Application of Čerenkov Radiation for Oxygenation and Surface Dose Assessment during External Beam Radiotherapy Rongxiao Zhang1, Adam Glaser2, Tatiana V. Esipova3, Stephen C. Kanick2, Scott C. Davis2, Sergei Vinogradov3, David Gladstone4, Brian W. Pogue1,2,4 1Department of Physics & Astronomy, 2Thayer School of Engineering, Dartmouth College, Hanover NH 03755 3Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA 19104. 4Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon NH 03755 Čerenkov Radiation Emission and Excited Luminescence (CREL) Sensitivity during External Beam Radiation Therapy: Monte Carlo and Tissue Phantom Studies Čerenkov Radiation Emission for Surface Dose Assessment During External Beam Radiotherapy Introduction System Introduction Previous research shows that many factors (beam types, SSD, field size, incident angle, curvature of the surface, etc) affect surface dose. Čerenkov radiation emission during external beam radiotherapy has been shown has similar distribution with radiation dose because they both suffer a similar energy lose rate profile. A fast time-gating system has been designed to measure the Čerenkov emission from the surface of solid water phantom and thus provide the information surface dose distribution. A 30cm*30cm*5cm sold water phantom was irradiated by electron beams with SSD=110cm and gamma beam with SSD=100cm for different field size, energies and incident angles. A fast time gating camera was synchronized to the LINAC pulses. Čerenkov photon emitted through the surface of the phantom have been imaged. Figure 3—Geometry and phantom optical properties of sensitivity simulation Čerenkov emission occurs when charged particles move through a dielectric medium at a phase velocity greater than the speed of light in that medium inelastically losing energy through electrical field interactions with the transiently polarized medium. Radiotherapy generates Čerenkov radiation emission in tissue, and spectral absorption features appearing in the emission spectrum can be used to quantify blood oxygen saturation (StO2) from the known absorptions of hemoglobin. Alternatively, the Čerenkov light can be used to excite an oxygen-sensitive phosphorescent probe, PtG4, whose NIR emission lifetime is directly sensitive to the tissue oxygen partial pressure (pO2). H=35cm D=70cm 1 Incident dose = the dose measured on the intended surface of the patient,but without the presence of the patient Surface dose = incident dose + scattered radiation from the body  Result System Phosphorescence lifetime and pO2 information have been recovered by fitting the decay of CREL with an exponential model. Figure 2C shows a gated spectrum measurement of CR from tissue mimicking phantoms with different StO2 (StO2=92% and StO2=5%). Figure 2D shows a continuous wavelength and gated spectrum measurement of CREL from tissue mimicking phantoms with different pO2 levels (pO2=141.95Torr and pO2=2.31Torr). In Figure 2E, the lifetime fitting of the fast time gated CREL intensity data is shown. The experiments were performed with a linear accelerator (Varian Clinic 2100C) at the Norris Cotton Cancer Center. As shown in Figure 1A, an 18MeV electron beam irradiated the entire top of the phantom. The measurement system consisted of a single fiber which collected the light at the boundary of the phantom in a circular spot, and guided the signal into a vertical line of fibers at the entrance slit of the spectrometer. The spectrometer was connected to a fast gated ICCD. Experiment and Simulation Electron beam and gamma photon beam of different field sizes, energies and incident angles have been imaged. Phase space files for corresponding beam has been adopted to simulate dose and local Čerenkov emission in a voxelised phantom in Geant4 based toolkit GAMOS. Results Figure 1—9MeV 10cm square electron beam images compared to corresponding simulation Table 1—Lifetime measurement of CREL Figure 1—System and gating time line   pO2=141.95Torr pO2=2.31Torr Lifetime values from fitting 20.79μs/(20.08μs, 21.56μs) 45.64μs/(45.13μs, 46.19μs) Reference lifetime values 21.29μs 45.62μs In Table 1, CREL lifetime values for different pO2 levels from fast gating and exponential fitting has been compared with the reference values. Figure 4—Sensitivity distribution and sensitivity-depth profiles for CR Figure 2—9MeV electron beam with field size from 6cm square to 20cm square LINAC pulses electrons in 5μs bursts at a repetition rate near 180 Hz, a fast time gated system was designed to measure the lifetime of CREL gating to these pulses. As shown in Figure 1B, the external radiotherapy beam triggers when the beam is on, to sample the CREL signal and reject sampling when the beam is off. By choosing the gate delays with respect to the trigger signal, the intensity of CREL at different time points was measured. In this work, we set the delays with respect to the falling edge of the trigger signal. The delays varied from 8μs to 200μs. Figure 3—6MV gamma beam with field size from 6cm square to 20cm square Phantom To couple Čerenkov Radiation (CR) with Phosphorescence Lifetime Imaging (PLI) we used dendritic phosphorescent probe PtG4. The absorption and emission spectrum of PtG4 has been shown in Figure 2A and Figure 2B. The phantoms were composed of water with 1% v/v Intralipid as a scattering standard and 1% v/v porcine whole blood as an absorber. PtG4 was added at a concentration of 5μM. Figure 5—Effective sampling depth and simulated spectrum of CR for different FBDs Figure 4—10cm square electron beam with energy from 6MeV to 18MeV Figure 2—Spectrum and lifetime measurement of CREL Figure 6--Sensitivity distribution and sensitivity-depth profiles for CREL Figure 5—9MV 10cm square electron beam (SSD = 110cm) with rotation angle from 0 to 60 degrees Figure 6—6MV gamma beam (SSD=100cm) with rotation angle from 0 to 60 degrees Conclusion CREL form PtG4 reveal the tissue pO2 value in the sampling region. Simulated detection sensitivity distributions show that both CR and CREL could be detected at depths of a few centimeters into tissue. The detected sensitivity profiles and effective sampling depth are highly dependent on the wavelength and the relative arrangement of external radiotherapy beams. The near-infrared wavelengths penetrate up to 20-30 mm while sensitivity to the blue, green and red wavelengths was substantially shallower. Information about the detected sensitivity distributions and effective sampling depths could be linked to treatment planning in order to spatially recover the regions where the signals have been detected. Detection Sensitivity Distribution Simulation Detection sensitivity of the system for CR and CREL has been simulated in the geometry shown in Figure 3A. Figure 3B shows the intersections of a typical simulation to show how the sensitivity distribution appeared in 3D. And Figure 3C shows the optical properties of the tissue mimicking phantom for the simulation for which is made of water, 1% Intralipid, 1% whole blood with StO2=0.9 and PtG4 with a concentration of 5μM. Conclusion Simulation shows that Čerenkov emission has similar distribution with radiation Dose. Thus, image of Čerenkov emission of the surface is a potential way for surface dose assessment. The acquisition time is about 40s each image and can be further reduced to be less than 5s by taking less frames of images andshielding the camera to improve SNR. Resolution could be as high as 0.5mm. Potential application would be imaging the surface dose distribution during external beam radiotherapy and daily Q&A.