Diagnostic accuracy of 2-hydroxyglutarate magnetic resonance spectroscopy in newly diagnosed brain mass and suspected recurrent gliomas

Abstract

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 posttreatment settings.

Methods: Long echo time (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 2 validation cohorts to assess the diagnostic performance.

Results: The optimal 2HG/creatine 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.

Fig. 1

Representative spectra from an IDH-mutant glioma patient in the discovery cohort. The white box in panel A shows the SVS location. A prominent 2HG peak was seen at 2.25 ppm in both SVS (2HG/Cr = 0.682, panel B) and the selected CSI spectrum (2HG/Cr = 0.852, panel D). The blue box in panel C shows the selected voxels contained within the abnormal hyperintense area on FLAIR images, and the red box shows the selected voxel for the representative CSI spectrum (D). The 75th percentile 2HG/Cr value of CSI was 0.719. In panels B and D, the black spectrum shows the raw data, red spectrum is the fitted data, and the blue spectrum shows the 2HG fit.

Fig. 2

Representative spectroscopies from an IDH-wildtype glioma patient in the preoperative cohort. Panel A shows the SVS location. No 2HG peak was seen at 2.25 ppm in either SVS (panel B) or the selected spectroscopy of CSI (panel D). The blue box in panel C shows the selected voxels contained within the abnormal hyperintense area on FLAIR images, and the red box shows the selected voxel for the representative CSI spectroscopy (D). The 75th percentile 2HG/Cr value of the CSI was 0. In panels B and D, the black spectrum shows the raw data, red spectrum is the fitted data, and the blue spectrum shows the 2HG fit.

Fig. 3

Representative spectra from an IDH-mutant glioma patient in the recurrent-lesion cohort. The presence of recurrent tumor was confirmed by surgery. Panel A shows the SVS location. No 2HG peak was seen at 2.25 ppm in SVS (panel B). However, CSI demonstrated the existence and the heterogeneous distribution of 2HG (panels C, D, E). The 2HG/Cr ratios ranged from 0.00 (panel E) to 3.50 (panel D), with the 75th percentile value of 0.68. The blue box in panel C shows the selected voxels contained within the abnormal hyperintense area on FLAIR images, and the red boxes show the selected voxels for the representative CSI spectra (panels D, E). In panels B and D, the black spectrum shows the raw data, red spectrum is the fitted data, and the blue spectrum shows the 2HG fit.