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Session: Pre-Clinical Modeling [Return to Session]

An in Vivo Oxygen Transport Model Describing the Physiological Impact On FLASH Radiotherapy

L Guo*, K Wang, Biomedical Imaging and Radiation Technology (BIRT) Laboratory, Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas


TU-D1030-IePD-F4-6 (Tuesday, 7/12/2022) 10:30 AM - 11:00 AM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 4

Purpose: Oxygen (O₂) depletion caused by ultra-high dose rate has been proposed to explain the radioresistant effect observed in FLASH. We developed a comprehensive model to describe the spatial and temporal dynamics of O₂ consumption and transport during FLASH in vivo. We investigate the change of oxygen enhancement ratio(OER), as function of physiological conditions i.e., tissue oxygenation, capillary geometry, blood flow velocity, as well as dose and dose rate, under various radiolytic O₂ depletion (ROD) conditions.

Methods: We considered time-dependent O₂ supply and consumption in 3D cylindrical geometry, incorporating blood flow linking the O₂ concentration ([O₂]) in the vessel to that within the tissue through the Hill equation, radial and axial diffusion of O₂, metabolic and zero-order radiolytic O₂ consumption and pulsed radiation structure. Time-evolved distributions of [O₂] were obtained by numerically solving perfusion-diffusion equations. The model enables computation of the dynamic variation of O₂ distribution, and relative change of OER (δ(ROD)) under various physiological and irradiation conditions in vivo.

Results: Large anoxic region is generated during FLASH irradiation because of radiolytic O₂ depletion rate far exceeding supply rate. Initial O₂ level and how it changes during irradiation determine δ(ROD) distribution, which strongly depends on physiological parameters, i.e. interpapillary spacing, and determines the amount of cells that can survive irradiation. We observed the δ(ROD) is affected by and sensitive to the interplay effect among physiological and radiation parameters. The saturation of FLASH normal tissue protection upon dose and dose rate is shown. No significant decrease in radiosensitivity within tissue region is observed beyond ~50 Gy/s. For a given dose rate, the change of radiosensitivity become minimum after certain dose level achieved.

Conclusion: Physiological conditions can potentially determine the FLASH efficacy in tissue protection. The FLASH effect may be observed under optimal combination of physiological parameters beyond radiation condition.

Funding Support, Disclosures, and Conflict of Interest: This study is funded by CPRIT RR200042. No conflict of interest.




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