Non-Invasive Assessment of Isocitrate Dehydrogenase-Mutant Gliomas Using Optimized Proton Magnetic Resonance Spectroscopy on a Routine Clinical 3-Tesla MRI.

PURPOSE

The isocitrate dehydrogenase () mutation has become one of the most important prognostic biomarkers in glioma management, indicating better treatment response and prognosis. mutations confer neomorphic activity leading to the conversion of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2HG). The purpose of this study was to investigate the clinical potential of proton MR spectroscopy (H-MRS) in identifying -mutant gliomas by detecting characteristic resonances of 2HG and its complex interplay with other clinically relevant metabolites.

MATERIALS AND METHODS

Thirty-two patients with suspected infiltrative glioma underwent a single-voxel (SVS, n = 17) and/or single-slice-multivoxel (H-MRSI, n = 15) proton MR spectroscopy (H-MRS) sequence with an optimized echo-time (97 ms) on 3T-MRI. Spectroscopy data were analyzed using the linear combination (LC) model. Cramér-Rao lower bound (CRLB) values of <40% were considered acceptable for detecting 2HG and <20% for other metabolites. Immunohistochemical analyses for determining mutational status were subsequently performed from resected tumor specimens and findings were compared with the results from spectral data. Mann-Whitney and chi-squared tests were performed to ascertain differences in metabolite levels between -mutant and -wild-type gliomas. Receiver operating characteristic (ROC) curve analyses were also performed.

RESULTS

Data from eight cases were excluded due to poor spectral quality or non-tumor-related etiology, and final data analyses were performed from 24 cases. Of these cases, 9/12 (75%) were correctly identified as -mutant or -wildtype gliomas through SVS and 10/12 (83%) through H-MRSI with an overall concordance rate of 79% (19/24). The sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 77%, 86%, and 70%, respectively. The metabolite 2HG was found to be significant in predicting -mutant gliomas through the chi-squared test ( < 0.01). The -mutant gliomas also had a significantly higher NAA/Cr ratio (1.20 ± 0.09 vs. 0.75 ± 0.12 = 0.016) and lower Glx/Cr ratio (0.86 ± 0.078 vs. 1.88 ± 0.66; = 0.029) than those with wild-type gliomas. The areas under the ROC curves for NAA/Cr and Glx/Cr were 0.808 and 0.786, respectively.

CONCLUSIONS

Noninvasive optimized H-MRS may be useful in predicting mutational status and 2HG may serve as a valuable diagnostic and prognostic biomarker in patients with gliomas.