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TOMOGRAPHY, June 2016, Volume 2, Issue 2: 94-105
DOI: 10.18383/j.tom.2016.00139

Improved Localisation for 2-hydroxyglutarate Detection at 3T Using Long-TE Semi-LASER

Adam Berrington1, Natalie L. Voets1, Puneet Plaha2, Sarah J. Larkin3, James Mccullagh4, Richard Stacey2, Muhammed Yildirim5, Christopher J. Schofield4, Peter Jezzard1, Tom Cadoux-Hudson2, Olaf Ansorge3, and Uzay E. Emir1

1Nuffield Department of Clinical Neurosciences, FMRIB Centre, John Radcliffe Hospital, University of Oxford, Oxford; 2Department of Neurosurgery, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford; 3Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford; 4Department of Chemistry, University of Oxford, Oxford; and 5Advanced Diagnostic Imaging, Philips Healthcare, The Netherlands

Abstract

2-hydroxyglutarate (2-HG) has emerged as a biomarker of tumor cell isocitrate dehydrogenase mutations that may enable the differential diagnosis of patients with glioma. At 3 T, detection of 2-HG with magnetic resonance spectroscopy is challenging because of metabolite signal overlap and spectral pattern modulation by slice selection and chemical shift displacement. Using density matrix simulations and phantom experiments, an optimized semi-LASER scheme (echo time = 110 milliseconds) considerably improves localization of the 2-HG spin system compared with that of an existing point-resolved spectroscopy sequence. This results in a visible 2-HG peak in the in vivo spectra at 1.9 ppm in the majority of isocitrate dehydrogenase-mutated tumors. 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 patients with glioma using the method presented here (mean Cramér–Rao lower bound: 10% ± 2%). Together with more robust 2-HG detection, long-echo time semi-LASER offers the potential to investigate tumor metabolism and stratify patients in vivo at 3 T.

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