Chan Mok-wah, Paul. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves [219-231]). / ACKNOWLEDGEMENTS / SUMMARY / LIST OF ABBREVIATIONS / Chapter CHAPTER 1. --- INTRODUCTION / Chapter 1.1 --- HISTORY --- p.1 / Chapter 1.2 --- RADIATION EXPOSURES OF THE POPULATION --- p.1 / Chapter 1.2.1 --- Introduction --- p.1 / Chapter 1.2.1 --- The Projected Expansion of Medical Exposures --- p.2 / Chapter 1.3 --- RADIATION HAZARDS --- p.6 / Chapter 1.3.1 --- Deterministic Effects --- p.6 / Chapter 1.3.2 --- Stochastic Effects --- p.7 / Chapter 1.3.3 --- Pre-natal Irradiation --- p.9 / Chapter 1.4 --- THE LOCAL SITUATION --- p.9 / Chapter 1.5 --- JUSTIFICATION OF THE STUDY OF LOCAL PATIENT DOSE --- p.10 / Chapter CHAPTER 2. --- THE MEDICAL EXPOSURES IN HONG KONG / Chapter 2.1 --- INTRODUCTION --- p.11 / Chapter 2.2 --- MAN-MADE RADIATION IN HONG KONG --- p.11 / Chapter 2.2.1 --- Occupational Exposure --- p.11 / Chapter 2.2.2 --- Radioactive Fall-out --- p.12 / Chapter 2.2.3 --- Nuclear Medicine --- p.12 / Chapter 2.2.4 --- Diagnostic Radiology --- p.12 / Chapter 2.3 --- THE FUTURE TREND --- p.13 / Chapter 2.4 --- THE CURRENT STUDY --- p.15 / Chapter CHAPTER 3. --- METHODS OF OPTIMISATION / Chapter 3.1 --- INTRODUCTION --- p.17 / Chapter 3.2 --- JUSTIFICATION OF DIAGNOSTIC RADIATION EXPOSURE --- p.17 / Chapter 3.3 --- OPTIMISATION OF DIAGNOSTIC RADIATION EXPOSURE --- p.18 / Chapter 3.4 --- THE CONTROL OF EXPOSURES --- p.19 / Chapter 3.4.1 --- The Control of Occupational Exposure --- p.19 / Chapter 3.4.2 --- The Control of Public Exposure --- p.20 / Chapter 3.4.3 --- The Control of Patient Exposure --- p.20 / Chapter 3.5 --- A PRACTICAL APPROACH TO CONTROL PATIENT EXPOSURES --- p.23 / Chapter 3.5.1 --- Intrumental Approach --- p.23 / Chapter 3.5.2 --- Technical Approach --- p.24 / Chapter 3.5.3 --- Administrative Approach --- p.25 / Chapter 3.6 --- CONCLUSION --- p.26 / Chapter CHAPTER 4. --- METHOD OF STUDY / Chapter 4.1 --- INTRODUCTION --- p.27 / Chapter 4.2 --- A WORKING SCHEME --- p.27 / Chapter 4.3 --- THE MEASUREMENT OF ESD --- p.29 / Chapter 4.3.1 --- Thermoluminescent Dosimetry --- p.29 / Chapter 4.3.2 --- The TL Material Adopted --- p.30 / Chapter 4.3.3 --- Irradiated of TLDs --- p.32 / Chapter 4.3.4 --- Readout of the Exposed TLDs --- p.32 / Chapter 4.3.5 --- Accuracy of Readings --- p.35 / Chapter 4.4 --- MONTE CARLO SIMULATION --- p.36 / Chapter 4.4.1 --- Introduction --- p.36 / Chapter 4.4.2 --- History --- p.38 / Chapter 4.4.3 --- The Principle --- p.38 / Chapter 4.4.4 --- Photon History --- p.40 / Chapter 4.4.5 --- The Use of Monte Carlo simulation in Organ Doses Estimation --- p.47 / Chapter 4.4.6 --- The Electron-Gamma-Shower (EGS4) Code System --- p.51 / Chapter 4.5 --- A LOCAL MATHEMATICAL PHANTOM --- p.52 / Chapter 4.5.1 --- Introduction --- p.52 / Chapter 4.5.2 --- An Ideal Mathematical Phantom --- p.52 / Chapter 4.5.3 --- Choice of Mathematical Phantom Model --- p.53 / Chapter 4.5.4 --- The Development of a Chinese Mathematical Phantom --- p.55 / Chapter 4.5.5 --- Results --- p.56 / Chapter 4.5.6 --- A Comparison --- p.60 / Chapter 4.6 --- A SUMMARY --- p.62 / Chapter CHAPTER 5. --- POPULATION STUDIES / Chapter 5.1 --- INTRODUCTION --- p.63 / Chapter 5.2 --- FREQUENCY SURVEY --- p.63 / Chapter 5.2.1 --- Survey in Private Sectors --- p.63 / Chapter 5.2.2 --- Surveyin Government Sectors --- p.64 / Chapter 5.3 --- DOSE SURVEY --- p.66 / Chapter 5.3.1 --- Selection of Regions and Projections --- p.66 / Chapter 5.3.2 --- Selection of Hospitals and Laboratories --- p.66 / Chapter 5.4 --- SAMPLE SIZE --- p.67 / Chapter CHAPTER 6. --- RESULTS / Chapter 6.1 --- INTRODUCTION --- p.68 / Chapter 6.2 --- SAMPLE SIZE --- p.68 / Chapter 6.3 --- AGE BAND AND SEX DISTRIBUTION --- p.68 / Chapter 6.4 --- THE MEASURED ESD --- p.75 / Chapter 6.4.1 --- Histograms of ESDs by Projection --- p.75 / Chapter 6.4.2 --- A Comparison of ESDs by Projection --- p.89 / Chapter 6.4.3 --- A Comparison of ESDs by Centre --- p.93 / Chapter 6.4.4 --- A Comparison of Collective ESDs by Centre --- p.96 / Chapter 6.5 --- THE ESTIMATED ORGAN DOSES --- p.103 / Chapter 6.5.1 --- Introduction --- p.103 / Chapter 6.5.2 --- Method --- p.103 / Chapter 6.5.3 --- Normalised Organ Doses --- p.105 / Chapter 6.5.4 --- Organ doses per Projection --- p.105 / Chapter 6.5.5 --- A Computerised programme --- p.119 / Chapter 6.6 --- A COMPARISON OF ORGAN DOSES ESTIMATED ON LOCAL AND NRPB MODELS --- p.152 / Chapter CHAPTER 7. --- SOURCES OF UNCERTAINTY / Chapter 7.1 --- UNCERTAINTITIES IN