The development of Monte Carlo techniques for the verification of radiotherapy treatments

Radiotherapy is a cancer treatment modality in which a dose of ionising radiation is delivered to a tumour. The accurate calculation of the dose to the patient is very important in the design of an effective therapeutic strategy. This study aimed to systematically examine the accuracy of the radiotherapy dose calculations performed by clinical treatment planning systems by comparison againstMonte Carlo simulations of the treatment delivery. A suite of software tools known as MCDTK (Monte Carlo DICOM ToolKit) was developed for this purpose, and is capable of: • Importing DICOM-format radiotherapy treatment plans and producing Monte Carlo simulation input files (allowing simple simulation of complex treatments), and calibrating the results; • Analysing the predicted doses of and deviations between the Monte Carlo simulation results and treatment planning system calculations in regions of interest (tumours and organs-at-risk) and generating dose-volume histograms, so that conformity with dose prescriptions can be evaluated. The code has been tested against various treatment planning systems, linear acceleratormodels and treatment complexities. Six clinical head and neck cancer treatments were simulated and the results analysed using this software. The deviations were greatest where the treatment volume encompassed tissues on both sides of an air cavity. This was likely due to the method the planning system used to model low density media.

Monte Carlo simulations of dynamic radiotherapy treatments

The effects of tumour motion during radiation therapy delivery have been widely investigated. Motion effects have become increasingly important with the introduction of dynamic radiotherapy delivery modalities such as enhanced dynamic wedges (EDWs) and intensity modulated radiation therapy (IMRT) where a dynamically collimated radiation beam is delivered to the moving target, resulting in dose blurring and interplay effects which are a consequence of the combined tumor and beam motion. Prior to this work, reported studies on the EDW based interplay effects have been restricted to the use of experimental methods for assessing single-field non-fractionated treatments. In this work, the interplay effects have been investigated for EDW treatments. Single and multiple field treatments have been studied using experimental and Monte Carlo (MC) methods. Initially this work experimentally studies interplay effects for single-field non-fractionated EDW treatments, using radiation dosimetry systems placed on a sinusoidaly moving platform. A number of wedge angles (60º, 45º and 15º), field sizes (20 × 20, 10 × 10 and 5 × 5 cm2), amplitudes (10-40 mm in step of 10 mm) and periods (2 s, 3 s, 4.5 s and 6 s) of tumor motion are analysed (using gamma analysis) for parallel and perpendicular motions (where the tumor and jaw motions are either parallel or perpendicular to each other). For parallel motion it was found that both the amplitude and period of tumor motion affect the interplay, this becomes more prominent where the collimator tumor speeds become identical. For perpendicular motion the amplitude of tumor motion is the dominant factor where as varying the period of tumor motion has no observable effect on the dose distribution. The wedge angle results suggest that the use of a large wedge angle generates greater dose variation for both parallel and perpendicular motions. The use of small field size with a large tumor motion results in the loss of wedged dose distribution for both parallel and perpendicular motion. From these single field measurements a motion amplitude and period have been identified which show the poorest agreement between the target motion and dynamic delivery and these are used as the „worst case motion parameters.. The experimental work is then extended to multiple-field fractionated treatments. Here a number of pre-existing, multiple–field, wedged lung plans are delivered to the radiation dosimetry systems, employing the worst case motion parameters. Moreover a four field EDW lung plan (using a 4D CT data set) is delivered to the IMRT quality control phantom with dummy tumor insert over four fractions using the worst case parameters i.e. 40 mm amplitude and 6 s period values. The analysis of the film doses using gamma analysis at 3%-3mm indicate the non averaging of the interplay effects for this particular study with a gamma pass rate of 49%. To enable Monte Carlo modelling of the problem, the DYNJAWS component module (CM) of the BEAMnrc user code is validated and automated. DYNJAWS has been recently introduced to model the dynamic wedges. DYNJAWS is therefore commissioned for 6 MV and 10 MV photon energies. It is shown that this CM can accurately model the EDWs for a number of wedge angles and field sizes. The dynamic and step and shoot modes of the CM are compared for their accuracy in modelling the EDW. It is shown that dynamic mode is more accurate. An automation of the DYNJAWS specific input file has been carried out. This file specifies the probability of selection of a subfield and the respective jaw coordinates. This automation simplifies the generation of the BEAMnrc input files for DYNJAWS. The DYNJAWS commissioned model is then used to study multiple field EDW treatments using MC methods. The 4D CT data of an IMRT phantom with the dummy tumor is used to produce a set of Monte Carlo simulation phantoms, onto which the delivery of single field and multiple field EDW treatments is simulated. A number of static and motion multiple field EDW plans have been simulated. The comparison of dose volume histograms (DVHs) and gamma volume histograms (GVHs) for four field EDW treatments (where the collimator and patient motion is in the same direction) using small (15º) and large wedge angles (60º) indicates a greater mismatch between the static and motion cases for the large wedge angle. Finally, to use gel dosimetry as a validation tool, a new technique called the „zero-scan method. is developed for reading the gel dosimeters with x-ray computed tomography (CT). It has been shown that multiple scans of a gel dosimeter (in this case 360 scans) can be used to reconstruct a zero scan image. This zero scan image has a similar precision to an image obtained by averaging the CT images, without the additional dose delivered by the CT scans. In this investigation the interplay effects have been studied for single and multiple field fractionated EDW treatments using experimental and Monte Carlo methods. For using the Monte Carlo methods the DYNJAWS component module of the BEAMnrc code has been validated and automated and further used to study the interplay for multiple field EDW treatments. Zero-scan method, a new gel dosimetry readout technique has been developed for reading the gel images using x-ray CT without losing the precision and accuracy.

