A braquiterapia de alta taxa de dose é uma das modalidades mais utilizadas em braquiterapia para o tratamento de câncer. Os diversos avanços tecnológicos, bem como a evolução das técnicas de tratamento tornaram a braquiterapia de alta taxa de dose uma das modalidades de estado da arte para o tratamento de alguns cânceres. Parte deste avanço é creditada à melhoria na acurácia e na prescrição de dose absorvida recomendada ao paciente, ao longo dos anos. Este avanço permite que atualmente seja possível realizar os cálculos dosimétricos, por meio de sistemas de planejamento computadorizado, considerando as heterogeneidades dos pacientes, tais como: tecidos e órgãos com composições diferentes da água (meio de referência em radioterapia), contorno do paciente individualizado, introdução de aplicadores, dentre outros. Tais avanços demandam o controle de qualidade destas ferramentas, com objetivo de assegurar que todo o processo de tratamento seja satisfatório e acurado. Até o momento, a comunidade carece de um sistema experimental capaz de avaliar, considerando os níveis de incerteza, se os sistemas de planejamento computadorizados são aptos a considerar a heterogeneidade dos tratamentos. Neste trabalho, apresentamos o desenvolvimento de medidas experimentais em um objeto simulador, com capacidade de mensurar as diferenças introduzidas pela heterogeneidade por meio de três técnicas dosimétricas experimentais: termoluminescência, filmes radiocrômicos e ionométrica. Os resultados experimentais foram comparados com as simulações de Monte Carlo e com um sistema de planejamento computadorizado comercial, apto a realizar correções de heterogeneidade em braquiterapia. Discutimos as principais etapas de desenvolvimento deste objeto simulador, seus resultados experimentais e as comparações com os demais sistemas. As conclusões e as etapas futuras deste projeto também são apresentadas. / High dose rate brachytherapy is one of the most widely used modalities in brachytherapy for cancer treatment The various technological advances and the development of treatment techniques have made high dose rate brachytherapy as one of the state of the art methods for the treatment of some cancers. Part of this progress is credited to the improvement in the accuracy and absorbed dose prescription recommended to patients over the years. This advance currently allows the possibility of performing dosimetric calculations, by means of computerized planning systems, considering the heterogeneity of patients, such as: tissues and organs with different water compositions (reference medium in radiotherapy), individualized patient\'s contour and introduction of applicators, among others. Such advances require quality control of these tools, in order to ensure that the entire treatment process is satisfactory and accurate. Nowadays, the community needs an experimental system capable of evaluating, since the uncertainty levels if the computerized planning systems are able to consider the heterogeneity of treatments. In this project, we present the development of experimental measurements into a phantom, capable of measuring the differences introduced by heterogeneity through three experimental dosimetric techniques: thermoluminescence, radiochromic films and ionometric. The experimental results were compared with the Monte Carlo simulations and a commercial treatment planning system able to perform correction of heterogeneity in brachytherapy. We discuss the main stages of development of this phantom, their experimental results and comparisons with other systems. The conclusions and future steps to complete this project are also presented.

