Radiation hardness of open Fabry-Pérot microcavities.

High-finesse microcavities offer a platform for compact, high-precision sensing by employing high-reflectivity, low-loss mirrors to create effective optical path lengths that are orders of magnitude larger than the device geometry. Here, we investigate the radiation hardness of Fabry-Pérot microcavities formed from dielectric mirrors deposited on the tips of optical fibers. The microcavities are irradiated under both conventional (∼ 0.1 Gy/s) and ultrahigh (FLASH, ∼ 20 Gy/s) radiotherapy dose rates. Within our measurement sensitivity of ∼ 40 ppm loss, we observe no degradation in the mirror absorption after irradiation with over 300 Gy accumulated dose. This result highlights the excellent radiation hardness of the dielectric mirrors forming the cavities, enabling new optics-based, real-time, in-vivo, tissue-equivalent radiation dosimeters with ∼ 10 micron spatial resolution (our motivation), as well as other applications in high-radiation environments.

Development of a hydrated electron dosimeter for radiotherapy applications: A proof of concept.

BACKGROUND: Hydrated electrons, which are short-lived products of radiolysis in water, increase the optical absorption of water, providing a pathway toward near-tissue-equivalent clinical radiation dosimeters. This has been demonstrated in high-dose-per-pulse radiochemistry research, but, owing to the weak absorption signal, its application in existing low-dose-per-pulse radiotherapy provided by clinical linear accelerators (linacs) has yet to be investigated. PURPOSE: The aims of this study were to measure the optical absorption associated with hydrated electrons produced by clinical linacs and to assess the suitability of the technique for radiotherapy (⩽ 1 cGy per pulse) applications. METHODS: 40 mW of 660-nm laser light was sent five passes through deionized water contained in a 10 × 4 × $\times 4\times$ 2 cm3 glass-walled cavity by using four broadband dielectric mirrors, two on each side of the cavity. The light was collected with a biased silicon photodetector. The water cavity was then irradiated by a Varian TrueBeam linac with both photon (10 MV FFF, 6 MV FFF, 6 MV) and electron beams (6 MeV) while monitoring the transmitted laser power for absorption transients. Radiochromic EBT3 film measurements were also performed for comparison. RESULTS: Examination of the absorbance profiles showed clear absorption changes in the water when radiation pulses were delivered. Both the amplitude and the decay time of the signal appeared consistent with the absorbed dose and the characteristics of the hydrated electrons. By using literature value for the hydrated electron radiation chemical yield (3.0±0.3), we inferred doses of 2.1±0.2 mGy (10 MV FFF), 1.3±0.1 mGy (6 MV FFF), 0.45±0.06 mGy (6 MV) for photons, and 0.47±0.05 mGy (6 MeV) for electrons, which differed from EBT3 film measurements by 0.6%, 0.8%, 10%, and 15.7%, respectively. The half-life of the hydrated electrons in the solution was ∼ 24 µ $\umu$ s. CONCLUSIONS: By measuring 660-nm laser light transmitted through a cm-scale, multi-pass water cavity, we observed absorption transients consistent with hydrated electrons generated by clinical linac radiation. The agreement between our inferred dose and EBT3 film measurements suggests this proof-of-concept system represents a viable pathway toward tissue-equivalent dosimeters for clinical radiotherapy applications.

Effects of incoming particle energy and cluster size on the G-value of hydrated electrons.

In hydrated electron (e-aq) dosimetry, absorbed radiation dose to water is measured by monitoring the concentration of radiation-induced e-aq. However, to obtain accurate dose, the radiation chemical yield of e-aq, G(e-aq), is needed for the radiation quality/setup under investigation. The aim of this study was to investigate the time-evolution of the G-values for the main generated reactive species during water radiolysis using GEANT4-DNA. The effects of cluster size and linear energy transfer (LET) on G(e-aq) were examined. Validity of GEANT4-DNA for calculation of G(e-aq) for clinically relevant energies was studied. Three scenarios were investigated with different phantom sizes and incoming electron energies (1 keV to 1 MeV). The time evolution of G(e-aq) was in good agreement with published data and did not change with decreasing phantom size. The time-evolution of the G-values increases with increasing LET for all radiolytic species. The particle tracks formed with high-energy electrons are separated and the resulting reactive species develop independently in time. With decreasing energy, the mean separation distance between reactive species decreases. The particle tracks might not initially overlap but will overlap shortly thereafter due to diffusion of reactive species, increasing the probability of e-aq recombination with other species. This also explains the decrease of G(e-aq) with cluster size and LET. Finally, if all factors are kept constant, as the incoming electron energy increases to clinically relevant energies, G(e-aq) remains similar to its value at 1 MeV, hence GEANT4-DNA can be used for clinically relevant energies.

