequency, were implemented in a MEGA‐PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow‐band E180 MEGA and another MEGA‐PRESS sequence with broad‐band E180 pulses were evaluated in six healthy subjects.ResultsThe 45.3‐ms E180 MEGA offered a difference‐edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad‐band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet‐resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N‐acetylaspartate at 12 mM.ConclusionNarrow‐band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.