Este trabalho tem por objetivo a composição e caracterização de um dosímetro à base de DL-Alanina e Ferro-ll em forma de gel para aplicações em dosimetría para campos de doses da radiação gama do Co-60 experimentadas em procedimentos de radioterapia. O aminoácido DL-Alanina é dissolvido em solução ácida contendo o Fe-ll e adicionado o gel. Procedeu-se a uma série de ensaios variando reagente a reagente e realizando procedimentos para avaliar o comportamento em função do tempo do gel dosimétrico obtido. Os espectros de absorção antes e após a irradiação apresentam máximos em 457 nm e 588 nm, respectivamente. Esses dois picos correspondem aos comprimentos de onda de absorção das espécies Fe-ll e Fe-lll, respectivamente; estando ambas as espécies em equilíbrio. Com a irradiação, ocorre a formação de radicais que oxidam o Fe-ll em Fe-lll, alterando com isso o balanço entre as duas espécies - daí o aumento da concentração de Fe-lll - fazendo com que mude a tonalidade do gel, sendo, portanto, possível de ser determinada a dose absorvida. Nas análises dos espectros e respectivas curvas dose-resposta observou-se que o gel dosimétrico apresenta linearidade no intervalo de doses entre 0,5 e 40 Gy. A partir dos resultados obtidos de linearidade, estabilidade e menor dose detectável - 0,3 Gy - conclui-se que o presente Gel Dosimétrico à base de DL-Alanina e Fe-ll apresenta excelente potencial para a finalidade que é proposto, qual seja a determinação do campo de doses em radioterapia e futura aplicação como padrão na determinação desses campos, em 3D, utilizando-se a técnica de Imagem por Ressonância Magnética - IRM. / The aim of this work is to develop a DL-Alanine, Fe-ll based gel dosimeter to be applied in the dosimetry of the Co-60 gamma-radiation fields in the dose range of radiation therapy procedures. The aminoacid DL-Alanine is dissolved in an acid solution containing the Fe-ll and added to the gel. A series of essays was performed with different chemicals and different procedures were made to evaluate the behavior of the obtained dosimetric gel as function of the time. The absorption spectra, before and after the irradiation, present maximum in 457 nm and 588 nm, respectively. These two peaks correspond to absorption wavelengths of the chemical species Fe-ll and Fe-lll, respectively, both species being in equilibrium. With the irradiation, the formation of the radicals that oxide the Fe-ll into Fe-lll occurs, altering the chemical balance of both species - hence the increase of the Fe-lll - and causing the gel to change its tonality, in such a way that it is possible to determine the absorved dose. In the analysis of the spectra and respective dose-response curves it was observed that the dosimetric gel shows linearity in dose range of 0.5 to 40 Gy. From the obtained linearity results, stability and lower detectable dose - 0,3 Gy - it is possible to conclude that the present DL-Alanine, Fe-ll based dosimetric gel presents an excellent potential to the application to which it is proposed, namely, the determination of the dose fields in radiation therapy and its future application as a standard in the determination of these fields, in 3D, using the Magnetic Resonance Imaging.

