Dataset Information

Improved localisation for 2-hydroxyglutarate detection at 3T using long-TE semi-LASER.

ABSTRACT: 2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumour cell IDH mutations that may enable the differential diagnosis of glioma patients. At 3 Tesla, detection of 2-HG with magnetic resonance spectroscopy is challenging because of metabolite signal overlap and a spectral pattern modulated by slice selection and chemical shift displacement. Using density matrix simulations and phantom experiments, an optimised semi-LASER scheme (TE = 110 ms) improves localisation of the 2-HG spin system considerably compared to an existing PRESS sequence. This results in a visible 2-HG peak in the in vivo spectra at 1.9 ppm in the majority of IDH mutated tumours. Detected concentrations of 2-HG were similar using both sequences, although the use of semi-LASER generated narrower confidence intervals. Signal overlap with glutamate and glutamine, as measured by pairwise fitting correlation was reduced. Lactate was readily detectable across glioma patients using the method presented here (mean CLRB: (10±2)%). Together with more robust 2-HG detection, long TE semi-LASER offers the potential to investigate tumour metabolism and stratify patients in vivo at 3T.

SUBMITTER: Berrington A

PROVIDER: S-EPMC4990123 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Improved localisation for 2-hydroxyglutarate detection at 3T using long-TE semi-LASER.

Berrington Adam A Voets Natalie L NL Plaha Puneet P Larkin Sarah J SJ Mccullagh James J Stacey Richard R Yildirim Muhammed M Schofield Christopher J CJ Jezzard Peter P Cadoux-Hudson Tom T Ansorge Olaf O Emir Uzay E UE

Tomography (Ann Arbor, Mich.) 20160601 2

2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumour cell IDH mutations that may enable the differential diagnosis of glioma patients. At 3 Tesla, detection of 2-HG with magnetic resonance spectroscopy is challenging because of metabolite signal overlap and a spectral pattern modulated by slice selection and chemical shift displacement. Using density matrix simulations and phantom experiments, an optimised semi-LASER scheme (TE = 110 ms) improves localisation of the 2-HG spin system co ...[more]

PMID: 27547821

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Project description:The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B1 limit of 15 μT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B0 shimming and voxel-based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 μT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts.

Project description:Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are frequently found in brain tumors, and the resulting onco-metabolite, 2-hydroxyglutarate (2HG), has been suggested to be a potential diagnostic and prognostic biomarker of the diseases. Indeed, recent studies have demonstrated the feasibility of non-invasively detecting 2HG by using proton magnetic resonance spectroscopy (1H-MRS). Due to severe spectral overlaps of 2HG with its background metabolites and spectral baselines, however, the majority of those previous studies employed spectral editing methods with long echo times (TEs) instead of the most commonly used short TE approach with spectral fitting. Consequently, the results obtained with spectral editing methods may potentially be prone to errors resulting from substantial signal loss due to relaxation. Given that the spectral region where the main signal of 2HG resides is particularly sensitive to spectral baseline in metabolite quantification, we have investigated the impact of incorporating voxel-specifically measured baselines into the spectral basis set on the performance of the conventional short TE approach in 2HG detection in rodent models (Fisher 344 rats; n = 19) of IDH1/2 mutant-overexpressing F98 glioma at 9.4T. Metabolite spectra were acquired (SPECIAL sequence) for a tumor region and the contralateral normal region of the brain for each animal. For the estimation of spectral baselines metabolite-nulled spectra were obtained (double-inversion-recovery SPECIAL sequence) for each individual voxels. Data were post-processed with and without the measured baselines using MRUI and LCModel-the two most widely used data post-processing packages. Our results demonstrate that in-vivo detection of 2HG using the conventional short TE approach is challenging even at 9.4T. However, incorporation of voxel-specifically measured spectral baselines may potentially improve its performance. Upon more thorough validation in a larger number of animals and more importantly in human patients, the potential utility of the proposed short TE acquisition with voxel-specific baseline measurement approach in 2HG detection may need to be considered in the study design.

Dataset Information

Improved localisation for 2-hydroxyglutarate detection at 3T using long-TE semi-LASER.

Publications

Improved localisation for 2-hydroxyglutarate detection at 3T using long-TE semi-LASER.

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