A high-precision image-guided platform for studying spinal cord toxicity under ultra-high dose rate electron irradiation

Abstract

Objective.While FLASH radiotherapy (FLASH-RT) is recognized for normal tissue sparing, its effect in mitigating the toxicity of late-responding organs remains uncertain, limiting clinical adoption. With its clinical importance and steep dose-response, spinal cord is an ideal model for evaluating the FLASH effect on late toxicity. This work introduces a robust image-guided research platform for high-precision irradiation at both conventional (CONV) and ultra-high dose rates (UHDR) to enable FLASH late toxicity studies using a rat spinal cord model.Approach.A modified LINAC was employed to irradiate the C1-T2 rat spinal cord with 18 MeV UHDR and CONV beams. A custom rat immobilization device, a portable x-ray imaging system, and an ion-chamber-based UHDR output monitoring system were integrated to ensure accurate C1-T2 localization and precise dose delivery. A Monte Carlo (MC) dose engine was developed to provide accurate dosimetry and support the interpretation ofin vivoresults. Scintillator measurements at UHDR were performed within the spinal cord to verify MC results and the precision of our platform.Results.We observed submillimeter deviation in C1-T2 localization between 2D x-ray and 3D cone beam computed tomography imaging, as well as between pre- and post-irradiation 2D x-ray assessments. Ion chamber readings showed linear correlation with UHDR output (R²= 1). MC calculations indicated uniform irradiation (<5% non-uniformity) along the central ∼13 mm cord, avoiding dose-volume effects. Our CONV beam exhibited dose distribution close to that of the UHDR beam, with differences < 3%, isolating dose rate as the only variable. Scintillator-measured dose agreed with MC within 4%, with a 100% gamma passing rate (2%/2 mm), confirming both MC accuracy and the platform's high-precision delivery.Significance.We developed the first comprehensive, image-guided preclinical platform for accurate UHDR and CONV irradiation to investigate FLASH-mitigated spinal cord toxicity in rats. This work thus establishes a robust foundation for systematic evaluation of the FLASH effect in late-responding organs and for assessing relevant clinical applicability of FLASH-RT.

Keywords: FLASH radiotherapy; late toxicity; preclinical radiation research; spinal cord.