Positional and angular tracking of HDR 192 Ir source for brachytherapy quality assurance using radiochromic film dosimetry.

PURPOSE: To quantify and verify the dosimetric impact of high-dose rate (HDR) source positional uncertainty in brachytherapy, and to introduce a model for three-dimensional (3D) position tracking of the HDR source based on a two-dimensional (2D) measurement. This model has been utilized for the development of a comprehensive source quality assurance (QA) method using radiochromic film (RCF) dosimetry including assessment of different digitization uncertainties. METHODS: An algorithm was developed and verified to generate 2D dose maps of the mHDR-V2 192 Ir source (Elekta, Veenendaal, Netherlands) based on the AAPM TG-43 formalism. The limits of the dosimetric error associated with source (0.9 mm diameter) positional uncertainty were evaluated and experimentally verified with EBT3 film measurements for 6F (2.0 mm diameter) and 4F (1.3 mm diameter) size catheters at the surface (4F, 6F) and 10 mm further (4F only). To quantify this uncertainty, a source tracking model was developed to incorporate the unique geometric features of all isodose lines (IDLs) within any given 2D dose map away from the source. The tracking model normalized the dose map to its maximum, then quantified the IDLs using blob analysis based on features such as area, perimeter, weighted centroid, elliptic orientation, and circularity. The Pearson correlation coefficients (PCCs) between these features and source coordinates (x, y, z, θy , θz ) were calculated. To experimentally verify the accuracy of the tracking model, EBT3 film pieces were positioned within a Solid Water® (SW) phantom above and below the source and they were exposed simultaneously. RESULTS: The maximum measured dosimetric variations on the 6F and 4F catheter surfaces were 39.8% and 36.1%, respectively. At 10 mm further, the variation reduced to 2.6% for the 4F catheter which is in agreement with the calculations. The source center (x, y) was strongly correlated with the low IDL-weighted centroid (PCC = 0.99), while the distance to source (z) was correlated with the IDL areas (PCC = 0.96) and perimeters (PCC = 0.99). The source orientation θy was correlated with the difference between high and low IDL-weighted centroids (PCC = 0.98), while θz was correlated with the elliptic orientation of the 60-90% IDLs (PCC = 0.97) for a maximum distance of z = 5 mm. Beyond 5 mm, IDL circularity was significant, therefore limiting the determination of θz (PCC ≤ 0.48). The measured positional errors from the film sets above and below the source indicated a source position at the bottom of the catheter (-0.24 ± 0.07 mm). CONCLUSIONS: Isodose line features of a 2D dose map away from the HDR source can reveal its spatial coordinates. RCF was shown to be a suitable dosimeter for source tracking and dosimetry. This technique offers a novel source QA method and has the potential to be used for QA of commercial and customized applicators.

Dose-response linearization in radiochromic film dosimetry based on multichannel normalized pixel value with an integrated spectral correction for scanner response variations.