COMPUTATION --- p.156 / Chapter 7.1.1 --- Inaccuracy of the Justaposition of Complex Human Anatomy and the X-ray Beam --- p.156 / Chapter 7.1.2 --- Statistical Uncertainties --- p.156 / Chapter 7.1.3 --- Attenuation Coefficient Uncertainties --- p.157 / Chapter 7.1.4 --- Anatomic Inexactitudes --- p.157 / Chapter 7.2 --- ERRORS CONTRIBUTED BY TLDs --- p.155 / Chapter 7.3 --- TOTAL POSSIBLE ERROR --- p.157 / Chapter 7.4 --- VERIFICATION OF THE RESULTS --- p.158 / Chapter 7.4.1 --- Verification of the Measured ESD --- p.158 / Chapter 7.4.2 --- Verification of the Estimated Organ Doses --- p.158 / Chapter CHAPTER 8. --- HEALTH IMPLICATIONS / Chapter 8.1 --- INTRODUCTION --- p.161 / Chapter 8.2 --- DATA SOURCE --- p.161 / Chapter 8.3 --- ASSUMPTIONS --- p.162 / Chapter 8.4 --- SOMATIC RISK --- p.162 / Chapter 8.4.1 --- Somatically Significant Dose (SSD) --- p.162 / Chapter 8.4.2 --- Results --- p.163 / Chapter 8.5 --- LEUKAEMIC RISK --- p.166 / Chapter 8.5.1 --- Leukaemically Significant Dose (LSD) --- p.166 / Chapter 8.5.2 --- Results --- p.167 / Chapter 8.6 --- GENETIC RISK --- p.170 / Chapter 8.6.1 --- Genetically Significant Dose (GSD) --- p.170 / Chapter 8.6.2 --- Results --- p.171 / Chapter 8.7 --- DISCUSSION --- p.174 / Chapter CHAPTER 9. --- DISCUSSION --- p.199 / Chapter 9.1 --- MEAN ESDs PER PROJECTION --- p.199 / Chapter 9.2 --- A COMPARISON OF MEAN ESDs BETWEEN LOCAL CENTRES --- p.200 / Chapter 9.3 --- A COMPARISON OF MEAN ESDs BETWEEN COUNTRIES --- p.202 / Chapter 9.4 --- EFFECTIVE DOSE PER EXAMINATION --- p.203 / Chapter 9.5 --- NEED FOR LOCAL ANTHROPOMORPHIC PHANTOM --- p.204 / Chapter 9.6 --- ORGAN DOSES WITH HIGH CANCER INDUCTION --- p.205 / Chapter 9.7 --- A DISTRIBUTION OF COLLECTIVE DOSES --- p.206 / Chapter 9.8 --- "A DISTRIBUTION OF SSD, LSD AND GSD" --- p.209 / Chapter 9.9 --- OVERALL RISK ESTIMATION --- p.212 / Chapter 9.10 --- POPULATION ORGAN DOSES --- p.213 / Chapter 9.11 --- SUMMARY --- p.214 / Chapter CHAPTER 10. --- CONCLUSION --- p.217 / REFERENCES --- p.R 1 - 12 / APPENDICES / Chapter A. --- RADIATION QUANTITIES USED IN PATIENT DOSIMETRY --- p.A 1 - 12 / Chapter B. --- QUALITY ASSURANCE --- p.B 1 - 14 / Chapter C. --- DOSE REDUCTION --- p.C 1 - 11 / Chapter D. --- REJECT ANALYSIS --- p.D 1 - 15 / Chapter E. --- PUBLISHED WORK IN DOSE MEASUREMENT --- p.E 1 - 18 / Chapter F. --- THERMOLUMINESCENT DOSIMETRY --- p.F 1 - 27 / Chapter G. --- A STUDY ON ANTHROPOMORPHIC PHANTOM --- p.G 1 - 4

La majorité des patients atteints d'un cancer sont soignés par la technique de la radiothérapie, l'une des trois principales modalités de traitement avec la chirurgie et la chimiothérapie. Elle consiste en la délivrance d'une radiation de haute énergie sur un volume cible. Son but est de détruire les cellules cancéreuses sans endommager les tissus sains. En pratique, on utilise divers outils numériques afin de prévoir de quelle manière sera déposée l'énergie dans le corps du patient. Ces méthodes peuvent néanmoins présenter des imprécisions ou un temps de calcul trop long pour leur utilisation en milieu clinique. Par conséquent, nous avons développé un nouveau modèle permettant de simuler le transport et le dépôt d'énergie de particules dans des tissus humains, de manière rapide et précise. De nouvelles installations permettant de traiter les patients de cette manière tout en effectuant une imagerie par résonance magnétique entrent actuellement sur le marché. Les champs magnétiques induits par cette technique ont pour effet secondaire et délétère de dévier les particules chargées, injectées ou créées dans le milieu, pouvant modifier fortement le dépôt d'énergie. Malgré cela, il n'existe actuellement pas de modèle permettant de rendre compte de ces effets de manière précise et rapide. Nous nous proposons d'introduire les effets magnétiques dans notre modèle afin de répondre à cette problématique. Nous appuyons la validation de notre modèle par des comparaisons numériques avec un code Monte-Carlo de référence, FLUKA, ainsi que par des comparaisons expérimentales effectuées à l'Institut Bergonié. / The majority of patients diagnosed with cancer are treated by radiotherapy, one of the principal treatment modality with surgery and chemotherapy. It consists in the delivery of high energy radiation on a target volume. It aims to destroy the cancerous cells without damaging sane tissues. In clinical practice, numerical tools are used in order to predict how the energy will be deposited in the patient's body. However, these methods can lack of accuracy