A braquiterapia de alta taxa de dose é uma das modalidades mais utilizadas em braquiterapia para o tratamento de câncer. Os diversos avanços tecnológicos, bem como a evolução das técnicas de tratamento tornaram a braquiterapia de alta taxa de dose uma das modalidades de estado da arte para o tratamento de alguns cânceres. Parte deste avanço é creditada à melhoria na acurácia e na prescrição de dose absorvida recomendada ao paciente, ao longo dos anos. Este avanço permite que atualmente seja possível realizar os cálculos dosimétricos, por meio de sistemas de planejamento computadorizado, considerando as heterogeneidades dos pacientes, tais como: tecidos e órgãos com composições diferentes da água (meio de referência em radioterapia), contorno do paciente individualizado, introdução de aplicadores, dentre outros. Tais avanços demandam o controle de qualidade destas ferramentas, com objetivo de assegurar que todo o processo de tratamento seja satisfatório e acurado. Até o momento, a comunidade carece de um sistema experimental capaz de avaliar, considerando os níveis de incerteza, se os sistemas de planejamento computadorizados são aptos a considerar a heterogeneidade dos tratamentos. Neste trabalho, apresentamos o desenvolvimento de medidas experimentais em um objeto simulador, com capacidade de mensurar as diferenças introduzidas pela heterogeneidade por meio de três técnicas dosimétricas experimentais: termoluminescência, filmes radiocrômicos e ionométrica. Os resultados experimentais foram comparados com as simulações de Monte Carlo e com um sistema de planejamento computadorizado comercial, apto a realizar correções de heterogeneidade em braquiterapia. Discutimos as principais etapas de desenvolvimento deste objeto simulador, seus resultados experimentais e as comparações com os demais sistemas. As conclusões e as etapas futuras deste projeto também são apresentadas. / High dose rate brachytherapy is one of the most widely used modalities in brachytherapy for cancer treatment The various technological advances and the development of treatment techniques have made high dose rate brachytherapy as one of the state of the art methods for the treatment of some cancers. Part of this progress is credited to the improvement in the accuracy and absorbed dose prescription recommended to patients over the years. This advance currently allows the possibility of performing dosimetric calculations, by means of computerized planning systems, considering the heterogeneity of patients, such as: tissues and organs with different water compositions (reference medium in radiotherapy), individualized patient\'s contour and introduction of applicators, among others. Such advances require quality control of these tools, in order to ensure that the entire treatment process is satisfactory and accurate. Nowadays, the community needs an experimental system capable of evaluating, since the uncertainty levels if the computerized planning systems are able to consider the heterogeneity of treatments. In this project, we present the development of experimental measurements into a phantom, capable of measuring the differences introduced by heterogeneity through three experimental dosimetric techniques: thermoluminescence, radiochromic films and ionometric. The experimental results were compared with the Monte Carlo simulations and a commercial treatment planning system able to perform correction of heterogeneity in brachytherapy. We discuss the main stages of development of this phantom, their experimental results and comparisons with other systems. The conclusions and future steps to complete this project are also presented.

High-dose morphine has been extensively used in the control of postoperative and cancer pain. Patients receiving prolonged administration of high-dose morphine are known to be associated with certain cardiovascular complications and tissue regeneration defects. This research thesis aims to investigate the biological effects and molecular mechanisms of high-dose morphine on the vascular endothelial function, angiogenesis and wound regeneration using murine models of morphine-dependence and cultured endothelial cell assays. Mice were subjected to placebo or morphine (20 mg/kg, i.p.) injection for consecutive 14 days. Aortas were harvested for assessment of vasomotor function by isometric force recordings. Protein expression p47phox (a major subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase) was determined by Western blotting. Generation of superoxide anions was detected under confocal microscope. Endothelium-dependent relaxations to acetylcholine were significantly reduced in morphine-treated animals, but were normalized by superoxide scavenging. Fluorescent densities of dihydroethidium and expression of p47phox were increased in the aorta of morphine-treated mice. In the second part of this thesis, the candidate determined the effects of high-dose morphine on angiogenesis and mobilization of endothelial progenitor cells (EPCs) in a mouse model of excisional wound injury. Excisional wound was created on control and morphine-dependent mice. Wound healing was compared by measuring the final-to-initial wound area ratio. Generation of superoxide anions in the wound was determined by luminol-enhanced chemiluminescence. Circulating mononuclear cells were isolated and measured for EPC (defined as CD34+/CD133+ cell) counts. In vivo and in vitro measurements of angiogenesis following morphine treatment were performed using the Matrigel assay. The results showed that wound closure was significantly reduced in mice treated with morphine when compared with controls, and higher levels of superoxide anions were generated in these wounds. High-dose morphine reduced numbers of circulating EPCs following creation of excisional wound. Matrigel assay showed impaired angiogenesis in animals and reduced capillary tube formation in cultured endothelial cells treated with high-concentration of morphine. Collectively, this research thesis demonstrated a number of novel findings. First, high-dose of morphine impairs vascular endothelial function by increased production of vascular superoxide anions. Activation of NADPH oxidase may be the molecular mechanisms responsible for reduced bioavailability of endothelium-derived NO. Second, systemic administration of high-dose morphine delays healing of excisional wounds and impairs angiogenesis. This antiangiogenic effect is associated with increased superoxide anions production and impaired mobilization of EPCs. In line with direct endothelial dysfunction, impaired angiogenesis and EPC mobilization resulted from high-dose morphine treatment may cause increased cardiovascular morbidity in human subjects receiving higher therapeutic dose of morphine.

