Diagnostic Accuracy of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy in Newly-Diagnosed Brain Mass and Suspected Recurrent Gliomas

Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly-diagnosed and post-treatment settings.

Methods: Long-TE (97 ms) SVS and CSI were acquired in 85 subjects, including a discovery cohort of 39 patients who had postoperative residual or recurrent glioma with confirmed IDH-mutation status and 6 normal volunteers, a prospective preoperative validation cohort of 24 patients with newly-diagnosed brain mass, and a prospective recurrent-lesion validation cohort of 16 previously-treated IDH-mutant glioma patients with suspected tumor recurrence. The optimal thresholds for both methods in diagnosing IDH status were determined by receiver operating characteristic analysis in the discovery cohort, and then applied to the two validation cohorts to assess the diagnostic performance.

Results: The optimal 2HG/Cr thresholds of SVS and 75th percentile CSI for IDH mutations were 0.11 and 0.23, respectively. When applied to the validation sets, the sensitivity, specificity and accuracy in distinguishing IDH-mutant gliomas in the preoperative cohort were 85.71%, 100.00% and 94.12% for SVS, and 100.00%, 69.23% and 81.82% for CSI, respectively. In the recurrent-lesion cohort, the sensitivity, specificity and accuracy for discriminating IDH-positive recurrent gliomas were 40.00%, 62.50% and 53.85% for SVS, and 66.67%, 100.00% and 86.67% for CSI, respectively.

Conclusions: 2HG MRS provides diagnostic utility for IDH-mutant gliomas both preoperatively and at time of suspected tumor recurrence. SVS has a better diagnostic performance for untreated IDH-mutant gliomas, whereas CSI demonstrates greater performance in identifying recurrent tumors.