or cost too much in terms of calculation time to be suitable for clinical use. As a consequence, we developed a new model able to calculate the transport and energy deposition of ionizing particles in human tissues, efficiently and accurately. New installations allowing the treatment of patients by radiotherapy while imaging them by Magnetic Resonance Imagery are currently marketed. The magnetic fields induced by this technology have as secondary and noxious effect to deflect the charged particles injected or created in the target medium, which might modify highly the deposited energy. Despite that, there aren't yet commercially available numerical solution allowing to reproduce these effects accurately and quickly. We implemented the magnetic effects in our model to. We validate our model by numerical comparisons with a reference Monte-Carlo code, FLUKA, and with experimental comparisons led in the Bergonié Institute (Bordeaux).

La fibrose radio-induite (FRI) est une complication tardive de la radiothérapie souvent associée à une réponse inflammatoire chronique et à un infiltrat de macrophages. Aujourd’hui, les macrophages sont pressentis comme des médiateurs cellulaires important dans le processus de fibrose mais leur rôle n’a jamais été étudié dans le contexte de la FRI. Dans une précédente étude nous avions montré que l’irradiation (IR) induit une polarisation M1 des macrophages cardiaques après irradiation de souris ApoE-/- et est associée un score de fibrose élevé, ce qui suggérait que la polarisation des macrophages pourrait contribuer à la fibrogénèse radio-induite. Afin de valider cette hypothèse, nous avons cherché à caractériser le rôle des macrophages dans la FRI en utilisant un modèle classique de fibrose pulmonaire chez la souris C57Bl/6 induit après IR thoracique à 16Gy. Nous avons caractérisé les phénotypes et la fonction des macrophages alvéolaires (MA) et interstitiels (MI). Durant la phase précoce, les résultats montrent une déplétion des MA accompagnée de la sécrétion de CXCL1, MCP-1 et de MCSF. Cette déplétion est suivie d’une repopulation suite au recrutement et à la prolifération des monocytes/macrophages d’origine médullaire. La nouvelle population de MA présente une polarisation hybride accompagnée d’une augmentation simultanée de la sécrétion de cytokines Th1 et Th2. Durant la phase tardive les MI présentent une polarisation de type M2 accompagnée d’une diminution des cytokines Th1 et d’une augmentation de cytokines Th2 dans le lysat tissulaire. Nous avons ensuite cherché à caractériser la contribution des MA hybrides vs MI M2 dans le processus de fibrose. Nous avons montré que contrairement au MA hybrides, les MI M2 étaient capables d’induire l’activation des fibroblastes in vitro et l’expression de TGF-β1. De plus, la déplétion des MA hybrides avec une administration intranasale de clodronate exacerbe la FRI et induit l’augmentation de l’infiltrat de MI M2. Ensuite, nous nous somme interrogés à la contribution du processus de fibrose dans la polarisation des macrophages. Après 24h de coculture entre fibroblastes irradiés et macrophages pulmonaires non irradiés, une sécrétion de cytokines telles que M-CSF et TIMP-1 qui pourraient stimuler l’activation des fibroblastes est observée. De plus, l’inhibition de la FRI avec de la pravastatine montre que l’inhibition de la fibrose est accompagnée d’une augmentation des MI M1 et d’une diminution des MI M2 dans le poumon. En résumé, nos résultats montrent une contribution opposée des Macrophages Alvéolaires et des Macrophages Interstitiels dans le processus de fibrose radio-induite ainsi qu’une contribution du processus de fibrose dans le type d’activation des Macrophages interstitiels formant ainsi une boucle d’activation fibrogénique chronique. / Radiation-induced fibrosis (RIF) is a delayed complication of radiotherapy often associated with chronic inflammatory process and macrophage infiltration. Nowadays, macrophages are suggested to be important cellular contributors to fibrogenic process, but their implication in the context of RIF has never been investigated. In a previous study we have shown that irradiation (IR) induced the polarization of cardiac macrophages into M1 in ApoE-/- mice and was associated with a high fibrosis score in ApoE-/- mice, suggesting that macrophage polarization could drive tissue sensitivity to ionizing radiation. This observation prompted us to investigate the role of macrophages in RIF using a classical experimental model of lung fibrosis