Sensory imagery in craving : from cognitive psychology to new treatments for addiction

Sensory imagery is a powerful tool for inducing craving because it is a key component of the cognitive system that underpins human motivation. The role of sensory imagery in motivation is explained by Elaborated Intrusion (EI) theory. Imagery plays an important role in motivation because it conveys the emotional qualities of the desired event, mimicking anticipated pleasure or relief, and continual elaboration of the imagery ensures that the target stays in mind. We argue that craving is a conscious state, intervening between unconscious triggers and consumption, and summarise evidence that interfering with sensory imagery can weaken cravings. We argue that treatments for addiction can be enhanced by the application of EI theory to maintain motivation, and assist in the management of craving in high-risk situations.

The formation of YBa2Cu3O7-x in melt-texture heat treatments

A study of the bulk formation of YBa2Cu3O7-x from the Y2BaCuO5 plus liquid regime reveals that phase formation occurs at appreciable rates below 950°C in air. This result has been observed for phase-pure YBa2Cu3O7-x starting material given two types of heat treatment: held at 1100°C and slow-cooled from 1030°C at 6°C/h or heat-treated isothermally. Differential thermal analysis, with a cooling rate of 10°C/min indicates that the degree of undercooling for the peritectic formation of YBa2Cu3O7-x is greater than 100°C. © 1994.

A safe system-based approach to selection of clear zones, safety barriers and other roadside treatments

On average, 560 fatal run-off-road crashes occur annually in Australia and 135 in New Zealand. In addition, there are more than 14,000 run-off-road crashes causing injuries each year across both countries. In rural areas, run-off-road casualty crashes constitute 50-60% of all casualty crashes. Their severity is particularly high with more than half of those involved sustaining fatal or serious injuries. This paper reviews the existing approach to roadside hazard risk assessment, selection of clear zones and hazard treatments. It proposes a modified approach to roadside safety evaluation and management. It is a methodology based on statistical modelling of run-off-road casualty crashes, and application of locally developed crash modification factors and severity indices. Clear zones, safety barriers and other roadside design/treatment options are evaluated with a view to minimise fatal and serious injuries – the key Safe System objective. The paper concludes with a practical demonstration of the proposed approach. The paper is based on findings from a four-year Austroads research project into improving roadside safety in the Safe System context.

Development of a practical design guide for balcony acoustic treatments

Balcony acoustic treatments can be demonstrated to provide important benefits in reducing road traffic noise within the balcony space and consequently internally for any adjacent room. The actual effect on road traffic noise is derived from a multitude of variables that can be broadly categorized into (a) acoustical and (b) geometrical for two distinct propagation volumes being (i) the street space, and (ii) the balcony space. A series of recent research activities in this area has incorporated the use of a combined image and diffuse source model, which can be used to predict the effect of balconies on road traffic noise for large number of scenarios. This paper investigates and presents a method and capability to summarize predictive data into user friendly guidelines aimed for use by acoustical professionals and architects and possible implementation in building design policies for environmental noise. The paper concludes with a presentation of the likely format of a potential design guide.

