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.

Spatial and temporal clusters of Barmah Forest virus disease in Queensland, Australia

Objective To identify the spatial and temporal clusters of Barmah Forest virus (BFV) disease in Queensland in Australia, using geographical information systems (GIS) and spatial scan statistic (SaTScan). Methods We obtained BFV disease cases, population and statistical local areas boundary data from Queensland Health and Australian Bureau of Statistics respectively during 1992-2008 for Queensland. A retrospective Poisson-based analysis using SaTScan software and method was conducted in order to identify both purely spatial and space-time BFV disease high-rate clusters. A spatial cluster size of a proportion of the population and a 200km circle radius and varying time windows from 1 month to 12 months were chosen (for the space-time analysis). Results The spatial scan statistic detected a most likely significant purely spatial cluster (including 23 SLAs) and a most likely significant space-time cluster (including 24 SLAs) in approximately the same location. Significant secondary clusters were also identified from both the analyses in several locations. Conclusions This study provides evidence of the existence of statistically significant BFV disease clusters in Queensland, Australia. The study also demonstrated the relevance and applicability of SaTScan in analysing on-going surveillance data to identify clusters to facilitate the development of effective BFV disease prevention and control strategies in Queensland, Australia.

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.

Retinal and choroidal thickness in myopic anisometropia

PURPOSE: To examine the foveal retinal thickness (RT) and subfoveal choroidal thickness (ChT) between the fellow eyes of myopic anisometropes. METHODS: Twenty-two young (mean age 23 ± 5 years), healthy myopic anisometropes (≥ 1 D spherical equivalent [SEq] anisometropia) without amblyopia or strabismus were recruited. Spectral domain optical coherence tomography (SD-OCT) was used to capture images of the retina and choroid. Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers then manually determined the RT and ChT at the centre of the fovea from each SD-OCT image, which were then averaged. Axial length was measured using optical low coherence biometry during relaxed accommodation. RESULTS: The mean absolute SEq anisometropia was 1.74 ± 0.95 D and the mean interocular difference in axial length was 0.58 ± 0.41 mm. There was a strong correlation between SEq anisometropia and the interocular difference in axial length (r = 0.90, p < 0.001). Measures of RT and ChT were highly correlated between the two observers (r = 0.99 and 0.97 respectively) and in close agreement (mean inter-observer difference: RT 1.3 ± 2.2 µm, ChT 1.5 ± 13.7 µm). There was no significant difference in RT between the more (218 ± 18 µm) and less myopic eyes (215 ± 18 µm) (p > 0.05). However, the mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 µm) compared to the fellow, less myopic eye (286 ± 58 µm) (p < 0.001). There was a moderate correlation between the interocular difference in ChT and the interocular difference in axial length (r = -0.50, p < 0.01). CONCLUSIONS: Foveal RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of our anisometropic cohort. The interocular difference in ChT correlated with the magnitude of axial anisometropia.

Correction of step artefact associated with MRI scanning of long bones

3D models of long bones are being utilised for a number of fields including orthopaedic implant design. Accurate reconstruction of 3D models is of utmost importance to design accurate implants to allow achieving a good alignment between two bone fragments. Thus for this purpose, CT scanners are employed to acquire accurate bone data exposing an individual to a high amount of ionising radiation. Magnetic resonance imaging (MRI) has been shown to be a potential alternative to computed tomography (CT) for scanning of volunteers for 3D reconstruction of long bones, essentially avoiding the high radiation dose from CT. In MRI imaging of long bones, the artefacts due to random movements of the skeletal system create challenges for researchers as they generate inaccuracies in the 3D models generated by using data sets containing such artefacts. One of the defects that have been observed during an initial study is the lateral shift artefact occurring in the reconstructed 3D models. This artefact is believed to result from volunteers moving the leg during two successive scanning stages (the lower limb has to be scanned in at least five stages due to the limited scanning length of the scanner). As this artefact creates inaccuracies in the implants designed using these models, it needs to be corrected before the application of 3D models to implant design. Therefore, this study aimed to correct the lateral shift artefact using 3D modelling techniques. The femora of five ovine hind limbs were scanned with a 3T MRI scanner using a 3D vibe based protocol. The scanning was conducted in two halves, while maintaining a good overlap between them. A lateral shift was generated by moving the limb several millimetres between two scanning stages. The 3D models were reconstructed using a multi threshold segmentation method. The correction of the artefact was achieved by aligning the two halves using the robust iterative closest point (ICP) algorithm, with the help of the overlapping region between the two. The models with the corrected artefact were compared with the reference model generated by CT scanning of the same sample. The results indicate that the correction of the artefact was achieved with an average deviation of 0.32 ± 0.02 mm between the corrected model and the reference model. In comparison, the model obtained from a single MRI scan generated an average error of 0.25 ± 0.02 mm when compared with the reference model. An average deviation of 0.34 ± 0.04 mm was seen when the models generated after the table was moved were compared to the reference models; thus, the movement of the table is also a contributing factor to the motion artefacts.

