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. METHODS: Percentage depth doses (PDDs) for the UHDR Mobetron were measured with both EDGE detectors and films. A detailed Monte Carlo (MC) model of the EDGE detector has been configured according to the blueprint provided by the manufacturer under an NDA agreement. Water/silicon dose ratios of EDGE detector for a series of mono-energetic electron beams have been calculated. The dependence of the water/silicon dose ratio on depth for a FLASH relevant electron beam was also studied. An analytical approach for the correction of PDD measured with EDGE detectors was established. RESULTS: Water/silicon dose ratio decreased with decreasing electron beam energy. For the Mobetron 9 MeV UHDR electron beam, the ratio decreased from 1.09 to 1.03 in the build-up region, maintained in range of 0.98-1.02 at the fall-off region and raised to a plateau in value of 1.08 at the tail. By applying the corrections, good agreement between the PDDs measured by the EDGE detector and those measured with film was achieved. CONCLUSIONS: Electron beam response of an UHDR capable EDGE detector was derived from first principles utilizing a sophisticated MC model. An analytical approach was validated for the PDDs of UHDR electron beams. The results demonstrated the capability of EDGE detector in measuring PDDs of UHDR electron beams.

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

PURPOSE: Large, rapid extracellular oxygen transients (ΔpO2) 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 pO2. Intracellular ΔpO2 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. METHODS AND MATERIALS: PpIX was induced in mouse skin through intraperitoneal injection of 250 mg/kg of aminolevulinic acid. The animals were also administered a 50 µL intradermal injection of 10 µM oxyphor G4 (PdG4) for phosphorescence lifetime pO2 measurement. Paired oxygen transients were quantified in leg or flank tissues while delivering 10 MeV electrons in 3 µs pulses at 360 Hz for a total dose of 10 to 28 Gy. RESULTS: Transient reductions in pO2 were quantifiable in both PpIX delayed fluorescence and oxyphor phosphorescence, corresponding to intracellular and extracellular pO2 values, respectively. Reponses were quantified for 10, 22, and 28 Gy doses, with ΔpO2 found to be proportional to the dose on average. The ΔpO2 values were dependent on initial pO2 in a logistic function. The average and standard deviations in ΔpO2 per dose were 0.56 ± 0.18 mm Hg/Gy and 0.43 ± 0.06 mm Hg/Gy for PpIX and oxyphor, respectively, for initial pO2 > 20 mm Hg. Although there was large variability in the individual animal measurements of ΔpO2, the average values demonstrated a direct and proportional correlation between intracellular and extracellular pO2 changes, following a linear 1:1 relationship. CONCLUSIONS: A fundamentally new approach to measuring intracellular oxygen depletion in living tissue showed that ΔpO2 transients seen during ultra-high dose rate radiation therapy matched those quantified using extracellular oxygen measurement. This approach could be translated to humans to quantify intracellular ΔpO2. The measurement of these transients could potentially allow the estimation of intracellular reactive oxygen species production.

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. PURPOSE: This study expands upon previous research using plastic scintillator discs for optical dosimetry for electron therapy treatments. We present the characterization of scintillator discs for in vivo x-ray dosimetry and describe additional considerations due to geometric complexities. METHODS: Plastic scintillator discs were coated with reflective white paint on all sides but the front surface. An anti-reflective, matte coating was applied to the transparent face to minimize specular reflection. A time-gated iCMOS camera imaged the discs under various irradiation conditions. In post-processing, background-subtracted images of the scintillators were fit with Gaussian-convolved ellipses to extract several parameters, including integral output, and observation angle. RESULTS: Dose linearity and x-ray energy independence were observed, consistent with ideal characteristics for a dosimeter. Dose measurements exhibited less than 5% variation for incident beam angles between 0° and 75° at the anterior surface and 0-60 ∘ $^\circ $ at the posterior surface for exit beam dosimetry. Varying the angle between the disc surface and the camera lens did not impact the integral output for the same dose up to 55°. Past this point, up to 75°, there is a sharp falloff in response; however, a correction can be used based on the detected width of the disc. The reproducibility of the integral output for a single disc is 2%, and combined with variations from the gantry angle, we report the accuracy of the proposed scintillator disc dosimeters as ±5.4%. CONCLUSIONS: Plastic scintillator discs have characteristics that are well-suited for in vivo optical dosimetry for x-ray radiotherapy treatments. Unlike typical point dosimeters, there is no inherent readout time delay, and an optical recording of the measurement is saved after treatment for future reference. While several factors influence the integral output for the same dose, they have been quantified here and may be corrected in post-processing.