BACKGROUND High dose rate Intraluminal Brachytherapy (HDRILBT) is one of the most used palliative treatment options for advanced esophageal cancer. The present study evaluates the role of additional chemotherapy in improving dysphagia free survival (DFS) and overall survival (OS) in patients with inoperable advanced esophageal cancer treated with brachytherapy. MATERIAL and METHODS 132 patients with advanced metastatic esophageal cancer with total or near total dysphagia were given HDRILBT to a dose of 18 Gray (Gy) in 3 fractions on alternate days. Intraluminal brachytherapy alone was performed on 98 patients. 34 patients received Epirubicin, 5-Fluorouracil, and Cisplatin (ECF) chemotherapy regimen after HDRILBT. The mean age of the whole group was 65 years (HDRILBT-71.41, HDRILBT+ECF-59.98; p<0.0001). Male: Female was 101:31 (HDRILBT 72:26; HDRILBT +ECF 29:5; p>0.05). The location incidence was GEJ: Lower Esophagus: Mid Esophagus: Cervical Esophagus 24:81:17:5 respectively; for the whole group HDRILBT- 17:57:16:4; HDRILBT+ECF-7:24:1:1; p>0.05. 78 patients presented with co-morbidities (cardiac) (HDRILBT- 59; HDRILBT+ECF- 19; p>0.05). 74 patients presented with distant metastasis (54 with HDRILBT and 20 with HDRILBT+ECF; p>0.05). The ECOG scores were as follows 0:1:2:3:4 15:52:51:12:2 (HDRILBT- 10:35:41:10:2; HDRILBT+ECF- 5:17:10:2:0; p=0.0014). All patients completed 3 fractions of HDRILBT. 34 patients received additional chemotherapy with ECF regimen. Selection of patients was done by the medical oncologist. Statistical analysis of data was done using the SAS statistical analysis software system. Univariate and multivariate analysis was done using the log rang test. RESULTS Patients who received additional ECF were younger (p< 0.001) and with a better performance status than those who received HDRILBT alone (p=0.0014). Mean DFS was higher for patients who had further chemotherapy treatment (232 days) vs. patients who had HDRILBT only (155 days) (p>0.05). The mean OS for HDRILBT + ECF was 266 days (p = 0.0010) compare with HDRILBT alone which was 155 days, when the effect of 10 prognostic factors was analyzed for DFS and OS. Only additional ECF after brachytherapy impacted on DFS while age (p<0.001) and performance status (p=0.0014) impacted on overall survival on univariate analysis. On multivariate analysis tumor length and nodal presentation (p<0.000) impacted on OS. The incidence of stricture and fistulae were similar. Chemotherapy related side effects: gastrointestinal tract (25 patients), neurotoxicities (2) and nephrotoxicities (2) were seen as a result of 5-FU and Cisplatin respectively. 18 patients completed at least 3 cycles of ECF. CONCLUSION Additional chemotherapy with ECF after HDRILBT improves the DFS and OS in selected patients with advanced esophageal cancer. These patients tend to be younger with better performance status, small tumor length and nodal metastasis. The incidence of complications is similar with more than 50% patients completing at least 3 cycles of chemotherapy. / Thesis / Master of Science (MSc)

Für die Therapie maligner intranasaler Neoplasien beim Hund existieren nur mäßig be-friedigende Behandlungsstrategien. Als Therapiemodalität der Wahl wird die Radiothe-rapie angesehen, die gegenwärtig v.a. in Form einer perkutanen Bestrahlung (Telethe-rapie) mit aufwendigen, bis zu 20 Fraktionen umfassenden Protokollen kurativer Intenti-on angewendet wird. Die erreichbaren Überlebenszeiten sind meist limitiert durch das Auftreten eines Rezidivs des Nasentumors innerhalb des Bestrahlungsfeldes, sodass eine Erhöhung der applizierten Gesamtdosis nötig erscheint. Dies ist jedoch im Rahmen einer Teletherapie aufgrund nicht vertretbarer akuter Nebenwirkungen nicht möglich. Alternativ steht die Brachytherapie zur Verfügung, die aufgrund ihrer physikalischen Charakteristika zur besseren Schonung des umliegenden Normalgewebes beiträgt. Ge-genwärtig existieren keine anderen Untersuchungen zur Anwendung der fraktionierten High-Dose-Rate-Brachytherapie bei Nasentumoren des Hundes. Ziel dieser Studie war es daher, die Durchführbarkeit dieser Therapiemodalität