Analysis of Cone-Beam CT using prior information

Treatment plans for conformal radiotherapy are based on an initial CT scan. The aim is to deliver the prescribed dose to the tumour, while minimising exposure to nearby organs. Recent advances make it possible to also obtain a Cone-Beam CT (CBCT) scan, once the patient has been positioned for treatment. A statistical model will be developed to compare these CBCT scans with the initial CT scan. Changes in the size, shape and position of the tumour and organs will be detected and quantified. Some progress has already been made in segmentation of prostate CBCT scans [1],[2],[3]. However, none of the existing approaches have taken full advantage of the prior information that is available. The planning CT scan is expertly annotated with contours of the tumour and nearby sensitive objects. This data is specific to the individual patient and can be viewed as a snapshot of spatial information at a point in time. There is an abundance of studies in the radiotherapy literature that describe the amount of variation in the relevant organs between treatments. The findings from these studies can form a basis for estimating the degree of uncertainty. All of this information can be incorporated as an informative prior into a Bayesian statistical model. This model will be developed using scans of CT phantoms, which are objects with known geometry. Thus, the accuracy of the model can be evaluated objectively. This will also enable comparison between alternative models.

Briefing paper on eTextbooks and third party eLearning products and their implications for Australian university libraries

The briefing paper was commissioned by the Council of Australian University Librarians (CAUL) to examine the current picture and evolving role of electronic textbooks (eTextbooks) and third party eLearning products in the academic arena. The study reviews industry trends, identifies the major players and considers the different stakeholder perspectives of eTextbook adoption. Within the context of learning and teaching in the digital age, specific areas of research, policy and practice are highlighted to consider the implications that eTextbooks might have for universities in general and for university libraries in particular. An environmental scan focused on the analysis of current developments and the anticipated future directions of digital learning resources in Australia, as well as in other major English speaking countries such as the United Kingdom and the United States. This research guided the development of key interview questions aimed at examining, at a deeper level, diverse stakeholder perspectives about the roles university libraries can play in the adoption of digital learning content.

Adaptive radiotherapy for virally mediated head and neck cancer : predicting which patients may benefit most

