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.

Keywords::

• Rat
• brain
• MRI
• pediatric
• fractionated whole-brain irradiation

Acknowledgements

The authors would like to thank Dr Craig Ferris for his collegiality and resource sharing.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was funded by a NIH Grant CA119990 to JBB. Additional personnel support was provided by NIH Grant CA112593 to MER, Department of Radiation Oncology and the Dalton McMichael Fund in Cancer Research.