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. METHODS: Time-resolved 2D beam monitoring was performed with a scintillation imaging system consisting of a 1 mm thick transparent scintillating sheet, imaged by a CMOS camera. The sheet was placed in a water bath perpendicular to a horizontal PBS proton beam axis. The scintillation light was reflected through a system of mirrors and captured by the camera with 500 frames per second (fps) for UHDR and 4 fps for conventional dose rates. The raw images were background subtracted, geometrically transformed, flat field corrected, and spatially filtered. The system was used for 2D spot and field profile measurements and compared to radiochromic films. Furthermore, spot positions were measured for UHDR irradiations. The measured spot positions were compared to the planned positions and the relative instantaneous dose rate to equivalent fiber-coupled point scintillator measurements. For in vivo application, the scintillating sheet was placed 1 cm upstream the right hind leg of non-anaesthetized mice submerged in the water bath. The mouse leg and sheet were both placed in a 5 cm wide spread-out Bragg peak formed from the mono-energetic proton beam by a 2D range modulator. The mouse leg position within the field was identified for both conventional and FLASH irradiations. For the conventional irradiations, the mouse foot position was tracked throughout the beam delivery, which took place through repainting. For FLASH irradiations, the delivered spot positions and relative instantaneous dose rate were measured. RESULTS: The pixel size was 0.1 mm for all measurements. The spot and field profiles measured with the scintillating sheet agreed with radiochromic films within 0.4 mm. The standard deviation between measured and planned spot positions was 0.26 mm and 0.35 mm in the horizontal and vertical direction, respectively. The measured relative instantaneous dose rate showed a linear relation with the fiber-coupled scintillator measurements. For in vivo use, the leg position within the field varied between mice, and leg movement up to 3 mm was detected during the prolonged conventional irradiations. CONCLUSIONS: The scintillation imaging system allowed for monitoring of UHDR proton PBS delivery in vivo with 0.1 mm pixel size and 2 ms temporal resolution. The feasibility of instantaneous dose rate measurements was demonstrated, and the system was used for validation of the mouse leg position within the field.

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. METHODS: The initial beamline geometry of the Mobetron was provided by the manufacturer, with the first-principal implementation realized in the Geant4-based GAMOS MC toolkit. The geometry and electron source characteristics, such as energy spectrum and beamline parameters, were tuned to match the central-axis percentage depth dose (PDD) and lateral profiles for the pristine beam measured during machine commissioning. The thickness of the small foil in secondary scatter affected the beam model dominantly and was fine tuned to achieve the best agreement with commissioning data. Validation of the MC beam modeling was performed by comparing the calculated PDDs and profiles with EBT-XD radiochromic film measurements for various combinations of applicators and inserts. RESULTS: The nominal 9 MeV electron FLASH beams were best represented by a Gaussian energy spectrum with mean energy of 9.9 MeV and variance (σ) of 0.2 MeV. Good agreement between the MC beam model and commissioning data were demonstrated with maximal discrepancy < 3% for PDDs and profiles. Hundred percent gamma pass rate was achieved for all PDDs and profiles with the criteria of 2 mm/3%. With the criteria of 2 mm/2%, maximum, minimum and mean gamma pass rates were (100.0%, 93.8%, 98.7%) for PDDs and (100.0%, 96.7%, 99.4%) for profiles, respectively. CONCLUSIONS: A validated MC beam model for the UHDR capable Mobetron is presented for the first time. The MC model can be utilized for direct dose calculation or to generate beam modeling input required for treatment planning systems for FLASH-RT planning. The beam model presented in this work should facilitate translational and clinical FLASH-RT for trials conducted on the Mobetron FLASH-IQ platform.

