Associating IDH and TERT Mutations in Glioma with Diffusion Anisotropy in Normal-Appearing White Matter

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-TERTsubgroups were first identified by the Kruskal-Wallis test, followed by Dunn-Sidak 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= .002) were significantly higher and the contralateral-ipsilateral hemispheric differences, Delta FA and Delta RA, (P< .001) were significantly lower in IDH only patients compared with TERT only, with a higher whole-brain normal-appearing white matter FA and RA (P= .01) and Delta FA and Delta RA (P= .002) compared to double positive patients. Whole-brain normal-appearing white matter ADC (P= .02), RD (P= .001), lambda(2)(P= .001), and lambda(3)(P= .001) were higher in IDH wild-type. Whole-brain normal-appearing white matter lambda(1)(AD) (P= .003), FA (P< .001), and RA (P= .003) were higher, but Delta lambda(1)(P= .002), Delta FA, and Delta RA (P< .001) were lower in IDH mutant versus IDH wild-type. Delta FA (P= .01) and Delta RA (P= .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.

Automated summary

IDH and TERT mutations in glioma have distinct microstructural changes in normal-appearing white matter, as revealed by DTI variables. The study found that IDH-only patients had higher FA and RA values and lower Delta FA and Delta RA values compared to TERT-only patients, while double-positive patients had intermediate values. Other microstructural differences were also observed between different mutation statuses.