First Retrospective QA of FAST-01 Clinical Treatment Fields Using High-Speed Quantitative Scintillation Imaging.

Purpose: To retrospectively validate the dose and dose rates delivered in XXX clinical trial fields via sub-millimeter spatial and <0.25 ms temporal resolution scintillation imaging.

Methods: An ultra-fast intensified CMOS camera (4.

Optimized scintillation imaging in low dose rate and bright room light conditions.

. To develop a robust method for non-contact surface dosimetry during Total Body Irradiation (TBI) that uses an optimally paired choice of scintillator material with camera photocathode and can work insensitively to the normal ambient room lighting conditions (∼500 Lux)..

Noise & mottle suppression methods for cumulative Cherenkov images of radiation therapy delivery.

Cherenkov imaging during radiotherapy provides a real time visualization of beam delivery on patient tissue, which can be used dynamically for incident detection or to review a summary of the delivered surface signal for treatment verification. Very few photons form the images, and one limitation is that the noise level per frame can be quite high, and mottle in the cumulative processed images can cause mild overall noise. This work focused on removing or suppressing noise via image postprocessing.

Robust Real-time Segmentation of Bio-Morphological Features in Human Cherenkov Imaging during Radiotherapy via Deep Learning.

Cherenkov imaging enables real-time visualization of megavoltage X-ray or electron beam delivery to the patient during Radiation Therapy (RT). Bio-morphological features, such as vasculature, seen in these images are patient-specific signatures that can be used for verification of positioning and motion management that are essential to precise RT treatment. However until now, no concerted analysis of this biological feature-based tracking was utilized because of the slow speed and accuracy of conventional image processing for feature segmentation.

Dynamic oxygen assessment techniques enable determination of anesthesia's impact on tissue.

Tissue oxygenation is well understood to impact radiosensitivity, with reports demonstrating a significant effect of breathing condition and anesthesia type on tissue oxygenation levels and radiobiological response. However, the temporal kinetics of intracellular and extracellular oxygenation have never been quantified, on the timescale that may affect radiotherapy studies. C57BL/6 mice were anesthetized using isoflurane at various percentages or ketamine/xylazine (ket/xyl: 100/10 mg/kg) (N = 48).

Commissioning an ultra-high-dose-rate electron linac with end-to-end tests.

. The FLASH effect can potentially be used to improve the therapeutic ratio of radiotherapy (RT) through delivery of Ultra-high-dose-rate (UHDR) irradiation. Research is actively being conducted to translate UHDR-RT and for this purpose the Mobetron is capable of producing electron beams at both UHDR and conventional dose rates for FLASH research and translation.

Quantitative, real-time scintillation imaging for experimental comparison of different dose and dose rate estimations in UHDR proton pencil beams.

Background: Ultra-high dose rate radiotherapy (UHDR-RT) has demonstrated normal tissue sparing capabilities, termed the FLASH effect; however, available dosimetry tools make it challenging to characterize the UHDR beams with sufficiently high concurrent spatial and temporal resolution. Novel dosimeters are needed for safe clinical implementation and improved understanding of the effect of UHDR-RT.

Purpose: Ultra-fast scintillation imaging has been shown to provide a unique tool for spatio-temporal dosimetry of conventional cyclotron pencil beam scanning (PBS) deliveries, indicating the potential use for characterization of UHDR PBS proton beams.

Electron beam response corrections for an ultra-high-dose-rate capable diode dosimeter.

Background: Ultra-high-dose-rate (UHDR) electron beams have been commonly utilized in FLASH studies and the translation of FLASH Radiotherapy (RT) to the clinic. The EDGE diode detector has potential use for UHDR dosimetry albeit with a beam energy dependency observed.

Purpose: The purpose is to present the electron beam response for an EDGE detector in dependence on beam energy, to characterize the EDGE detector's response under UHDR conditions, and to validate correction factors derived from the first detailed Monte Carlo model of the EDGE diode against measurements, particularly under UHDR conditions.

