O8.02 * MONITORING OF TREATMENT RESPONSE IN IDH-MUTANT GLIOMAS WITH IN-VIVO 3D MAGNETIC RESONANCE SPECTROSCOPY

Abstract

The hallmark metabolic alteration in mutant IDH gliomas is the production of R-2-hydroxyglutarate (2HG). 2HG can be measured in-vivo by magnetic resonance spectroscopy of patients, representing an ideal biomarker for IDH mutant gliomas. 3D mapping of 2HG and other metabolites is important to capture tumor heterogeneity and for longitudinal studies where changes in size and shape of tumors during treatment makes positioning of a single voxel or a single slice difficult to appropriately match over time. A 3D 2HG map provides selectivity and specificity for the spatial extent of tumor in all directions, and can thereby reduce variance in longitudinal MRS studies. Here we present results obtained with a 3D MR spectroscopic imaging (MRSI) that edits 2HG with high efficiency. Measurements were performed in 20 mutant IDH1 glioma patients who were consented under an IRB-approval. A robust and efficient 3D MRSI sequence for 2HG imaging was newly developed. Spectra were fitted with LCModel software and metabolic maps were obtained from the fitted signal. All experiments were performed on a whole-body 3T MR scanner (Tim Trio with VB17 software, Siemens, Erlangen), using body coil for transmit and a 32-channel head coil for receive. Prior to receiving adjuvant therapy, detectable levels of 2HG were measured in all patients that had not undergone gross total resection. 3D metabolic maps were obtained for 2HG and several important metabolites for assessing brain tumors, such as total choline (Cho), N-acetyl-aspartate (NAA), glutamate and glutamine (Glx), and lactate (Lac). All metabolites were measured simultaneously within a single acquisition, 2HG and Glx maps were obtained from the difference spectra, while the other metabolites were obtained from the off-resonance spectra. In 9 patients who have undergone both pre- and post-treatment scans, 4 demonstrated marked decrease in the level of 2HG at the first time point after completion of adjuvant therapy. The remainder demonstrated partial reduction of 2HG, with no patients demonstrating increased 2HG levels. We demonstrate 3D imaging of 2HG is clinically feasible in patients with IDH1 mutated gliomas. Further validation and development is underway for longitudinal quantification of 2HG levels during treatment of IDH mutant gliomas. Acknowledgements: Burroughs-Wellcome Career Award, NCI/NIH 1K22CA178269-01 and 1P50CA165962-01, Harvard-MIT Koch Institute Bridge Project.