Reduced diffusion in normal appearing white matter of glioma patients following radio(chemo)therapy

Background and purpose Standard treatment of high grade gliomas includes gross tumour resection followed by radio(chemo)therapy. Radiotherapy inevitably leads to irradiation of normal brain tissue. The goal of this prospective, longitudinal study was to use MRI to quantify normal appearing white and grey matter changes following radiation treatment as a function of dose and time after radiotherapy. Materials and methods Pre-radiotherapy (proton or photon therapy) MRI and follow-up MRIs collected in 3 monthly intervals thereafter were analysed for 22 glioma patients and included diffusion tensor imaging, quantitative T1, T2* and proton density mapping. Abnormal tissue was excluded from analysis. MR signal changes were quantified within different dose bin regions for grey and white matter and subsequently for whole brain white matter. Results We found significant reductions in mean diffusivity, radial diffusivity, axial diffusivity and T2* in normal appearing white matter regions receiving a radiation dose as low as 10–20 Gy within the observational period of up to 18 months. The magnitude of these changes increased with the received radiation dose and progressed with time after radiotherapy. Whole brain white matter also showed a significant reduction in radial diffusivity as a function of radiation dose and time after radiotherapy. No significant changes were observed in grey matter. Conclusion Diffusion tensor imaging and T2* imaging revealed normal appearing white matter changes following radiation treatment. The changes were dose dependant and progressed over time. Further work is needed to understand the underlying tissue changes and to correlate the observed diffusion changes with late brain malfunctions.