Presenter of 1 Presentation
PHOSPHORESCENCE-BASED OXIMETRY FOR RADIOTHERAPY
Author Of 4 Presentations
PHOSPHORESCENCE-BASED OXIMETRY FOR RADIOTHERAPY
ULTRAFAST TRACKING OF OXYGEN DYNAMICS DURING PROTON FLASH
Abstract
Background and Aims
Radiotherapy at ultrahigh dose rates (FLASH, >40Gy/sec) compared to conventional radiotherapy (CR; <1 Gy/sec) has been shown to provide an advantage by selective protection of normal versus tumor tissue. Depletion of molecular oxygen causing radioprotection has been proposed to underpin the FLASH effect, however no experimental data have been presented to test this hypothesis. Our goal was to assess the oxygen dynamics during and following proton FLASH versus CR.
Methods
Measurements of oxygen were performed in vitro (solutions in sealed vials) and in vivo in mice (healthy leg muscle and tumors) using the phosphorescence quenching method with probe Oxyphor PtG4 at rates reaching 3 measurements/millisecond during proton irradiation delivered with CR or FLASH dose rates.
Results
In closed systems in vitro the rate of oxygen depletion is oxygen-independent for both FLASH and CR when [O2]>~70 μM. The g-values are lower for FLASH than for CR by ~15%. In vivo oxygen is depleted upon FLASH with rates that correlate with baseline pO2 (partial pressure of oxygen) values throughout the entire pO2 range: at 30-40 mmHg (normal tissue) a 30 Gy FLASH (100 Gy/s) results in ΔpO2 of -8 mmHg, while at 5-7 mmHg (tumor) ΔpO2 is only -1 mmHg.
Conclusions
This study features the first demonstration of the phosphorescence quenching oximetry at ultrafast rates and in the presence of proton radiation. Oxygen depletion by FLASH in vitro was found to be smaller than by CR, and appears to correlate with baseline pO2 values, being greater for normal tissue than for tumors.
CHERENKOV EXCITED LUMINESCENCE IMAGING OF DOSE AND OXYGEN IN TISSUE
Abstract
Background and Aims
During linac irradiation Cherenkov light is induced in tissue as part of the dose deposition process. This instantaneous light intensity can be used to excite molecular probes, and the signal is directly proportional to the instantaneous dose rate. Thus, during FLASH irradiation, it is possible to use this signal to sense the concentration of molecules and probes in tissue, as is investigated here.
Methods
In vivo measurement of light was done by time-gated intensified cameras that are synchronized to the linac pulses of a 10 MeV FLASH linac. Full emission spectrum light from tissue is imaged for a signal that is proportional to the Cherenkov light coming off the tissue surface. Time-delayed luminescence is imaged with different sequences of time are used to measure the emission kinetics of molecular probe Oxyphor 2P over the course of 50 microseconds after the pulse.
Results
The imaging of Cherenkov can be calibrated to dose (+/-0.5Gy accuracy) for a fixed geometry and fixed tissue optical properties. The imaging of scintillator patches is possible for quantitative dose, independent of the tissue optical properties(+/-0.1Gy accuracy). The imaging of oxygenation is possible for sensing local pO2 from up to 5 pulses of radiation to obtain a reliable lifetime (+/-1mmHg accuracy), with the camera settings used currently.
Conclusions
Pulse to pulse sensing of dose and tissue metabolism is critical to understanding the dose delivered and the tissue responses to FLASH. The tools of Cherenkov luminescence imaging can be deployed with a single time-gated camera to sense dose delivered or tissue oxygenation.
IN VIVO QUANTIFICATION OF OXYGEN DEPLETION BY ELECTRON FLASH IRRADIATION
Abstract
Background and Aims
The major hypothesis for the underlying mechanism of normal tissue sparing by FLASH has focused on oxygen depletion, however no experimental data have been presented to support it. The aim of this study was to assess changes in tissue oxygenation in vivo produced by FLASH irradiation.
Methods
Oxygen measurements were performed in vivo and in vitro using the phosphorescence quenching method and molecular probe Oxyphor 2P. The changes in oxygenation were quantified in response to irradiation by a 10 MeV electron beam operating at either ultra-high dose rates (UHDR) reaching 300 Gy/s or at conventional dose rates of 0.1 Gy/s.
Results
In vitro experiments with 5% BSA solutions resulted in oxygen depletion g-values of 0.19-0.21 mmHg/Gy for conventional irradiation and 0.16-0.17 mmHg/Gy for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3±0.3 mmHg in normal tissue and 1.0±0.2 mmHg in tumor tissue (p-value < 0.00001), while no changes in oxygenation were observed from a single fraction of 20 Gy applied at conventional dose rates.
Conclusions
In vitro experiments with 5% BSA solutions resulted in oxygen depletion g-values of 0.19-0.21 mmHg/Gy for conventional irradiation and 0.16-0.17 mmHg/Gy for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3±0.3 mmHg in normal tissue and 1.0±0.2 mmHg in tumor tissue (p-value < 0.00001), while no changes in oxygenation were observed from a single fraction of 20 Gy applied at conventional dose rates.