AN EVALUATION OF THE CONSISTENCY OF IMRT PATIENT-SPECIFIC QA TECHNIQUES

To ensure the integrity of an intensity modulated radiation therapy (IMRT) treatment, each plan must be validated through a measurement-based quality assurance (QA) procedure, known as patient specific IMRT QA. Many methods of measurement and analysis have evolved for this QA. There is not a standard among clinical institutions, and many devices and action levels are used. Since the acceptance criteria determines if the dosimetric tools’ output passes the patient plan, it is important to see how these parameters influence the performance of the QA device. While analyzing the results of IMRT QA, it is important to understand the variability in the measurements. Due to the different form factors of the many QA methods, this reproducibility can be device dependent. These questions of patient-specific IMRT QA reproducibility and performance were investigated across five dosimeter systems: a helical diode array, radiographic film, ion chamber, diode array (AP field-by-field, AP composite, and rotational composite), and an in-house designed multiple ion chamber phantom. The reproducibility was gauged for each device by comparing the coefficients of variation (CV) across six patient plans. The performance of each device was determined by comparing each one’s ability to accurately label a plan as acceptable or unacceptable compared to a gold standard. All methods demonstrated a CV of less than 4%. Film proved to have the highest variability in QA measurement, likely due to the high level of user involvement in the readout and analysis. This is further shown by how the setup contributed more variation than the readout and analysis for all of the methods, except film. When evaluated for ability to correctly label acceptable and unacceptable plans, two distinct performance groups emerged with the helical diode array, AP composite diode array, film, and ion chamber in the better group; and the rotational composite and AP field-by-field diode array in the poorer group. Additionally, optimal threshold cutoffs were determined for each of the dosimetry systems. These findings, combined with practical considerations for factors such as labor and cost, can aid a clinic in its choice of an effective and safe patient-specific IMRT QA implementation.

Fission track analyses of ODP Hole 129-800A samples

Four models of fission track annealing in apatite are compared with measured fission track lengths in samples from Site 800 in the East Mariana Basin, Ocean Drilling Program Leg 129, given an independently determined temperature history. The temperature history of Site 800 was calculated using a one-dimensional, compactive, conductive heat flow model assuming two end-member thermal cases: one for cooling of Jurassic ocean crust that has experienced no subsequent heating, and one for cooling of Cretaceous ocean crust. Because the samples analyzed were only shallowly buried and because the tectonic history of the area since sample deposition is simple, resolution of the temperature history is high. The maximum temperature experienced by the sampled bed is between 16°-21°C and occurs at 96 Ma; temperatures since the Cretaceous have dropped in spite of continued pelagic sediment deposition because heat flow has continued to decay exponentially and bottom-water temperatures have dropped. Fission tracks observed within apatite grains from the sampled bed are 14.6 +/- 0.1 µm (1 sigma) long. Given the proposed temperature history of the samples, one unpublished and three published models of fission track annealing predict mean track lengths from 14.8 to 15.9 µm. These models require temperatures as much as 40°C higher than the calculated paleotemperature maximum of the sampled bed to produce the same degree of track annealing. Measured and predicted values are different because annealing models are based on extrapolation of high temperature laboratory data to geologic times. The model that makes the closest prediction is based on the greatest number of experiments performed at low temperature and on an apatite having composition closest to that of the core samples.

Fission track age determinations of rocks from north Greenland

Apatite fission track (FT) ages and length characteristics of samples obtained from Cambrian to Paleocene-aged sandstones collected along the margin of Nares Strait in Ellesmere Island in the Canadian Arctic Archipelago are dominated by a thermal history related to Paleogene relative plate movements between Greenland and Ellesmere Island. A preliminary inverse FT thermal model for a Cambrian (Archer Fiord Formation) sandstone in the hanging wall of the Rawlings Bay thrust at Cape Lawrence is consistent with Paleocene exhumational cooling, likely as a result of erosion of the thrust. This suggests that thrusting at Cape Lawrence occurred prior to the onset of Eocene compression, likely due to transpression during earlier strikeslip along the strait. Models for samples from volcaniclastic sandstones of the Late Paleocene Pavy Formation (from Cape Back and near Pavy River), and a sandstone from the Late Paleocene Mount Lawson Formation (at Split Lake, near Makinson Inlet) are also consistent with minor burial heating following known periods of basaltic volcanism in Baffin Bay and Davis Strait (c. 61-59 Ma), or related tholeiitic volcanism and intrusive activity (c. 55-54 Ma). Thermal models for samples from sea level dykes from around Smith Sound suggest a period of Late Cretaceous - Paleocene heating prior to final cooling during Paleocene time. These model results imply that Paleocene tectonic movements along Nares Strait were significant, and provide limited support for the former existence of the Wegener Fault. Apatite FT data from central Ellesmere Island suggest however, that cooling there occurred during Early Eocene time (c. 50 Ma), which was likely a result of erosion of thrusts during Eurekan compression. This diachronous cooling suggests that Eurekan deformation was partitioned at discrete intervals across Ellesmere Island, and thus it is likely that displacements along the strait were much less than the 150 km that has been previously suggested for the Wegener Fault.

