Dose-dependent white matter damage after brain radiotherapy

Radiother Oncol. 2016 Nov;121(2):209-216. doi: 10.1016/j.radonc.2016.10.003. Epub 2016 Oct 21.

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.

Keywords: Diffusion tensor imaging; MRI; Radiation; Radiotherapy; White matter; b-Value.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / radiotherapy*
  • Cranial Irradiation / adverse effects*
  • Diffusion Tensor Imaging
  • Dose-Response Relationship, Radiation
  • Female
  • Glioma / diagnostic imaging
  • Glioma / radiotherapy*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • White Matter / radiation effects*