Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 µm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 µm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: a Monte Carlo simulation

Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV photon spectrum, and a kilovoltage photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp photons and MV photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage photons have the longest range in water as compared to protons and MV photons, e.g. they cause a dose enhancement 20 times higher than the one caused by protons 10 μm away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target.

MANIPULATION OF IONS, ELECTRONS, AND PHOTONS IN 2D MATERIALS BY ION INTERCALATION

2D materials have attracted tremendous attention due to their unique physical and chemical properties since the discovery of graphene. Despite these intrinsic properties, various modification methods have been applied to 2D materials that yield even more exciting results. Among all modification methods, the intercalation of 2D materials provides the highest possible doping and/or phase change to the pristine 2D materials. This doping effect highly modifies 2D materials, with extraordinary electrical transport as well as optical, thermal, magnetic, and catalytic properties, which are advantageous for optoelectronics, superconductors, thermoelectronics, catalysis and energy storage applications. To study the property changes of 2D materials, we designed and built a planar nanobattery that allows electrochemical ion intercalation in 2D materials. More importantly, this planar nanobattery enables characterization of electrical, optical and structural properties of 2D materials in situ and real time upon ion intercalation. With this device, we successfully intercalated Li-ions into few layer graphene (FLG) and ultrathin graphite, heavily dopes the graphene to 0.6 x 10^15 /cm2, which simultaneously increased its conductivity and transmittance in the visible range. The intercalated LiC6 single crystallite achieved extraordinary optoelectronic properties, in which an eight-layered Li intercalated FLG achieved transmittance of 91.7% (at 550 nm) and sheet resistance of 3 ohm/sq. We extend the research to obtain scalable, printable graphene based transparent conductors with ion intercalation. Surfactant free, printed reduced graphene oxide transparent conductor thin film with Na-ion intercalation is obtained with transmittance of 79% and sheet resistance of 300 ohm/sq (at 550 nm). The figure of merit is calculated as the best pure rGO based transparent conductors. We further improved the tunability of the reduced graphene oxide film by using two layers of CNT films to sandwich it. The tunable range of rGO film is demonstrated from 0.9 um to 10 um in wavelength. Other ions such as K-ion is also studied of its intercalation chemistry and optical properties in graphitic materials. We also used the in situ characterization tools to understand the fundamental properties and improve the performance of battery electrode materials. We investigated the Na-ion interaction with rGO by in situ Transmission electron microscopy (TEM). For the first time, we observed reversible Na metal cluster (with diameter larger than 10 nm) deposition on rGO surface, which we evidenced with atom-resolved HRTEM image of Na metal and electron diffraction pattern. This discovery leads to a porous reduced graphene oxide sodium ion battery anode with record high reversible specific capacity around 450 mAh/g at 25mA/g, a high rate performance of 200 mAh/g at 250 mA/g, and stable cycling performance up to 750 cycles. In addition, direct observation of irreversible formation of Na2O on rGO unveils the origin of commonly observed low 1st Columbic Efficiency of rGO containing electrodes. Another example for in situ characterization for battery electrode is using the planar nanobattery for 2D MoS2 crystallite. Planar nanobattery allows the intrinsic electrical conductivity measurement with single crystalline 2D battery electrode upon ion intercalation and deintercalation process, which is lacking in conventional battery characterization techniques. We discovered that with a “rapid-charging” process at the first cycle, the lithiated MoS2 undergoes a drastic resistance decrease, which in a regular lithiation process, the resistance always increases after lithiation at its final stage. This discovery leads to a 2- fold increase in specific capacity with with rapid first lithiated MoS2 composite electrode material, compare with the regular first lithiated MoS2 composite electrode material, at current density of 250 mA/g.

New bodipy dyads for two-photons fluorescence imaging in cells

Fluorescent probes are essential tools for studying biological systems. The last decade has witnessed particular interest in the development of two-photon excitable probes, due to their advantageous features in tissue imaging compared to the corresponding one-photon probes [1]. Recently, we have designed and synthetized an aminonaphthalimide–BODIPY derivative as energy transfer cassettes and were found to show very fast and efficient BODIPY fluorescence sensitization [2]. This was observed upon one- and two-photon excitation, which extends the application range of the investigated bichromophoric dyads in terms of accessible excitation wavelengths. In order to increase the two-photon absorption of the system aminonaphthalimide fluorophore was replace with a Prodan analog (BODIPY dyad 1), which presents found a variety of applications as probes and labels in biology [3]. The two-photon absorption cross-section  of the dyads is significantly incremented by the presence of the 6-acetyl-2-naphthylamine donor group. The emission maximum of a BODIPY fluorophore can significantly be red-shifted in comparison to their precursors by conjugation with aromatic aldehydes. [4] We use a synthetic strategy to obtain BODIPY dyad 2 that incorporates an imidazole ring. This molecule can be used in biological media as a near-neutral pH indicator based on one- and two-photon excitable BODIPY acceptor.

