Magnetic resonance spectroscopy (MRS) is uniquely capable of measuring biochemicals in the human body noninvasively and thus widely used for evaluating molecular changes in brain tumors. MRS identification of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH) mutant gliomas provides the first in vivo imaging biomarker specific to a genetic mutation, making the diagnosis of IDH mutant gliomas possible without surgery. 2HG also has significant predictive value with respect to the stage and survival in gliomas because an IDH mutation carries a favorable prognosis. Following our 2HG MRS development (Choi et al. Nat Med 2012), we translated the MRS protocol into clinical MR scanners world...

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Magnetic resonance spectroscopy (MRS) is uniquely capable of measuring biochemicals in the human body noninvasively and thus widely used for evaluating molecular changes in brain tumors. MRS identification of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH) mutant gliomas provides the first in vivo imaging biomarker specific to a genetic mutation, making the diagnosis of IDH mutant gliomas possible without surgery. 2HG also has significant predictive value with respect to the stage and survival in gliomas because an IDH mutation carries a favorable prognosis. Following our 2HG MRS development (Choi et al. Nat Med 2012), we translated the MRS protocol into clinical MR scanners worldwide (currently 27 institutions), with our initial CPRIT award. In particular, a 2HG MRS pipeline was implemented at UT Southwestern, by which raw MRS data can be processed in a user-independent fashion and the 2HG estimation is transferred to clinicians. The goal of this renewal application is to develop MRS imaging biomarkers of malignancy in gliomas. Based on prior cell-culture studies and our preliminary data, we hypothesize that increased metabolism of glycine and glutamine accelerates cell proliferation and cause poor patient outcomes in gliomas. We will evaluate metabolic alterations in 150 adult patients with gliomas preoperatively, using our recently-developed high-resolution 3D MRS imaging method (DRAG-EPSI). We will examine association of metabolite levels with tumor cell proliferation rate (MIB-1 labeling index) and overall survival of patients. Success of the project will enable clinicians to assess the malignancy status at any stages of a tumor and predict patient outcome noninvasively, without need of external agent injection and tumor biopsy. Importantly, the MRS imaging protocol of the proposed study can be easily translated into standard MR scanners because the MRS data acquisition and analysis scheme is similar to the method that was already translated.

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