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. Additions to the air system allow for retraction of the x-ray target from the beamline when the 10 MV photon mode is selected. With the carousel set to an empty port, this grants access to the higher current pristine electron beam normally used to produce clinical photon fields. Monitoring signals related to the automatic frequency control system allows for tuning of the waveguide while the machine is in a hold state so a stable beam is produced from the initial pulse. A pulse counting system implemented on an field-programmable gate array-based controller platform controls the delivery to a desired number of pulses. Beam profiles were measured with Gafchromic film. Pulse-by-pulse dosimetry was measured using a custom electrometer designed around the EDGE diode. RESULTS: This method reliably produces a stable UHDR electron beam. Open-field measurements of the 16-cm full-width, half-maximum gaussian beam saw average dose rates of 432 Gy/s at treatment isocenter. Pulse overshoots were limited and ramp up was eliminated. Over the last year, there have been no recorded incidents that resulted in machine downtime due to the UHDR conversions. CONCLUSIONS: Stable 10 MeV UHDR beams were generated to produce an average dose rate of 432 Gy/s at the treatment room isocenter. With a reliable pulse-counting beam control system, consistent doses can be delivered for FLASH experiments with the ability to accommodate a wide range of field sizes, source-to-surface distances, and other experimental apparatus that may be relevant for future clinical translation.

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

Objective. 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.Approach. Conventional and UHDR pencil beam scanning (PBS) PT irradiation of freshex vivoporcine tissue and tissue-mimicking plastic phantom was imaged using intensified complementary metal-oxide-semiconductor(CMOS) cameras. The optical emission from tissue was characterized during conventional irradiation using both blue and red-sensitive intensifiers to ensure adequate spectral coverage. Spectral characterization was performed using bandpass filters between the lens and sensor. Imaging of conventional proton fields (240 MeV, 10 nA) was performed at 100 Hz frame rate, while UHDR PBS proton delivery (250 MeV, 99 nA) was recorded at 1 kHz frame rate. Dependence of optical emission yield on proton energy was studied using an optical tissue-mimicking plastic phantom and a range shifter. Finally, we demonstrated fast beam tracking capability of fast camera towardsin vivomonitoring of FLASH PT.Main results. Under conventional treatment dose rates optical emission was imaged with single spot resolution. Spot profiles were found to agree with the treatment planning system calculation within >90% for all spectral bands and spot intensity was found to vary with spectral filtration. The resultant polychromatic emission presented a maximum intensity at 650 nm and decreasing signal at lower wavelengths, which is consistent with expected attenuation patterns of high fat and muscle tissue. For UHDR beam imaging, optical yield increased with higher proton energy. Imaging at 1 kHz allowed continuous monitoring of delivery during porcine tissue irradiation, with clear identification of individual dwell positions. The number of dwell positions matched the treatment plan in total and per row showing adequate temporal capability of iCMOS imaging.Significance. For the first time, this study characterizes optical emission from tissue during PT and demonstrates our capability of fast optical tracking of pencil proton beam on the tissue anatomy in both conventional and UHDR setting. Similar to the Cherenkov imaging in radiotherapy, this imaging modality could enable a seamless, independent validation of PT treatments.

