Clustering effects in nanoparticle-enhanced ß- emitting internal radionuclide therapy: a Monte Carlo study.

We investigate the effects of an increase in the production of secondary electrons when a ß - source commonly used in internal radionuclide therapy, 67Cu, is radiolabelled to a super-paramagnetic iron oxide nanoparticle (SPION), with specific emphasis on the role of SPION cluster size and geometry. A positive relationship is found between the degree to which the nanoparticles are clustered and the associated radio-enhancement effects, with cluster population size playing a major role, as well as SPION separation within a cluster and the distance between clusters. Our simulation results indicate that SPIONs labelled with 67Cu can induce a nonlinear amplification in the number of secondary electrons produced of up to 4% in bulk, with localised regions of nearer inter-SPION separation producing an increase of over 400% for a 20 nm average SPION separation. Such variation in enhancement due to local concentration effects may help identify clinical strategies that enhance efficacy for a given radiation dosage, or achieve equal efficacy with reduced radiation dosage.

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.

Impact of fluorescence emission from gold atoms on surrounding biological tissue-implications for nanoparticle radio-enhancement.

The addition of gold nanoparticles within target tissue (i.e. a tumour) to enhance the delivered radiation dose is a well studied radiotherapy treatment strategy, despite not yet having been translated into standard clinical practice. While several studies have used Monte Carlo simulations to investigate radiation dose enhancement by Auger electrons emitted from irradiated gold nanoparticles, none have yet considered the effects due to escaping fluorescence photons. Geant4 was used to simulate a water phantom containing 10 mg ml-1 uniformly dispersed gold (1% by mass) at 5 cm depth. Incident monoenergetic photons with energies either side of the gold K-edge at 73 keV and 139.5 keV were chosen to give the same attenuation contrast against water, where water is used as a surrogate for biological tissue. For 73 keV incident photons, adding 1% gold into the water phantom enhances the energy deposited in the phantom by a factor of ≈1.9 while 139.5 keV incident photons give a lower enhancement ratio of ≈1.5. This difference in enhancement ratio, despite the equivalent attenuation ratios, can be attributed to energy carried from the target into the surrounding volume by fluorescence photons for the higher incident photon energy. The energy de-localisation is maximal just above the K-edge with 36% of the initial energy deposit in the phantom lost to escaping fluorescence photons. Conversely we find that the absorption of more photons by gold in the phantom reduces the number of scattered photons and hence energy deposited in the surrounding volume by up to 6% for incident photons below the K-edge. For incident photons above the K-edge this is somewhat offset by fluorescence. Our results give new insight into the previously unstudied centimetre scale energy deposition outside a target, which will be valuable for the future development of treatment plans using gold nanoparticles. From these results, we can conclude that gold nanoparticles delivered to a target tumour are capable of increasing dose to the tumour whilst simultaneously decreasing scatter dose to surrounding healthy tissue.

Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol.

Gold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies ∼70 eV, substantially lower than that of liquid water ∼78 eV. Monte Carlo simulations for 10-50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of ∼1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol.

Polarisation-based coincidence event discrimination: an in silico study towards a feasible scheme for Compton-PET.

Current positron emission tomography (PET) systems use temporally localised coincidence events discriminated by energy and time-of-flight information. The two annihilation photons are in an entangled polarisation state and, in principle, additional information from the polarisation correlation of photon pairs could be used to improve the accuracy of coincidence classification. In a previous study, we demonstrated that in principle, the polarisation correlation information could be transferred to an angular correlation in the distribution of scattered photon pairs in a planar Compton camera system. In the present study, we model a source-phantom-detector system using Geant4 and we develop a coincidence classification scheme that exploits the angular correlation of scattered annihilation quanta to improve the accuracy of coincidence detection. We find a [Formula: see text] image quality improvement in terms of the peak signal-to-noise ratio when scattered coincidence events are discriminated solely by their angular correlation, thus demonstrating the feasibility of this novel classification scheme. By integrating scatter events (both single-single and single-only) with unscattered coincidence events discriminated using conventional methods, our results suggest that Compton-PET may be a promising candidate for optimal emission tomographic imaging.

