Incorporation of Edited MRS into Clinical Practice May Improve Care of Patients with<i>IDH</i>-Mutant Glioma

Abstract

<h3>ABSTRACT</h3> <h3>BACKGROUND AND PURPOSE:</h3> Isocitrate dehydrogenase (<i>IDH</i>) mutation and 1p/19q codeletion classify adult-type diffuse gliomas into three tumor subtypes with distinct prognosis. We aimed to evaluate the performance of edited magnetic resonance spectroscopy (MRS) 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. <h3>MATERIALS AND METHODS:</h3> Subjects with presumed low-grade glioma, eligible for surgery (<i>cohort 1</i>), and subjects with IDH-mutant glioma, previously treated and with progressive disease (<i>cohort 2</i>) were prospectively examined with a singlevoxel Mescher–Garwood point-resolved spectroscopy sequence at 3 T. Spectra were quantified using LCModel. The Cramér-Rao lower bounds (CRLB) threshold was set to 20%. Integrated histomolecular analysis according to the 2021 WHO classification was considered as a ground truth. <h3>RESULTS:</h3> Thirty-four consecutive subjects were enrolled. Due to poor spectra quality and lack of histological specimen, data from 26 subjects was analyzed. Twenty-one belonged to cohort <i>1</i> [11 females; median age: 42 years] and 5 to cohort <i>2</i> [3 females; median age: 48 years]. Edited MRS showed 100% specificity for detection of <i>IDH</i> mutation and 91% specificity for prediction of 1p/19q codeletion status. Sensitivities for prediction of <i>IDH</i> and 1p/19q codeletion were 62% and 33%, respectively. The median CRLB values were 14% (13 – 32) for <i>IDH</i>-mutant and 572% (554 – 999) for <i>IDH</i>-wild-type tumors. The time between MRS and surgery was longer for low-grade than high-grade gliomas (p = .03), yet the time between MRS and WHO diagnosis did not differ between grades (p = .07), possibly reflecting molecular analyses induced delays in high-grade gliomas. <h3>CONCLUSIONS:</h3> Our results, acquired in a clinic setting, confirmed that edited MRS 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 MRS into clinical workflow is desirable. ABBREVIATIONS: 2HG = D-2-hydroxyglutarate; Cth = cystathionine. CRLB: Cramér-Rao lower bound; IDH: isocitrate dehydrogenase.

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