Background and purpose: Radiation-induced changes in brain tissue may relate to post-radiotherapy (RT) cognitive decline. Our aim is to investigate changes of the brain microstructural properties after exposure to radiation during clinical protocols of RT using diffusion MRI (dMRI). Methods and Materials: The susceptibility of tissue changes to radiation was investigated in a clinically heterogenic cohort (age, pathology, tumor location, type of surgery) consisting of 121 scans of 18 patients (10 females). The imaging dataset included 18 planning CTs and 103 dMRI scans (range 2-14, median = 6 per patient) assessing pre-operative, post-operative pre-RT and post-RT states. Diffusion tensor imaging (DTI) metrics were estimated from all scans for a region-of-interest based linear relation analysis between mean dose and change in DTI metrics, while partial volume effects were regressed out. Results: The largest regional dose dependency with mean diffusivity appear in the white matter of the frontal pole in the left hemisphere by an increase of 2.61 %/(Gy x year). Full brain-wise, pooled results for white matter show fractional anisotropy to decrease by 0.85 %/(30Gy x year); mean diffusivity increase by 9.17 %/(30Gy x year); axial diffusivity increase by 7.30%/(30Gy x year) and radial diffusivity increases by 10.63%/(30Gy x year). Conclusions: White matter is susceptible to radiation with some regional variability where diffusivity metrics demonstrate the largest relative sensitivity. This suggests that dMRI is a promising tool in assessing microstructural changes after RT, which can help in understanding treatment-induced cognitive decline.