developed in C57Bl/6 mice after 16Gy thorax-IR. We profiled both alveolar macrophages (AM) and interstitial macrophages (IM). During the acute phase we found AM depletion associated with CXCL1, MCP-1 and M-CSF secretion, followed by a repopulation phase mediated by recruitment and proliferation of monocytes/macrophages from the bone marrow. Interestingly, the newly recruited AM exhibited a yet never described hybrid polarization (M1/M2), associated with the up-regulation of both Th1 and Th2 cytokines. At delayed times points, IM were M2-polarized and associated with downregulation of Th1 cytokines and upregulation of Th2 cytokines in tissue lysates. These results suggest a differential contribution of hybrid AM vs M2 IM to fibrogenesis. Interestingly, in contrast to activated hybrid AM, activated M2 IM were able to induce fibroblast activation in vitro mediated by an enhanced TGF-β1 expression. Therefore, specific depletion of hybrid AM using intranasal administration of clodrosome increased RIF score and enhanced M2 IM infiltration. We next evaluated if the fibrogenic process can in turn affect macrophage polarization. Interestingly, after coculture of irradiated fibroblast with non-irradiated pulmonary macrophages, secretion of cytokines such as M-CSF and TIMP-1, which can stimulate macrophage activation, was observed. Furthermore, RIF inhibition using pravastatin treatment showed that fibrosis inhibition was associated with a decrease in M2 IM accompanied by an increase in M1 IM, but had no effect on polarization of AM. These present study shows a dual and opposite contribution of alevolar versus intertitial macrophages in RIF and the contribution of the fibrogenic process to IM polarization, resulting thereby in a chronical fibrogenic loop.

Sobrevida após radioterapia em pacientes com glioma de alto grau Introdução: Gliomas de alto grau são os principais tumores primários do sistema nervoso central em adultos, cujo prognóstico permanece invariavelmente ruim, mesmo com a terapia atual: cirurgia e quimioirradiação. Na radioterapia utiliza-se de técnicas conformacionais (3DRT) e de intensidade modulada do feixe (IMRT). Objetivos: Avaliar a sobrevida dos pacientes tratados na instituição e os fatores que influenciam os resultados. Métodos: Análise retrospectiva dos tratamentos terapêuticos de pacientes diagnosticados com gliomas de alto grau entre 2009 e 2014 e tratados com radioterapia no Serviço de Radioterapia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCRP-USP). Resultados: A sobrevida mediana obtida foi 16,63 meses, 29 pacientes (61,7%) foram à óbito e os demais encontravam-se em seguimento até o momento da análise. IMRT correspondeu à modalidade de tratamento em 68,1% dos casos, a duração média da radioterapia foi de 56 dias, com intervalo médio (demora) entre cirurgia e o início da radioterapia de 61,7 dias (27 a 123 dias). Observamos que idade, ressecção macroscópica total, tipo histológico e utilização de temozolomida adjuvante influenciaram a taxa de sobrevida (p<0,05). A sobrevida global estimada é de 18 meses (estimativa Kaplan Meyer). Nossa série avaliou os pacientes tratados e os dados corroboram os já relatados na literatura, respaldando o protocolo de tratamento institucional. / Introduction: High-grade gliomas are the main primary tumors of the central nervous system in adults, it`s prognosis remains invariably bad, even with current therapy: chemoradiation after surgery. Radiotherapy is currently employed as conformational techniques (3DRT) or intensity modulated beam (IMRT) with or without temozolomide. Objectives: To evaluate survival of patients treated with radiation and factors influencing results. Methods: Retrospective analysis of patients diagnosed with high-grade gliomas between 2009 and 2014 and treated with radiotherapy at the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCRP-USP). Results: Median survival was 16.63 months, 29 patients (61.7%) died and the others were in follow-up at the time of analysis. IMRT was used in 68.1% of cases, the mean duration of radiotherapy obtained of 56 days, with a mean interval (delay) between the surgery/diagnosis and radiotherapy was 61.7 days (27-123 days). We found that age, total gross resection, histological type and use of adjuvant temozolomide influenced the survival rate (p <0.05). The estimated overall survival was 18 months (Kaplan Meyer estimator). Our data was similar to those reported in the literature, supporting the institutional treatment protocol.