Evaluation of piezoelectric PVDF polymers for use in space environments. III. Comparison of the effects of vacuum UV and gamma radiation

Films of piezoelectric PVDF and P(VDF-TrFE) were exposed to vacuum UV (115-300 nm VUV) and -radiation to investigate how these two forms of radiation affect the chemical, morphological, and piezoelectric properties of the polymers. The extent of crosslinking was almost identical in both polymers after -irradiation, but surprisingly, was significantly higher for the TrFE copolymer after VUV-irradiation. Changes in the melting behavior were also more significant in the TrFE copolymer after VUV-irradiation due to both surface and bulk crosslinking, compared with only surface crosslinking for the PVDF films. The piezoelectric properties (measured using d33 piezoelectric coefficients and D-E hysteresis loops) were unchanged in the PVDF homopolymer, while the TrFE copolymer exhibited more narrow D-E loops after exposure to either - or VUV-radiation. The more severe damage to the TrFE copolymer in comparison with the PVDF homopolymer after VUV-irradiation is explained by different energy deposition characteristics. The short wavelength, highly energetic photons are undoubtedly absorbed in the surface layers of both polymers, and we propose that while the longer wavelength components of the VUV-radiation are absorbed by the bulk of the TrFE copolymer causing crosslinking, they are transmitted harmlessly in the PVDF homopolymer.

Contrast enhancement of EPID images via difference imaging : a feasibility study

In this study, the feasibility of difference imaging for improving the contrast of electronic portal imaging device (EPID) images is investigated. The difference imaging technique consists of the acquisition of two EPID images (with and without the placement of an additional layer of attenuating medium on the surface of the EPID)and the subtraction of one of these images from the other. The resulting difference image shows improved contrast, compared to a standard EPID image, since it is generated by lower-energy photons. Results of this study show that, ¯rstly, this method can produce images exhibiting greater contrast than is seen in standard megavoltage EPID images and that, secondly, the optimal thickness of attenuating material for producing a maximum contrast enhancement may vary with phantom thickness and composition. Further studies of the possibilities and limitations of the di®erence imaging technique, and the physics behind it, are therefore recommended.

Validation and automation of the DYNJAWS component module of the BEAMnrc Monte Carlo code

The purpose of this work is to validate and automate the use of DYNJAWS; a new component module (CM) in the BEAMnrc Monte Carlo (MC) user code. The DYNJAWS CM simulates dynamic wedges and can be used in three modes; dynamic, step-and-shoot and static. The step-and-shoot and dynamic modes require an additional input file defining the positions of the jaw that constitutes the dynamic wedge, at regular intervals during its motion. A method for automating the generation of the input file is presented which will allow for the more efficient use of the DYNJAWS CM. Wedged profiles have been measured and simulated for 6 and 10 MV photons at three field sizes (5 cm x 5 cm , 10 cm x10 cm and 20 cm x 20 cm), four wedge angles (15, 30, 45 and 60 degrees), at dmax and at 10 cm depth. Results of this study show agreement between the measured and the MC profiles to within 3% of absolute dose or 3 mm distance to agreement for all wedge angles at both energies and depths. The gamma analysis suggests that dynamic mode is more accurate than the step-and-shoot mode. The DYNJAWS CM is an important addition to the BEAMnrc code and will enable the MC verification of patient treatments involving dynamic wedges.

Extreme ultraviolet (EUV) degradation of poly(olefin sulfone)s : towards applications as EUV photoresists

Poly(olefin sulfone)s, formed by the reaction of sulfur dioxide (SO2) and an olefin, are known to be highly susceptible to degradation by radiation and thus have been identified as candidate materials for chain scission-based extreme ultraviolet lithography (EUVL) resist materials. In order to investigate this further, the synthesis and characterisation of two poly(olefin sulfone)s namely poly(1-pentene sulfone) (PPS) and poly(2-methyl-1-pentene sulfone) (PMPS), was achieved and the two materials were evaluated for possible chain scission EUVL resist applications. It was found that both materials possess high sensitivities to EUV photons; however; the rates of outgassing were extremely high. The only observed degradation products were found to be SO2 and the respective olefin suggesting that depolymerisation takes place under irradiation in a vacuum environment. In addition to depolymerisation, a concurrent conversion of SO2 moieties to a sulfide phase was observed using XPS.