Intracellular Oxygen Transient Quantification in Vivo During Ultra-High Dose Rate FLASH Radiation Therapy.

Purpose: Large, rapid extracellular oxygen transients (ΔpO) have been measured in vivo during ultra-high dose rate radiation therapy; however, it has been unclear if they match intracellular oxygen levels. Here, the endogenously produced protoporphyrin IX (PpIX) delayed fluorescence signal was measured as an intracellular in-vivo oxygen sensor to quantify these transients, with direct comparison to extracellular pO. Intracellular ΔpO is closer to the cellular DNA, the site of major radiobiological damage, and therefore should help elucidate radiochemical mechanisms of the FLASH effect and potentially be translated to human tissue measurement.

Technical note: Visual, rapid, scintillation point dosimetry for in vivo MV photon beam radiotherapy treatments.

Background: While careful planning and pre-treatment checks are performed to ensure patient safety during external beam radiation therapy (EBRT), inevitable daily variations mean that in vivo dosimetry (IVD) is the only way to attain the true delivered dose. Several countries outside the US require daily IVD for quality assurance. However, elsewhere, the manual labor and time considerations of traditional in vivo dosimeters may be preventing frequent use of IVD in the clinic.

Two-dimensional time-resolved scintillating sheet monitoring of proton pencil beam scanning FLASH mouse irradiations.

Background: Dosimetry in pre-clinical FLASH studies is essential for understanding the beam delivery conditions that trigger the FLASH effect. Resolving the spatial and temporal characteristics of proton pencil beam scanning (PBS) irradiations with ultra-high dose rates (UHDR) requires a detector with high spatial and temporal resolution.

Purpose: To implement a novel camera-based system for time-resolved two-dimensional (2D) monitoring and apply it in vivo during pre-clinical proton PBS mouse irradiations.

Rapid Switching of a C-Series Linear Accelerator Between Conventional and Ultrahigh-Dose-Rate Research Mode With Beamline Modifications and Output Stabilization.

Purpose: In this study, a C-series linear accelerator was configured to enable rapid and reliable conversion between the production of conventional electron beams and an ultrahigh-dose-rate (UHDR) electron beamline to the treatment room isocenter for FLASH radiation therapy. Efforts to tune the beam resulted in a consistent, stable UHDR beamline.

Methods And Materials: The linear accelerator was configured to allow for efficient switching between conventional and modified electron output modes within 2 minutes.

First Monte Carlo beam model for ultra-high dose rate radiotherapy with a compact electron LINAC.

Background: FLASH radiotherapy based on ultra-high dose rate (UHDR) is actively being studied by the radiotherapy community. Dedicated UHDR electron devices are currently a mainstay for FLASH studies.

Purpose: To present the first Monte Carlo (MC) electron beam model for the UHDR capable Mobetron (FLASH-IQ) as a dose calculation and treatment planning platform for preclinical research and FLASH-radiotherapy (RT) clinical trials.

Imaging and characterization of optical emission fromtissue during conventional and UHDR PBS proton therapy.

. Imaging of optical photons emitted from tissue during radiotherapy is a promising technique for real-time visualization of treatment delivery, offering applications in dose verification, treatment monitoring, and retrospective treatment plan comparison. This research aims to explore the feasibility of intensified imaging of tissue luminescence during proton therapy (PT), under both conventional and ultra-high dose rate (UHDR) conditions.

Subsurface fluorescence time-of-flight imaging using a large-format single-photon avalanche diode sensor for tumor depth assessment.

Significance: Fluorescence guidance is used clinically by surgeons to visualize anatomical and/or physiological phenomena in the surgical field that are difficult or impossible to detect by the naked eye. Such phenomena include tissue perfusion or molecular phenotypic information about the disease being resected. Conventional fluorescence-guided surgery relies on long, microsecond scale laser pulses to excite fluorescent probes.

Characterization of Cherenkov imaging parameters and positional constraints on an O-ring linear accelerator.

