While spatial dose conformity delivered to a target volume has been pushed to its practical limits with advanced treatment planning and delivery, investigations in novel temporal dose delivery are unfolding new mechanisms. Recent advances in ultra-high dose radiotherapy, abbreviated as FLASH, indicate the potential for reduction in healthy tissue damage while preserving tumor control. FLASH therapy relies on very high dose rate of > 40Gy/s with sub-second temporal beam modulation, taking a seemingly opposite direction from the conventional paradigm of fractionated therapy. FLASH brings unique challenges to dosimetry, beam control, and verification, as well as complexity of radiobiological effective dose through altered tissue response. In this review, we compare the dosimetric methods capable of operating under high dose rate environments. Due to excellent dose-rate independence, superior spatial (∼ <1 mm) and temporal (∼ns) resolution achievable with Cherenkov and scintillation-based detectors, we show that luminescent detectors have a key role to play in the development of FLASH, as the field rapidly progresses toward clinical adaptation. Additionally, we show that the unique ability of certain luminescence-based methods to provide tumor oxygenation maps in real-time with submillimeter resolution can elucidate the radiobiological mechanisms behind the FLASH effect. In particular, such techniques will be crucial for understanding the role of oxygen in mediating the FLASH effect.

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Objective. Existing ultra-high dose rate (UHDR) electron sources lack dose rate independent dosimeters and a calibrated dose control system for accurate delivery. In this study, we aim to develop a custom single-pulse dose monitoring and a real-time dose-based control system for a FLASH enabled clinical linear accelerator (Linac). Approach. A commercially available point scintillator detector was coupled to a gated integrating amplifier and a real-time controller for dose monitoring and feedback control loop. The controller was programmed to integrate dose for each radiation pulse and stop the radiation beam when the prescribed dose was delivered. Additionally, the scintillator was mounted in a solid water phantom and placed underneath mice skin for in vivo dose monitoring. The scintillator was characterized in terms of its radiation stability, mean dose-rate ( D ̇ m ), and dose per pulse (D p) dependence. Main results. The D p exhibited a consistent ramp-up period across ∼4–5 pulse. The plastic scintillator was shown to be linear with D ̇ m (40–380 Gy s−1) and D p (0.3–1.3 Gy Pulse−1) to within +/− 3%. However, the plastic scintillator was subject to significant radiation damage (16%/kGy) for the initial 1 kGy and would need to be calibrated frequently. Pulse-counting control was accurately implemented with one-to-one correspondence between the intended and the actual delivered pulses. The dose-based control was sufficient to gate on any pulse of the Linac. In vivo dosimetry monitoring with a 1 cm circular cut-out revealed that during the ramp-up period, the average D p was ∼0.045 ± 0.004 Gy Pulse−1, whereas after the ramp-up it stabilized at 0.65 ± 0.01 Gy Pulse−1. Significance. The tools presented in this study can be used to determine the beam parameter space pertinent to the FLASH effect. Additionally, this study is the first instance of real-time dose-based control for a modified Linac at ultra-high dose rates, which provides insight into the tool required for future clinical translation of FLASH-RT.

Purpose: We demonstrate the feasibility of optical imaging as a quality assurance tool for static small beamlets, and pretreatment verification tool for radiosurgery and volumetric-modulated arc therapy (VMAT) plans. Methods: Small static beams and clinical VMAT plans were simulated in a treatment planning system (TPS) and delivered to a cylindrical tank filled with water-based liquid scintillator. Emission was imaged using a blue-sensitive, intensified CMOS camera time-gated to the linac pulses. For static beams, percentage depth and cross beam profiles of projected intensity distribution were compared to TPS data. Two-dimensional (2D) gamma analysis was performed on all clinical plans, and the technique was tested for sensitivity against common errors (multileaf collimator position, gantry angle) by inducing deliberate errors in the VMAT plans control points. The technique's detection limits for spatial resolution and the smallest number of control points that could be imaged reliably were also tested. The sensitivity to common delivery errors was also compared against a commercial 2.5D diode array dosimeter. Results: A spatial resolution of 1 mm was achieved with our imaging setup. The optical projected percentage depth intensity profiles agreed to within 2% relative to the TPS data for small static square beams (5, 10, and 50 mm 2 ). For projected cross beam profiles, a gamma pass rate >99% was achieved for a 3%/1 mm criteria. All clinical plans passed the 3%/3 mm criteria with >95% passing rate. A static 5 mm beam with 20 Monitor Units could be measured with an average percent difference of 5.5 AE 3% relative to the TPS. The technique was sensitive to multileaf collimator errors down to 1 mm and gantry angle errors of 1°. Conclusions: Optical imaging provides ample spatial resolution for imaging small beams. The ability to faithfully image down to 20 MU of 5 mm, 6 MV beamlets prove the ability to perform quality assurance for each control point within dynamic plans. The technique is sensitive to small offset errors in gantry angles and multileaf collimator (MLC) leaf positions, and at certain scenario, it exhibits higher sensitivity than a commercial 2.5D diode array.