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. However, this technique only provides two-dimensional information; crucial depth information, such as the location of malignancy below the tissue surface, is not provided. Aim: We developed a depth sensing imaging technique using light detection and ranging (LiDAR) time-of-flight (TOF) technology to sense the depth of target tissue while overcoming the influence of tissue optical properties and fluorescent probe concentration. Approach: The technology is based on a large-format (512×512 pixel), binary, gated, single-photon avalanche diode (SPAD) sensor with an 18 ps time-gate step, synchronized with a picosecond pulsed laser. The fast response of the sensor was developed and tested for its ability to quantify fluorescent inclusions at depth and optical properties in tissue-like phantoms through analytical model fitting of the fast temporal remission data. Results: After calibration and algorithmic extraction of the data, the SPAD LiDAR technique allowed for sub-mm resolution depth sensing of fluorescent inclusions embedded in tissue-like phantoms, up to a maximum of 5 mm in depth. The approach provides robust depth sensing even in the presence of variable tissue optical properties and separates the effects of fluorescence depth from absorption and scattering variations. Conclusions: LiDAR TOF fluorescence imaging using an SPAD camera provides both fluorescence intensity images and the temporal profile of fluorescence, which can be used to determine the depth at which the signal is emitted over a wide field of view. The proposed tool enables fluorescence imaging at a higher depth in tissue and with higher spatial precision than standard, steady-state fluorescence imaging tools, such as intensity-based near-infrared fluorescence imaging, optical coherence tomography, Raman spectroscopy, or confocal microscopy. Integration of this technique into a standard surgical tool could enable rapid, more accurate estimation of resection boundaries, thereby improving the surgeon's efficacy and efficiency, and ultimately improving patient outcomes.

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

Objective. 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.Approach. Imaging parameters were probed by acquiring triggering data Cherenkov image frames for simplistic beams on the Halcyon and comparing the analyzed metrics with those from the TrueBeam platform. Camera position was analyzed by performing 3D rendering of patient treatment plans for various sites and iterating over camera positions to assess treatment area visibility.Main results. Commercial Cherenkov imaging systems are compatible with the pulse timing of the Halcyon, and this platform design favorably impacts signal to noise in Cherenkov image frames. Additionally, ideal camera placement is treatment site dependent and is always within a biconical zone of visibility centered on the isocenter. Visibility data is provided for four treatment sites, with suggestions for camera placement based on room dimensions. Median visibility values were highest for right breast plans, with values of 80.33% and 68.49% for the front and rear views respectively. Head and neck plans presented with the lowest values at 26.44% and 38.18% respectively.Significance. This work presents the first formal camera positional analysis for Cherenkov imaging on any platform and serves as a template for performing similar work for other irradiation platforms. Additionally, this study confirms the Cherenkov imaging parameters do not need to be changed for optimal imaging on the Halcyon. Lastly, the presented methodology provides a framework which could be further expanded to other optical imaging systems which rely on line of sight visibility to the patient.

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. Normal skin damage was tracked by clinical observation to determine the time to moist desquamation, an endpoint which was verified by histopathology. Tumors were inoculated on the right flank of the mice, then received UHDR-RT or CONV-RT at 1 × 11 Gy, 1 × 15, 1 × 25, 3 × 6 and 3 × 8 Gy, and time to tumor tripling volume was determined. Tumors also received 1 × 11, 1 × 15, 3 × 6 and 3 × 8 Gy doses for assessment of CD8+/CD4+ tumor infiltrate and genetic expression 96 h postirradiation. All irradiations of the mouse tumor or flank skin were performed with megavoltage electron beams (10 MeV, 270 Gy/s for UHDR-RT and 9 MeV, 0.12 Gy/s for CONV-RT) delivered via a clinical linear accelerator. Tumor control was statistically equal for similar doses of UHDR-RT and CONV-RT in B16F10 and GL261 murine tumors. There were variable qualitative differences in genetic expression of immune and cell damage-associated pathways between UHDR and CONV irradiated B16F10 tumors. Compared to CONV-RT, UHDR-RT resulted in an increased latent period to skin desquamation after a single 25 Gy dose (7 days longer). Time to moist skin desquamation did not significantly differ between UHDR-RT and CONV-RT after a 30 Gy dose. The histomorphological characteristics of skin damage were similar for UHDR-RT and CONV-RT. These studies demonstrated similar tumor control responses for equivalent single and fractionated radiation doses, with variable difference in expression of tumor progression and immune related gene pathways. There was a modest UHDR-RT skin sparing effect after a 1 × 25 Gy dose but not after a 1 × 30 Gy dose.

