Effects Of Brain Radiation On Normal Appearing White Matter In Children: A Diffusion Tensor Imaging (Dti) Study

New developments in radiation therapy have contributed to significant improvements in long-term cure rate in children diagnosed with brain tumors. However, radiation therapy, even if administered at relatively low doses, has been associated with adverse effects on brain tissue. In this prospective study, DTI was applied to evaluate early delayed effects of radiation on white matter integrity in children irradiated for solid brain tumors and ALL. Twelve patients (9 boys, mean age 11.4 ± 3.9 years, age range 5.5 - 18.6 years) were examined. The patients were evaluated at baseline and at 6-months follow-up post radiation. The majority of patients received cranio-spinal irradiation; some patients also underwent a boost treatment to the posterior fossa or received radiation only to a targeted region of the brain. DTI data were acquired using a single-shot diffusion-weighted spin-echo echo-planar imaging sequence at 1.5 Tesla. Using a region of interest (ROI) methodology, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in 15 different fiber tracts in both cerebral hemispheres. Only regions with normal appearance on conventional MRI were included. To evaluate the dose delivered to the specific ROIs, ADC and FA maps were co-registered with the radiation plans using the CT simulation scan. Linear mixed effects (LME) models were used to determine factors associated with changes in ADC and FA after radiation therapy. General linear model ANOVA was applied to evaluate ADC and FA changes in individual ROIs. LME analyses revealed significant differences in ADC and FA changes among studied white matter regions (interaction term radiation dose x region: p < 0.05 in both analyses). No significant hemispheric differences or an effect of age at radiation treatment were detected. With increasing radiation dose, ADC increased in the corpus callosum (combined data from the genu, body, and splenium, p < 0.05) and in the internal capsule (combined data from the anterior and posterior limbs, p < 0.05). With increasing radiation dose, FA decreased in the corpus callosum (combined data from genu, body and splenium, p < 0.05) and in the frontal white matter (combined data from two separate ROIs, p < 0.05). Of the evaluated brain regions, the most prominent changes at 6 months after completion of radiation were detected in the corpus callosum. Increase in ADC and decrease in FA with increasing radiation dose are suggestive of a higher sensitivity of the corpus callosum to early delayed injury. Our results suggest that DTI is a sensitive method to detect early changes in specific white matter tracts, following radiation therapy for pediatric brain tumors.