A aferição da dose por técnica de dosimetria in vivo garante que a dose calculada pelo sistema de planejamento seja àquela entregue pelo acelerador linear (AL) durante a radioterapia, garantindo assim os processos de controle de qualidade. O objetivo deste trabalho foi validar a técnica de controle de qualidade em IMRT utilizando filme radiocrômico. Foram analisados 47 planejamentos de IMRT de três regiões: próstata, cabeça e pescoço e crânio. Para cada planejamento utilizouse um filme radiocrômico EBT2 acoplado ao cabeçote do acelerador linear através de uma bandeja preparada para o filme. A leitura e posterior análise da dose pontual e distribuição de dose após 24 horas, foi realizada em sofware desenvolvido em MatLab. O índice de aprovação foi de 92%. Quatro planos foram reprovados em pelo menos 1 critério, sendo 3 de cabeça e pescoço e 1 de crânio. Os resultados da dosimetria in vivo com filme radiocrômico foi validada, podendo ser considerada uma técnica confiável e prática na aferição da dose em radioterapia. / The measurement of dose, using the in vivo technique dosimetry, ensures that the dose calculated by the planning system is exactly the same as the dose delivered in linear accelerator, this ensures quality assurance in radiotherapy. The objective of this study was to evaluate the quality control techinique of IMRT treatments using radiochromic film. We analyzed 47 IMRT plans, which divided into three regions: Prostate, head and neck, and skull. For each plan, we used a radiochromic film coupled in linear accelerator head by a tray prepared to film placement. The film was stored for 24 hours after irradiation. Reading and analysis of point dose and 2D dose distribution were performed after this period. ll plans analyzed, the approval rating was 92%, and the others were flunked at least one criterion. Based on the results obtained in vivo dosimetry with radiochromic film was validated. This technique is reliable and practical to measure the dose delivered by linear accelerator.

A partir de um melhor entendimento sobre a radiossensibilidade do câncer de próstata, com a redefinição de parâmetros radiobiológicos, atualmente os esquemas hipofracionados de próstata tornaram-se um dos principais desafios da radioterapia moderna. Associado a este conhecimento, o emprego de técnicas precisas de radioterapia possibilitaram a entrega de maiores doses por fração, com manutenção da toxicidade e melhor controle de qualidade dos planos de tratamento. Pretendemos avaliar a implementação da radioterapia tridimensional computadorizada (3D-CRT) ou intensidade modulada do feixe (IMRT) utilizando o regime de hipofracionamento moderado (70 Gy em 28 frações) em pacientes com neoplasia localizada da próstata na rotina do departamento de radioterapia do Hospital das Clínicas da FMRP-USP. Avaliação da viabilidade técnica e do impacto financeiro na utilização da radioterapia hipofracionada na instituição. / Evaluate the implementation of computerized three-dimensional radiation therapy (3D-CRT) or intensity modulated beam (IMRT) using moderate hypofractionation schedule (70 Gy in 28 fractions) in patients with localized prostate cancer (no metastasis lymph node or distant metastasis) in routine of department of radiotherapy of the Hospital of FMRP-USP. Assessment of technical feasibility and financial impact on the use of hypofractionated radiotherapy in the institution.

