Magnetic Resonance Spectroscopy Imaging of 2-Hydroxyglutarate in Brain Tumors at 3T and 7T In Vivo

The identification of 2-hydroxyglutarate (2HG) by 1H magnetic resonance spectroscopy (MRS) in patients with isocitrate dehydrogenase mutant gliomas is a significant breakthrough in neuro-oncology imaging. 2HG is the first imaging biomarker that is specific to a genetic mutation in gliomas, making the diagnosis of IDH mutant gliomas possible without biopsy. 2HG also has a significant predictive value with respect to the stage and survival in gliomas because IDH mutation carries a favorable prognosis. Gliomas are highly heterogeneous and infiltrative in malignant transformation and recur beyond the borders of the initial tumor mass. Therefore, a high-resolution 3D imaging platform to measure 2HG rapidly has an outstanding strength for monitoring IDH-mutant tumors. The present work aims to develop new techniques that provide meaningful estimation of 2HG and other metabolites in gliomas in vivo. As the first topic, novel triple refocusing MRS was developed at 3T for improving the 2HG signal sensitivity and specificity compared to prior methods. The optimized triple refocusing sequence conferred excellent discrimination of the 2HG 2.25-ppm signal from the adjacent resonances and consequently improved the precision of 2HG estimation substantially. Another accomplishment was development of fast high-resolution imaging of 2HG in patients at 3T and 7T. A new echo-planar spectroscopic imaging (EPSI) readout was designed incorporating dual-readout alternated gradients (DRAG-EPSI). At 7T, DRAG-EPSI was utilized for increasing the spectral width for fully covering the spectral region of interest, which is not possible with conventional EPSI. DRAG-EPSI was used for 2D imaging of 2HG in 5 patients at 7T. At 3T, at which the spectral width of conventional EPSI is sufficiently large for covering the spectral region of interest, DRAG-EPSI was utilized for reducing the readout gradient strengths, thereby improving the imaging performance and patient compliance. DRAG-EPSI induced frequency drifts smaller by 5.5-fold and acoustic noise lower by 25 dB compared with conventional EPSI. In a 19-min scan, DRAG-EPSI produced, for the first time, 3D imaging of 2HG with precision at a resolution of 10×10×10 mm3 at 3T. Data from 4 patients indicated that DRAG-EPSI may provide reliable 3D high-resolution imaging of 2HG at 3T in vivo.