The significance of balcony acoustic treatments in mitigating urban road traffic noise

Urban road traffic noise in cities is an ongoing and increasing problem across much of the world. Consequently a large amount of effort is expended in attempts to address this problem, especially in the area of acoustic design of buildings. Acoustic design policies developed by government authorities will typically focus on required transport noise reductions through a building façade to meet a specified internal noise levels. The significance of balcony acoustic treatments has been highlighted in recent decades yet this area has potentially been considered less important than the need for acoustic isolation of building facades. This paper outlines recent research that has been conducted in determining the significance of balcony acoustic treatments in mitigating urban road traffic noise. It summarizes recent literature, some of which focuses on technological advances in the knowledge of balcony acoustic design and some literature discusses the overall aims and benefits of balcony acoustic design. The aim of this paper is to promote the use of balcony acoustic design as a significant element in the overall solution towards mitigating road traffic noise in modern cities.

Monte Carlo verification of intensity modulated radiotherapy treatments using EPIDS

Purpose: Electronic Portal Imaging Devices (EPIDs) are available with most linear accelerators (Amonuk, 2002), the current technology being amorphous silicon flat panel imagers. EPIDs are currently used routinely in patient positioning before radiotherapy treatments. There has been an increasing interest in using EPID technology tor dosimetric verification of radiotherapy treatments (van Elmpt, 2008). A straightforward technique involves the EPID panel being used to measure the fluence exiting the patient during a treatment which is then compared to a prediction of the fluence based on the treatment plan. However, there are a number of significant limitations which exist in this Method: Resulting in a limited proliferation ot this technique in a clinical environment. In this paper, we aim to present a technique of simulating IMRT fields using Monte Carlo to predict the dose in an EPID which can then be compared to the measured dose in the EPID. Materials: Measurements were made using an iView GT flat panel a-SI EPfD mounted on an Elekta Synergy linear accelerator. The images from the EPID were acquired using the XIS software (Heimann Imaging Systems). Monte Carlo simulations were performed using the BEAMnrc and DOSXVZnrc user codes. The IMRT fieids to be delivered were taken from the treatment planning system in DICOMRT format and converted into BEAMnrc and DOSXYZnrc input files using an in-house application (Crowe, 2009). Additionally. all image processing and analysis was performed using another in-house application written using the Interactive Data Language (IDL) (In Visual Information Systems). Comparison between the measured and Monte Carlo EPID images was performed using a gamma analysis (Low, 1998) incorporating dose and distance to agreement criteria. Results: The fluence maps recorded by the EPID were found to provide good agreement between measured and simulated data. Figure 1 shows an example of measured and simulated IMRT dose images and profiles in the x and y directions. "A technique for the quantitative evaluation of dose distributions", Med Phys, 25(5) May 1998 S. Crowe, 1. Kairn, A. Fielding, "The Development of a Monte Carlo system to verify Radiotherapy treatment dose calculations", Radiotherapy & Oncology, Volume 92, Supplement 1, August 2009, Pages S71-S71.

Effect of CT electron density identification on Monte Carlo simulations of radiotherapeutic treatments

Introduction: The accurate identification of tissue electron densities is of great importance for Monte Carlo (MC) dose calculations. When converting patient CT data into a voxelised format suitable for MC simulations, however, it is common to simplify the assignment of electron densities so that the complex tissues existing in the human body are categorized into a few basic types. This study examines the effects that the assignment of tissue types and the calculation of densities can have on the results of MC simulations, for the particular case of a Siemen’s Sensation 4 CT scanner located in a radiotherapy centre where QA measurements are routinely made using 11 tissue types (plus air). Methods: DOSXYZnrc phantoms are generated from CT data, using the CTCREATE user code, with the relationship between Hounsfield units (HU) and density determined via linear interpolation between a series of specified points on the ‘CT-density ramp’ (see Figure 1(a)). Tissue types are assigned according to HU ranges. Each voxel in the DOSXYZnrc phantom therefore has an electron density (electrons/cm3) defined by the product of the mass density (from the HU conversion) and the intrinsic electron density (electrons /gram) (from the material assignment), in that voxel. In this study, we consider the problems of density conversion and material identification separately: the CT-density ramp is simplified by decreasing the number of points which define it from 12 down to 8, 3 and 2; and the material-type-assignment is varied by defining the materials which comprise our test phantom (a Supertech head) as two tissues and bone, two plastics and bone, water only and (as an extreme case) lead only. The effect of these parameters on radiological thickness maps derived from simulated portal images is investigated. Results & Discussion: Increasing the degree of simplification of the CT-density ramp results in an increasing effect on the resulting radiological thickness calculated for the Supertech head phantom. For instance, defining the CT-density ramp using 8 points, instead of 12, results in a maximum radiological thickness change of 0.2 cm, whereas defining the CT-density ramp using only 2 points results in a maximum radiological thickness change of 11.2 cm. Changing the definition of the materials comprising the phantom between water and plastic and tissue results in millimetre-scale changes to the resulting radiological thickness. When the entire phantom is defined as lead, this alteration changes the calculated radiological thickness by a maximum of 9.7 cm. Evidently, the simplification of the CT-density ramp has a greater effect on the resulting radiological thickness map than does the alteration of the assignment of tissue types. Conclusions: It is possible to alter the definitions of the tissue types comprising the phantom (or patient) without substantially altering the results of simulated portal images. However, these images are very sensitive to the accurate identification of the HU-density relationship. When converting data from a patient’s CT into a MC simulation phantom, therefore, all possible care should be taken to accurately reproduce the conversion between HU and mass density, for the specific CT scanner used. 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 (RBWH), Brisbane, Australia. The authors are grateful to the staff of the RBWH, especially Darren Cassidy, for assistance in obtaining the phantom CT data used in this study. The authors also wish to thank Cathy Hargrave, of QUT, for assistance in formatting the CT data, using the Pinnacle TPS. Computational resources and services used in this work were provided by the HPC and Research Support Group, QUT, Brisbane, Australia.

