An image-guided high-precision research platform for ultra-high dose rate spinal cord toxicity studies

TL;DR

This paper presents a novel, highly precise image-guided platform for delivering ultra-high dose rate and conventional radiotherapy to rat spinal cords, enabling detailed studies of late toxicity effects of FLASH radiotherapy.

Contribution

It introduces the first comprehensive preclinical platform combining advanced imaging, dosimetry, and delivery systems for high-precision FLASH studies in the spinal cord.

Findings

Achieved submillimeter accuracy in irradiation setup.

Verified dose delivery precision with scintillator and Monte Carlo simulations.

Demonstrated uniform irradiation along the rat spinal cord with minimal dose difference.

Abstract

Objective: While FLASH radiotherapy is recognized for short-term normal tissue sparing, its durability in late-responding organs remains uncertain, limiting clinical adoption. With its clinical importance and steep dose-response, the spinal cord is an ideal model for evaluating FLASH effect on late toxicity. This work introduces a robust image-guided research platform for high-precision irradiation at both CONV and 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 interpretation of in vivo results. Scintillator measurements were performed within the spinal cord to verify MC results and the precision of our platform. Results: We achieved submillimeter C1-T2 setup accuracy and maintained submillimeter intrafraction motion. Ion chamber readings showed linear correlation with UHDR output. MC indicated uniform irradiation along the central ~13 mm cord. Our CONV beam exhibited distribution close to that of the UHDR beam, with difference <3%, isolating dose rate as the only variable. Scintillator-measured dose agreed with MC within 4%, 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 determining clinical applicability of FLASH.