Purpose CCD cameras are employed to image scintillation and Cherenkov radiation in external beam radiotherapy. This is achieved by gating the camera to the linear accelerator (Linac) output. A direct output signal line from the linac is not always accessible and even in cases where such a signal is accessible, a physical wire connected to the output port can potentially alter Linac performance through electrical feedback. A scintillating detector for stray radiation inside the Linac room was developed to remotely time‐gate to linac pulses for camera‐based dosimetry. Methods A scintillator coupled silicon photomultiplier detector was optimized and systematically tested for location sensitivity and for use with both x rays and electron beams, at different energies and field sizes. Cherenkov radiation emitted due to static photon beams was captured using the remote trigger and compared to the images captured using a wired trigger. The issue of false‐positive event detection, due to additional neutron activated products with high energy beams, was addressed. Results The designed circuit provided voltage >2.5 V even for distances up to 3 m from the isocenter with a 6 MV, 5 × 5 cm beam, using a Ø3 × 20 mm3 Bi4Ge3O12 (BGO) crystal. With a larger scintillator size, the detector could be placed even beyond 3 m distance. False‐positive triggering was reduced by a coincidence detection scheme. Negligible fluctuations were observed in time‐gated imaging of Cherenkov intensity emitted from a water phantom, when comparing directly connected vs this remote triggering approach. Conclusion The remote detector provides untethered synchronization to linac pulses. It is especially useful for remote Cherenkov imaging or remote scintillator dosimetry imaging during radiotherapeutic procedures when a direct line signal is not accessible.

High dose rate conditions, coupled with problems related to small field dosimetry, make dose characterization for FLASH-RT challenging. Most conventional dosimeters show significant dependence on dose rate at ultra-high dose rate conditions or fail to provide sufficiently fast temporal data for pulse to pulse dosimetry. Here fast 2D imaging of radioluminescence from a water and quinine phantom was tested for dosimetry of individual 4 μs linac pulses. Methods: A modified clinical linac delivered an electron FLASH beam of >50 Gy/s to clinical isocenter. This modification removed the x-ray target and flattening filter, leading to a beam that was symmetric and gaussian, as verified with GafChromic EBT-XD film. Lateral projected 2D dose distributions for each linac pulse were imaged in a quinine-doped water tank using a gated intensified camera, and an inverse Abel transform reconstruction provided 3D images for on-axis depth dose values. A total of 20 pulses were delivered with a 10 MeV, 1.5 cm circular beam, and beam with jaws wide open (40 × 40 cm 2 ), and a 3D dose distribution was recovered for each pulse. Beam output was analyzed on a pulse by pulse basis. Results: The R p , D max , and the R 50 measured with film and optical methods agreed to within 1 mm for the 1.5 cm circular beam and the beam with jaws wide open. Cross beam profiles for both beams agreed with film data with >95% passing rate (2%/2 mm gamma criteria). The optical central axis depth dose agreed with film data, except for near the surface. A temporal pulse analysis revealed a ramp-up period where the dose per pulse increased for the first few pulses and then stabilized. Conclusions: Optical imaging of radioluminescence was presented as a valuable tool for establishing a baseline for the recently initiated electron FLASH beam at our institution.