MRIgRT head and neck anthropomorphic QA phantom: Design, development, reproducibility, and feasibility study.

PURPOSE: The purpose of this paper was to design, manufacture, and evaluate a tissue equivalent, dual magnetic resonance/computed tomography (MR/CT) visible anthropomorphic head and neck (H&N) phantom. This phantom was specially designed as an end-to-end quality assurance (QA) tool for MR imaging guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials. METHOD: The MRIgRT H&N phantom was constructed using a water-fillable acrylic shell and a custom insert that mimics an organ at risk (OAR) and target structures. The insert consists of a primary and secondary planning target volume (PTV) manufactured of a synthetic Clear Ballistic gel, an acrylic OAR and surrounding tissue fabricated using melted Superflab. Radiochromic EBT3 film and thermoluminescent detectors (TLDs) were used to measure the dose distribution and absolute dose, respectively. The phantom was evaluated by conducting an end-to-end test that included: imaging on a GE Lightspeed CT simulator, planning on Monaco treatment planning software (TPS), verifying treatment setup with MR, and irradiating on Elekta's 1.5 T Unity MR linac system. The phantom was irradiated three times using the same plan to determine reproducibility. Three institutions, equipped with either ViewRay MRIdian 60 Co or ViewRay MRIdian Linac, were used to conduct a feasibility study by performing independent end-to-end studies. Thermoluminescent detectors were evaluated in both reproducibility and feasibility studies by comparing ratios of measured TLD to reported TPS calculated values. Radiochromic film was used to compare measured planar dose distributions to expected TPS distributions. Film was evaluated by using an in-house gamma analysis software to measure the discrepancies between film and TPS. RESULTS: The MRIgRT H&N phantom on the Unity system resulted in reproducible TLD doses (SD < 1.5%). The measured TLD to calculated dose ratios for the Unity system ranged from 0.94 to 0.98. The Viewray dose result comparisons had a larger range (0.95-1.03) but these depended on the TPS dose calculations from each site. Using a 7%/4 mm gamma analysis, Viewray institutions had average axial and sagittal passing rates of 97.3% and 96.2% and the Unity system had average passing rates of 97.8% and 89.7%, respectively. All of the results were within the Imaging and Radiation Oncology Core in Houston (IROC-Houston) standard credentialing criteria of 7% on TLDs, and >85% of pixels passing gamma analysis using 7%/4 mm on films. CONCLUSIONS: An MRIgRT H&N phantom that is tissue equivalent and visible on both CT and MR was developed. The results from initial reproducibility and feasibility testing of the MRIgRT H&N phantom using the tested MGIgRT systems suggests the phantom's potential utility as a credentialing tool for NCI-clinical trials.

MRIgRT dynamic lung motion thorax anthropomorphic QA phantom: Design, development, reproducibility, and feasibility study.

PURPOSE: To design, manufacture, and evaluate a dynamic magnetic resonance imaging/computed tomography (MRI/CT)-compatible anthropomorphic thorax phantom used to credential MR image-guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials. METHOD: The dynamic anthropomorphic thorax phantom was constructed from a water-fillable acrylic shell that contained several internal structures representing radiation-sensitive organs within the thoracic region. A custom MR/CT visible cylindrical insert was designed to simulate the left lung with a centrally located tumor target. The surrounding lung tissue was constructed from a heterogeneous in-house mixture using petroleum jelly and miniature (2-4 mm diameter) styrofoam balls and the tumor structure was manufactured from liquid PVC plastic. An MR conditional pneumatic system was developed to allow the MRIgRT insert to move in similar inhale/exhale motions. TLDs and radiochromic EBT3 film were inserted into the phantom to measure absolute point doses and dose distributions, respectively. The dynamic MRIgRT thorax phantom was evaluated through a reproducibility study and a feasibility study. Comprehensive end-to-end examinations were done where the phantom was imaged on a CT, an IMRT treatment plan was created and an MR image was captured to verify treatment setup. Then, the phantom was treated on an MRIgRT system. The reproducibility study evaluated how well the phantom could be reproduced in an MRIgRT system by irradiating three times on an Elekta's 1.5 T Unity system. The phantom was shipped to three independent institutions and was irradiated on either an MRIdian cobalt-60 (60 Co) or an MRIdian linear accelerator system. Treatment evaluations used TLDs and radiochromic film to compare the planned treatment reported on the treatment planning software against the measured dose on the dosimeters. RESULTS: The phantom on the Unity system had reproducible TLD doses measurements (SD < 1.5%). The measured TLD to calculated dose ratios from the reproducibility and feasibility studies ranged from 0.93 to 1.01 and 0.96 to 1.03, respectively. Using a 7%/5 mm gamma analysis criteria, the reproducibility and feasibility studies resulted in an average passing rate of 93.3% and 96.8%, respectively. No difference was noted in the results between the MRIdian 60 Co and MRIdian 6 MV linac delivery to the phantom and all treatment evaluations were within IROC-Houston's acceptable criterion. CONCLUSIONS: A dosimetrically tissue equivalent, CT/MR visible, motion-enabled anthropomorphic MRIgRT thorax phantom was constructed to simulate a lung cancer patient and was evaluated as an appropriate NIH credentialing tool used for MRIgRT systems.

