Feasibility of a mini-pig model of radiation-induced brain injury to one cerebral hemisphere. Academic Article uri icon

abstract

  • BACKGROUND: Radiation-induced brain injury is a common concern for survivors of adult and pediatric brain cancer. Pre-clinically, rodent models are the standard approach to evaluate mechanisms of injury and test new therapeutics for this condition. However, these rodent models fail to recapitulate the radiological and histological characteristics of the clinical disease. METHODS: Here we describe a hemispheric mini-pig model of radiation-induced brain injury generated with a clinical 6 MV photon irradiator and evaluated with a clinical 3T MRI. Two pairs of Yucatan mini-pigs each received either 15Gy or 25Gy to the left brain hemisphere. Quality of intensity modulated radiation therapy treatment plans was evaluated retrospectively with parameters reported according to ICRU guidelines. The pigs were observed weekly to check for any outright signs of neurological impairment. The pigs underwent anatomical MRI examination before irradiation and up to 6months post-irradiation. Immediately after the last imaging time point, the pigs were euthanized and their brains were collected for histopathological assessment. RESULTS: Analysis of the dose volume histograms showed that 93% of the prescribed dose was delivered to at least 93% of the target volume in the left hemisphere. Organs at risk excluded from the target volume received doses below clinical safety thresholds. For the pigs that received a 25Gy dose, progressive neurological impairment was observed starting at 2months post-irradiation leading to the need for euthanasia by 3-4months. On MRI, these two animals presented with diffuse white matter pathology consistent with the human disease that progressed to outright radiation necrosis and severe brain swelling. Histology was consistent with the final MRI evaluation. The pigs that received a 15Gy dose appeared normal all the way to 6months post-irradiation with no obvious neurological impairment or lesions on MRI or histopathology. CONCLUSION: Based on our results, a mini-pig model of radiation-induced brain injury is feasible though some optimization is still needed. The mini-pig model produced lesions on MRI that are consistent with the human disease and which are not seen in rodent models. Our data shows that the ideal radiation dose for this model likely lies between 15 and 25Gy.

published proceedings

  • Radiat Oncol

author list (cited authors)

  • Athanasiadi, I., Perez, W. D., Plantenga, J. M., Jones-Hall, Y., & Perez-Torres, C. J.

complete list of authors

  • Athanasiadi, Ilektra||Perez, Whitney D||Plantenga, Jeannie M||Jones-Hall, Yava||Perez-Torres, Carlos J

publication date

  • January 1, 2021 11:11 AM