PURPOSE: To introduce a model that reproducibly linearizes the response from radiochromic film (RCF) dosimetry systems at extended dose range. To introduce a correction method, generated from the same scanned images, which corrects for scanner temporal response variation and scanner bed inhomogeneity. METHODS: Six calibration curves were established for different lot numbers of EBT3 GAFCHROMIC™ film model based on four EPSON scanners [10000XL (2 units), 11000XL, 12000XL] at three different centers. These films were calibrated in terms of absorbed dose to water based on TG51 protocol or TRS398 with dose ranges up to 40 Gy. The film response was defined in terms of a proposed normalized pixel value ( n P V RGB ) as a summation of first-order equations based on information from red, green, and blue channels. The fitting parameters of these equations are chosen in a way that makes the film response equal to dose at the time of calibration. An integrated set of correction factors (one per color channel) was also introduced. These factors account for the spatial and temporal changes in scanning states during calibration and measurements. The combination of n P V RGB and this "fingerprint" correction formed the basis of this new protocol and it was tested against net optical density ( n e t O D X = R , G , B ) single-channel dosimetry in terms of accuracy, precision, scanner response variability, scanner bed inhomogeneity, noise, and long-term stability. RESULTS: Incorporating multichannel features (RGB) into the normalized pixel value produced linear response to absorbed dose (slope of 1) in all six RCF dosimetry systems considered in this study. The "fingerprint" correction factors of each of these six systems displayed unique patterns at the time of calibration. The application of n P V RGB to all of these six systems could achieve a level of accuracy of ± 2.0% in the dose range of interest within modeled uncertainty level of 2.0%-3.0% depending on the dose level. Consistent positioning of control and measurement film pieces and integrating the multichannel correction into the response function formalism mitigated possible scanner response variations of as much as ± 10% at lower doses and scanner bed inhomogeneity of ± 8% to the established level of uncertainty at the time of calibration. The system was also able to maintain the same level of accuracy after 3 and 6 months post calibration. CONCLUSIONS: Combining response linearity with the integrated correction for scanner response variation lead to a sustainable and practical RCF dosimetry system that mitigated systematic response shifts and it has the potential to reduce errors in reporting relative information from the film response.

Dose measurements nearby low energy electronic brachytherapy sources using radiochromic film.

PURPOSE: We investigate the effect of the GafChromic™ film EBT3 model absorbed dose energy response when used for dose measurements around low-energy photon sources. Monte Carlo based correction procedure in synergy with appropriate calibration curves was shown to provide more accurate absorbed dose (either relative or absolute). An assessment was made of possible dose errors that might be encountered if such energy dependent response is ignored. METHODS: We measured PDDs in water from a Xoft 50 kVp source using EBT3 film, and compared to PDD measurements acquired with a PTW-TN34013 parallel-plate ionization chamber. For the x-ray source, we simulated spectra using the EGSnrc (BEAMnrc) Monte Carlo code, and calculated Half Value Layer (HVL) at different distances from the source in water. Measurement strips of EBT3 film were positioned at distances of 2-6 cm from the Xoft source in a water phantom using a custom-made holder and irradiated simultaneously. RESULTS: Our results show that film calibration curves obtained at beam qualities near the effective energy of the Xoft 50 kVp source in water lead to variation in absorbed dose energy dependence of the response of around 5%. However, if the calibration curve was established in an MV beam quality, the error in absorbed dose could be as large as 20%. CONCLUSION: Accurate dose measurements using radiochromic films at low photon energies require that the radiochromic film dosimetry system be calibrated at appropriate corresponding low energies, as large absorbed dose errors are expected when film calibration is performed in MV beam qualities.

Monte Carlo simulations of different CT X-ray energy spectra within CTDI phantom and the influence of its changes on radiochromic film measurements.

PURPOSE: In this work we use Monte Carlo simulations to investigate change in Computed tomography (CT) X-ray energy spectra between exposures in air and within CT dose index (CTDI) phantom. While the results of these simulations will be relevant when measuring CTDI with any dosimeter, we apply the appropriate beam quality change correction for CTDI measurements using XR-QA2 model GafChromic™ film. METHODS: Dose profiles were measured with film strips, sandwiched between acrylic rods cut in half, placed within CTDI phantoms and scanned before and after irradiation with document scanner in reflective mode. Reference dosimetry system was calibrated in terms of air kerma in air, which was converted into absorbed dose using ratio of mass-energy absorption coefficients water-to-air for a given beam quality, following the AAPM TG-61 protocol. RESULTS: Beam qualities for all film positions within CTDI phantom show beam softening for HVLs above 6 mm Al and beam hardening for HVLs bellow 6 mm Al. Calculated CTDI values using HVL in air for all CTDI positions, and those calculated using the appropriate calibration curves based on beam quality correction show for Head CTDI phantom differences ranging from 0.3% to 2.1% and for Body CTDI phantom from 2.5% to 5.7%. CONCLUSIONS: We describe method for CTDI measurements using radiochromic film dosimetry protocol corrected by the beam quality change within the phantom. Our results show differences in CTDI measurements of up to 5.7% when compared to using film calibration curves for beam quality in air.