Background: Recent clinical studies have demonstrated an emerging subgroup of head and neck cancers that are virally mediated. This disease appears to be a distinct clinical entity with patients presenting younger and with more advanced nodal disease, having lower tobacco and alcohol exposure and highly radiosensitive tumours. This means they are living longer, often with the debilitating functional side effects of treatment. The primary objective of this study was to determine how virally mediated nasopharyngeal and oropharyngeal cancers respond to radiation therapy treatment. The aim was to determine risk categories and corresponding adaptive treatment management strategies to proactively manage these patients. Method/Results: 121 patients with virally mediated, node positive nasopharyngeal or oropharyngeal cancer who received radiotherapy treatment with curative intent between 2005 and 2010 were studied. Relevant patient demographics including age, gender, diagnosis, TNM stage, pre-treatment nodal size and dose delivered was recorded. Each patient’s treatment plan was reviewed to determine if another computed tomography (re-CT) scan was performed and at what time point (dose/fraction) this occurred. The justification for this re-CT was determined using four categories: tumour and/or nodal regression, weight loss, both or other. Patients who underwent a re-CT were further investigated to determine whether a new plan was calculated. If a re-plan was performed, the dosimetric effect was quantified by comparing dose volume histograms of planning target volumes and critical structures from the actual treatment delivered and the original treatment plan. Preliminary results demonstrated that 25/121 (20.7%) patients required a re-CT and that these re-CTs were performed between fractions 20 to 25 of treatment. The justification for these re-CTs consisted of a combination of tumour and/or nodal regression and weight loss. 16/25 (13.2%) patients had a replan calculated. 9 (7.4%) of these replans were implemented clinically due to the resultant dosimetric effect calculated. The data collected from this assessment was statistically analysed to identify the major determining factors for patients to undergo a re-CT and/or replan. Specific factors identified included nodal size and timing of the required intervention (i.e. how when a plan is to be adapted). This data was used to generate specific risk profiles that will form the basis of a biologically guided adaptive treatment management strategy for virally mediated head and neck cancer. Conclusion: Preliminary data indicates that virally mediated head and neck cancers respond significantly during radiation treatment (tumour and/or nodal regression and weight loss). Implications of this response are the potential underdosing or overdosing of tumour and/or surrounding critical structures. This could lead to sub-optimal patient outcomes and compromised quality of life. Consequently, the development of adaptive treatment strategies that improve organ sparing for this patient group is important to ensure delivery of the prescribed dose to the tumour volume whilst minimizing the dose received to surrounding critical structures. This could reduce side effects and improve overall patient quality of life. The risk profiles and associated adaptive treatment approaches developed in this study will be tested prospectively in the clinical setting in Phase 2 of this investigation.

Efficient real-time face detection for high resolution surveillance applications

This paper presents an efficient face detection method suitable for real-time surveillance applications. Improved efficiency is achieved by constraining the search window of an AdaBoost face detector to pre-selected regions. Firstly, the proposed method takes a sparse grid of sample pixels from the image to reduce whole image scan time. A fusion of foreground segmentation and skin colour segmentation is then used to select candidate face regions. Finally, a classifier-based face detector is applied only to selected regions to verify the presence of a face (the Viola-Jones detector is used in this paper). The proposed system is evaluated using 640 x 480 pixels test images and compared with other relevant methods. Experimental results show that the proposed method reduces the detection time to 42 ms, where the Viola-Jones detector alone requires 565 ms (on a desktop processor). This improvement makes the face detector suitable for real-time applications. Furthermore, the proposed method requires 50% of the computation time of the best competing method, while reducing the false positive rate by 3.2% and maintaining the same hit rate.

A strong quantitative trait locus for wing length on chromosome 2 in a wild population of great reed warblers

Wing length is a key character for essential behaviours related to bird flight such as migration and foraging. In the present study, we initiate the search for the genes underlying wing length in birds by studying a long-distance migrant, the great reed warbler (Acrocephalus arundinaceus). In this species wing length is an evolutionary interesting trait with pronounced latitudinal gradient and sex-specific selection regimes in local populations. We performed a quantitative trait locus (QTL) scan for wing length in great reed warblers using phenotypic, genotypic, pedigree and linkage map data from our long-term study population in Sweden. We applied the linkage analysis mapping method implemented in GRIDQTL (a new web-based software) and detected a genome-wide significant QTL for wing length on chromosome 2, to our knowledge, the first detected QTL in wild birds. The QTL extended over 25 cM and accounted for a substantial part (37%) of the phenotypic variance of the trait. A genome scan for tarsus length (a bodysize-related trait) did not show any signal, implying that the wing-length QTL on chromosome 2 was not associated with body size. Our results provide a first important step into understanding the genetic architecture of avian wing length, and give opportunities to study the evolutionary dynamics of wing length at the locus level. This journal is© 2010 The Royal Society.

