A Feasibility Study of Preclinical Ocular X-Ray FLASH Radiation Therapy

Ultrahigh-dose-rate radiation therapy (FLASH RT) has not previously been studied for the treatment of ocular targets. This work describes the feasibility of ocular FLASH irradiation of a single mouse eye using kilovoltage x-ray sources with rotating anode technology.

A 75-kW-powered rotating anode kilovoltage x-ray source was implemented for FLASH and conventional (CONV) dose-rate irradiation of superficial targets in small animals. A docking immobilization device was designed to facilitate irradiation of an individual mouse eye. Mouse positioning reproducibility was assessed via Hausdorff distance and Dice similarity coefficients of features from cone beam computed tomographies (CT) of immobilized animals. Thermoluminescent dosimeters and Gafchromic film dosimeters were used to characterize output (dose rate), depth dose rate, and to assess geometric parameters of the beam. In a pilot study of ocular irradiation, healthy C57BL/6J mouse eyes were irradiated to doses of up to 26 Gy at either FLASH or CONV dose rates. Retinal function was assessed 2 months following irradiation using electroretinography. Morphologic changes were evaluated via histopathology.

Animal setup was highly reproducible, with typical Hausdorff distances between bony features of 0.34 mm and Dice similarity coefficient of 0.92 for surface features. At FLASH irradiation settings, dose rates of 52.6 ± 2.6 Gy/s were measured using in vivo thermoluminescent dosimeters. CONV dose rates of 1.1 ± 0.1 Gy/s were achievable with the same setup by minimizing the input current. Following irradiation to 26 Gy, retinal function was preserved for FLASH-irradiated eyes but significantly impaired in CONV-irradiated eyes. Histopathology assessment confirmed significant inner retinal atrophy in CONV-irradiated eyes that was absent in FLASH-irradiated eyes.

Irradiation of the mouse eye was feasible at FLASH and CONV dose rates by the orthovoltage x-ray using the rotating anode x-ray source. A pilot study of ocular irradiation in healthy mice demonstrated sparing effects of FLASH on the mouse retina.