Na radioterapia, o planejamento é parte fundamental do tratamento de um paciente. Para que o planejamento seja bem sucedido, o físico deve utilizar parâmetros físicos baseados na interação da radiação com a matéria para determinar a dose no volume alvo. Esses parâmetros são obtidos a partir de campos com dimensões bem definidas (geralmente quadrados), porém, na radioterapia é comum aparecer campos irregulares. Para resolver este problema, utilizam-se métodos que convertem esses campos irregulares em equivalentes de campos quadrados. Quando se tem campos pequenos, a aproximação de Sterling (algoritmo que permite a obtenção do campo quadrado equivalente a partir da razão entre quatro vezes a área efetiva de irradiação pelo perímetro que a envolve) é bem sucedida, porém quando o campo é muito grande e irregular, esta relação mais tão eficiente. Para tal caso, tem-se um método conhecido por Método de Clarkson. O método de Clarkson é um algoritmo que utiliza valores obtidos a partir de funções que relacionam a interação da radiação com a matéria, tais como, Razão Espalhamento Ar (SAR) e Razão Tecido Ar (TAR), para determinar especialmente campos quadrados equivalentes de campos irregulares e de grandes dimensões ou para calcular a dose de radiação em um ponto do paciente. A utilização deste método é muito trabalhosa, pois exige muitas horas de trabalho manual de um profissional especializado. Este trabalho desenvolveu um programa que analisa uma magem digital de um campo irregular, como os campos encontrados frequentemente no tratamento de linfomas do tipo Hodgking (manto), e determina um campo regular equivalente a este. As incertezas entre o método de Clarkson manual e o programado foram de ( -0,52 ± 0,60 )% e validam o programa desenvolvido. / Radiotherapy has a fundamental part that is the patient treatment planning. For its success, the medical physicist has to use physical parameters based on the radiation interaction with the matter, in this case the patient; in order to determine the radiation absorbed dose in the selected target volume. The physical parameters normally are related to regular radiation field sizes, although irregular fields can be also used in some treatments. To overcome this problem there are methods that convert irregular fields in regular fields, such as a square one. For small fields the Sterling\'s Method (technique to calculate equivalent square fields making use of ratio four times the effective area of irradiation by is perimeter) can be used. However, this method is not adequate for large irregular field. In this case, the Clarkson\'s Method is used. The Clarkson\'s Method uses values functions, such as Scattering-Air Ratio (SAR) and Tissue-Air Ratio (TAR), related with radiation interaction of with matter, to determine equivalent square fields from those large irregular ones or to calculate the radiation absorbed dose in the point of interest in a patient The application this method takes time, once it needs a considerable time from the medical physicist attention and also from the equipment. In this work, a software was developed to analyse digital images of large irregular fields, such as fields found in treatment of Hodgkin\'s disease (mantle) correlating them to regular equivalent fields. The uncertainty between the manual Clarkson and the programmed was inferred as ( -0,52 ± 0,60 )%, what can validate the program developed.

A dosimetria na radioterapia é realizada periodicamente como parte do controle de qualidade tanto dos equipamentos como dos tratamentos dos pacientes. O dosímetro convencional utilizado para essa finalidade é a câmara de ionização, no entanto, ela pode apresentar limitações quando se necessita de um dosímetro que possua resoluções espacial e temporal altas. Este trabalho tem como objetivo a caracterização do dosímetro de antraceno para radiação de fótons radioterápicos. O antraceno é um cristal orgânico cintilador com vantagens de ser praticamente equivalente à água e tecido mole em feixes radioterápicos e com possibilidade de possuir volume de detecção e tamanho pequenos, para utilizar em radiocirurgia e dosimetria in vivo. Neste trabalho, a caracterização do dosímetro de antraceno foi realizada obtendo-se o sinal de cintilação em função da sua granulosidade média, diâmetro da sua cápsula interna, dose absorvida, taxa de dose absorvida, energia do feixe de radiação e sua resolução espacial, sendo essa última realizada por três métodos diferentes relacionados e equivalentes: (função de espalhamento de borda (FEB), função de espalhamento linear (FEL) e função de transferência de modulação (MTF)). Os feixes de fótons utilizados para as irradiações do cintilador foram os de 60 Co (1,25 MeV), 137 Cs (0,661 MeV) e raios X (energias efetivas de 28,4; 46,5; 48,5; 94,0 e 106,0 keV). A instrumentação utilizada para a detecção do sinal do cintilador foi composta por uma fibra óptica, fotomultiplicadora, fonte de alta tensão, eletrômetro e multímetro. Dos dados obtidos, a contribuição da radiação Cerenkov, produzida na fibra óptica, foi subtraída, e as seguintes características dos sinais resultantes puderam ser inferidas: quanto maior a granulosidade maior o sinal de cintilação detectado; a dependência do sinal com o diâmetro interno da sua cápsula aumenta proporcionalmente com o cubo do diâmetro; dependência linear do sinal com a dose absorvida; independência com a taxa de dose absorvida; dependência linear para baixas energias e independência para altas energia do feixe. Além disso, das resoluções espaciais encontradas pelos três métodos diferentes, aquela calculada pelo método MTF é a que mais se aproximou das dimensões do detector (1,6 mm), tendo sido obtido um valor igual a 1,43+/-0,07 mm. Dos resultados foi possível caracterizar o dosímetro de antraceno de modo que sua utilização em trabalhos futuros seja mais adequada. / New radiotherapy techniques such as intensity-modulated radiation therapy and stereotactic radiosurgery have increased the need for dosimeters that can provide measurements in real time with high spatial resolution. Organic scintillation dosimeters are able to measure with accuracy small radiation fields and fields with high gradients, besides having advantages such as water and soft tissue equivalence and the possibility to be used in vivo. Anthracene is an organic scintillator crystal with the highest known scintillation efficiency among organic scintillation materials. The objective of this work is to characterize the antracene as a dosimeter under radiotherapic photons energies, analysing its signal against average granulosity, intern capsule diameter, absorbed dose, absorbed dose rate, photon energy and its spatial resolution; with the last one analysed under three methods (edge spread function, line spread function and modulation transfer function). The photons energies used were 1.25 MeV ( 60 Co), 0.661 MeV ( 137 Cs) and X-rays (effective energies of 28.4; 46.5; 48.5; 94.0 e 106.0 keV). The scintillation detection system consisted of an optical fiber with one end attached to the anthracene capsule and the other to a photomultiplier tube mantained by power supply followed by an electrometer. Once Cerenkov radiation occurs in the optical fiber, it was removed from the total scintillation signal trough the subtraction of the signal, taken irradiating the optical fiber without the anthracene attached to one of its extremity. From results obtained, one can infer that the dosimeter signal increases proportionally with average granulosity and intern capsule diameter. The signal is linearly dependent of absorbed dose, linearly dependent of low photons energies and independent for high photons energies, as well as independent of the absorbed dose rate. From the spatial resolution values obtained it was possible to infer that the one obtained through modulation transfer function, 1.43+/-0.07 mm, was the one that approximated the most to the actual dosimeter physical size (1.6 mm). From the characteristics obtained with this work, we think that future projects involving the anthracene will be carried out more properly.