Optimization of HDRBT boost dose delivery for patients with rectal cancer.

PURPOSE: We describe methods to improve dose delivery for patients with rectal cancer receiving boost brachytherapy after external beam radiotherapy. METHODS AND MATERIALS: Patients with rectal cancer who were ineligible or refusing surgery are treated with external beam radiotherapy and subsequently with three weekly image-guided volume-adapted high-dose-rate brachytherapy boosts of 10 Gy to the residual clinical target volume, for a total of 30 Gy in three fractions. Tungsten shielding placed at the center of intracavitary mold applicator and double-balloon technique was used to improve dose conformity to the target. RESULTS: Our results show that the use of tungsten shield and double balloon reduces the dose gradient within the target volume to receive the prescription boost dose of 10 Gy from maximum dose of 60 Gy down to 20 Gy. CONCLUSIONS: We outlined two methods for achieving higher high-dose-rate brachytherapy dose conformity using the tungsten shielding rods (to spare contralateral healthy tissues) and double-balloon technique (to decrease dose gradient within the target to minimize dose to the proximal mucosa).

An investigation into the INTRABEAM miniature x-ray source dosimetry using ionization chamber and radiochromic film measurements.

PURPOSE: Intraoperative radiotherapy using The INTRABEAM System (Carl Zeiss Meditec AG, Jena, Germany), a miniature low-energy x-ray source, has proven to be an effective modality in the treatment of breast cancer. However, some uncertainties remain in its dosimetry. In this work, we investigated the INTRABEAM system dosimetry by performing ionization chamber and radiochromic film measurements of absorbed dose in a water phantom. METHODS: Ionization chamber measurements were performed with a PTW 34013 parallel-plate soft x-ray chamber at source to detector distances of 5 to 30 mm calculated using (a) the dose formula consistent with the TARGIT breast protocol (TARGIT), (b) the formula recommended by the manufacturer (Zeiss), and (c) the recently proposed CQ formalism of Watson et al. (Physics in Medicine & Biology, 2018;63:015016) EBT3 Gafchromic film measurements were made at the same depths in water. To account for the energy dependence of EBT3 film, multiple dose response calibration curves were employed across a range of photon beam qualities relevant to the INTRABEAM spectrum in water. RESULTS: At all depths investigated, the TARGIT dose was significantly lower than that measured by the Zeiss and CQ methods, as well as film. These dose differences ranged from 14% to as large as 80%. In general, the doses measured by film, and the Zeiss and CQ methods were in good agreement to within measurement uncertainties (5-6%). CONCLUSIONS: These results suggest that the TARGIT dose underestimates the physical dose to water from the INTRABEAM source. Understanding the correlation between the TARGIT and physical dose is important for any studies wishing to make dosimetric comparisons between the INTRABEAM and other radiation emitting devices.

Physics aspects of the Papillon technique-Five decades later.

PURPOSE: The Papillon technique using 50-kVp soft X-rays to treat rectal adenocarcinomas was developed and clinically implemented in the 1960s. We describe differences between accurate dosimetry and clinical implementation of this technique that is extending from its very inception to date. METHODS AND MATERIALS: A renaissance of the Papillon technique occurred with two recently introduced 50-kVp systems: Papillon+ by Ariane and a custom-made rectal applicator (consisting of a surface applicator inserted into a proctoscope) by iCAD's Xoft Axxent Electronic Brachytherapy (eBT) System (iCad, Inc., Sunnyvale, CA). In contrast to the initial design, we investigated the impact of introducing a plastic lid, which would provide more reproducible and more accurate dose delivery across the rectal adenocarcinoma patient population. We use both parallel-plate chamber and radiochromic film dosimeters to determine differences in basic dosimetry characteristics (beam half-value layers, outputs, percent depth doses, and profiles) between the Xoft Electronic Brachytherapy rectal applicator system with and without the plastic lid in place. RESULTS: Compared to the open-cone applicator, the proposed applicator with the plastic lid produces a slightly harder (more penetrating) beam quality (half-value layer of 1.4 vs. 1.3-mm Al), but with reduced output (by 33%), and a slightly broader beam with flatness not worse than 3% and symmetry not worse than 2%. CONCLUSIONS: In addition to characterizing beam properties modified by the possible introduction of the plastic cap, we also pointed out and addressed misconceptions in the use of radiochromic films for dose measurements at low-energy photon beams.

Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen-sensitive prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high-risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next-generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy. METHODS: Using a number of androgen-dependent (LNCaP, PC3-T877A) and androgen-independent (C4-2, 22RV1, PC3, PC3-AR V7) cell lines, the effect of ENZA as a radiosensitizer was studied alone or in combination with ADT and/or XRT. Cell viability and cell survival were assessed, along with determination of cell cycle arrest, DNA damage response and repair, apoptosis and senescence. RESULTS: Our results indicated that either ENZA alone (in AR positive, androgen-dependent PCa cells) or in combination with ADT (in AR positive, hormone-insensitive PCa cells) potentiates radiation response [Dose enhancement factor (DEF) of 1.75 in LNCAP and 1.35 in C4-2] stronger than ADT + XRT conditions. Additionally, ENZA sensitized androgen dependent PCa cells to XRT in a schedule-dependent manner, where concurrent administration of ENZA and radiation lead to a maximal radiosensitization when compared to either drug administration prior or after XRT. In LNCaP cells, ENZA treatment significantly prolonged the presence of XRT-induced phospho-γH2AX up to 24 h after treatment; suggesting enhanced DNA damage. It also significantly increased XRT-induced apoptosis and senescence. CONCLUSIONS: Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ADT. We have also observed that its efficacy is schedule dependent and related to increased levels of DNA damage and a delay of DNA repair processes. Finally, the initial abrogation of DNA-PKcs activity by AR inhibition and its subsequent recovery might represent an important mechanism by which PCa cells acquire resistance to combined anti-androgen and XRT treatment. This work suggests a new use of ENZA in combination with XRT that could be applicable in clinical trial settings for patients with early and intermediate hormone responsive disease.

Dose comparison between TG-43-based calculations and radiochromic film measurements of the Freiburg flap applicator used for high-dose-rate brachytherapy treatments of skin lesions.

PURPOSE: Current high-dose-rate brachytherapy skin treatments with the Freiburg flap (FF) applicator are planned with treatment planning systems based on the American Association of Physicists in Medicine TG-43 data sets, which assume full backscatter conditions in dose calculations. The aim of this work is to describe an experimental method based on radiochromic film dosimetry to evaluate dose calculation accuracy during surface treatments with the FF applicator at different depths and bolus thicknesses. METHODS AND MATERIALS: Absolute doses were measured using a reference EBT3 radiochromic film dosimetry system within a Solid Water phantom at different depths (0, 0.5, 1, 2, and 3 cm) with respect to the phantom surface. The impact of bolus (up to 3-cm thickness) placed on top of the applicator was investigated for two clinical loadings created using Oncentra MasterPlan: 5 cm × 5 cm and 11 cm × 11 cm. RESULTS: For smaller loading and depths beyond 2 cm and for larger loading and depths beyond 1 cm, the dose difference was less than 3% (±4%). At shallower depths, differences of up to 6% (±4%) at the surface were observed if no bolus was added. The addition of 2-cm bolus for the smaller loading and 1 cm for larger loading minimized the difference to less than 3% (±4%). CONCLUSIONS: For typical FF applicator loading sizes, the actual measured dose was 6% (±4%) lower at the skin level when compared with TG-43. Additional bolus above the FF was shown to decrease the dose difference. The consideration of change in clinical practice should be carefully investigated in light of clinical reference data.

Dual-Energy CT: Balance Between Iodine Attenuation and Artifact Reduction for the Evaluation of Head and Neck Cancer.

