Real-time optical oximetry during FLASH radiotherapy using a phosphorescent nanoprobe

Abstract

The rapid depletion of oxygen during irradiation at ultra-high dose rate calls for tissue oximeters capable of high temporal resolution. This study demonstrates a water-soluble phosphorescent nanoprobe and fiber-coupled instrument, which together are used to measure the kinetics of oxygen depletion at 200 Hz during irradiation of in vitro solutions.

Keywords: FLASH radiotherapy; Nanoparticles; Oximetry; Oxygen; Phosphorimetry.

Figure 1:

Overview of experimental setup and calibration. (A) Schematic of the fiber-coupled phosphorimeter used in this study. (B) Liquid sample in OxyGenie container placed on the irradiation stage. (C) Same sample coupled to the optical fiber and covered by an enclosure to shut out ambient light. (D) Picture of the phosphorimeter. (E) Representative phosphorimeter output measured during CDR irradiation, displaying periodic exponential decays from nanoprobe. Irregular peaks (black arrows) caused by Cherenkov radiation were removed before fitting. (F) Exponential fitting scheme consisting of a single exponential, background exponential, and offset. (G) Stern-Volmer relationship (R^2 >0.99) relating oxygen concentration with measured nanoprobe lifetime.

Figure 2:

Real-time measurements of oxygen depletion in phosphate-buffered saline (PBS) samples under (A) ultra-high dose-rate (UHDR; 90 Gy/s) and (B) conventional dose-rate (CDR; 0.079 Gy/s) irradiation. (C) Summary showing yields of oxygen depletion as a function of initial oxygen concentration. (D-F) Same data, shown for PBS samples containing 5 mM 2-mercaptoethanol (2-ME), a free radical scavenger. Error bars represent standard deviation of individual O₂ measurements.