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BACKGROUND AND PURPOSE: IDH and TERT 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 IDH and TERT associations and classifications with DTI reported microstructure in normal-appearing white matter. MATERIALS AND METHODS:Retrospective data from patients imaged between March 2012 and February 2016 were analyzed by grouping them as IDH-TERT subgroups and by IDH and TERT mutation status. DTI variables in the IDH-TERT subgroups were first identified by the Kruskal-Wallis test, followed by Dunn-Sidák multiple comparisons with Bonferroni correction. IDH and TERT mutations were compared with the Mann-Whitney U test. Classification by thresholding was tested using receiver operating characteristic analysis. RESULTS: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) (P ¼ .002) were significantly higher and the contralateral-ipsilateral hemispheric differences, DFA and DRA, (P , .001) were significantly lower in IDHonly patients compared with TERTonly, with a higher whole-brain normal-appearing white matter FA and RA (P ¼ .01) and DFA and DRA (P ¼ .002) compared to double positive patients. Whole-brain normal-appearing white matter ADC (P ¼ .02), RD (P ¼ .001), l 2 (P ¼ .001), and l 3 (P ¼ .001) were higher in IDH wild-type. Whole-brain normal-appearing white matter l 1 (AD) (P ¼ .003), FA (P , .001), and RA (P ¼ .003) were higher, but Dl 1 (P ¼ .002), DFA, and DRA (P , .001) were lower in IDH mutant versus IDH wild-type. DFA (P ¼ .01) and DRA (P ¼ .02) were significantly higher in TERT mutant versus TERT wild-type.CONCLUSIONS: Axial and nonaxial diffusivities, anisotropy indices in the normal-appearing white matter and their interhemispheric differences demonstrated microstructural differences between IDH and TERT mutations, with the potential for classification methods.ABBREVIATIONS: AD ¼ axial diffusivity; AUC ¼ area under the curve; DAI ¼ diffusion anisotropy indices; DN ¼ double negative; DP ¼ double positive; FA ¼ fractional anisotropy; HMeD ¼ hemispherical mean differences; LBTh ¼ lower bound thresholding; mut ¼ mutant; NAWM ¼ normal-appearing white matter; NPV ¼ negative predictive value; PPV ¼ positive predictive value; RA ¼ relative anisotropy; RD ¼ radial diffusivity; ROC ¼ receiver operating characteristic; UBTh ¼ upper bound thresholding; WB ¼ whole brain; wt ¼ wild-type

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