Foi desenvolvido um programa para fusão de imagens médicas para utilização nos sistemas de planejamento de tratamento de radioterapia CAT3D e de radiocirurgia MNPS. Foi utilizada uma metodologia de maximização da informação mútua para fazer a fusão das imagens de modalidades diferentes pela medida da dependência estatística entre os pares de voxels. O alinhamento por pontos referenciais faz uma aproximação inicial para o processo de otimização não linear pelo método de downhill simplex para gerar o histograma conjugado. A função de transformação de coordenadas utiliza uma interpolação trilinear e procura pelo valor de máximo global em um espaço de 6 dimensões, com 3 graus de liberdade para translação e 3 graus de liberdade para rotação, utilizando o modelo de corpo rígido. Este método foi avaliado com imagens de TC, RM e PET do banco de dados da Universidade Vanderbilt, para verificar sua exatidão pela comparação das coordenadas de transformação de cada fusão de imagens com os valores de referência. O valor da mediana dos erros de alinhamento das imagens foi de 1,6 mm para a fusão de TC-RM e de 3,5 mm para PET-RM, com a exatidão dos padrões de referência estimada em 0,4 mm para TC-RM e 1,7 mm para PET-RM. Os valores máximos de erros foram de 5,3 mm para TC-RM e de 7,4 mm para PET-RM e 99,1% dos erros foram menores que o tamanho dos voxels das imagens. O tempo médio de processamento para a fusão de imagens foi de 24 s. O programa foi concluído com sucesso e inserido na rotina de 59 serviços de radioterapia, dos quais 42 estão no Brasil e 17 na América Latina. Este método não apresenta limitações quanto às resoluções diferentes das imagens, tamanhos de pixels e espessuras de corte. Além disso, o alinhamento pode ser realizado com imagens transversais, coronais ou sagitais. / Software for medical images fusion was developed for utilization in CAT3D radiotherapy and MNPS radiosurgery treatment planning systems. A mutual information maximization methodology was used to make the image registration of different modalities by measure of the statistical dependence between the voxels pairs. The alignment by references points makes an initial approximation to the non linear optimization process by downhill simplex method for estimation of the joint histogram. The coordinates transformation function use a trilinear interpolation and search for the global maximum value in a 6 dimensional space, with 3 degree of freedom for translation and 3 degree of freedom for rotation, by making use of the rigid body model. This method was evaluated with CT, MR and PET images from Vanderbilt University database to verify its accuracy by comparison of transformation coordinates of each images fusion with gold-standard values. The median of images alignment error values was 1.6 mm for CT-MR fusion and 3.5 mm for PET-MR fusion, with gold-standard accuracy estimated as 0.4 mm for CT-MR fusion and 1.7 mm for PET-MR fusion. The maximum error values were 5.3 mm for CT-MR fusion and 7.4 mm for PET-MR fusion, and 99.1% of alignment errors were images subvoxels values. The mean computing time was 24 s. The software was successfully finished and implemented in 59 radiotherapy routine services, of which 42 are in Brazil and 17 are in Latin America. This method doesn’t have limitation about different resolutions from images, pixels sizes and slice thickness. Besides, the alignment may be accomplished by axial, coronal or sagital images.

