Rodent Model of Brain Radionecrosis Using Clinical LINAC-Based Stereotactic Radiosurgery

Our purpose was to develop a rodent model of brain radionecrosis using clinical linear accelerator based stereotactic radiosurgery.

Single fraction maximum prescription points in the mouse's left hemisphere were irradiated using linear accelerator-based stereotactic radiosurgery with multiple arcs at 60 (n = 5), 100 (n = 5), and 140 (n = 5) Gy. Rats (n = 6) were similarly treated with 140 Gy. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to track radiation injury in mice over weeks (100 and 140 Gy) or months (60 Gy). Target accuracy was measured by the distance from the prescription point to the center of the earliest Gd-MRI enhancement. Confirmation of necrosis via histology was performed at the subject endpoints.

Radiation injury as indicated by Gd-MRI was first identified at 2 weeks (140 Gy), 4 to 6 weeks (100 Gy), and 8 months (60 Gy). A volumetric time course showed rapid growth in the volume of Gd-MRI signal enhancement after the appearance of apparent necrosis. Histopathologic features were consistent with radionecrosis.

The presented method uses a commonly available clinical linear accelerator to induce radiation necrosis in both mice and rats. The treatment is modeled after patient therapy for a more direct model of human tissue under a range of doses used in clinical neuro-ablation techniques. The short time to onset of apparent necrosis, accurate targeting of the prescription point, high incidence of necrosis, and similar pathologic features make this a suitable animal model for further research in radionecrosis.