Polycarbonate based nonchemically amplified photoresists for extreme ultraviolet lithography

Some initial EUVL patterning results for polycarbonate based non-chemically amplified resists are presented. Without full optimization the developer a resolution of 60 nm line spaces could be obtained. With slight overexposure (1.4 × E0) 43.5 nm lines at a half pitch of 50 nm could be printed. At 2x E0 a 28.6 nm lines at a half pitch of 50 nm could be obtained with a LER that was just above expected for mask roughness. Upon being irradiated with EUV photons, these polymers undergo chain scission with the loss of carbon dioxide and carbon monoxide. The remaining photoproducts appear to be non-volatile under standard EUV irradiation conditions, but do exhibit increased solubility in developer compared to the unirradiated polymer. The sensitivity of the polymers to EUV light is related to their oxygen content and ways to increase the sensitivity of the polymers to 10 mJ cm-2 is discussed.

Photoclickable surfaces for profluorescent covalent polymer coatings

The nitrile imine-mediated tetrazole-ene cycloaddition reaction (NITEC) is introduced as a powerful and versatile conjugation tool to covalently ligate macromolecules onto variable (bio)surfaces. The NITEC approach is initiated by UV irradiation and proceeds rapidly at ambient temperature yielding a highly fluorescent linkage. Initially, the formation of block copolymers by the NITEC methodology is studied to evidence its efficacy as a macromolecular conjugation tool. The grafting of polymers onto inorganic (silicon) and bioorganic (cellulose) surfaces is subsequently carried out employing the optimized reaction conditions obtained from the macromolecular ligation experiments and evidenced by surface characterization techniques, including X-ray photoelectron spectroscopy and FT-IR microscopy. In addition, the patterned immobilization of variable polymer chains onto profluorescent cellulose is achieved through a simple masking process during the irradiation. Photoinduced nitrile imine-alkene 1,3-dipolar cycloaddition (NITEC) is employed to covalently bind well-defined polymers onto silicon oxide or cellulose. A diaryl tetrazole-functionalized molecule is grafted via silanization or amidification, respectively. Under UV light, a reactive nitrile imine rapidly forms and reacts with maleimide-functionalized polymers yielding a fluorescent linkage. Via a masking method, polymeric fluorescent patterns are achieved.

The effect of very small air gaps on small field dosimetry

The purpose of this study was to investigate the effect of very small air gaps (less than 1 mm) on the dosimetry of small photon fields used for stereotactic treatments. Measurements were performed with optically stimulated luminescent dosimeters (OSLDs) for 6 MV photons on a Varian 21iX linear accelerator with a Brainlab μMLC attachment for square field sizes down to 6 mm × 6 mm. Monte Carlo simulations were performed using EGSnrc C++ user code cavity. It was found that the Monte Carlo model used in this study accurately simulated the OSLD measurements on the linear accelerator. For the 6 mm field size, the 0.5 mm air gap upstream to the active area of the OSLD caused a 5.3 % dose reduction relative to a Monte Carlo simulation with no air gap. A hypothetical 0.2 mm air gap caused a dose reduction > 2 %, emphasizing the fact that even the tiniest air gaps can cause a large reduction in measured dose. The negligible effect on an 18 mm field size illustrated that the electronic disequilibrium caused by such small air gaps only affects the dosimetry of the very small fields. When performing small field dosimetry, care must be taken to avoid any air gaps, as can be often present when inserting detectors into solid phantoms. It is recommended that very small field dosimetry is performed in liquid water. When using small photon fields, sub-millimetre air gaps can also affect patient dosimetry if they cannot be spatially resolved on a CT scan. However the effect on the patient is debatable as the dose reduction caused by a 1 mm air gap, starting out at 19% in the first 0.1 mm behind the air gap, decreases to < 5 % after just 2 mm, and electronic equilibrium is fully re-established after just 5 mm.

Temporal summation of intrinsically photosensitive retinal ganglion cell (ipRGC) contributions to the human pupil.

