Dose-dependent early white matter alterations in patients with brain metastases after radiotherapy

Purpose Previous diffusion tensor imaging (DTI) studies have mainly focused on dose-dependent white matter (WM) alterations 1 month to 1 year after radiation therapy (RT) with a tract-average method. However, WM alterations immediately after RT are subtle, resulting in early WM alterations that cannot be detected by tract-average methods. Therefore, we performed a study with an along-tract method in patients with brain metastases to explore the early dose–response pattern of WM alterations after RT. Methods Sixteen patients with brain metastases underwent DTI before and 1–3 days after brain RT. DTI metrics, such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD), were calculated. Along-tract statistics were then used to resample WM fibre streamlines and generate a WM skeleton fibre tract. DTI metric alterations (post_RT-pre_RT DTI metrics) and the planned doses (max or mean doses) were mapped to 18 WM tracts. A linear fixed model was performed to analyse the main effect of dose on DTI metric alterations. Results AD alterations in the left hemispheric uncinated fasciculus (UNC_L) were associated with max doses, in which decreased AD alterations were associated with higher doses. Conclusion Our findings may provide pathological insight into early dose-dependent WM alterations and may contribute to the development of max dose-constrained RT techniques to protect brain microstructure in the UNC_L.