Investigation of TLD and EBT3 performance under the presence of 1.5T, 0.35T, and 0T magnetic field strengths in MR/CT visible materials.

PURPOSE: The aim of this study was to investigate thermoluminescent dosimeters (TLD) and radiochromic EBT3 film inside MR/CT visible geometric head and thorax phantoms in the presence of: 0, 0.35, and 1.5 T magnetic fields. METHODS: Thermoluminescent Dosimeters reproducibility studies were examined by irradiating IROC-Houston's TLD acrylic block five times under 0 and 1.5 T configurations of Elekta's Unity system and three times under 0 and 0.35 T configurations of ViewRay's MRIdian Cobalt-60 (60 Co) system. Both systems were irradiated with an equivalent 10 × 10 cm2 field size, and a prescribed dose of 3 Gy to the maximum depth deposition (dmax). EBT3 film and TLDs were investigated using two geometrical Magnetic Resonance (MR)-guided Radiation Therapy (MRgRT) head and thorax phantoms. Each geometrical phantom had eight quadrants that combined to create a centrally located rectangular tumor (3 × 3 × 5 cm3 ) surrounded by tissue to form a 15 × 15 × 15 cm3 cubic phantom. Liquid polyvinyl chloride plastic and Superflab were used to simulate the tumor and surrounding tissue in the head phantom, respectively. Synthetic ballistic gel and a heterogeneous in-house mixture were used to construct the tumor and surrounding tissue in the thorax phantom, respectively. EBT3 and double-loaded TLDs were used in the phantoms to compare beam profiles and point dose measurements with and without magnetic fields. GEANT4 Monte Carlo simulations were performed to validate the detectors for both Unity 0 T/1.5 T and MRIdian 0 T/0.35 T configurations. RESULTS: Average TLD block measurements which, compared the magnetic field effects (magnetic field vs 0 T) on the Unity and MRIdian systems, were 0.5% and 0.6%, respectively. The average ratios between magnetic field effects for the geometric thorax and head phantoms under the Unity system were -0.2% and 1.6% and for the MRIdian system were 0.2% and -0.3%, respectively. Beam profiles generated with both systems agreed with Monte Carlo measurements and previous literature findings. CONCLUSIONS: TLDs and EBT3 film dosimeters could potentially be used in MR/CT visible tissue equivalent phantoms that will experience a magnetic field environment.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Comparing stochastic proton interactions simulated using TOPAS-nBio to experimental data from fluorescent nuclear track detectors.

Whilst Monte Carlo (MC) simulations of proton energy deposition have been well-validated at the macroscopic level, their microscopic validation remains lacking. Equally, no gold-standard yet exists for experimental metrology of individual proton tracks. In this work we compare the distributions of stochastic proton interactions simulated using the TOPAS-nBio MC platform against confocal microscope data for Al2O3:C,Mg fluorescent nuclear track detectors (FNTDs). We irradiated [Formula: see text] mm3 FNTD chips inside a water phantom, positioned at seven positions along a pristine proton Bragg peak with a range in water of 12 cm. MC simulations were implemented in two stages: (1) using TOPAS to model the beam properties within a water phantom and (2) using TOPAS-nBio with Geant4-DNA physics to score particle interactions through a water surrogate of Al2O3:C,Mg. The measured median track integrated brightness (IB) was observed to be strongly correlated to both (i) voxelized track-averaged linear energy transfer (LET) and (ii) frequency mean microdosimetric lineal energy, [Formula: see text], both simulated in pure water. Histograms of FNTD track IB were compared against TOPAS-nBio histograms of the number of terminal electrons per proton, scored in water with mass-density scaled to mimic Al2O3:C,Mg. Trends between exposure depths observed in TOPAS-nBio simulations were experimentally replicated in the study of FNTD track IB. Our results represent an important first step towards the experimental validation of MC simulations on the sub-cellular scale and suggest that FNTDs can enable experimental study of the microdosimetric properties of individual proton tracks.

Reference dosimetry in magnetic fields: formalism and ionization chamber correction factors.