beim Hund erstmals zu unter-suchen und die akuten und chronischen Nebenwirkungen sowie die erzielbare progres-sionsfreie Zeit und die Überlebenszeit zu dokumentieren. Im Zeitraum von 2001 bis 2007 gingen 18 Hunde in die Studie ein. Das diagnostische Vorgehen beinhaltete neben einer klinischen Untersuchung und der Röntgenuntersu-chung von Nase und Thorax auch die kernspintomographische Beurteilung der Nasen-höhlen und eine nachfolgende Rhinoskopie inklusive Biopsie. Die Therapie bestand aus zwei wöchentlichen Fraktionen, bei denen in Vollnarkose über einen in der Nasenhöhle applizierten Katheter mithilfe des Radioisotops 192Iridium jeweils 5 Gy appliziert wurden. Die damit über vier Wochen erreichte Gesamtdosis lag bei 40 Gy, und entsprach damit der biologischen Effizienz einer perkutan applizierten konventionell fraktionierten Ge-samtdosis von circa 60 Gy. Im Anschluss an die Therapie wurden die Hunde monatlich klinisch untersucht und die auftretenden Nebenwirkungen anhand des Radiation Morbi-dity Scores der VRTOG beschrieben. Es wurden außerdem weiterführende Untersu-chungen in Form von MRT, Rhinoskopie und Biopsie durchgeführt. Die aufgetretenen Nebenwirkungen waren mit denen in der Literatur nach Teletherapie beschriebenen vergleichbar, beziehungsweise fielen im Bereich von Augen und Maulschleimhaut ge-ringer aus. Nebenwirkungen im Bereich der Haut traten in Form von Alopezie, Hyper-pigmentation oder Leukotrichie auf. Im Bereich der Nasenschleimhaut zeigten fast alle Hunde eine leichte chronische Rhinitis. Als problematische Nebenwirkungen traten bei drei Patienten Osteoradionekrosen auf, die einer aufwendigeren chirurgischen Versor-gung bedurften. Die mediane progressionsfreie Zeit lag bei 13 Monaten, die mediane Überlebenszeit bei 17 Monaten. Die Adenokarzinome wiesen die längste Überlebens-zeit auf, dies war jedoch aufgrund der insgesamt kleinen Patientenzahl nicht signifikant. Ein Zusammenhang zwischen dem Tumorstadium und der progessionsfreien Zeit oder Überlebenszeit bestand nicht. Bei dem beschriebenen Protokoll handelt es sich um eine unter klinischen Bedingungen praktikable Therapieform, die mit ihren insgesamt acht Fraktionen für Besitzer und Tier wesentlich weniger belastend ist als teletherapeutische kurative Protokolle mit 12-20 Fraktionen. Gleichzeitig gelingt es, eine Gesamtdosis von verhältnismäßig hoher biolo-gischer Effizienz zu applizieren, ohne jedoch stärkere Nebenwirkungen in Kauf nehmen zu müssen. Im Bereich von Auge und Maulschleimhaut sind die Nebenwirkungen sogar geringer. Bei einem kleinen Teil der Patienten treten jedoch auch hier, ebenso wie nach teletherapeutischen Protokollen, problematische chronische Nebenwirkungen auf, die die Lebensqualität der betroffenen Tiere beeinträchtigen und die einer aufwendigeren Therapie zwingend bedürfen. Die mit diesem Protokoll erreichten Remissions- und Ü-berlebenszeiten sind mit denen aus der Literatur vergleichbar bis tendenziell besser. Aufgrund der oben genannten Vorteile erscheint die vorgestellte Therapie daher als Al-ternative zu Teletherapie bei der Behandlung kaniner Nasentumoren durchaus geeig-net. Weitere Studien mit größeren Patientenzahlen unter Einbeziehung einer anders therapierten Kontrollgruppe sind jedoch notwendig

Für die Therapie maligner intranasaler Neoplasien beim Hund existieren nur mäßig be-friedigende Behandlungsstrategien. Als Therapiemodalität der Wahl wird die Radiothe-rapie angesehen, die gegenwärtig v.a. in Form einer perkutanen Bestrahlung (Telethe-rapie) mit aufwendigen, bis zu 20 Fraktionen umfassenden Protokollen kurativer Intenti-on angewendet wird. Die erreichbaren Überlebenszeiten sind meist limitiert durch das Auftreten eines Rezidivs des Nasentumors innerhalb des Bestrahlungsfeldes, sodass eine Erhöhung der applizierten Gesamtdosis nötig erscheint. Dies ist jedoch im Rahmen einer Teletherapie aufgrund nicht vertretbarer akuter Nebenwirkungen nicht möglich. Alternativ steht die Brachytherapie zur Verfügung, die aufgrund ihrer physikalischen Charakteristika zur besseren Schonung des umliegenden Normalgewebes beiträgt. Ge-genwärtig existieren keine anderen