An external field prior for the hidden Potts model with application to cone-beam computed tomography

In images with low contrast-to-noise ratio (CNR), the information gain from the observed pixel values can be insufficient to distinguish foreground objects. A Bayesian approach to this problem is to incorporate prior information about the objects into a statistical model. A method for representing spatial prior information as an external field in a hidden Potts model is introduced. This prior distribution over the latent pixel labels is a mixture of Gaussian fields, centred on the positions of the objects at a previous point in time. It is particularly applicable in longitudinal imaging studies, where the manual segmentation of one image can be used as a prior for automatic segmentation of subsequent images. The method is demonstrated by application to cone-beam computed tomography (CT), an imaging modality that exhibits distortions in pixel values due to X-ray scatter. The external field prior results in a substantial improvement in segmentation accuracy, reducing the mean pixel misclassification rate for an electron density phantom from 87% to 6%. The method is also applied to radiotherapy patient data, demonstrating how to derive the external field prior in a clinical context.

MITIE C-Arm - Advanced innovation in education

Aim: In 2013 QUT introduced the Medical Imaging Training Immersive Environment (MITIE) as a virtual reality (VR) platform that allowed students to practice general radiography. The system software has been expanded to now include C-Arm. The aim of this project was to investigate the use of this technology in the pedagogy of undergraduate medical imaging students who have limited to no experience in the use of the C-Arm clinically. Method: The Medical Imaging Training Immersive Environment (MITIE) application provides students with realistic and fully interactive 3D models of C-Arm equipment. As with VR initiatives in other health disciplines (1–2) the software mimics clinical practice as much as possible and uses 3D technology to enhance 3D spatial awareness and realism. The application allows students to set up and expose a virtual patient in a 3D environment as well as creating the resultant “image” for comparison with a gold standard. Automated feedback highlights ways for the student to improve their patient positioning, equipment setup or exposure factors. The students' equipment knowledge was tested using an on line assessment quiz and surveys provided information on the students' pre-clinical confidence scale, with post-clinical data comparisons. Ethical approval for the project was provided by the university ethics panel. Results: This study is currently under way and this paper will present analysis of initial student feedback relating to the perceived value of the application for confidence in a high risk environment (i.e. operating theatre) and related clinical skills development. Further in-depth evaluation is ongoing with full results to be presented. Conclusion: MITIE C-Arm has a development role to play in the pre-clinical skills training for Medical Radiation Science students. It will augment their theoretical understanding prior to their clinical experience. References 1. Bridge P, Appleyard R, Ward J, Phillips R, Beavis A. The development and evaluation of a virtual radiotherapy treatment machine using an immersive visualisation environment. Computers and Education 2007; 49(2): 481–494. 2. Gunn T, Berry C, Bridge P et al. 3D Virtual Radiography: Development and Initial Feedback. Paper presented at the 10th Annual Scientific Meeting of Medical Imaging and Radiation Therapy, March 2013 Hobart, Tasmania.

Field size consistency of nominally matched linacs

Given that there is increasing recognition of the effect that submillimetre changes in collimator position can have on radiotherapy beam dosimetry, this study aimed to evaluate the potential variability in small field collimation that may exist between otherwise matched linacs. Field sizes and field output factors were measured using radiochromic film and an electron diode, for jaw- and MLC-collimated fields produced by eight dosimetrically matched Varian iX linacs (Varian Medical Systems, Palo Alto, USA). This study used nominal sizes from 0.6×0.6 to 10×10 cm215 , for jaw-collimated fields,and from 1×1 to 10×10 cm216 , for MLC-collimated fields, delivered from a zero (head up, beam directed vertically downward) gantry angle. Differences between the field sizes measured for the eight linacs exceeded the uncertainty of the film measurements and the repositioning uncertainty of the jaws and MLCs on one linac. The dimensions of fields defined by MLC leaves were more consistent between linacs, while also differing more from their nominal values than fields defined by orthogonal jaws. The field output factors measured for the different linacs generally increased with increasing measured field size for the nominal 0.6×0.6 and 1×1 cm2 fields, and became consistent between linacs for nominal field sizes of 2×2 cm2 25 and larger. The inclusion in radiotherapy treatment planning system beam data of small field output factors acquired in fields collimated by jaws (rather than the more-reproducible MLCs), associated with either the nominal or the measured field sizes, should be viewed with caution. The size and reproducibility of the fields (especially the small fields) used to acquire treatment planning data should be investigated thoroughly as part of the linac or planning system commissioning process. Further investigation of these issues, using different linac models, collimation systems and beam orientations, is recommended.