. With the introduction of Cherenkov imaging technology on the Halcyon O-ring linear accelerator platform, we seek to demonstrate the imaging feasibility and optimize camera placement..

Comparison of Tumor Control and Skin Damage in a Mouse Model after Ultra-High Dose Rate Irradiation and Conventional Irradiation.

Recent studies suggest ultra-high dose rate radiation treatment (UHDR-RT) reduces normal tissue damage compared to conventional radiation treatment (CONV-RT) at the same dose. In this study, we compared first, the kinetics and degree of skin damage in wild-type C57BL/6 mice, and second, tumor treatment efficacy in GL261 and B16F10 dermal tumor models, at the same UHDR-RT and CONV-RT doses. Flank skin of wild-type mice received UHDR-RT or CONV-RT at 25 Gy and 30 Gy.

Characterization of a diode dosimeter for UHDR FLASH radiotherapy.

Background: Ultra-high dose rate (UHDR) FLASH beams typically deliver dose at rates of  >40 Gy/sec. Characterization of these beams with respect to dose, mean dose rate, and dose per pulse requires dosimeters which exhibit high temporal resolution and fast readout capabilities.

Purpose: A diode EDGE Detector with a newly designed electrometer has been characterized for use in an UHDR electron beam and demonstrated appropriateness for UHDR FLASH radiotherapy dosimetry.

Fluorescence-guided and molecularly-guided debridement: identifying devitalized and infected tissue in orthopaedic trauma.

Following orthopaedic trauma, bone devitalization is a critical determinant of complications such as infection or nonunion. Intraoperative assessment of bone perfusion has thus far been limited. Furthermore, treatment failure for infected fractures is unreasonably high, owing to the propensity of biofilm to form and become entrenched in poorly vascularized bone.

Color-resolved Cherenkov imaging allows for differential signal detection in blood and melanin content.

Significance: High-energy x-ray delivery from a linear accelerator results in the production of spectrally continuous broadband Cherenkov light inside tissue. In the absence of attenuation, there is a linear relationship between Cherenkov emission and deposited dose; however, scattering and absorption result in the distortion of this linear relationship. As Cherenkov emission exits the absorption by tissue dominates the observed Cherenkov emission spectrum.

Ultra-fast, high spatial resolution single-pulse scintillation imaging of synchrocyclotron pencil beam scanning proton delivery.

To demonstrates the ability of an ultra-fast imaging system to measure high resolution spatial and temporal beam characteristics of a synchrocyclotron proton pencil beam scanning (PBS) system.An ultra-fast (1 kHz frame rate), intensified CMOS camera was triggered by a scintillation sheet coupled to a remote trigger unit for beam on detection. The camera was calibrated using the linear (> 0.

Failure Mode and Effects Analysis for Experimental Use of FLASH on a Clinical Accelerator.

Purpose: The use of a linear accelerator (LINAC) in ultrahigh-dose-rate (UHDR) mode can provide a conduit for wider access to UHDR FLASH effects, sparing normal tissue, but care needs to be taken in the use of such systems to ensure errors are minimized. The failure mode and effects analysis was carried out in a team that has been involved in converting a LINAC between clinical use and UHDR experimental mode for more than 1 year after the proposed methods of TG100.

Methods And Materials: A team of 9 professionals with extensive experience were polled to outline the process map and workflow for analysis, and developed fault trees for potential errors, as well as failure modes that would result.

Protoporphyrin IX delayed fluorescence imaging: a modality for hypoxia-based surgical guidance.

Significance: Hypoxia imaging for surgical guidance has never been possible, yet it is well known that most tumors have microregional chronic and/or cycling hypoxia present as well as chaotic blood flow. The ability to image oxygen partial pressure (pO2) is therefore a unique control of tissue metabolism and can be used in a range of disease applications to understand the complex biochemistry of oxygen supply and consumption.

Aim: Delayed fluorescence (DF) from the endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique reporter of the local oxygen partial pressure in tissue.