The development of Monte Carlo techniques for the verification of radiotherapy treatments

Introduction: Recent advances in the planning and delivery of radiotherapy treatments have resulted in improvements in the accuracy and precision with which therapeutic radiation can be administered. As the complexity of the treatments increases it becomes more difficult to predict the dose distribution in the patient accurately. Monte Carlo (MC) methods have the potential to improve the accuracy of the dose calculations and are increasingly being recognised as the ‘gold standard’ for predicting dose deposition in the patient [1]. This project has three main aims: 1. To develop tools that enable the transfer of treatment plan information from the treatment planning system (TPS) to a MC dose calculation engine. 2. To develop tools for comparing the 3D dose distributions calculated by the TPS and the MC dose engine. 3. To investigate the radiobiological significance of any errors between the TPS patient dose distribution and the MC dose distribution in terms of Tumour Control Probability (TCP) and Normal Tissue Complication Probabilities (NTCP). The work presented here addresses the first two aims. Methods: (1a) Plan Importing: A database of commissioned accelerator models (Elekta Precise and Varian 2100CD) has been developed for treatment simulations in the MC system (EGSnrc/BEAMnrc). Beam descriptions can be exported from the TPS using the widespread DICOM framework, and the resultant files are parsed with the assistance of a software library (PixelMed Java DICOM Toolkit). The information in these files (such as the monitor units, the jaw positions and gantry orientation) is used to construct a plan-specific accelerator model which allows an accurate simulation of the patient treatment field. (1b) Dose Simulation: The calculation of a dose distribution requires patient CT images which are prepared for the MC simulation using a tool (CTCREATE) packaged with the system. Beam simulation results are converted to absolute dose per- MU using calibration factors recorded during the commissioning process and treatment simulation. These distributions are combined according to the MU meter settings stored in the exported plan to produce an accurate description of the prescribed dose to the patient. (2) Dose Comparison: TPS dose calculations can be obtained using either a DICOM export or by direct retrieval of binary dose files from the file system. Dose difference, gamma evaluation and normalised dose difference algorithms [2] were employed for the comparison of the TPS dose distribution and the MC dose distribution. These implementations are spatial resolution independent and able to interpolate for comparisons. Results and Discussion: The tools successfully produced Monte Carlo input files for a variety of plans exported from the Eclipse (Varian Medical Systems) and Pinnacle (Philips Medical Systems) planning systems: ranging in complexity from a single uniform square field to a five-field step and shoot IMRT treatment. The simulation of collimated beams has been verified geometrically, and validation of dose distributions in a simple body phantom (QUASAR) will follow. The developed dose comparison algorithms have also been tested with controlled dose distribution changes. Conclusion: The capability of the developed code to independently process treatment plans has been demonstrated. A number of limitations exist: only static fields are currently supported (dynamic wedges and dynamic IMRT will require further development), and the process has not been tested for planning systems other than Eclipse and Pinnacle. The tools will be used to independently assess the accuracy of the current treatment planning system dose calculation algorithms for complex treatment deliveries such as IMRT in treatment sites where patient inhomogeneities are expected to be significant. Acknowledgements: Computational resources and services used in this work were provided by the HPC and Research Support Group, Queensland University of Technology, Brisbane, Australia. Pinnacle dose parsing made possible with the help of Paul Reich, North Coast Cancer Institute, North Coast, New South Wales.

Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments

To identify potential migraine therapeutics, extracts of eighteen plants were screened to detect plant constituents affecting ADP induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of the seven plants exhibiting significant inhibition of platelet function were reanalysed in the presence of polyvinyl pyrrolidone (PVP) to remove polyphenolic tannins that precipitate proteins. Two of these extracts no longer exhibited inhibition of platelet activity after removal of tannins. However, extracts of Crataegus monogyna, Ipomoea pes-caprae, Eremophila freelingii, Eremophila longifolia, and Asteromyrtus symphyocarpa still potently inhibited ADP induced human platelet [14C]5-HT release in vitro, with levels ranging from 62 to 95% inhibition. I. pes-caprae, and C. monogyna also caused significant inhibition of ADP induced platelet aggregation. All of these plants have been previously used as traditional headache treatments, except for C. monogyna which is used primarily for protective effects on the cardiovascular system. Further studies elucidating the compounds that are responsible for these anti-platelet effects are needed to determine their exact mechanism of action.

Correcting radiation survey data to account for increased leakage during intensity modulated radiotherapy treatments

Purpose Intensity modulated radiotherapy (IMRT) treatments require more beam-on time and produce more linac head leakage to deliver similar doses to conventional, unmodulated, radiotherapy treatments. It is necessary to take this increased leakage into account when evaluating the results of radiation surveys around bunkers that are, or will be, used for IMRT. The recommended procedure of 15 applying a monitor-unit based workload correction factor to secondary barrier survey measurements, to account for this increased leakage when evaluating radiation survey measurements around IMRT bunkers, can lead to potentially-costly over estimation of the required barrier thickness. This study aims to provide initial guidance on the validity of reducing the value of the correction factor when applied to different radiation barriers (primary barriers, doors, maze walls and other walls) by 20 evaluating three different bunker designs. Methods Radiation survey measurements of primary, scattered and leakage radiation were obtained at each of five survey points around each of three different radiotherapy bunkers and the contribution of leakage to the total measured radiation dose at each point was evaluated. Measurements at each survey point were made with the linac gantry set to 12 equidistant positions from 0 to 330o, to 25 assess the effects of radiation beam direction on the results. Results For all three bunker designs, less than 0.5% of dose measured at and alongside the primary barriers, less than 25% of the dose measured outside the bunker doors and up to 100% of the dose measured outside other secondary barriers was found to be caused by linac head leakage. Conclusions Results of this study suggest that IMRT workload corrections are unnecessary, for 30 survey measurements made at and alongside primary barriers. Use of reduced IMRT workload correction factors is recommended when evaluating survey measurements around a bunker door, provided that a subset of the measurements used in this study are repeated for the bunker in question. Reduction of the correction factor for other secondary barrier survey measurements is not recommended unless the contribution from leakage is separetely evaluated.

Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension

The synthesis and evaluation of novel resveratrol-based nitroxides have been explored for the potential treatment of hypertension. New methodology for the direct aryl iodination of isoindoline and isoindoline nitroxide using periodic acid and potassium iodide in concentrated sulphuric acid was developed. Diiodinated tetramethyl and tetraethyl isoindolines and a tetramethyl isoindoline nitroxide were prepared in excellent yields (70 – 82%). A diiodinated tetraethyl isoindoline nitroxide was generated from the corresponding nitroxide in modest yield (37%) alongside iodinated nitrones. The mono-iodinated species were also generated in modest yields (34 – 48%). Incorporation of the nitroxide unit into the structure of resveratrol was achieved using palladium-catalysed Heck coupling. Use of the previously prepared iodo products 5-iodo-1,1,3,3-tetramethylisoindolin-2-yloyl 18 and 5,6-diiodo-1,1,3,3-tetramethylisoindolin-2-yloyl 22 gave resveratrol nitroxides 12 and 13 in yields of 50% (optimized) and 1.6% respectively. Preliminary evaluation of the resveratrol analogue 12 as a treatment for hypertension was undertaken in the DOCA-salt rat model. A reduction in systolic blood pressure as well as alleviation of ventricular hypertrophy was observed. A larger study involving the DOCA salt rats is currently in progress.