O presente estudo avaliou a composição química da dentina radicular de dentes submetidos à radioterapia por meio de Espectroscopia Raman Confocal (ERC). Vinte pré-molares inferiores humanos homólogos foram selecionados e distribuídos em dois grupos (n=10) de acordo com a irradiação: não irradiados e irradiados, submetidos à radioterapia fraccionada com raios-X de 6 MV. Os dentes foram seccionados e submetidos à análise da composição química da dentina radicular submetida à radioterapia por meio de ERC, em relação aos picos de fosfato, carbonato e amidas I, II e III. Foi utilizada objetiva de 40x (Olympus), com luz de comprimento de onda de 785 nm, compreendendo a faixa espectral de 400 - 1800 cm-1, na região de baixa frequência, com resolução espacial de 2 &micro;m. Para a geração do espectro, a potência do laser utilizada foi de 21 mW e o tempo de exposição de 5 segundos. A intensidade dos picos fosfato - PO43- (590 cm-1) e carbonato - CO32- (1070 cm-1) no ERC são proporcionais à quantidade de conteúdo inorgânico, enquanto que a amida I (1670 cm-1), II (1453 cm-1) e III (1267 cm-1) são proporcionais ao conteúdo orgânico (colágeno). Os dados obtidos foram submetidos à análise estatística (Teste T, P<0,05) para amostras independentes, avaliando-se a influência da radioterapia nos valores de fosfato, carbonato e amidas I, II e III em diferentes regiões radiculares. Em região de dentina radicular intracanal, o grupo irradiado (1,23&plusmn;0,06) apresentou menores valores de fosfato quando comparado ao grupo não irradiado (1,40&plusmn;0,18) (P<0,05). Em relação ao carbonato, foi observado que os dentes irradiados (1,56&plusmn;0,06) apresentaram menores valores quando comparados ao grupo não irradiado (1,42&plusmn;0,10) (P<0,05). Para os picos de amida, não foi observada diferença estatística entre os grupos em amida I (P=0,295) e amida II (P=0,792). No entanto, o tratamento radioterápico reduziu significativamente os valores de amida III do grupo irradiado (1,05&plusmn;0,19) em comparação ao grupo não irradiado (1,28&plusmn;0,24). Quando avaliada a região da dentina radicular média, o grupo irradiado (1,30&plusmn;0,12) apresentou menores valores de fosfato quando comparado ao grupo não irradiado (1,48&plusmn;0,22) (P<0,05); e em relação aos valores de carbonato (P=0,859), amida I (P=0,785), amida II (P=0,771) e amida III (P=0,338) não foi observada diferença estatística entre eles. Na análise em cemento, não houve diferenças estatísticas entre os grupos irradiado e não irradiado para os valores de fosfato (P=0,448), carbonato (P=0,575) e amida I (P=0,225), amida II (P=0,437) e amida III (P=0,187). Dessa forma, pode-se concluir que a radioterapia promoveu alterações nos picos de amida III, indicando modificação estrutural do colágeno. / The present study was to evaluate the root dentin chemical composition of teeth submitted to radiotherapy by Confocal Raman Spectroscopy (CRS). Twenty inferior human homologues premolars were selected and divided in two groups (n = 10) according to the irradiation protocol: non Irradiated and irradiated, submitted to fractional X-ray radiotherapy of 6 MV. The teeth were sectioned and submitted to the analysis of the chemical composition of radicular dentin submitted to radiotherapy by CRS, evaluating the phosphate, carbonate and amides I, II and III peaks. A 40x objective (Olympus) was used, generating a light with a 785 nm wavelength, comprising the spectral range of 400-1800 cm-1 in the low frequency region with spatial resolution of 2 &micro;m. For the spectrum generating the laser power used was 21 mW and the exposure time was 5 seconds. The intensity of the phosphate - PO43- (590 cm-1) and carbonate - CO32- (1070 cm-1) peaks in the CRS are proportional to the amount of inorganic content while the amide I (1670 cm-1), II (1453 cm-1) and III (1267 cm-1) are proportional to organic content (collagen). The data were submitted to statistical analysis (Test T, P<0.05) for independent samples, evaluating the influence of radiotherapy on the phosphate, carbonate and amide I, II and III values in different root regions. In the intracanal dentin root region, the irradiated group (1.23 ± 0.06) had lower phosphate values when compared to the non-irradiated group (1.40 ± 0.18) (P<0.05). In relation to the carbonate, it was observed that the irradiated teeth (1.56 + 0.06) had lower values than the non-irradiated group (1.42 + 0.10) (P<0.05). The amide peaks has no statistical difference observed between the groups in relation to the amide I (P=0,295) and amide II (P=0,792). However, the radiotherapeutic treatment significantly reduced the amide III values of the irradiated group (1.05 + 0.19) compared to the non-irradiated group (1.28 + 0.24). When the middle radicular dentin region was evaluated, the irradiated group (1.30 ± 0.12) had lower phosphate values when compared to the non-irradiated group (1.48 ± 0.22) (P<0.05); and in relation to the carbonate (P=0.859), amide I (P=0.785), amide II (P=0,771) and amide III (P=0,338) peaks no statistical difference was showed between irradiated and non-irradiated teeth. In the cement analysis, there was no statistical difference between the irradiated and non-irradiated groups for the phosphate (p = 0.448), carbonate (P=0.575), amide I P=0.225), amide II (P=0,437) and amide III (P=0,187) values. In conclusion, the radiotherapy was able to promote alterations in the amide III, changing the collagen structure.