Correction for human head motion in helical x-ray CT.

Correction for rigid object motion in helical CT can be achieved by reconstructing from a modified source-detector orbit, determined by the object motion during the scan. This ensures that all projections are consistent, but it does not guarantee that the projections are complete in the sense of being sufficient for exact reconstruction. We have previously shown with phantom measurements that motion-corrected helical CT scans can suffer from data-insufficiency, in particular for severe motions and at high pitch. To study whether such data-insufficiency artefacts could also affect the motion-corrected CT images of patients undergoing head CT scans, we used an optical motion tracking system to record the head movements of 10 healthy volunteers while they executed each of the 4 different types of motion ('no', slight, moderate and severe) for 60 s. From these data we simulated 354 motion-affected CT scans of a voxelized human head phantom and reconstructed them with and without motion correction. For each simulation, motion-corrected (MC) images were compared with the motion-free reference, by visual inspection and with quantitative similarity metrics. Motion correction improved similarity metrics in all simulations. Of the 270 simulations performed with moderate or less motion, only 2 resulted in visible residual artefacts in the MC images. The maximum range of motion in these simulations would encompass that encountered in the vast majority of clinical scans. With severe motion, residual artefacts were observed in about 60% of the simulations. We also evaluated a new method of mapping local data sufficiency based on the degree to which Tuy's condition is locally satisfied, and observed that areas with high Tuy values corresponded to the locations of residual artefacts in the MC images. We conclude that our method can provide accurate and artefact-free MC images with most types of head motion likely to be encountered in CT imaging, provided that the motion can be accurately determined.

Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level.

Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone-seeking radionuclide that is currently used for treating osteoblastic bone metastases associated with prostate cancer. The stochastic nature of alpha emission, hits and energy deposition poses some challenges for estimating radiation damage. In this paper we investigate the distribution of hits to cells by multiple alpha particles corresponding to a typical clinically delivered dose using a Monte Carlo model to simulate the stochastic effects. The number of hits and dose deposition were recorded in the cytoplasm and nucleus of each cell. Alpha particle tracks were also visualized. We found that the stochastic variation in dose deposited in cell nuclei ([Formula: see text]40%) can be attributed in part to the variation in LET with pathlength. We also found that [Formula: see text]18% of cell nuclei receive less than one sigma below the average dose per cell ([Formula: see text]15.4 Gy). One possible implication of this is that the efficacy of cell kill in alpha particle therapy need not rely solely on ionization clustering on DNA but possibly also on indirect DNA damage through the production of free radicals and ensuing intracellular signaling.

A rigid motion correction method for helical computed tomography (CT).

We propose a method to compensate for six degree-of-freedom rigid motion in helical CT of the head. The method is demonstrated in simulations and in helical scans performed on a 16-slice CT scanner. Scans of a Hoffman brain phantom were acquired while an optical motion tracking system recorded the motion of the bed and the phantom. Motion correction was performed by restoring projection consistency using data from the motion tracking system, and reconstructing with an iterative fully 3D algorithm. Motion correction accuracy was evaluated by comparing reconstructed images with a stationary reference scan. We also investigated the effects on accuracy of tracker sampling rate, measurement jitter, interpolation of tracker measurements, and the synchronization of motion data and CT projections. After optimization of these aspects, motion corrected images corresponded remarkably closely to images of the stationary phantom with correlation and similarity coefficients both above 0.9. We performed a simulation study using volunteer head motion and found similarly that our method is capable of compensating effectively for realistic human head movements. To the best of our knowledge, this is the first practical demonstration of generalized rigid motion correction in helical CT. Its clinical value, which we have yet to explore, may be significant. For example it could reduce the necessity for repeat scans and resource-intensive anesthetic and sedation procedures in patient groups prone to motion, such as young children. It is not only applicable to dedicated CT imaging, but also to hybrid PET/CT and SPECT/CT, where it could also ensure an accurate CT image for lesion localization and attenuation correction of the functional image data.

