OS04.7 Diagnostic Accuracy of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy in Newly Diagnosed Brain Mass and Suspected Recurrent Glioma
Authors: Y. Zhou, M. Zhou, H. Liao, B. Rowland, N. Arvold, D. Reardon, P. Wen, A. Lin, R. Y. Huang
Journal: Neuro-Oncology (2017)

BACKGROUND: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2-HG) in brain gliomas that can be detected by magnetic resonance spectroscopy (MRS). We examined the diagnostic accuracy of 2HG-Single-voxel spectroscopy (SVS) and multi-voxel Chemical shift imaging (CSI) in both newly diagnosed and post-treatment settings. METHODS: 2HG-MRS was performed in 50 subjects including a discovery cohort consisting of 22 patients who had: residual or recurrent tumor with histologically confirmed IDH mutation status (19 mutant; 3 wild type) and 6 normal volunteers; a preoperative validation cohort of 14 patients with newly diagnosed brain mass; and a post-treatment validation cohort of 8 patients presenting with suspected recurrent IDH mutant glioma after receiving prior treatment. 2HG MRS was conducted on 3T MRI with a 32 channel head coil. SVS was acquired using PRESS (TE1/2: 21/76 ms for a total of 97 ms, TR: 2000 ms), voxel size of 20 × 20 × 20 mm3. CSI was acquired using single slice semi-LASER chemical shift imaging sequence (TE1/2: 21/76 ms, TR: 1700 ms, 1.5 cm voxel resolution) with typical excitation volumes about 80 × 80 × 15 mm3 in order to include both the lesion and contralateral normal tissue. Metabolite concentrations for both SVS and CSI were quantified using LCModel. All concentrations were normalized by the total creatine value. Using receiver operating characteristic (ROC) analysis of the discovery cohort, we determined the optimal thresholds for both SVS and CSI techniques in determining IDH status. These thresholds were then applied to the two validation cohorts to determine the sensitivity, specificity and accuracy of 2HG-MRS in these two clinical settings. Results: In the discovery cohort, the mean 2HG/Cr concentration measured on SVS for IDH mutant tumors was 0.40 (95% CI: 0.15~0.65) compared to 0.05 (95% CI: -0.02~0.12) for non-IDH controls (P=0.00). 90th percentile CSI also demonstrated a significant difference between IDH mutant and controls: 0.35 (95% CI: 0.25~0.45) and 0.13 (95% CI: -0.05~0.31) respectively (P=0.03). Based on ROC analysis, the optimal thresholds of 2HG/Cr in SVS and 90th percentile CSI for IDH 1/2 mutant detection were 0.16 and 0.28, respectively. When applied to validation sets, the sensitivity, specificity and accuracy in distinguishing IDH mutation and IDH wild type in a preoperative validation cohort were 83%, 100% and 93% for SVS; and 83%, 100% and 93% for CSI, respectively. In the post-treatment validation cohort, the sensitivity, specificity and accuracy for discriminating IDH positive recurrence lesion were 50%, 67% and 60% for SVS; and 50%, 100% and 75% for CSI, respectively. CONCLUSION: 2HG-MRS provides diagnostic utility for IDH mutant gliomas both preoperatively and at time of suspected tumor recurrence. CSI demonstrated greater performance in identifying recurrent tumor compared to SVS.