Fast scanning electron microscope (FSEM)

High magnification and large depth of field with a temporal resolution of less than 100 microseconds are possible using the present invention which combines a linear electron beam produced by a tungsten filament from an SX-40A Scanning Electron Microscope (SEM), a magnetic deflection coil with lower inductance resulting from reducing the number of turns of the saddle-coil wires, while increasing the diameter of the wires, a fast scintillator, photomultiplier tube, photomultiplier tube base, and signal amplifiers and a high speed data acquisition system which allows for a scan rate of 381 frames per second and 256.times.128 pixel density in the SEM image at a data acquisition rate of 25 MHz. The data acquisition and scan position are fully coordinated. A digitizer and a digital waveform generator which generates the sweep signals to the scan coils run off the same clock to acquire the signal in real-time.

Mapping of multiple quantitative trait loci affecting bovine spongiform encephalopathy

A whole-genome scan was conducted to map quantitative trait loci (QTL) for BSE resistance or susceptibility. Cows from four half-sib families were included and 173 microsatellite markers were used to construct a 2835-cM (Kosambi) linkage map covering 29 autosomes and the pseudoautosomal region of the sex chromosome. Interval mapping by linear regression was applied and extended to a multiple-QTL analysis approach that used identified QTL on other chromosomes as cofactors to increase mapping power. In the multiple-QTL analysis, two genome-wide significant QTL (BTA17 and X/Y ps) and four genome-wide suggestive QTL (BTA1, 6, 13, and 19) were revealed. The QTL identified here using linkage analysis do not overlap with regions previously identified using TDT analysis. One factor that may explain the disparity between the results is that a more extensive data set was used in the present study. Furthermore, methodological differences between TDT and linkage analyses may affect the power of these approaches.

Retinal and choroidal thickness in myopic anisometropia

Purpose: To compare the retinal thickness (RT) and choroidal thickness (ChT) between the fellow eyes of non-amblyopic myopic anisometropes. Methods: The eyes of 22 non-amblyopic myopic anisometropes (1 D spherical equivalent refraction [SER] anisometropia) were examined using spectral domain optical coherence tomography (SD-OCT). Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers manually determined the RT and ChT from each SD-OCT image up to 2.5 mm nasal and temporal to the fovea. Axial length (AXL) was measured using optical low coherence biometry during relaxed accommodation. Results: The mean SER anisometropia was 1.74 ± 0.95 D and the mean interocular AXL difference was 0.58 ± 0.41 mm. There was no significant difference in foveal RT between the fellow eyes (P > 0.05). Mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 μm compared to the fellow, less myopic eye (286 ± 58 μm) (P < 0.001). There was a moderate correlation between the interocular difference in subfoveal ChT and the interocular difference in AXL (r = -0.50, P < 0.01). Asian anisometropes displayed more regionally symmetrical (nasal-temporal)interocular differences in ChT profile compared to Caucasians. Conclusions: RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of this anisometropic cohort. The interocular asymmetry in ChT correlated with the interocular difference in AXL.

Segmentation of cone-beam CT using a hidden Markov random field with informative priors

Purpose: Flat-detector, cone-beam computed tomography (CBCT) has enormous potential to improve the accuracy of treatment delivery in image-guided radiotherapy (IGRT). To assist radiotherapists in interpreting these images, we use a Bayesian statistical model to label each voxel according to its tissue type. Methods: The rich sources of prior information in IGRT are incorporated into a hidden Markov random field (MRF) model of the 3D image lattice. Tissue densities in the reference CT scan are estimated using inverse regression and then rescaled to approximate the corresponding CBCT intensity values. The treatment planning contours are combined with published studies of physiological variability to produce a spatial prior distribution for changes in the size, shape and position of the tumour volume and organs at risk (OAR). The voxel labels are estimated using the iterated conditional modes (ICM) algorithm. Results: The accuracy of the method has been evaluated using 27 CBCT scans of an electron density phantom (CIRS, Inc. model 062). The mean voxel-wise misclassification rate was 6.2%, with Dice similarity coefficient of 0.73 for liver, muscle, breast and adipose tissue. Conclusions: By incorporating prior information, we are able to successfully segment CBCT images. This could be a viable approach for automated, online image analysis in radiotherapy.