Untersuchungen zur Anwendung der fraktionierten High-Dose-Rate-Brachytherapie bei Nasentumoren des Hundes. Ziel dieser Studie war es daher, die Durchführbarkeit dieser Therapiemodalität beim Hund erstmals zu unter-suchen und die akuten und chronischen Nebenwirkungen sowie die erzielbare progres-sionsfreie Zeit und die Überlebenszeit zu dokumentieren. Im Zeitraum von 2001 bis 2007 gingen 18 Hunde in die Studie ein. Das diagnostische Vorgehen beinhaltete neben einer klinischen Untersuchung und der Röntgenuntersu-chung von Nase und Thorax auch die kernspintomographische Beurteilung der Nasen-höhlen und eine nachfolgende Rhinoskopie inklusive Biopsie. Die Therapie bestand aus zwei wöchentlichen Fraktionen, bei denen in Vollnarkose über einen in der Nasenhöhle applizierten Katheter mithilfe des Radioisotops 192Iridium jeweils 5 Gy appliziert wurden. Die damit über vier Wochen erreichte Gesamtdosis lag bei 40 Gy, und entsprach damit der biologischen Effizienz einer perkutan applizierten konventionell fraktionierten Ge-samtdosis von circa 60 Gy. Im Anschluss an die Therapie wurden die Hunde monatlich klinisch untersucht und die auftretenden Nebenwirkungen anhand des Radiation Morbi-dity Scores der VRTOG beschrieben. Es wurden außerdem weiterführende Untersu-chungen in Form von MRT, Rhinoskopie und Biopsie durchgeführt. Die aufgetretenen Nebenwirkungen waren mit denen in der Literatur nach Teletherapie beschriebenen vergleichbar, beziehungsweise fielen im Bereich von Augen und Maulschleimhaut ge-ringer aus. Nebenwirkungen im Bereich der Haut traten in Form von Alopezie, Hyper-pigmentation oder Leukotrichie auf. Im Bereich der Nasenschleimhaut zeigten fast alle Hunde eine leichte chronische Rhinitis. Als problematische Nebenwirkungen traten bei drei Patienten Osteoradionekrosen auf, die einer aufwendigeren chirurgischen Versor-gung bedurften. Die mediane progressionsfreie Zeit lag bei 13 Monaten, die mediane Überlebenszeit bei 17 Monaten. Die Adenokarzinome wiesen die längste Überlebens-zeit auf, dies war jedoch aufgrund der insgesamt kleinen Patientenzahl nicht signifikant. Ein Zusammenhang zwischen dem Tumorstadium und der progessionsfreien Zeit oder Überlebenszeit bestand nicht. Bei dem beschriebenen Protokoll handelt es sich um eine unter klinischen Bedingungen praktikable Therapieform, die mit ihren insgesamt acht Fraktionen für Besitzer und Tier wesentlich weniger belastend ist als teletherapeutische kurative Protokolle mit 12-20 Fraktionen. Gleichzeitig gelingt es, eine Gesamtdosis von verhältnismäßig hoher biolo-gischer Effizienz zu applizieren, ohne jedoch stärkere Nebenwirkungen in Kauf nehmen zu müssen. Im Bereich von Auge und Maulschleimhaut sind die Nebenwirkungen sogar geringer. Bei einem kleinen Teil der Patienten treten jedoch auch hier, ebenso wie nach teletherapeutischen Protokollen, problematische chronische Nebenwirkungen auf, die die Lebensqualität der betroffenen Tiere beeinträchtigen und die einer aufwendigeren Therapie zwingend bedürfen. Die mit diesem Protokoll erreichten Remissions- und Ü-berlebenszeiten sind mit denen aus der Literatur vergleichbar bis tendenziell besser. Aufgrund der oben genannten Vorteile erscheint die vorgestellte Therapie daher als Al-ternative zu Teletherapie bei der Behandlung kaniner Nasentumoren durchaus geeig-net. Weitere Studien mit größeren Patientenzahlen unter Einbeziehung einer anders therapierten Kontrollgruppe sind jedoch notwendig

Published Article / Worldwide, uterine cervical cancer is one of the most frequently occurring cancers in women, with more than 80% of these cases occurring in developing countries. The South African screening policy and screening program, implemented in 2001, attempt to reduce this incidence of cervical cancer in South Africa. It is essential to treat these women with the best modalities available. This retrospective study focused specifically on the curative potential of radiotherapy administered to patients at the Oncology Department, Bloemfontein, since a new modality of high dose-rate intracavitary brachytherapy was implemented in 1994. Late radiation complications were also investigated.