PURPOSE: Magnetic resonance imaging-guided radiotherapy (MRIgRT) provides superior soft-tissue contrast and real-time imaging compared with standard image-guided RT, which uses x-ray based imaging. Several groups are developing integrated MRIgRT machines. Reference dosimetry with these new machines requires accounting for the effects of the magnetic field on the response of the ionization chambers used for dose calibration. Here, the authors propose a formalism for reference dosimetry with integrated MRIgRT devices. The authors also examined the suitability of the TPR10 (20) and %dd(10)x beam quality specifiers in the presence of magnetic fields and calculated detector correction factors to account for the effects of the magnetic field for a range of detectors. METHODS: The authors used full-head and point-source Monte Carlo models of an MR-linac along with detailed detector models of an Exradin A19, an NE2571, and several PTW Farmer chambers to calculate magnetic field correction factors for six commercial ionization chambers in three chamber configurations. Calculations of ionization chamber response (performed with geant4) were validated with specialized Fano cavity tests. %dd(10)x values, TPR10 (20) values, and Spencer-Attix water-to-air restricted stopping power ratios were also calculated. The results were further validated against measurements made with a preclinical functioning MR-linac. RESULTS: The TPR10 (20) was found to be insensitive to the presence of the magnetic field, whereas the relative change in %dd(10)x was 2.4% when a transverse 1.5 T field was applied. The parameters chosen for the ionization chamber calculations passed the Fano cavity test to within ∼0.1%. Magnetic field correction factors varied in magnitude with detector orientation with the smallest corrections found when the chamber was parallel to the magnetic field. CONCLUSIONS: Reference dosimetry can be performed with integrated MRIgRT devices by using magnetic field correction factors, but care must be taken with the choice of beam quality specifier and chamber orientation. The uncertainties achievable under this formalism should be similar to those of conventional formalisms, although this must be further quantified.

Commissioning dose computation models for spot scanning proton beams in water for a commercially available treatment planning system.

PURPOSE: To present our method and experience in commissioning dose models in water for spot scanning proton therapy in a commercial treatment planning system (TPS). METHODS: The input data required by the TPS included in-air transverse profiles and integral depth doses (IDDs). All input data were obtained from Monte Carlo (MC) simulations that had been validated by measurements. MC-generated IDDs were converted to units of Gy mm(2)/MU using the measured IDDs at a depth of 2 cm employing the largest commercially available parallel-plate ionization chamber. The sensitive area of the chamber was insufficient to fully encompass the entire lateral dose deposited at depth by a pencil beam (spot). To correct for the detector size, correction factors as a function of proton energy were defined and determined using MC. The fluence of individual spots was initially modeled as a single Gaussian (SG) function and later as a double Gaussian (DG) function. The DG fluence model was introduced to account for the spot fluence due to contributions of large angle scattering from the devices within the scanning nozzle, especially from the spot profile monitor. To validate the DG fluence model, we compared calculations and measurements, including doses at the center of spread out Bragg peaks (SOBPs) as a function of nominal field size, range, and SOBP width, lateral dose profiles, and depth doses for different widths of SOBP. Dose models were validated extensively with patient treatment field-specific measurements. RESULTS: We demonstrated that the DG fluence model is necessary for predicting the field size dependence of dose distributions. With this model, the calculated doses at the center of SOBPs as a function of nominal field size, range, and SOBP width, lateral dose profiles and depth doses for rectangular target volumes agreed well with respective measured values. With the DG fluence model for our scanning proton beam line, we successfully treated more than 500 patients from March 2010 through June 2012 with acceptable agreement between TPS calculated and measured dose distributions. However, the current dose model still has limitations in predicting field size dependence of doses at some intermediate depths of proton beams with high energies. CONCLUSIONS: We have commissioned a DG fluence model for clinical use. It is demonstrated that the DG fluence model is significantly more accurate than the SG fluence model. However, some deficiencies in modeling the low-dose envelope in the current dose algorithm still exist. Further improvements to the current dose algorithm are needed. The method presented here should be useful for commissioning pencil beam dose algorithms in new versions of TPS in the future.

SU-E-T-22: Is the Residual Range a Universal Quantity to Specify the Quality of Modulated Proton Beams?

