PURPOSE: To evaluate a helical tomotherapy-based rodent radiosurgery platform that reproduces human image-guided radiosurgery treatment to study radiobiologic effects of stereotactic radiosurgery on lung tissues using functional magnetic resonance imaging (MRI). METHODS AND MATERIALS: Hypofractionated radisourgery (20 Gy x 3) was delivered to the right lung of three New Zealand rabbits using Helical TomoTherapy with MVCT image guidance. Contrast-enhanced MR perfusion, hyperpolarized helium-3 MR ventilation, and CT were obtained before radiation and monthly for 4 months after radiation. All MRI was performed on a 1.5-T whole-body scanner with broad-band capabilities. RESULTS: Precise dose delivery to 1.6 cc of the lower right lung was achieved without additional immobilization. No deficits were detected at baseline with respect to perfusion and ventilation. Lung perfusion deficits in the irradiated lung regions began at 2 months after radiation and worsened with time. No ventilation deficits were observed after radiation. Decrease in lung CT density in irradiated regions was observed after radiation, but the changes were less significant than those in perfusion MRI. CONCLUSIONS: We demonstrated that highly conformal radiation can be reproducibly delivered to a small volume of rodent lung on a widely available clinical unit. The radiation-induced lung injury can be detected as early as 2 months after radiation with perfusion MRI. The primary pattern of injury agrees with previously reported endothelial damage to radiosurgical radiation doses. This experimental design provides a cost-effective methodology for producing radiosurgical injuries in rodents that reproduces current human treatments for studying radiation injury and agents that might affect it.