The cytoplasm as a radiation target: an in silico study of microbeam cell irradiation.

We performed in silico microbeam cell irradiation modelling to quantitatively investigate ionisations resulting from soft x-ray and alpha particle microbeams targeting the cytoplasm of a realistic cell model. Our results on the spatial distribution of ionisations show that as x-rays are susceptible to scatter within a cell that can lead to ionisations in the nucleus, soft x-ray microbeams may not be suitable for investigating the DNA damage response to radiation targeting the cytoplasm alone. In contrast, ionisations from an ideal alpha microbeam are tightly confined to the cytoplasm, but a realistic alpha microbeam degrades upon interaction with components upstream of the cellular target. Thus it is difficult to completely rule out a contribution from alpha particle hits to the nucleus when investigating DNA damage response to cytoplasmic irradiation. We find that although the cytoplasm targeting efficiency of an alpha microbeam is better than that of a soft x-ray microbeam (the probability of stray alphas hitting the nucleus is 0.2% compared to 3.6% for x-rays), stray alphas produce more ionisations in the nucleus and thus have greater potential for initiating damage responses therein. Our results suggest that observed biological responses to cytoplasmic irradiation include a small component that can be attributed to stray ionisations in the nucleus resulting from the stochastic nature of particle interactions that cause out-of-beam scatter. This contribution is difficult to isolate experimentally, thus demonstrating the value of the in silico approach.

Towards optimal imaging with PET: an in silico feasibility study.

The efficacy of Positron Emission Tomography (PET) imaging relies fundamentally on the ability of the system to accurately identify true coincidence events. With existing systems, this is currently accomplished with an energy acceptance criterion followed by correction techniques to remove suspected false coincidence events. These corrections generally result in signal and contrast loss and thus limit the PET system's ability to achieve optimum image quality. A key property of annihilation radiation is that the photons are polarised with respect to each other. This polarisation correlation offers a potentially powerful discriminator, independent of energy, to accurately identify true events. In this proof of concept study, we investigate how photon polarisation information can be exploited in PET imaging by developing a method to discriminate true coincidences using the polarisation correlation of annihilation pairs. We implement this method using a Geant4 PET simulation of a GE Advance/Discovery LS system and demonstrate the potential advantages of the polarisation coincidence selection method over a standard energy criterion method. Current PET ring detectors are not capable of exploiting the polarisation correlation of the photon pairs. Compton PET systems, however are promising candidates for this application. We demonstrate the feasibility of a two-component Compton camera system in identifying true coincidences with Monte Carlo simulations. Our study demonstrates the potential of improving signal gain using polarisation, particularly for high photon emission rates. We also demonstrate the ability of the Compton camera at exploiting this polarisation correlation in PET.

Optimisation of the imaging and dosimetric characteristics of an electronic portal imaging device employing plastic scintillating fibres using Monte Carlo simulations.

A Monte Carlo model of a novel electronic portal imaging device (EPID) has been developed using Geant4 and its performance for imaging and dosimetry applications in radiotherapy has been characterised. The EPID geometry is based on a physical prototype under ongoing investigation and comprises an array of plastic scintillating fibres in place of the metal plate/phosphor screen in standard EPIDs. Geometrical and optical transport parameters were varied to investigate their impact on imaging and dosimetry performance. Detection efficiency was most sensitive to variations in fibre length, achieving a peak value of 36% at 50 mm using 400 keV x-rays for the lengths considered. Increases in efficiency for longer fibres were partially offset by reductions in sensitivity. Removing the extra-mural absorber surrounding individual fibres severely decreased the modulation transfer function (MTF), highlighting its importance in maximising spatial resolution. Field size response and relative dose profile simulations demonstrated a water-equivalent dose response and thus the prototype's suitability for dosimetry applications. Element-to-element mismatch between scintillating fibres and underlying photodiode pixels resulted in a reduced MTF for high spatial frequencies and quasi-periodic variations in dose profile response. This effect is eliminated when fibres are precisely matched to underlying pixels. Simulations strongly suggest that with further optimisation, this prototype EPID may be capable of simultaneous imaging and dosimetry in radiotherapy.