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. METHODS: Dose linearity, mean dose rate, and dose per pulse dependencies of the EDGE Detector were quantified and compared with dosimeters including a W1 scintillator detector, radiochromic film, and ionization chamber that were irradiated with a 10 MeV UHDR beam. The dose, dose rate, and dose per pulse were controlled via an in-house developed scintillation-based feedback mechanism, repetition rate of the linear accelerator, and source-to-surface distance, respectively. Depth-dose profiles and temporal profiles at individual pulse resolution were compared to the film and scintillation measurements, respectively. The radiation-induced change in response sensitivity was quantified via irradiation of ∼5kGy. RESULTS: The EDGE Detector agreed with film measurements in the measured range with varying dose (up to 70 Gy), dose rate (nearly 200 Gy/s), and dose per pulse (up to 0.63 Gy/pulse) on average to within 2%, 5%, and 1%, respectively. The detector also agreed with W1 scintillation detector on average to within 2% for dose per pulse (up to 0.78 Gy/pulse). The EDGE Detector signal was proportional to ion chamber (IC) measured dose, and mean dose rate in the bremsstrahlung tail to within 0.4% and 0.2% respectively. The EDGE Detector measured percent depth dose (PDD) agreed with film to within 3% and per pulse output agreed with W1 scintillator to within -6% to +5%. The radiation-induced response decrease was 0.4% per kGy. CONCLUSIONS: The EDGE Detector demonstrated dose linearity, mean dose rate independence, and dose per pulse independence for UHDR electron beams. It can quantify the beam spatially, and temporally at sub millisecond resolution. It's robustness and individual pulse detectability of treatment deliveries can potentially lead to its implementation for in vivo FLASH dosimetry, and dose monitoring.

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. Fluorescence-guided surgery and molecularly-guided surgery could be used to evaluate the viability of bone and soft tissue and detect the presence of planktonic and biofilm-forming bacteria. This proceedings paper discusses the motivation behind developing this technology and our most recent preclinical and clinical results.

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. Spectroscopic interpretation of this effects may help to better relate Cherenkov emission to ionizing radiation dose delivered during radiotherapy. Aim: In this study, we examined how color Cherenkov imaging intensity variations are caused by absorption from both melanin and hemoglobin level variations, so that future Cherenkov emission imaging might be corrected for linearity to delivered dose. Approach: A custom, time-gated, three-channel intensified camera was used to image the red, green, and blue wavelengths of Cherenkov emission from tissue phantoms with synthetic melanin layers and varying blood concentrations. Our hypothesis was that spectroscopic separation of Cherenkov emission would allow for the identification of attenuated signals that varied in response to changes in blood content versus melanin content, because of their different characteristic absorption spectra. Results: Cherenkov emission scaled with dose linearly in all channels. Absorption in the blue and green channels increased with increasing oxy-hemoglobin in the blood to a greater extent than in the red channel. Melanin was found to absorb with only slight differences between all channels. These spectral differences can be used to derive dose from measured Cherenkov emission. Conclusions: Color Cherenkov emission imaging may be used to improve the optical measurement and determination of dose delivered in tissues. Calibration for these factors to minimize the influence of the tissue types and skin tones may be possible using color camera system information based upon the linearity of the observed signals.

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

Objective.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.Approach.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 (R2> 0.9922) dose response of a single spot beam to varying currents. Film taken for the single spot beam was used to produce a scintillation intensity to absolute dose calibration.Main results. Spatial alignment was confirmed with the film, where thexandy-profiles of the single spot cumulative image agreed within 1 mm. A sample brain patient plan was analyzed to demonstrate dose and temporal accuracy for a clinically-relevant plan, through agreement within 1 mm to the planned and delivered spot locations. The cumulative dose agreed with the planned dose with a gamma passing rate of 97.5% (2 mm/3%, 10% dose threshold).Significance. This is the first system able to capture single-pulse spatial and temporal information for the unique pulse structure of a synchrocyclotron PBS systems at conventional dose rates, enabled by the ultra-fast sampling frame rate of this camera. This study indicates that, with continued camera development and testing, target applications in clinical and FLASH proton beam characterization and validation are possible.

