Radiation therapy effects on white matter fiber tracts of the limbic circuit

Purpose: To segment fiber tracts in the limbic circuit and to assess their sensitivity to radiation therapy (RT). Methods: Twelve patients with brain metastases who had received fractionated whole brain radiation therapy to 30 Gy or 37.5 Gy were included in the study. Diffusion weighted images were acquired pre-RT, at the end of RT, and 1-month post-RT. The fornix, corpus callosum, and cingulum were extracted from diffusion weighted images by combining fiber tracking and segmentation methods based upon characteristics of the fiber bundles. Cingulum was segmented by a seed-based tractography, fornix by a region of interests (ROI)-based tractography, and corpus callosum by a level-set segmentation algorithm. The radiation-induced longitudinal changes of diffusion indices of the structures were evaluated. Results: Significant decreases were observed in the fractional anisotropy of the posterior part of the cingulum, fornix, and corpus callosum from pre-RT to end of RT by -14.0, -12.5, and -5.2, respectively (p 0.001), and from pre-RT to 1-month post-RT by -11.9, -12.8, and -6.4, respectively (p 0.001). Moreover, significant increases were observed in the mean diffusivity of the corpus callosum and the posterior part of the cingulum from pre-RT to end of RT by 6.8 and 6.5, respectively, and from pre-RT to 1-month post-RT by 8.5 and 6.3, respectively. The increase in the radial diffusivity primarily contributed to the significant decrease in the fractional anisotropy, indicating that demyelination is the predominant radiation effect on the white matter structures. Conclusions: Our findings indicate that the fornix and the posterior part of the cingulum are significantly susceptible to radiation damage. We have developed robust computer-aided semiautomatic segmentation and fiber tracking tools to facilitate the ROI delineation of critical structures, which is important for assessment of radiation damage in a longitudinal fashion.