Desenvolvimento e caracterização de câmaras de ionização especiais para feixes de tomografia computadorizada

O uso de Tomografia Computadorizada (CT) para procedimentos de imagiologia vem crescendo cada vez mais devido aos avanços da tecnologia dos equipamentos de CT, que permitem a obtenção de imagens com melhor resolução do que por outras técnicas, sendo consequentemente responsável pelo aumento da dose de radiação no paciente durante o procedimento. Isso acarretou uma maior preocupação com as doses recebidas pelos pacientes que se submetem a esse tipo de exame. Para a realização da dosimetria de feixes de CT, o instrumento mais utilizado é a câmara de ionização do tipo lápis, pois este dosímetro apresenta uma resposta uniforme ao feixe de radiação incidente em todos os ângulos. A câmara convencional que se encontra disponível no mercado apresenta um comprimento de volume sensível de 10 cm; entretanto, alguns estudos têm mostrado que esse dosímetro tem subestimado os valores de dose. Portanto, neste trabalho optou-se por desenvolver no Laboratório de Calibração de Instrumentos do Instituto de Pesquisas Energéticas e Nucleares (LCI-IPEN/CNEN) duas câmaras de ionização, fazendo uso de materiais nacionais de baixo custo, com comprimentos de volume sensível de 10 cm e 30 cm. A caracterização destas câmaras foi realizada e os resultados se apresentaram dentro dos limites recomendáveis internacionais. Como uma aplicação, as câmaras desenvolvidas, juntamente com uma câmara comercial, foram testadas em um tomógrafo clínico. As câmaras de ionização desenvolvidas foram analisadas de maneira completa, para os seus possíveis usos.

Effect of inspiratory flow on methacholine challenge in children

Regulation of inspiratory flow alters the outcomes of the methacholine (MHC) challenge in adults and cough receptor sensitivity in children. The effect of inspiratory flow on the reproducibility of the MHC challenge in children is unknown. The aim of this study was to evaluate the effect of inspiratory flow alteration on the repeatabilty of the MHC challenge in children with and without asthma. Twenty-five children undertook the MHC challenge on three different days by using a dosimeter connected to a setup that allowed regulation of inspiratory flow and pattern. Children were randomized to commence the challenges at 20 or 60 L/min, and the last challenge was performed at 20 L/min. The within-subject standard deviation, 95% range for change, and doubling dose for the differing inspiratory flow (20 vs. 60 L/min) was more than twice that of when inspiratory flow was maintained at 20 L/min for both occasions. The range of the limits of agreement of the Bland and Altman plot was smaller when inspiratory flow was constant. For short-term comparative individual studies in children, inspiratory flow should be regulated. Laboratories and research measuring change in airway hyperrepsonsiveness to MHC should determine and report reproducibility indices of the challenge so airway hyperresponsiveness changes can be interpreted meaningfully.