Neste trabalho são apresentados os resultados obtidos com diodos resistentes a danos de radiação dos tipos fusão zonal padrão (FZ), fusão zonaI com difusão de oxigênio (DOFZ) e Czochralski magnético (MCz) em dosimetria de processamento por radiação gama. Estes dispositivos de junção p+-n-n+ foram manufaturados por Okmetic Oyj. (Vantaa, Finland) e processados no Centro de Microeletrônica da Universidade de Tecnologia de Helsinki no âmbito da colaboração RD50 do CERN. As sondas dosimétricas, baseadas nos dispositivos FZ, DOFZ and MCz, foram projetadas para operar sem tensão de polarização no modo de corrente direta como dosímetros on-line de radiação. As irradiações foram realizadas no Centro de Tecnologia das Radiações (CTR) no IPEN-CNEN/SP usando a fonte de 60Co (Gammacell 220 Nordion) com a taxa de dose de aproximadamente 2,4 kGy/h. A resposta em corrente de cada diodo foi medida em função do tempo de exposição em intervalos de dose desde 5 kGy até 50 kGy atingindo a dose total absorvida 275 kGy. Os resultados obtidos demonstraram um significante decréscimo da fotocorrente gerada em todos os dispositivos para doses totais absorvidas superiores a aproximadamente 25 kGy. Para reduzir este efeito, as amostras foram pré-irradiadas com raios gama do 60Co a uma dose de 700 kGy, para saturar a produção de armadilhas no volume sensível do diodo. Depois da pré-irradiação, apesar de serem menos sensíveis, todos os dispositivos apresentaram sinais de corrente estáveis mesmo para a dose total absorvida de 275 kGy. A fim de monitorar possíveis efeitos de danos de radiação VII produzidos nos diodos, as correntes de fuga e capacitância destes dispositivos foram medidas em função da dose total absorvida. As curvas de calibração dos dosímetros mostraram respostas quadráticas com coeficientes de correlação maiores do que 0,9999 para doses totais absorvidas de até 275 kGy. A comparação entre as respostas dosimétricas dos diodos estudados evidenciou que o melhor resultado foi obtido com o MCz que exibiu maiores sensibilidade e estabilidade do que os dispositivos FZ e DOFZ. No entanto, é importante notar que todos os diodos pré-irradiados podem ser utilizados como dosímetros em aplicações de processamento por radiação gama. / In this work we report on results obtained with rad-hard Standard Float Zone (FZ), Diffusion Oxygenated Float Zone (DOFZ) and Magnetic Czochralski (MCz) silicon diodes in gamma radiation processing dosimetry. These p+-n-n+ junction devices were manufactured by Okmetic Oyj. (Vantaa, Finland) and processed by the Microelectronics Center of Helsinki University of Technology in the framework of the CERN RD50 Collaboration. The dosimetric probes, based on FZ, DOFZ and MCz devices, were designed to operate without bias voltage in the direct current mode as on-line radiation dosimeter. The irradiations were performed in the Radiation Technology Center (CTR) at IPEN-CNEN/SP using a 60Co source (Gammacell 220 Nordion) with a dose rate around of 2.4 kGy/h. The current response of each diode was measured as a function of the exposure time in steps from 5 kGy up to 50 kGy to achieve a total absorbed dose of 275 kGy. The results obtained showed a significant decrease in the photocurrent generated in all devices for total absorbed doses higher than approximately 25 kGy. To reduce this effect, the samples were pre-irradiated with 60Co gamma rays at 700 kGy in order to saturate the trap production in the diodes sensitive volume. After pre-irradiation, despite of being less sensitive, all devices exhibited more stable photocurrent signals, even for total absorbed doses of 275 kGy. To monitor possible gamma radiation damage effects produced on the diodes, their dynamic leakage current and capacitance were measured as a function of the absorbed dose. IX The calibration curves of the dosimeters showed quadratic responses with correlation coefficient higher than 0.9999 for total absorbed dose up to 275 kGy. The comparison among the dosimetric response of the diodes studied evidenced that the best result was achieved with the MCz which exhibited higher sensitivity and stability than the FZ and DOFZ devices. However, it is important to note that all pre-irradiated diodes can be used as gamma dosimeters in radiation processing applications.