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. The team scored the categories of severity magnitude, occurrence likelihood, and detectability potential in a scale of 1 to 10, so that a risk priority number (RPN = severity×occurrence×detectability) could be assessed for each. RESULTS: A total of 46 potential failure modes were identified, including 5 with an RPN >100. These failure modes involved (1) patient set up, (2) gating mechanisms in delivery, and (3) detector in the beam stop mechanism. The identified methods to mitigate errors included the (1) use of a checklist post conversion, (2) use of robust radiation detectors, (3) automation of quality assurance and beam consistency checks, and (4) implementation of surface guidance during beam delivery. CONCLUSIONS: The failure mode and effects analysis process was considered critically important in this setting of a new use of a LINAC, and the expert team developed a higher level of confidence in the ability to safely move UHDR LINAC use toward expanded research access.

One Year of Clinic-Wide Cherenkov Imaging for Discovery of Quality Improvement Opportunities in Radiation Therapy.

PURPOSE: Cherenkov imaging is clinically available as a radiation therapy treatment verification tool. The aim of this work was to discover the benefits of always-on Cherenkov imaging as a novel incident detection and quality improvement system through review of all imaging at our center. METHODS AND MATERIALS: Multicamera Cherenkov imaging systems were permanently installed in 3 treatment bunkers, imaging continuously over a year. Images were acquired as part of normal treatment procedures and reviewed for potential treatment delivery anomalies. RESULTS: In total, 622 unique patients were evaluated for this study. We identified 9 patients with treatment anomalies occurring over their course of treatment, which were only detected with Cherenkov imaging. Categorizing each event indicated issues arising in simulation, planning, pretreatment review, and treatment delivery, and none of the incidents were detected before this review by conventional measures. The incidents identified in this study included dose to unintended areas in planning, dose to unintended areas due to positioning at treatment, and nonideal bolus placement during setup. CONCLUSIONS: Cherenkov imaging was shown to provide a unique method of detecting radiation therapy incidents that would have otherwise gone undetected. Although none of the events detected in this study reached the threshold of reporting, they identified opportunities for practice improvement and demonstrated added value of Cherenkov imaging in quality assurance programs.

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. PpIX is endogenously synthesized by mitochondria in most tissues, and the particular property of DF emission is directly related to low microenvironmental oxygen concentration. Here, it is shown that PpIX has a unique emission in hypoxic tumor tissue regions, which is measured as a DF signal in the red to near-infrared spectrum. Approach: A time-gated imaging system was used for PpIX DF for wide field direct mapping of pO2 changes. Acquiring both prompt and DF in a rapid sequential cycle allowed for imaging oxygenation in a way that was insensitive to the PpIX concentration. By choosing adequate parameters, the video rate acquisition of pO2 images could be achieved, providing real-time tissue metabolic information. Results: In this report, we show the first demonstration of imaging hypoxia signals from PpIX in a pancreatic cancer model, exhibiting >5X contrast relative to surrounding normal oxygenated tissues. Additionally, tissue palpation amplifies the signal and provides intuitive temporal contrast based upon neoangiogenic blood flow differences. Conclusions: PpIX DF provides a mechanism for tumor contrast that could easily be translated to human use as an intrinsic contrast mechanism for oncologic surgical guidance.

Clinical implementation of the first Cherenkov imaging system in a community-based hospital.

Purpose: To document experiences with one year of clinical implementation of the first Cherenkov imaging system and share the methods that we developed to utilize Cherenkov imaging to improve treatment delivery accuracy in real-time. Methods: A Cherenkov imaging system was installed commissioned and calibrated for clinical use. The optimal room lighting conditions and imaging setup protocols were developed to optimize both image quality and patient experience. The Cherenkov images were analyzed for treatment setup and beam delivery verification. Results: We have successfully implemented a clinical Cherenkov imaging system in a community-based hospital. Several radiation therapy patient setup anomalies were found in 1) exit dose to the contralateral breast, 2) dose to the chin due to head rotation for a supraclavicular field, 3) intrafractional patient motion during beam delivery, and 4) large variability (0.5 cm to 5 cm) in arm position between fractions. The system was used to deliver deep inspiration breath hold (DIBH) treatment delivery of an electron treatment beam. Clinical process and procedures were improved to mitigate the identified issues to ensure treatment delivery safety and to improve treatment accuracy. Conclusion: The Cherenkov imaging system has proven to be a valuable clinical tool for the improvement of treatment delivery safety and accuracy at our hospital. With only minimal training the therapists were able to adjust or correct treatment positions during treatment delivery as needed. With future Cherenkov software developments Cherenkov imaging systems could provide daily surface guided radiotherapy (SGRT) and real time treatment delivery quality control for all 3D and clinical setup patients without adding additional radiation image dose as in standard kV, MV and CBCT image verifications. Cherenkov imaging can greatly improve clinical efficiency and accuracy, making real time dose delivery consistency verification and SGRT a reality.