The development and applications of the combined use of NMR and ultrasound

The objective of the research carried out in this report was to observe the first ever in-situ sonochemical reaction in the NMR Spectrometer in the megahertz region of ultrasound. Several reactions were investigated as potential systems for a sonochemical reaction followed by NMR spectroscopy. The primary problem to resolve when applying ultrasound to a chemical reaction is that of heating. Ultrasound causes the liquid to move and produces 'hot spots' resulting in an increase in sample temperature. The problem was confronted by producing a device that would counteract this effect and so remove the need to account for heating. However, the design of the device limited the length of time during which it would function. Longer reaction times were required to enable observations to be carried out in the NMR spectrometer. The fIrst and most obvious reactions attempted were those of the well-known ultrasonic dosimeter. Such a reaction would, theoretically, enable the author to simultaneously observe a reaction and determine the exact power entering the system for direct comparison of results. Unfortunately, in order to monitor the reactions in the NMR spectrometer the reactant concentrations had to be signifIcantly increased, which resulted in a notable increase in reaction time, making the experiment too lengthy to follow in the time allocated. The Diels-Alder Reaction is probably one of the most highly investigated reaction systems in the field of chemistry and it was this to which the author turned her attention. Previous authors have carried out ultrasonic investigations, with considerable success, for the reaction of anthracene with maleic anhydride. It was this reaction in particular that was next attempted. The first ever sonochemically enhanced reaction using a frequency of ultrasound in the megahertz (MHz) region was successfully carried out as bench experiments. Due to the complexity of the component reactants the product would precipitate from the solution and because the reaction could only be monitored by its formation, it was not possible to observe the reaction in the NMR spectrometer. The solvolysis of 2-chloro-2-methylpropane was examined in various solvent systems; the most suitable of which was determined to be aqueous 2-methylpropan-2-ol. The experiment was successfully enhanced by the application of ultrasound and monitored in-situ in the NMR spectrometer. The increase in product formation of an ultrasonic reaction over that of a traditional thermal reaction occurred. A range of 1.4 to 2.9 fold improvement was noted, dependent upon the reaction conditions investigated. An investigation into the effect of sonication upon a large biological molecule, in this case aqueous lysozyme, was carried out. An easily observed effect upon the sample was noted but no explanation for the observed effects could be established.

Advanced Applications of 3D Dosimetry and 3D Printing in Radiation Therapy

As complex radiotherapy techniques become more readily-practiced, comprehensive 3D dosimetry is a growing necessity for advanced quality assurance. However, clinical implementation has been impeded by a wide variety of factors, including the expense of dedicated optical dosimeter readout tools, high operational costs, and the overall difficulty of use. To address these issues, a novel dry-tank optical CT scanner was designed for PRESAGE 3D dosimeter readout, relying on 3D printed components and omitting costly parts from preceding optical scanners. This work details the design, prototyping, and basic commissioning of the Duke Integrated-lens Optical Scanner (DIOS).

The convex scanning geometry was designed in ScanSim, an in-house Monte Carlo optical ray-tracing simulation. ScanSim parameters were used to build a 3D rendering of a convex ‘solid tank’ for optical-CT, which is capable of collimating a point light source into telecentric geometry without significant quantities of refractive-index matched fluid. The model was 3D printed, processed, and converted into a negative mold via rubber casting to produce a transparent polyurethane scanning tank. The DIOS was assembled with the solid tank, a 3W red LED light source, a computer-controlled rotation stage, and a 12-bit CCD camera. Initial optical phantom studies show negligible spatial inaccuracies in 2D projection images and 3D tomographic reconstructions. A PRESAGE 3D dose measurement for a 4-field box treatment plan from Eclipse shows 95% of voxels passing gamma analysis at 3%/3mm criteria. Gamma analysis between tomographic images of the same dosimeter in the DIOS and DLOS systems show 93.1% agreement at 5%/1mm criteria. From this initial study, the DIOS has demonstrated promise as an economically-viable optical-CT scanner. However, further improvements will be necessary to fully develop this system into an accurate and reliable tool for advanced QA.

Pre-clinical animal studies are used as a conventional means of translational research, as a midpoint between in-vitro cell studies and clinical implementation. However, modern small animal radiotherapy platforms are primitive in comparison with conventional linear accelerators. This work also investigates a series of 3D printed tools to expand the treatment capabilities of the X-RAD 225Cx orthovoltage irradiator, and applies them to a feasibility study of hippocampal avoidance in rodent whole-brain radiotherapy.