OBJECTIVE: Dual-energy computed tomography high energy virtual monochromatic images (VMIs) can reduce artifact but suppress iodine attenuation in enhancing tumor. We investigated this trade-off to identify VMI(s) that strike the best balance between iodine detection and artifact reduction. METHODS: The study was performed using an Alderson radiation therapy phantom. Different iodine solutions (based on estimated tumor iodine content in situ using dual-energy computed tomography material decomposition) and different dental fillings were investigated. Spectral attenuation curves and quality index (QI: 1/SD) were evaluated. RESULTS: The relationship between iodine attenuation and QI depends on artifact severity and iodine concentration. For low to average concentration solutions degraded by mild to moderate artifact, the iodine attenuation and QI curves crossed at 95 keV. CONCLUSIONS: High energy VMIs less than 100 keV can achieve modest artifact reduction while preserving sufficient iodine attenuation and could represent a useful additional reconstruction for evaluation of head and neck cancer.

Radiochromic film-based quality assurance for CT-based high-dose-rate brachytherapy.

PURPOSE: In the past, film dosimetry was developed into a powerful tool for external beam radiotherapy treatment verification and quality assurance. The objective of this work was the development and clinical testing of the EBT3 model GafChromic film based brachytherapy quality assurance (QA) system. METHODS AND MATERIALS: Retrospective dosimetry study was performed to test a patient-specific QA system for preoperative endorectal brachytherapy that uses a radiochromic film dosimetry system. A dedicated phantom for brachytherapy applicator used for rectal cancer treatment was fabricated enabling us to compare calculated-to-measured dose distributions. Starting from the same criteria used for external beam intensity-modulated radiation therapy QA (3%, 3 mm), passing criteria for high- and low-dose gradient regions were subsequently determined. Finally, we investigated the QA system's sensitivity to controlled source positional errors on selected patient plans. RESULTS: In low-dose gradient regions, measured dose distributions with criteria of 3%, 3 mm barely passed the test, as they showed 95% passing pixels. However, in the high-dose gradient region, a more stringent condition could be established. Both criteria of 2%, 3 mm and 3%, 2 mm with gamma function calculated using normalization to the same absolute dose value in both measured and calculated dose distributions, and matrix sizes rescaled to match each other showed more than 95% of pixels passing, on average, for 15 patient plans analyzed. CONCLUSIONS: Although the necessity of the patient-specific brachytherapy QA needs yet to be justified, we described a radiochromic film dosimetry-based QA system that can be a part of the brachytherapy commissioning process, as well as yearly QA program.

Characterization of calibration curves and energy dependence GafChromic™ XR-QA2 model based radiochromic film dosimetry system.

PURPOSE: The authors investigated the energy response of XR-QA2 GafChromic™ film over a broad energy range used in diagnostic radiology examinations. The authors also made an assessment of the most suitable functions for both reference and relative dose measurements. METHODS: Pieces of XR-QA2 film were irradiated to nine different values of air kerma in air, following reference calibration of a number of beam qualities ranging in HVLs from 0.16 to 8.25 mm Al, which corresponds to effective energy range from 12.7 keV to 56.3 keV. For each beam quality, the authors tested three functional forms (rational, linear exponential, and power) to assess the most suitable function by fitting the delivered air kerma in air as a function of film response in terms of reflectance change. The authors also introduced and tested a new parameter χ = netΔR·e(m netΔR) that linearizes the inherently nonlinear response of the film. RESULTS: The authors have found that in the energy range investigated, the response of the XR-QA2 based radiochromic film dosimetry system ranges from 0.222 to 0.420 in terms of netΔR at K(air)(air) = 8 cGy. For beam qualities commonly used in CT scanners (4.03-8.25 mm Al), the variation in film response (netΔR at K(air)(air) = 8 cGy) amounts to ± 5%, while variation in K(air)(air) amounts to ± 14%. CONCLUSIONS: Results of our investigation revealed that the use of XR-QA2 GafChromic™ film is accompanied by a rather pronounced energy dependent response for beam qualities used for x-ray based diagnostic imaging purposes. The authors also found that the most appropriate function for the reference radiochromic film dosimetry would be the power function, while for the relative dosimetry one may use the exponential response function that can be easily linearized.