A novel optical calorimetry approach is proposed for the dosimetry of therapeutic radiation, based on the optical technique of Digital Holographic Interferometry (DHI). This detector determines the radiation absorbed dose to water by measurement of the refractive index variations arising from radiation induced temperature increases. The output consists of a time series of high resolution, two dimensional images of the spatial distribution of the projected dose map across the water sample. This absorbed dose to water is measured directly, independently of radiation type, dose rate and energy, and without perturbation of the beam. These are key features which make DHI a promising technique for radiation dosimetry. A prototype DHI detector was developed, with the aim of providing proof-of-principle of the approach. The detector consists of an optical laser interferometer based on a lensless Fourier transform digital holography (LFTDH) system, and the associated mathematical reconstruction of the absorbed dose. The conceptual basis was introduced, and a full framework was established for the measurement and analysis of the results. Methods were developed for mathematical correction of the distortions introduced by heat di usion within the system. Pilot studies of the dosimetry of a high dose rate Ir-192 brachytherapy source and a small eld proton beam were conducted in order to investigate the dosimetric potential of the technique. Results were validated against independent models of the expected radiation dose distributions. Initial measurements of absorbed dose demonstrated the ability of the DHI detector to resolve the minuscule temperature changes produced by radiation in water to within experimental uncertainty. Spatial resolution of approximately 0.03 mm/pixel was achieved, and the dose distribution around the brachytherapy source was accurately measured for short irradiation times, to within the experimental uncertainty. The experimental noise for the prototype detector was relatively large and combined with the occurrence of heat di usion, means that the method is predominantly suitable for high dose rate applications. The initial proof-of-principle results con rm that DHI dosimetry is a promising technique, with a range of potential bene ts. Further development of the technique is warranted, to improve on the limitations of the current prototype. A comprehensive analysis of the system was conducted to determine key requirements for future development of the DHI detector to be a useful contribution to the dosimetric toolbox of a range of current and emerging applications. The sources of measurement uncertainty are considered, and methods suggested to mitigate these. Improvement of the signal-to-noise ratio, and further development of the heat transport corrections for high dose gradient regions are key areas of focus highlighted for future development.

The objective of this study was to evaluate galvanic corrosion potential under various pH conditions, buffering capacities, and corrosion inhibitors including zinc orthophosphate (ZOP) and orthophosphate (OP). Bench-scale dump-and-fill experiments evaluated metals release from a lead and copper couple under stagnant conditions. Key findings from this study were that increasing DIC from 3 to 7 or 17 mg CaCO3/L significantly reduced lead release with or without corrosion inhibitor; however, the lowest lead concentrations were observed in water conditions with corrosion inhibitor addition. However, addition of 20 mg PO4/L as OP exacerbated lead release in some cases; though dissolved lead release was always below 28 µg/L, particulate lead was as much as 4 times greater compared to no corrosion inhibitor. Overall, this study demonstrated the potential of high dose ZOP and OP for lead corrosion control in drinking water, however, overdosing OP can lead to exacerbated particulate concentrations.