As an alternative material to lead, a novel 3D-printable tungsten-composite ABS plastic, GMASS, was tested to create precisely-shaped blocks. Film studies show virtually all primary radiation at 225 kVp can be attenuated by GMASS blocks of 0.5cm thickness. A state-of-the-art software, BlockGen, was used to create custom hippocampus-shaped blocks from medical image data, for any possible axial treatment field arrangement. A custom 3D printed bite block was developed to immobilize and position a supine rat for optimal hippocampal conformity. An immobilized rat CT with digitally-inserted blocks was imported into the SmART-Plan Monte-Carlo simulation software to determine the optimal beam arrangement. Protocols with 4 and 7 equally-spaced fields were considered as viable treatment options, featuring improved hippocampal conformity and whole-brain coverage when compared to prior lateral-opposed protocols. Custom rodent-morphic PRESAGE dosimeters were developed to accurately reflect these treatment scenarios, and a 3D dosimetry study was performed to confirm the SmART-Plan simulations. Measured doses indicate significant hippocampal sparing and moderate whole-brain coverage.

Multifunctional anthraquinone-based sensors: UV, O2and time

An anthraquinone dye, Remazol brilliant blue R, RBBR, is used to create an indicator which can function as: (i) a UV dosimeter, (ii) an O2 indicator and (iii) a ‘Consume within’ indicator, CWI, for fresh, refrigerated foods. The dye is encapsulated in an ink containing a polymer, glycerol and a UV-activated semiconductor photocatalyst, titanium dioxide. When cast as a film, the dye is readily reduced by the TiO2 photocatalyst nanoparticles, thereby changing the colour of the film from blue to yellow, via a transitional green colour. The RBBR indicator is appropriately formulated, and covered with a film of Sellotape, which acts as an O2 barrier, so as to act as a sunburn warning indicator for people with skin type II. In the absence of the layer of Sellotape the RBBR indicator is used as an, albeit slow, sensor for measuring ambient levels of O2. Finally, by keeping the Sellotape layer, a UV-activated, yellow-coloured, RBBR indicator film is found to take ca. 42 h at 5 °C in ambient air to attain a green colour, and, on this basis, it is demonstrated as a possible CWI for refrigerated fresh foods.

Caracterização in vitro de um dosímetro de fibra ótica para braquiterapia de HDR

Recentemente foi desenvolvido um dosímetro baseado em fibras cintilantes (BCF-12 da companhia Saint Gobain Crystals com 1 e 0,5 mm de diâmetro e 5 mm de comprimento) para braquiterapia de baixa taxa de dose, em particular a braquiterapia direcionada para o tratamento do cancro da próstata. Este utiliza um novo fotomultiplicador de estado sólido dado pelo nome de MPPC - MultiPixel Photon Counter da companhia Hamamatsu Photonics (Japão). Nesta dissertação é estudado o mesmo dosímetro para a modalidade de braquiterapia de elevada taxa de dose (HDR). A informação sobre a dose neste tipo de dosímetros é obtida a partir de sinais óticos (em vez de sinais elétricos), que são imunes a interferências elétricas e eletromagnéticas. Adicionalmente as pequenas dimensões das fibras oferecem uma excelente resolução espacial e uma invasão mínima para uso em dosimetria in vivo, permitindo medir a dose diretamente ou próximo ao tumor e em tempo real. A sua utilização em braquiterapia para o cancro da próstata constitui-se assim como uma vantagem, uma vez que as fibras podem ser inseridas diretamente nos aplicadores utilizados neste tipo de tratamentos. Apesar de tudo, este tipo de dosímetros possui algumas desvantagens, como por exemplo a luz de Cherenkov e a fluorescência (forma de ruído dada pelo nome de stem effect) que, e a contrário da luz produzida pela fibra cintilante, não são diretamente proporcionais à energia depositada. Contudo, e para energias praticadas em braquiterapia de HDR, nesta dissertação, mostrou-se que este problema é pouco significativo dado que a percentagem de contribuição destes efeitos para o sinal medido é menor que 1% (ou 5% para distâncias menores que 25 mm). Ao longo desta dissertação é feita a caraterização do dosímetro (em modo corrente e impulso) e das suas várias partes em ambiente de laboratório e clínico. Nestes estudos o dosímetro, além de exibir uma boa reprodutibilidade (variação máxima de 3% entre medidas), mostrou uma alta linearidade para uma ampla gama de doses, assim como uma sensibilidade (µGy) semelhante à de uma câmara de ionização, tornando-o adequado para braquiterapia de HDR (tratamento que envolve altos gradientes de dose). Complementarmente, a sua grande versatilidade e simples utilização possibilita a sua aplicação prática em outras modalidades radioterapêuticas.