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.