Analyses of regional radiosensitivity of white matter structures along tract axes using novel white matter segmentation and diffusion imaging biomarkers

Abstract

Background and purpose: Brain radiotherapy (RT) can cause white matter damage and downstream neurocognitive decline. We developed a computational neuroimaging tool to regionally partition individual white matter tracts, then analyze regional changes in diffusion metrics of white matter damage following brain RT. Materials and methods: RT dose, diffusion metrics and white matter tract structures were extracted and mapped to a reference brain for 49 patients who received brain RT, and underwent diffusion tensor imaging pre- and 9–12 months post-RT. Based on their elongation, 23 of 48 white matter tracts were selected. The Tract-Crawler software was developed in MATLAB to create cross-sectional slice planes normal to a tract’s computed medial axis. We then performed slice- and voxel-wise analysis of radiosensitivity, defined as percent change in mean diffusivity (MD) and fractional anisotropy (FA) as a function of dose relative to baseline. Results: Distinct patterns of FA/MD radiosensitivity were seen for specific tracts, including the corticospinal tract, medial lemniscus, and inferior cerebellar peduncle, in particular at terminal ends. These patterns persisted for corresponding tracts in left and right hemispheres. Local sensitivities were as high as 40%/Gy (e.g., voxel-wise: −39 ± 31%/Gy in right corticospinal tract FA, −45 ± 25%/Gy in right inferior cerebellar peduncle FA), p < 0.05. Conclusions: Tract-Crawler, a novel tool to visualize and analyze cuts of white matter structures normal to medial axes, was used to demonstrate that particular white matter tracts exhibit significant regional variations in radiosensitivity based on diffusion biomarkers. Keywords: Radiation therapy, White matter, Diffusion tensor imaging