1. Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas
- Author
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Adam W. Autry, Marisa Lafontaine, Llewellyn Jalbert, Elizabeth Phillips, Joanna J. Phillips, Javier Villanueva-Meyer, Mitchel S. Berger, Susan M. Chang, and Yan Li
- Subjects
IDH ,Cancer Research ,Magnetic Resonance Spectroscopy ,Oncology and Carcinogenesis ,Receptors, Antigen, T-Cell ,Glutarates ,Rare Diseases ,Clinical Research ,Receptors ,Humans ,Oncology & Carcinogenesis ,Cancer ,Brain Neoplasms ,Neurosciences ,Image-guided ,Glioma ,T-Cell ,Isocitrate Dehydrogenase ,Brain Disorders ,Brain Cancer ,MRSI ,Neurology ,Oncology ,D-2-Hydroxyglutarate ,Antigen ,Mutation ,Biomedical Imaging ,Neurology (clinical) ,Tumor Suppressor Protein p53 ,Lower-grade glioma ,Inositol - Abstract
Purpose Prognostically favorable IDH-mutant gliomas are known to produce oncometabolite D-2-hydroxyglutarate (2HG). In this study, we investigated metabolite-based features of patients with grade 2 and 3 glioma using 2HG-specific in vivo MR spectroscopy, to determine their relationship with image-guided tissue pathology and predictive role in progression-free survival (PFS). Methods Forty-five patients received pre-operative MRIs that included 3-D spectroscopy optimized for 2HG detection. Spectral data were reconstructed and quantified to compare metabolite levels according to molecular pathology (IDH1R132H, 1p/19q, and p53); glioma grade; histological subtype; and T2 lesion versus normal-appearing white matter (NAWM) ROIs. Levels of 2HG were correlated with other metabolites and pathological parameters (cellularity, MIB-1) from image-guided tissue samples using Pearson’s correlation test. Metabolites predictive of PFS were evaluated with Cox proportional hazards models. Results Quantifiable levels of 2HG in 39/42 (93%) IDH+ and 1/3 (33%) IDH– patients indicated a 91.1% apparent detection accuracy. Myo-inositol/total choline (tCho) showed reduced values in astrocytic (1p/19q-wildtype), p53-mutant, and grade 3 (vs. 2) IDH-mutant gliomas (p p p p p p = 0.002), total NAA (R = − 0.61; p = 0.002) and cellularity (R = 0.37; p = 0.04) but not MIB-1. Increasing levels of 2HG/tCr (p = 0.0007, HR 5.594) and thresholding (≥ 0.905, median value; p = 0.02) predicted adverse PFS. Conclusion In vivo 2HG detection can reasonably be achieved on clinical scanners and increased levels may signal adverse PFS.
- Published
- 2022