PURPOSE: To investigate the validity of using the residual range as a universal quantity to specify the quality of modulated proton beams. METHODS: We used TOPAS (Tool for Particle Simulation), an application of the Geant4 toolkit, to simulate absorbed dose and stopping-power distributions from a commercial passive scattering nozzle. We used the standard physics lists from Geant4 in the simulations. All particles were included, as well as physics models for nuclear interactions. No variance reduction techniques were used. Dose and averaged stopping-power as functions of depth were scored in a water box with 320 scoring volumes of 15 × 15 × 0.1 cm3 . Stopping-power spectra were scored in a15 × 15 × 0.1 cm3 volume located in the middle of SOBPs. All particles were considered in the dose scoring. Only protons (primary and secondary) were considered in the scoring of stopping-power. RESULTS: For the same residual range, differences in averaged stopping-power values of up to 13% were observed for a 200 MeV beam with modulations of 4 cm and 8 cm, respectively. Simulations of four modulated proton energies with the same SOBP of 8 cm showed differences of up to 13% in the averaged stopping-power values even in the SOBP region. We also simulated stopping power spectra in the middle of 8 cm SOBPs for four modulated proton energies. The averaged stopping-power values calculated from the spectra were within 3%, however, their distributions were very different with full width at half-maximum 150% larger for the 250 MeV beam compared to that of the 140 MeV beam. CONCLUSION: Large differences in the averaged stopping-power values and stopping-power spectra were observed for the same residual range. Determining whether these differences have a significant effect on the response of radiation detectors exposed to proton beams requires further investigation. Natural Sciences and Engineering Research Council of Canada and Ontario Graduate Scholarship Program, Ontario Ministry of Training, Colleges and Universities.

SU-E-T-91: Validation of Geant4 Physics for Ionization Chamber Calculations in Radiotherapy Photon Beams.

PURPOSE: To determine the accuracy of the GEANT4 Monte Carlo toolkit for ionization chamber calculations in radiotherapy photon beams. METHODS: First, we used the Fano cavity example included in the GEANT4 distribution to validate calculations under Fano conditions. We determined a combination of parameters and physics list that provided results consistent within +/- 0.5% with the Fano theorem. Next we performed simulations to investigate the accuracy of using GEANT4 for ionization chamber calculations. Eight ionization chambers were modeled using detailed manufacturer specifications including A1, A1SL, NE2571, PTW30010, PTW30012, PTW31010, PTW31014 and PTW31016. The absorbed dose to water for a cylindrical water cavity and the absorbed dose to air in the ionization chambers' cavities were scored for 1.25 MeV photons. The ratio of these quantities was then compared to values from EGSnrc simulations. RESULTS: Simulations using the Fano cavity example yielded results within +/- 0.5% with the Fano theorem across 1.25, 3 and 4 MeV incident photon energies. The most accurate and consistent results were obtained using the G4eIonisation ionization model and G4GoudsmitSaundersonMscModel multiple scattering (MS) model with a maximum step size limitation of 0.001 mm, which yielded results accurate to +/- 0.3% for all energies. This set of parameters and physics processes as well as the G4UrbanMscModel93 MS model were used for the ionization chamber calculations. The calculated quantities were compared to those used in Muir and Rogers 2010 (Med. Phys. 37: 5939-5950) and agreed to within sub-percentage differences for most chambers. CONCLUSIONS: The GEANT4 toolkit can achieve sub-percentage accuracy for ionization chamber calculations in radiotherapy photon beams. This is achieved by using either the G4GoudsmitSaundersonMscModel or G4UrbanMscModel93 MS models. Although less accurate (+/- 0.5%), simulations employing the G4UrbanMscModel93 MS model are on average two orders magnitude faster than that of the G4GoudsmitSaundersonMscModel MS model (+/- 0.3%). Natural Sciences and Engineering Research Council of Canada.

SU-E-T-90: Investigation of Different Bleaching Wavelengths on the Absorbed-Dose Sensitivity of NanoDot OSLDs Exposed to 6 MV X-Ray Beams.

PURPOSE: To determine the effect of different bleaching wavelengths on the luminescence response of Al2 O3 :C optically stimulated luminescence detectors (OSLDs) exposed to accumulated doses of 6 MV photon beams. METHODS: OSLDs of the nanoDot type were used and readout with a microStar InLight reader. To determine the effect of different bleaching wavelengths on the luminescence response of nanoDot OSLDs, we optically reset (bleached) the OSLDs with 26 W fluorescent lamps in two modes: (i) directly under the lamps for 10, 120 and 600 min; and (ii) with a long pass filter for 55, 600 and 2400 min. The long pass filter blocks wavelengths below 495 nm, hence the longer bleaching duration to attain equivalent OSL signals as bleaching directly under the lamps. Changes in the sensitivity of the nanoDot OSLDs were determined for an irradiation-readout-bleaching-readout cycle, after irradiations with 1 and 10 Gy dose fractions. RESULTS: The nanoDot OSLDs presented a linear response to dose up to 2 Gy and supra-linear response afterwards. They produced different OSL signal loss and fading behaviors for doses of 1 and 10 Gy. OSLDs bleached for 120 min and 600 min without and with the filter in 1 Gy fractions, did not exhibit any significant change in sensitivity over an accumulated dose of 7 Gy. The OSLDs exposed with 10 Gy fractions exhibited a small under-response when bleached with filter, and an over-response when bleached directly without filter. CONCLUSIONS: The nanoDot OSLDs may be reused without a significant sensitivity change for accumulated doses below 7 Gy. However, for accumulated doses beyond 10 Gy, nanoDot OSLDs show significant sensitivity change and hence, need to be recalibrated for reuse. We also concluded that the light spectrum used to reset the OSLDs has an influence on the sensitivity of the detectors. Natural Sciences and Engineering Research Council of Canada.

