Radiation-induced cognitive impairment and altered diffusion tensor imaging in a juvenile rat model of cranial radiotherapy

Abstract

Purpose: To assess the long-term effects of fractionated whole brain irradiation (fWBI) using diffusion tensor imaging (DTI) and behavior in a pediatric rodent model for the clinical presentation of adult pediatric cancer survivors.Materials and methods: Five-week-old, male F344xBN rats were randomized to receive 0, 5, or 6.5 Gy fractions biweekly for 3 weeks, resulting in Sham, Irradiated-30 (IR-30) and IR-39 Gy total dose groups. Magnetic Resonance Imaging occurred at 1, 3, 6 and 9 months with behavioral assessment at 10–11 months post-fWBI.Results: Irradiation reduced brain size (p < 0.001) and body weight (p < 0.001) proportionate to dose. At 1 month post-fWBI and throughout follow-up, diffusion was reduced in IR-30 and IR-39 relative to shams (p < 0.001). IR-30 but not IR-39 rats were impaired relative to Shams on the reversal trial of the Morris Water Maze (p < 0.05), and IR-30 rats preferred a striatum- mediated strategy (p < 0.06).Conclusions: Hippocampal performance was impaired in IR-30 but not IR-39 animals. While gross size differences exist, white matter integrity is preserved in rats after fWBI at 5 weeks. This significant departure from childhood cancer survivors and single fraction rodent studies where white matter degradation is a prominent feature are discussed.