Simulation of real-time EPID images during IMRT using Monte-Carlo.

This study is part of a project concerned with real-time EPID-based verification of the incremental dose delivered during IMRT radiation treatments. Three automated Monte-Carlo methods are devised to calculate the differential dose delivered to the EPID during treatment. All methods break down the normalized total monitor units into a number of equally spaced segments. A method models the dynamic simulation as a series of static fields, each field corresponding to an IMRT segment or a sub-segment. Another method models each segment as a separate dynamic IMRT file. A third method, which modifies the DYNVMLC module of the BEAMnrc code, uses the full-MLC file. The MLC positions for the simulated photons are sequentially selected within DYNVMLC to correspond to individual segments of the delivery. A bash script calls the BEAM shared-library to calculate and store the EPID dose for each segment. Validation is performed by comparing the average dose contributed by all segments with the dose predicted by a canonical dynamic IMRT simulation that uses the same MLC file. The best results are achieved by the methods based on dynamic simulations (where leaf positions within a segment are interpolated for simulated photons) whose normalized root mean square error is at the most 0.2% over the focal area. EPID images can be predicted for individual segments (or smaller intervals) of an IMRT delivery using Monte-Carlo methods. The MLC file can be externally spliced or a simple modification of the DYNVMLC code can achieve accurate results.

Estimation of effective imaging dose for kilovoltage intratreatment monitoring of the prostate position during cancer radiotherapy.

Kilovoltage intratreatment monitoring (KIM) is a novel real-time localization modality where the tumor position is continuously measured during intensity modulated radiation therapy (IMRT) or intensity modulated arc therapy (IMAT) by a kilovoltage (kV) x-ray imager. Adding kV imaging during therapy adds radiation dose. The additional effective dose is quantified for prostate radiotherapy and compared to dose from other localization modalities. The software PCXMC 2.0 was used to calculate the effective dose delivered to a phantom as a function of imager angle and field size for a Varian On-Board Imager. The average angular effective dose was calculated for a field size of 6 cm × 6 cm. The average angular effective dose was used in calculations for different treatment scenarios. Treatment scenarios considered were treatment type and fractionation. For all treatment scenarios, (i.e. conventionally fractionated and stereotactic body radiotherapy (SBRT), IMRT and IMAT), the total KIM dose at 1 Hz ranged from 2-10 mSv. This imaging dose is less than the Navotek radioactive implant dose (64 mSv) and a standard SBRT cone beam computed tomography pretreatment scan dose (22 mSv) over an entire treatment regime. KIM delivers an acceptably low effective dose for daily use as a real-time image-guidance method for prostate radiotherapy.

Radiation damage on sub-cellular scales: beyond DNA.

This study investigates a model cell as a target for low-dose radiation using Monte Carlo simulations. Mono-energetic electrons and photons are used with initial energies between 10 and 50 keV, relevant to out-of-field radiotherapy scenarios where modern treatment modalities expose relatively large amounts of healthy tissue to low-dose radiation, and also to microbeam cell irradiation studies which show the importance of the cytoplasm as a radiation target. The relative proportions of number of ionizations and total energy deposit in the nucleus and cytoplasm are calculated. We show that for a macroscopic dose of no more than 1 Gy only a few hundred ionizations occur in the nucleus volume whereas the number of ionizations in the cytoplasm is over a magnitude larger. We find that the cell geometry can have an appreciable effect on the energy deposit in the cell and can cause a nonlinear increase in energy deposit with cytoplasm density. We also show that changing the nucleus volume has negligible effect on the total energy deposit but alters the relative proportion deposited in the nucleus and cytoplasm; the nucleus volume must increase to approximately the same volume as the cytoplasm before the energy deposit in the nucleus matches that in the cytoplasm. Additionally we find that energy deposited by electrons is generally insensitive to spatial variations in chemical composition, which can be attributed to negligible differences in electron stopping power for cytoplasm and nucleus materials. On the other hand, we find that chemical composition can affect energy deposited by photons due to non-negligible differences in attenuation coefficients. These results are of relevance in considering radiation effects in healthy cells, which tend to have smaller nuclei. Our results further show that the cytoplasm and organelles residing therein can be important targets for low-dose radiation damage in healthy cells and warrant investigation as much as the conventional focus of a high-dose radiation DNA target in tumour cells.