Computational dose visualization & comparison in total skin electron treatment suggests superior coverage by the rotational versus the Stanford technique.

INTRODUCTION/BACKGROUND: The goal of Total Skin Electron Therapy (TSET) is to achieve a uniform surface dose, although assessment of this is never really done and typically limited points are sampled. A computational treatment simulation approach was developed to estimate dose distributions over the body surface, to compare uniformity of (i) the 6 pose Stanford technique and (ii) the rotational technique. METHODS: The relative angular dose distributions from electron beam irradiation was calculated by Monte Carlo simulation for cylinders with a range of diameters, approximating body part curvatures. These were used to project dose onto a 3D body model of the TSET patient's skin surfaces. Computer animation methods were used to accumulate the dose values, for display and analysis of the homogeneity of coverage. RESULTS: The rotational technique provided more uniform coverage than the Stanford technique. Anomalies of under dose were observed in lateral abdominal regions, above the shoulders and in the perineum. The Stanford technique had larger areas of low dose laterally. In the rotational technique, 90% of the patient's skin was within ±10% of the prescribed dose, while this percentage decreased to 60% or 85% for the Stanford technique, varying with patient body mass. Interestingly, the highest discrepancy was most apparent in high body mass patients, which can be attributed to the loss of tangent dose at low angles of curvature. DISCUSSION/CONCLUSION: This simulation and visualization approach is a practical means to analyze TSET dose, requiring only optical surface body topography scans. Under- and over-exposed body regions can be found, and irradiation could be customized to each patient. Dose Area Histogram (DAH) distribution analysis showed the rotational technique to have better uniformity, with most areas within 10% of the umbilicus value. Future use of this approach to analyze dose coverage is possible as a routine planning tool.

Performance comparison of quantitative metrics for analysis of in vivo Cherenkov imaging incident detection during radiotherapy.

OBJECTIVES: Examine the responses of multiple image similarity metrics to detect patient positioning errors in radiotherapy observed through Cherenkov imaging, which may be used to optimize automated incident detection. METHODS: An anthropomorphic phantom mimicking patient vasculature, a biological marker seen in Cherenkov images, was simulated for a breast radiotherapy treatment. The phantom was systematically shifted in each translational direction, and Cherenkov images were captured during treatment delivery at each step. The responses of mutual information (MI) and the γ passing rate (%GP) were compared to that of existing field-shape matching image metrics, the Dice coefficient, and mean distance to conformity (MDC). Patient images containing other incidents were analyzed to verify the best detection algorithm for different incident types. RESULTS: Positional shifts in all directions were registered by both MI and %GP, degrading monotonically as the shifts increased. Shifts in intensity, which may result from erythema or bolus-tissue air gaps, were detected most by %GP. However, neither metric detected beam-shape misalignment, such as that caused by dose to unintended areas, as well as currently employed metrics (Dice and MDC). CONCLUSIONS: This study indicates that different radiotherapy incidents may be detected by comparing both inter- and intrafractional Cherenkov images with a corresponding image similarity metric, varying with the type of incident. Future work will involve determining appropriate thresholds per metric for automatic flagging. ADVANCES IN KNOWLEDGE: Classifying different algorithms for the detection of various radiotherapy incidents allows for the development of an automatic flagging system, eliminating the burden of manual review of Cherenkov images.