Bayesian computational methods for spatial analysis of images

This thesis introduces a new way of using prior information in a spatial model and develops scalable algorithms for fitting this model to large imaging datasets. These methods are employed for image-guided radiation therapy and satellite based classification of land use and water quality. This study has utilized a pre-computation step to achieve a hundredfold improvement in the elapsed runtime for model fitting. This makes it much more feasible to apply these models to real-world problems, and enables full Bayesian inference for images with a million or more pixels.

Anatomical modelling of the pregnant radiotherapy patient

This study aimed to take existing anatomical models of pregnant women, currently used for radiation pro-tection and nuclear medicine dose calculations, and adapt them for use in the calculation of fetal dose from external beam radiotherapy (EBRT). The models investigated were ‘KATJA’, which was provided as an MCNPX geometry file, and ‘RPI-P6’, which was provided in a simple, voxelized bina-ry format. In-house code was developed, to convert both mod-els into an `egsphant’ format, suitable for use with DOSXYZnrc. The geometries and densities of the resulting phantoms were evaluated and found to accurately represent the source data. As an example of the use of the phantoms, the delivery of a cranial EBRT treatment was simulated using the BEAMnrc and DOSXYZnrc Monte Carlo codes and the likely out-of-field doses to the fetus in each model was calculated. The results of these calculations showed good agreement (with-in one standard deviation) between the doses calculated in KATJA and PRI-P6, despite substantial anatomical differ-ences between the two models. For a 36 Gy prescription dose to a 233.2 cm3 target in the right brain, the mean doses calcu-lated in a region of interest covering the entire uterus were 1.0 +/- 0.6 mSv for KATJA and 1.3 +/- 0.9 mSv for RPI-P6. This work is expected to lead to more comprehensive studies of EBRT treatment plan design and its effects on fetal dose in the future.

Suitability of diodes for point dose measurements in IMRT/VMAT beams

This study investigated a potential source of inaccuracy for diode measurements in modulated beams; the effect of diode housing asymmetry on measurement results. The possible effects of diode housing asymmetry on the measurement of steep dose gradients were evaluated by measuring 5x5 cm2 beam profiles, with three cylindrical diodes and two commonly used ionization chambers, with each dosimeter positioned in a 3D scanning water tank with its stem perpendicular to the beam axis (horizontal) and parallel to the direction of scanning. The resulting profiles were used to compare the penumbrae measured with the diode stem pointing into (equivalent to a “stem-first” setup) and out of the field (equivalent to a “stem-last” setup) in order to evaluate the effects of dosimeter alignment and thereby identify the effects of dosimeter asymmetry. The stem-first and stem-last orientations resulted in differences of up to 0.2 mm in the measured 20-80% penumbra widths and differences of up to 0.4 mm in the off axis position of the 90% isodose. These differences, which are smaller than previously reported for older model dosimeters, were apparent in the profile results for both diodes and small volume ionization chambers. As an extension to this study, the practical use of all five dosimeters was exemplified by measuring point doses in IMRT test beams. These measurements showed good agreement (within 2%) between the diodes and the small volume ionization chamber, with all of these dosimeters being able to identify a region 3% under-dosage which was not identified by a larger volume (6 mm diameter) ionization chamber. The results of this work should help to remove some of the barriers to the use of diodes for modulated radiotherapy dosimetry in the future.

Interplay of MLC, gantry and respiratory motion during DCAT delivery

This study investigated the possible interplay effects arising from the treatment of moving targets using the dynamic conformal arc therapy (DCAT) technique. Dose from a modulated test beam was measured, with and without phantom motion and with and without a 30o arc rotation, using a diode array placed on a sinusoidally moving platform. Measurements were repeated at five different collimator angles (0, 22.5, 45, 67.5 and 90o), at two different dose rates (300 and 600 MU/min). Results showed that the effect of respiratory motion on the measured dose distribution increased slightly when the beams were delivered as arcs, rather than with a static gantry angle, and that this effect increased substantially as the collimator angle was increased from 0o (MLC motion perpendicular to respiratory motion) to 90o (MLC motion parallel to respiratory motion). The dose oscillations arising from interplay between phantom and MLC motion were found to increase in magnitude when the dose rate was increased. These results led to the development of simple recommendations for minimizing the negative effects of motion interplay on DCAT dose distributions

