Dose-dependent white matter damage after brain radiotherapy

脑放射治疗后剂量依赖性白质损伤

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Abstract

BACKGROUND AND PURPOSE: Brain radiotherapy is limited in part by damage to white matter, contributing to neurocognitive decline. We utilized diffusion tensor imaging (DTI) with multiple b-values (diffusion weightings) to model the dose-dependency and time course of radiation effects on white matter. MATERIALS AND METHODS: Fifteen patients with high-grade gliomas treated with radiotherapy and chemotherapy underwent MRI with DTI prior to radiotherapy, and after months 1, 4-6, and 9-11. Diffusion tensors were calculated using three weightings (high, standard, and low b-values) and maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ(∥)), and radial diffusivity (λ(⊥)) were generated. The region of interest was all white matter. RESULTS: MD, λ(∥), and λ(⊥) increased significantly with time and dose, with corresponding decrease in FA. Greater changes were seen at lower b-values, except for FA. Time-dose interactions were highly significant at 4-6months and beyond (p<.001), and the difference in dose response between high and low b-values reached statistical significance at 9-11months for MD, λ(∥), and λ(⊥) (p<.001, p<.001, p=.005 respectively) as well as at 4-6months for λ(∥) (p=.04). CONCLUSIONS: We detected dose-dependent changes across all doses, even <10Gy. Greater changes were observed at low b-values, suggesting prominent extracellular changes possibly due to vascular permeability and neuroinflammation.

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