Practical considerations for reporting surface dose in external beam radiotherapy: a 6 MV X-ray beam study.

In this study, we assessed the accuracy of surface doses determined by direct measurement and treatment planning system (TPS) calculations, relative to benchmark Monte Carlo (MC) doses calculated at 70 µm for a 6 MV, 10 × 10 cm clinical radiotherapy beam. In a homogeneous phantom with both open and fixed wedged fields, we found that the relative dose measured with an Attix chamber underestimates the MC calculated surface dose by 2.9 %, while the relative dose measured with EBT2 Gafchromic film overestimates the MC surface dose by 0.9 %. There was a significant over-response of up to 20 % in doses calculated at < 2 mm depth with the Eclipse analytic anisotropic algorithm (AAA) compared to corresponding MC doses for an open field. This drops to < 2 % at 2 mm depth. In a heterogeneous phantom, EBT2 film overestimates relative dose by up to 3.1 % compared to the MC calculated surface dose. The AAA relative dose calculated in a heterogeneous phantom at 2 mm depth agrees to within 1.5 % with the MC doses calculated at the same depth, but overestimates the MC surface dose (at 70 µm) by up to 2.5 %. Our results suggest that TPS doses evaluated near the surface be reported with a depth that should be at least 2 mm and this should be taken into consideration in the planned target volume for treatments where surface dose is a constraining factor. Our study demonstrates the usefulness of EBT2 film for measuring surface dose: under homogeneous conditions, the effective point of measurement of EBT2 film can be considered equivalent to the clinical skin depth of 70 µm.

SU-E-I-109: Sensitivity Analysis of an Electronic Portal Imaging Device Monte Carlo Model to Variations in Optical Transport Parameters.

PURPOSE: To investigate the sensitivity of a Monte Carlo (MC) model of a standard clinical amorphous silicon (a-Si) electron portal imaging device (EPID) to variations in optical photon transport parameters. METHODS: The Geant4 MC toolkit was used to develop a comprehensive model of an indirect-detection a-Si EPID incorporating x-ray and optical photon transport. The EPID was modeled as a series of uniform layers with properties specified by the manufacturer (PerkinElmer, Santa Clara, CA) of a research EPID at our centre. Optical processes that were modeled include bulk absorption, Rayleigh scattering, and boundary processes (reflection and refraction). Model performance was evaluated by scoring optical photons absorbed by the a-Si photodiode as a function of radial distance from a point source of x-rays on an event-by-event basis (0.025 mm resolution). Primary x-ray energies were sampled from a clinical 6 MV photon spectrum. Simulations were performed by varying optical transport parameters and the resulting point spread functions (PSFs) were compared. The optical parameters investigated include: x-ray transport cutoff thresholds; absorption path length; optical energy spectrum; refractive indices; and the 'roughness' of boundaries within phosphor screen layers. RESULTS: The transport cutoffs and refractive indices studied were found to minimally affect resulting PSFs. A monoenergetic optical spectrum slightly broadened the PSF in comparison with the use of a polyenergetic spectrum. The absorption path length only significantly altered the PSF when decreased drastically. Variations in the treatment of boundaries noticeably broadened resulting PSFs. CONCLUSIONS: Variation in optical transport parameters was found to affect resulting PSF calculations. Current work is focusing on repeating this analysis with a coarser resolution more typical of a commercial a-Si EPID to observe if these effects continue to alter the EPID PSF. Experimental measurement of the EPID line spread function to validate these results is also underway. Cancer Institute NSW Research Equipment Grants 10/REG/1-20 and 10/REG/1-10 Cancer Council NSW Grant, ID RG 11-06 NHMRC Project Grant, ID569211 The University of Sydney Postgraduate Research Scholarship in Medical Physics SWSCS Radiation Oncology Student Scholarship, 2012.

