AssociatingIDHandTERTMutations in Glioma with Diffusion Anisotropy in Normal-Appearing White Matter

Abstract

<h3>BACKGROUND AND PURPOSE:</h3> <i>IDH</i> and <i>TERT</i> mutations might infiltratively manifest within normal-appearing white matter with specific phenotypes such as microstructural changes undetectable by standard MR imaging contrasts but potentially associable with DTI variables. The aim of this retrospective glioma study was to statistically investigate <i>IDH</i> and <i>TERT</i> associations and classifications with DTI reported microstructure in normal-appearing white matter. <h3>MATERIALS AND METHODS:</h3> Retrospective data from patients imaged between March 2012 and February 2016 were analyzed by grouping them as <i>IDH</i>–<i>TERT</i> subgroups and by <i>IDH</i> and <i>TERT</i> mutation status. DTI variables in the <i>IDH-TERT</i> subgroups were first identified by the Kruskal-Wallis test, followed by Dunn-Šidák multiple comparisons with Bonferroni correction. <i>IDH</i> and <i>TERT</i> mutations were compared with the Mann-Whitney <i>U</i> test. Classification by thresholding was tested using receiver operating characteristic analysis. <h3>RESULTS:</h3> Of 170 patients, 70 patients (mean age, 43.73 [SD, 15.32] years; 40 men) were included. Whole-brain normal-appearing white matter fractional anisotropy (FA) and relative anisotropy (RA) (<i>P</i> = .002) were significantly higher and the contralateral-ipsilateral hemispheric differences, ΔFA and ΔRA, (<i>P</i> &lt; .001) were significantly lower in IDHonly patients compared with TERTonly, with a higher whole-brain normal-appearing white matter FA and RA (<i>P</i> = .01) and ΔFA and ΔRA (<i>P</i> = .002) compared to double positive patients. Whole-brain normal-appearing white matter ADC (<i>P</i> = .02), RD (<i>P</i> = .001), λ₂ (<i>P</i> = .001), and λ₃ (<i>P</i> = .001) were higher in <i>IDH</i> wild-type. Whole-brain normal-appearing white matter λ₁ (AD) (<i>P</i> = .003), FA (<i>P</i> &lt; .001), and RA (<i>P</i> = .003) were higher, but Δλ₁ (<i>P</i> = .002), ΔFA, and ΔRA (<i>P</i> &lt; .001) were lower in <i>IDH</i> mutant versus <i>IDH</i> wild-type. ΔFA (<i>P</i> = .01) and ΔRA (<i>P</i> = .02) were significantly higher in <i>TERT</i> mutant versus <i>TERT</i> wild-type. <h3>CONCLUSIONS:</h3> Axial and nonaxial diffusivities, anisotropy indices in the normal-appearing white matter and their interhemispheric differences demonstrated microstructural differences between <i>IDH</i> and <i>TERT</i> mutations, with the potential for classification methods.