SU-E-T-98: Towards Cell Nucleus Microdosimetry: Construction of a Confocal Laser-Scanning Fluorescence Microscope to Readout Fluorescence Nuclear Track Detectors (FNTDs).

PURPOSE: To construct a custom confocal laser scanning microscope (CLSM) capable of resolving individual proton tracks in the volume of an Al2 O3 :C,Mg fluorescent nuclear track detector (FNTD). The spatial resolution of the FNTD technique is at the sub-micrometer scale. Therefore the FNTD technique has the potential to perform radiation measurements at the cell nucleus scale. METHODS: The crystal volume of an FNTD contains defects which become fluorescent F2+ centers after trapping delta electrons from ionizing radiation. These centers have an absorption band centered at 620 nm and an emission band in the near infrared. Events of energy deposition in the crystal are read-out using a CLSM with sub-micrometer spatial resolution. Excitation light from a 635 nm laser is focused in the crystal volume by an objective lens. Fluorescence is collected back through the same path, filtered through a dichroic mirror, and focused through a small pinhole onto an avalanche photodiode. Lateral scanning of the focal point is performed with a scanning mirror galvanometer, and axial scanning is performed using a stepper-motor stage. Control of electronics and image acquisition was performed using a custom built LabVIEW VI and further image processing was done using Java. The system was used to scan FNTDs exposed to a 6 MV x-ray beam and an unexposed FNTD. RESULTS: Fluorescence images above the unexposed background were obtained at scan depths ranging from 5 - 10 micrometer below the crystal surface using a 100 micrometer pinhole size. CONCLUSIONS: Further work needs to be done to increase the resolution and the signal to noise ratio of the images so that energy deposition events may be identified more easily. Natural Sciences and Engineering Research Council of Canada.

SU-E-T-87: The Effect of Bleaching Wavelengths on the Regeneration of the Optically Stimulated Luminescence Signal of NanoDot Dosimeters Pre-Exposed to High-Doses.

PURPOSE: To investigate the effect of bleaching wavelengths on the regeneration of optically stimulated luminescence (OSL) signals in Al2 O3 :C nanoDot dosimeters pre-exposed to high doses. Regeneration is the increase in the OSL signal during storage of a bleached nanoDot that was previously pre-exposed to a high dose. This phenomenon affects the accuracy of a calibration protocol proposed by Jursinic 2010 (Med. Phys. 37:102) in which pre-exposure of nanoDots to a high-dose was used to minimize changes in the sensitivity of the detector as a function of accumulated dose. METHODS: Al2 O3 :C OSLDs of the type nanoDot were used throughout this study. Readout was performed using the microStar reader. Bleaching of the OSLDs was performed with four 26 W fluorescent light bulbs in two modes: (i) directly under the lamps; and (ii) with the aid of a long-pass optical filter placed over the nanoDots, partially blocking wavelengths below 495 nm. Eighteen nanoDots were pre-exposed to 1 kGy dose. Then the pre-exposed nanoDots were bleached in two sets of 9 to very low residual OSL signals using bleaching modes (i) and (ii) for 12 h and 45 h, respectively. The nanoDots were then stored in dark and readout after various time intervals to monitor the regeneration of the OSL signal. RESULTS: We fitted the regeneration of the OSL signal using a saturation function and obtained rise-time values of 563 h and 630 h, for bleaching modes (i) and (ii), respectively. At the saturation level, the equivalent doses were about 1.18 Gy and 0.38 Gy for modes (i) and (ii), respectively. CONCLUSIONS: The regeneration rates of nanoDot OSLDs pre-exposed to high doses depend on the bleaching light wavelength used to reset the detectors. A bleaching source that has a low component of wavelengths below 495 nm can minimize the regeneration of the OSL signal. Natural Sciences and Engineering Research Council of Canada.