Purpose: IpRGCs mediate non-image forming functions including photoentrainment and the pupil light reflex (PLR). Temporal summation increases visual sensitivity and decreases temporal resolution for image forming vision, but the summation properties of nonimage forming vision are unknown. We investigated the temporal summation of inner (ipRGC) and outer (rod/cone) retinal inputs to the PLR. Method: The consensual PLR of the left eye was measured in six participants with normal vision using a Maxwellian view infrared pupillometer. Temporal summation was investigated using a double-pulse protocol (100 ms stimulus pairs; 0–1024 ms inter-stimulus interval, ISI) presented to the dilated fellow right eye (Tropicamide 1%). Stimulus lights (blue λmax = 460 nm; red λmax = 638 nm) biased activity to inneror outer retinal inputs to non-image forming vision. Temporal summation was measured suprathreshold (15.2 log photons.cm−2.s−1 at the cornea) and subthreshold (11.4 log photons.cm−2.s−1 at the cornea). Results: RM-ANOVAs showed the suprathreshold and subthreshold 6 second post illumination pupil response (PIPR: expressed as percentage baseline diameter) did not significantly vary for red or blue stimuli (p > .05). The PIPR for a subthreshold red 16 ms double-pulse control condition did not significantly differ with ISI (p > .05). The maximum constriction amplitude for red and blue 100 ms double- pulse stimuli did not significantly vary with ISI (p > .05). Conclusion: The non-significant changes in suprathreshold PIPR and subthreshold maximum pupil constriction indicate that inner retinal ipRGC inputs and outer retinal photoreceptor inputs to the PLR do not show temporal summation. The results suggest a fundamental difference between the temporal summation characteristics of image forming and non-image forming vision.

A pre-treatment verification tool for IMRT based on EPID measurements and a GEANT4 back projection application

The aim of this work is to develop software that is capable of back projecting primary fluence images obtained from EPID measurements through phantom and patient geometries in order to calculate 3D dose distributions. In the first instance, we aim to develop a tool for pretreatment verification in IMRT. In our approach, a Geant4 application is used to back project primary fluence values from each EPID pixel towards the source. Each beam is considered to be polyenergetic, with a spectrum obtained from Monte Carlo calculations for the LINAC in question. At each step of the ray tracing process, the energy differential fluence is corrected for attenuation and beam divergence. Subsequently, the TERMA is calculated and accumulated to an energy differential 3D TERMA distribution. This distribution is then convolved with monoenergetic point spread kernels, thus generating energy differential 3D dose distributions. The resulting dose distributions are accumulated to yield the total dose distribution, which can then be used for pre-treatment verification of IMRT plans. Preliminary results were obtained for a test EPID image comprised of 100 9 100 pixels of unity fluence. Back projection of this field into a 30 cm9 30 cm 9 30 cm water phantom was performed, with TERMA distributions obtained in approximately 10 min (running on a single core of a 3 GHz processor). Point spread kernels for monoenergetic photons in water were calculated using a separate Geant4 application. Following convolution and summation, the resulting 3D dose distribution produced familiar build-up and penumbral features. In order to validate the dose model we will use EPID images recorded without any attenuating material in the beam for a number of MLC defined square fields. The dose distributions in water will be calculated and compared to TPS predictions.

Calculation of dose kernels for radiotherapy applications using the GEANT 4 Monte Carlo toolkit

Dose kernels may be used to calculate dose distributions in radiotherapy (as described by Ahnesjo et al., 1999). Their calculation requires use of Monte Carlo methods, usually by forcing interactions to occur at a point. The Geant4 Monte Carlo toolkit provides a capability to force interactions to occur in a particular volume. We have modified this capability and created a Geant4 application to calculate dose kernels in cartesian, cylindrical, and spherical scoring systems. The simulation considers monoenergetic photons incident at the origin of a 3 m x 3 x 9 3 m water volume. Photons interact via compton, photo-electric, pair production, and rayleigh scattering. By default, Geant4 models photon interactions by sampling a physical interaction length (PIL) for each process. The process returning the smallest PIL is then considered to occur. In order to force the interaction to occur within a given length, L_FIL, we scale each PIL according to the formula: PIL_forced = L_FIL 9 (1 - exp(-PIL/PILo)) where PILo is a constant. This ensures that the process occurs within L_FIL, whilst correctly modelling the relative probability of each process. Dose kernels were produced for an incident photon energy of 0.1, 1.0, and 10.0 MeV. In order to benchmark the code, dose kernels were also calculated using the EGSnrc Edknrc user code. Identical scoring systems were used; namely, the collapsed cone approach of the Edknrc code. Relative dose difference images were then produced. Preliminary results demonstrate the ability of the Geant4 application to reproduce the shape of the dose kernels; median relative dose differences of 12.6, 5.75, and 12.6 % were found for an incident photon energy of 0.1, 1.0, and 10.0 MeV respectively.