Predicting the need for adaptive radiotherapy in head and neck cancer

Background and purpose Adaptive radiotherapy (ART) can account for the dosimetric impact of anatomical change in head and neck cancer patients; however it can be resource intensive. Consequently, it is imperative that patients likely to require ART are identified. The purpose of this study was to find predictive factors that identify oropharyngeal squamous cell carcinoma (OPC) and nasopharyngeal carcinoma (NPC) patients more likely to need ART. Materials and methods One hundred and ten patients with OPC or NPC were analysed. Patient demographics and tumour characteristics were compared between patients who were replanned and those that were not. Factors found to be significant were included in logistic regression models. Risk profiles were developed from these models. A dosimetric analysis was performed. Results Nodal disease stage, pre-treatment largest involved node size, diagnosis and initial weight (categorised in 2 groups) were identified as significant for inclusion in the model. Two models were found to be significant (p = 0.001), correctly classifying 98.2% and 96.1% of patients respectively. Three ART risk profiles were developed. Conclusion Predictive factors identifying OPC or NPC patients more likely to require ART were reported. A risk profile approach could facilitate the effective implementation of ART into radiotherapy departments through forward planning and appropriate resource allocation.

Effects of compression on lymphoedema during resistance exercise in women with breast cancer-related lymphoedema: A randomised, cross-over trial

Background The use of compression garments during exercise is recommended for women with breast cancer-related lymphoedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomised, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphoedema status and its associated symptoms in women with breast cancer-related lymphoedema. Methods Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphoedema completed two resistance exercise sessions, one with compression and one without, in a randomised order separated by a 14 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphoedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphoedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. Results There was no difference in lymphoedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. Conclusions An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphoedema in women with breast cancer-related lymphoedema.

Use of 3D printed materials as tissue-equivalent phantoms

This study used the specific example of 3D printing with acrylonitrile butadiene styrene (ABS) as a means to investigate the potential usefulness of benchtop rapid prototyping as a technique for producing patient specific phantoms for radiotherapy dosimetry. Three small cylinders and one model of a human lung were produced via in-house 3D printing with ABS, using 90%, 50%, 30% and 10% ABS infill densities. These phantom samples were evaluated in terms of their geometric accuracy, tissue equivalence and radiation hardness, when irradiated using a range of clinical radiotherapy beams. The measured dimensions of the small cylindrical phantoms all matched their planned dimensions, within 1mm. The lung phantom was less accurately matched to the lung geometry on which it was based, due to simplifications introduced during the phantom design process. The mass densities, electron densities and linear attenuation coefficients identified using CT data, as well as the results of film measurements made using megavoltage photon and electron beams, indicated that phantoms printed with ABS, using infill densities of 30% or more, are potentially useful as lung- and tissue-equivalent phantoms for patient-specific radiotherapy dosimetry. All cylindrical 3D printed phantom samples were found to be unaffected by prolonged radiation and to accurately match their design specifications. However, care should be taken to avoid oversimplifying anatomical structures when printing more complex phantoms.

Audience response systems can facilitate communal course feedback

Background At Queensland University of Technology (QUT), the Bachelor of Radiation Therapy course evaluation has previously suffered from low online survey participation rates. A communal instantaneous feedback event using an audience response system (ARS) was evaluated as a potential solution to this problem. The aims of the project were to determine the extent to which this feedback event could be facilitated by ARS technology and to evaluate the impact the technology made on student satisfaction and engagement. Methods Students were invited to a timetabled session to provide feedback on individual study units and the course overall. They provided quantitative Likert-style responses to prompts for each unit and the course using an ARS as well as anonymous typed qualitative comments. Data collection was performed live so students were able to view collective class responses. This prompted further discussion and enabled a prospective action plan to be developed. To inform future ARS use, students were asked for their opinions on the feedback method. Results Despite technological difficulties, student evaluation indicated that all responders enjoyed the session and the opportunity to view the combined responses. All students felt that useful feedback was generated and that this method should be used in the future. The student attendance and response rates were high, and it was clear that the session had led to the development of some insightful qualitative feedback comments. Conclusions: An ARS contributed well to the collection of course feedback in a communal and interactive environment. Students found it enjoyable to use, and it helped to stimulate useful qualitative comments

Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Targeting Antiapoptotic Genes Upregulated by Androgen Withdrawal Using Antisense Oligodeoxynucleotides to Enhance Androgen-and Chemo-Sensitivity in Prostate Cancer

Androgen withdrawal is the only effective form of systemic therapy for men with advanced disease, producing symptomatic and/or objective response in 80% of patients. Unfortunately, androgen independent (AI) progression and death occurs within a few years in the majority of these cases (6). Prostate cancer is highly chemoresistant, with objective response rates of 10% and no demonstrated survival benefit (28). Hormone refractory prostate cancer (HRPC) is therefore the main obstacle to improving the survival and quality of life in patients with advanced disease, and novel therapeutic strategies that target the molecular basis of androgen and chemoresistance are required.

The introduction of an Inter-professional learning unit: staff and student perspectives

Background The School of Clinical Sciences comprises a number of health disciplines including podiatry, paramedic science, pharmacy, medical imaging and radiation therapy. A new inter-professional unit was introduced in 2014, which covered key introductory learnings applicable for future health practitioners. This study examined teaching staff and student perspectives about their experience with the new unit for first year students. Methods Qualitative interviews with teaching staff (n=9) and focus group interviews with students (5 groups which ranged in size from 4-30) were conducted. Extensive notes were taken during the interviews Issues emerging from the interviews were identified and organised according to themes and subthemes. Results Four major themes were identified namely: Something new; To be or not to be that is the question; Advantages of the new unit; and Areas for improvement. Previous staff experience with inter-professional learning (IPL) had been ad-hoc, whereas the new unit brought together several disciplines in a planned and deliberate way. There was strong philosophical agreement about the value of IPL but some debate about the extent to which the unit provided IPL experience. The unit was seen as assisting students’ social and academic adjustment to university and provided opportunity for professional socialisation, exposure to macro and micro aspects of the Australian health care system and various types of communication. For podiatry students it was their first opportunity to formally meet and work with other podiatry students and moved their identity from ‘university student’ to ‘podiatry student’. Other positives included providing the opportunity for staff and students to interact at an early stage with the perceived benefit of reducing attrition. Areas for unit improvement included institutional arrangements, unit administration aspects and assessment. Conclusion The unit was seen as beneficial by staff and students however, students were more polarised in their views than staff. There was a tension between feeling apart of and learning about one's own profession and feeling apart of and learning about the roles of other health professionals in relation to patient care and the health care system.

Use of electronic portal imaging devices for electron treatment verification

This study aims to help broaden the use of electronic portal imaging devices (EPIDs) for pre-treatment patient positioning verification, from photon-beam radiotherapy to photon- and electron-beam radiotherapy, by proposing and testing a method for acquiring clinicallyuseful EPID images of patient anatomy using electron beams, with a view to enabling and encouraging further research in this area. EPID images used in this study were acquired using all available beams from a linac configured to deliver electron beams with nominal energies of 6, 9, 12, 16 and 20 MeV, as well as photon beams with nominal energies of 6 and 10 MV. A widely-available heterogeneous, approximately-humanoid, thorax phantom was used, to provide an indication of the contrast and noise produced when imaging different types of tissue with comparatively realistic thicknesses. The acquired images were automatically calibrated, corrected for the effects of variations in the sensitivity of individual photodiodes, using a flood field image. For electron beam imaging, flood field EPID calibration images were acquired with and without the placement of blocks of water-equivalent plastic (with thicknesses approximately equal to the practical range of electrons in the plastic) placed upstream of the EPID, to filter out the primary electron beam, leaving only the bremsstrahlung photon signal. While the electron beam images acquired using a standard (unfiltered) flood field calibration were observed to be noisy and difficult to interpret, the electron beam images acquired using the filtered flood field calibration showed tissues and bony anatomy with levels of contrast and noise that were similar to the contrast and noise levels seen in the clinically acceptable photon beam EPID images. The best electron beam imaging results (highest contrast, signal-to-noise and contrast-to-noise ratios) were achieved when the images were acquired using the higher energy electron beams (16 and 20 MeV) when the EPID was calibrated using an intermediate (12 MeV) electron beam energy. These results demonstrate the feasibility of acquiring clinically-useful EPID images of patient anatomy using electron beams and suggest important avenues for future investigation, thus enabling and encouraging further research in this area. There is manifest potential for the EPID imaging method proposed in this work to lead to the clinical use of electron beam imaging for geometric verification of electron treatments in the future.