Diffusion decrease in normal-appearing white matter structures following photon or proton irradiation indicates differences in regional radiosensitivity

Abstract

Purpose: Radio(chemo)therapy (RCT) as part of the standard treatment of glioma patients, inevitably leads to radiation exposure of the tumor-surrounding normal-appearing (NA) tissues. The effect of radiotherapy on the brain microstructure can be assessed by magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI). The aim of this study was to analyze regional DTI changes of white matter (WM) structures and to determine their dose- and time-dependency.

Methods: As part of a longitudinal prospective clinical study (NCT02824731), MRI data of 23 glioma patients treated with proton or photon beam therapy were acquired at three-monthly intervals until 36 months following irradiation. Mean, radial and axial diffusivity (MD, RD, AD) as well as fractional anisotropy (FA) were investigated in the NA tissue of 15 WM structures and their dependence on radiation dose, follow-up time and distance to the clinical target volume (CTV) was analyzed in a multivariate linear regression model. Due to the small and non-comparable patient numbers for proton and photon beam irradiation, a separate assessment of the findings per treatment modality was not performed.

Results: Four WM structures (i.e., internal capsule, corona radiata, posterior thalamic radiation, and superior longitudinal fasciculus) showed statistically significantly decreased RD and MD after RT, whereas AD decrease and FA increase occurred less frequently. The posterior thalamic radiation showed the most pronounced changes after RCT [i.e., ΔRD = -8.51 % (p = 0.012), ΔMD = -6.14 % (p = 0.012)]. The DTI changes depended significantly on mean dose and time.

Conclusion: Significant changes in DTI for WM substructures were found even at low radiation doses. These findings may prompt new radiation dose constraints sparing the vulnerable structures from damage and subsequent side-effects.

Keywords: Diffusion-tensor imaging; Magnetic resonance imaging; Primary brain tumor; Proton beam irradiation; White matter structures.