The measurement of backscatter factors of kilovoltage X-ray beams using Gafchromic™ EBT2 film.

Backscatter factors are essential in the determination of radiation dose for kilovoltage X-ray beams. The accurate measurement of backscatter factors in water (B (W)) is difficult and published values are based largely on Monte Carlo calculations. A number of studies have found that the measurement of B (W) in the energy range from 50 to 300 kVp is possible using Gafchromic EBT film, but this film is no longer commercially available. In this work, we evaluated whether the newer Gafchromic EBT2 film is suitable for the determination of B (W) for kilovoltage X-ray beams. B (W) were measured with Gafchromic EBT2 film for beam qualities of 50, 100 and 280 kVp and field sizes of 2, 3, 4 and 6 cm diameter and compared with tabulated values published in the AAPM TG-61 protocol. We found that rotation of the film position during readout had a small but non-negligible effect on the optical density readings. The agreement between measured and published B (W) was better than 3%, with the largest difference of occurring for the 2 cm diameter field with the 50 kVp X-ray beam. However, these differences are consistent with the total estimated uncertainty for the measurements, as calculated by the ISO GUM. Our results demonstrate that Gafchromic EBT2 film is a suitable dosimeter for B (W) measurements for clinical kilovoltage X-ray beams.

An investigation of backscatter factors for kilovoltage x-rays: a comparison between Monte Carlo simulations and Gafchromic EBT film measurements.

Backscatter factors are important parameters in the determination of dose for kilovoltage x-ray beams. However, backscatter factors are difficult to measure experimentally, and tabulated values are based largely on Monte Carlo calculations. In this study we have determined new backscatter factors by both experimental and Monte Carlo methods, and compared them with existing backscatter factors published in the AAPM TG-61 protocol. The purpose of this study is twofold: (1) to evaluate the overall effectiveness of using Gafchromic EBT film for backscatter factor measurements and (2) to determine whether existing Monte Carlo-calculated backscatter factors need to be updated. We measured backscatter factors using Gafchromic EBT film for three field sizes (2, 4 and 6 cm diameter cones) and three kilovoltage beam qualities, including 280 kVp for which similar measurements have not previously been reported. We also present new Monte Carlo-calculated backscatter factors obtained using the EGSnrc/BEAMnrc code system to simulate the Pantak kilovoltage x-ray unit used in our measurements. The results were compared with backscatter factors tabulated in the AAPM TG-61 protocol for kilovoltage x-ray dosimetry. The largest difference between our measured and calculated backscatter factors and the AAPM TG-61 values was found to be 2.5%. This agreement is remarkably good, considering that the AAPM TG-61 values consist of a combination of experimental and Monte Carlo calculations obtained over 20 years ago using different measurement techniques, as well as older Monte Carlo code and cross-section data. Furthermore, our Monte Carlo-calculated backscatter factors agree within 1% with the AAPM TG-61 values for all beam qualities and field sizes. Our Gafchromic film measurements had slightly larger differences with the AAPM TG-61 backscatter factors, up to approximately 2% for the 6 cm diameter cone at a beam quality of 50 kVp. The largest difference in backscatter factors, of 2.5%, was found between Monte Carlo-calculated and Gafchromic film-measured data for the 100 kVp x-ray beam with the 4 cm diameter cone. The differences in backscatter factors between the three data sets (measurements, calculations and published values) are all within the uncertainties from our Gafchromic film measurements and Monte Carlo calculations. Our results demonstrate the suitability of using Gafchromic EBT film to measure equipment-specific backscatter factors for kilovoltage x-ray beams over the entire energy range and also confirm that backscatter factors published in kilovoltage dosimetry protocols still remain valid.