Phantom Scatter and the A-SI EPID

Introduction: The use of amorphous-silicon electronic portal imaging devices (a-Si EPIDs) for dosimetry is complicated by the effects of scattered radiation. In photon radiotherapy, primary signal at the detector can be accompanied by photons scattered from linear accelerator components, detector materials, intervening air, treatment room surfaces (floor, walls, etc) and from the patient/phantom being irradiated. Consequently, EPID measurements which presume to take scatter into account are highly sensitive to the identification of these contributions. One example of this susceptibility is the process of calibrating an EPID for use as a gauge of (radiological) thickness, where specific allowance must be made for the effect of phantom-scatter on the intensity of radiation measured through different thicknesses of phantom. This is usually done via a theoretical calculation which assumes that phantom scatter is linearly related to thickness and field-size. We have, however, undertaken a more detailed study of the scattering effects of fields of different dimensions when applied to phantoms of various thicknesses in order to derive scattered-primary ratios (SPRs) directly from simulation results. This allows us to make a more-accurate calibration of the EPID, and to qualify the appositeness of the theoretical SPR calculations. Methods: This study uses a full MC model of the entire linac-phantom-detector system simulated using EGSnrc/BEAMnrc codes. The Elekta linac and EPID are modelled according to specifications from the manufacturer and the intervening phantoms are modelled as rectilinear blocks of water or plastic, with their densities set to a range of physically realistic and unrealistic values. Transmissions through these various phantoms are calculated using the dose detected in the model EPID and used in an evaluation of the field-size-dependence of SPR, in different media, applying a method suggested for experimental systems by Swindell and Evans [1]. These results are compared firstly with SPRs calculated using the theoretical, linear relationship between SPR and irradiated volume, and secondly with SPRs evaluated from our own experimental data. An alternate evaluation of the SPR in each simulated system is also made by modifying the BEAMnrc user code READPHSP, to identify and count those particles in a given plane of the system that have undergone a scattering event. In addition to these simulations, which are designed to closely replicate the experimental setup, we also used MC models to examine the effects of varying the setup in experimentally challenging ways (changing the size of the air gap between the phantom and the EPID, changing the longitudinal position of the EPID itself). Experimental measurements used in this study were made using an Elekta Precise linear accelerator, operating at 6MV, with an Elekta iView GT a-Si EPID. Results and Discussion: 1. Comparison with theory: With the Elekta iView EPID fixed at 160 cm from the photon source, the phantoms, when positioned isocentrically, are located 41 to 55 cm from the surface of the panel. At this geometry, a close but imperfect agreement (differing by up to 5%) can be identified between the results of the simulations and the theoretical calculations. However, this agreement can be totally disrupted by shifting the phantom out of the isocentric position. Evidently, the allowance made for source-phantom-detector geometry by the theoretical expression for SPR is inadequate to describe the effect that phantom proximity can have on measurements made using an (infamously low-energy sensitive) a-Si EPID. 2. Comparison with experiment: For various square field sizes and across the range of phantom thicknesses, there is good agreement between simulation data and experimental measurements of the transmissions and the derived values of the primary intensities. However, the values of SPR obtained through these simulations and measurements seem to be much more sensitive to slight differences between the simulated and real systems, leading to difficulties in producing a simulated system which adequately replicates the experimental data. (For instance, small changes to simulated phantom density make large differences to resulting SPR.) 3. Comparison with direct calculation: By developing a method for directly counting the number scattered particles reaching the detector after passing through the various isocentric phantom thicknesses, we show that the experimental method discussed above is providing a good measure of the actual degree of scattering produced by the phantom. This calculation also permits the analysis of the scattering sources/sinks within the linac and EPID, as well as the phantom and intervening air. Conclusions: This work challenges the assumption that scatter to and within an EPID can be accounted for using a simple, linear model. Simulations discussed here are intended to contribute to a fuller understanding of the contribution of scattered radiation to the EPID images that are used in dosimetry calculations. Acknowledgements: This work is funded by the NHMRC, through a project grant, and supported by the Queensland University of Technology (QUT) and the Royal Brisbane and Women's Hospital, Brisbane, Australia. The authors are also grateful to Elekta for the provision of manufacturing specifications which permitted the detailed simulation of their linear accelerators and amorphous-silicon electronic portal imaging devices. Computational resources and services used in this work were provided by the HPC and Research Support Group, QUT, Brisbane, Australia.