Abstract
Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are detected in up to 75% grade II-III (lower grade) gliomas. IDH1/2 mutations result in the neomorphic synthesis of the oncometabolite 2-hydroxyglutarate (2HG). The detection of 2HG could help for a non-invasive diagnosis, the clinical follow-up, and possibly the screening of patients for targeted, anti IDH1-mutated therapy. 2HG screening is a useful marker to detect the presence of IDH1/2 mutations. A magnetic resonance spectroscopy (MRS) study of 2HG on phantoms has been already performed by our group. AIM: To investigate methods for in vivo detection by MRS of 2HG on glioma patients. METHODS: Spectra from 12 patients with lower grade gliomas were acquired with a 1H-MRS single-voxel PRESS sequence with TE = 30 ms. The subsequent patients were acquired using a tailored PRESS sequence with TE = 97 ms (TE1 = 32 ms, TE2 = 65 ms). Both groups were studied using a clinical MR 3T scanner (Philips Achieva) with a 32 channel head coil. The MR protocol included two MRS acquisition for each subject: a voxel within the tumor and one contralateral. The voxel size was 2x1.5x1.5 cm3 for all the acquisitions for both sequences. Metabolite concentrations were estimated by linear combination analysis and a simulated basis set using LCModel software (version 6.3). After histopathological diagnosis IDH1/2 analysis were performed by immunochemistry and/or PCR. Results from 1H-MRS and immunochemistry or PCR were compared. RESULTS: Our data showed that spectra at TE = 30 ms are not specific: 4 patient carrying wild type gliomas and 8 carrying IDH mutated gliomas resulted in 2 false positive and 5 false negative respectively. The sequence at 97 ms resulted more specific: 4 patient carrying wild type glioma and 2 carrying IDH mutated glioma were correctly identified (0 false positive and 0 false negative, respectively). Moreover the sequence with short TE detected 2HG in the contralateral region in 5 cases, while the sequence with longer TE did not dectect 2HG in contralateral region. DISCUSSION: Our preliminary data suggest that MRS TE =97 ms is specific for 2HG detection. A larger number of samples will be required to confirm the accuracy of the technique.We will also pair the ex vivo detection by MRS with 2HG quantification by HPLC on tumoral samples and other biological fluids.
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