Incorporation of Edited MRS into Clinical Practice May Improve Care of Patients with IDH-Mutant Glioma.

Abstract

Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion classify adult-type diffuse gliomas into 3 tumor subtypes with distinct prognoses. We aimed to evaluate the performance of edited MR spectroscopy for glioma subtyping in a clinical setting, via the quantification of D-2-hydroxyglutarate (2HG) and cystathionine. The delay between this noninvasive classification and the integrated histomolecular analysis was also quantified. Subjects with presumed low-grade gliomas eligible for surgery (cohort 1) and subjects with IDH-mutant gliomas previously treated and with progressive disease (cohort 2) were prospectively examined with a single-voxel Mescher-Garwood point-resolved spectroscopy sequence at 3T. Spectra were quantified using LCModel. The Cramér-Rao lower bounds threshold was set to 20%. Integrated histomolecular analysis according to the 2021 WHO classification was considered as ground truth. Thirty-four consecutive subjects were enrolled. Due to poor spectra quality and lack of histologic specimens, data from 26 subjects were analyzed. Twenty-one belonged to cohort 1 (11 women; median age, 42 years); and 5, to cohort 2 (3 women; median age, 48 years). Edited MR spectroscopy showed 100% specificity for detection of IDH-mutation and 91% specificity for the prediction of 1p/19q-codeletion status. Sensitivities for the prediction of IDH and 1p/19q codeletion were 69% and 33%, respectively. The median Cramér-Rao lower bounds values were 16% (13%-28%) for IDH-mutant and 572% (554%-999%) for IDH wild type tumors. The time between MR spectroscopy and surgery was longer for low-grade than for high-grade gliomas (P = .03), yet the time between MR spectroscopy and WHO diagnosis did not differ between grades (P = .07), possibly reflecting molecular analyses-induced delays in high-grade gliomas. Our results, acquired in a clinic setting, confirmed that edited MR spectroscopy is highly specific for both IDH-mutation and 1p/19q-codeletion predictions and can provide a faster prognosis stratification. In the upcoming IDH-inhibitor treatment era, incorporation of edited MR spectroscopy into clinical workflow is desirable.