Aufgrund der hohen Patientendosen bei der CT und des möglichen Strahlenrisikos ist es wichtig, daß die Patientendosis bestimmt werden kann und optimiert wird. Die Bestimmung der Patientendosis erfolgt durch Berechnung mit Hilfe von Konversionsfaktoren oder Messung meist mit Hilfe von Thermolumineszenzdosimetern und einem gewebeäquivalenten anthropomorphen Phantom. Ein Problem bei der Dosisberechnung liegt darin, daß nicht für alle Geräte spezifische Konversionsfaktoren exisitieren. Probleme bei der Dosismessung liegen darin, daß das gewebeäquivalente Phantom sehr teuer ist, die Handhabung auf dem CT-Tisch umständlich und die Auswertung der Dosimeter zeitaufwendig ist. Eine Lösungsmöglichkeit ist die Verwendung des Computertomographie-Dosisindex CTDI und des Dosislängenproduktes, zwei Dosisgrößen, die sich aus Messungen in einfachen zylindrischen Plexiglasphantomen ableiten lassen. Der CTDI ist heute beim Hersteller erfragbar. Nach eigenen vergleichenden Untersuchungen liefert der CTDI einen brauchbaren Wert für die Dosen der Organe, die vollständig in der Untersuchungsregion liegen. Das Dosislängenprodukt korreliert sehr gut mit der effektiven Dosis, die als Vergleichsmaß für das angenommene Strahlenrisiko herangezogen wird. Es ist hilfreich zur einfachen und schnellen Abschätzung der effektiven Dosis, wenn keine geeigneten Konversionsfaktoren vorliegen. Zu den Möglichkeiten der Dosisoptimierung gehören die Reduzierung des Gesamt-mAs-Produktes durch Erhöhung des pitch bei der Spiral-Technik, die Niedrigdosis-CT für bestimmte Fragestellungen und die Bleiabdeckung von Organen außerhalb der Untersuchungsregion. Eine weitere Möglichkeit ist die Dosisbeschränkung. Hierzu sieht die Patientenrichtlinie der Europäischen Gemeinschaft von 1997 die Etablierung von diagnostischen Referenzwerten vor. Im Working Document der europäischen Kommission werden der CTDI und das DLP als Referenzdosisgrößen vorgeschlagen. Dabei wird das 3. Quartil der mittleren Dosiswerte von allen untersuchten Zentren als Referenzwert verwendet. Das Problem ist, daß die vorgeschlagenen Referenzwerte sich auf Ergebnisse einer älteren Dosiserhebung an konventionellen CT-Geräten aus den späten 80-er Jahren stützen. Eine aktuelle von uns durchgeführte Dosiserhebung in Berlin zeigt, daß die Werte für CTDI und DLP bei der Spiral-CT deutlich geringer sind als bei der konventionellen CT. Die vorgeschlagenen Referenzwerte sind für die Spiral-CT also zu hoch. Bei der Aufstellung von neuen Referenzwerten sollten daher die Dosiswerte für die Spiral-CT besondere Berücksichtigung finden. / Due to the high radiation dose to the patient in CT and the possible radiation risk it is important to determine and to optimize the patient dose. The determination of the patient dose is performed by calculation with the help of conversion factors or measurement mostly with the help of thermoluminescence dosemeters and tissue-equivalent anthropomorphic phantom. Problem in dose calculation occurs when machine specific conversion factors are not available. Problems in dose measurement are the very high cost of tissue-equivalent phantom, the difficulty in the handling of the phantom on the patient desk and the time consuming reading of the dosemeters. A possible solution is the use of computed tomography dose index (CTDI) and dose length product. These are two dose quantities that can be derived from measurements in simple cylindrical polymethylmetacrylate phantoms. CTDI can be provided by the manufacturer. According to own comparative examinations CTDI provides a useful value for the dose of organs, that lie completely within the examination region. The dose length product shows very good correlation with the effective dose, that is used to compare the supposed radiation risk from different examinations. It is useful for a simple and quick estimation of the effective dose when appropriate conversion factors are not provided. Possibilities to optimize the patient dose are reduction of the total mAs-product by increasing the pitch in spiral CT, low dose CT for some clinical questions and lead shielding of organs outside the examination region. A further possibility is the dose restriction. For this the Council Directive of 1997 of the European Union provides that diagnostic reference levels are established. In the Working Document of the European Commission CTDI and dose length product are proposed as reference dose quantities. The third quartile of the average dose values in all examined centers is used as reference dose values. Problem is , that the proposed reference dose values are derived from the results of an older survey on conventional CT machines in the late eighties. A topical survey performed by us in Berlin shows that the values for CTDI and dose length product are lower for spiral CT than for conventional CT. Therefore the proposed reference dose values are too high for spiral CT machines. In the establishment of new reference dose values particularly the dose values of spiral CT should be considered.

Depuis son introduction dans les années 1970, le scanner est devenu une technique d’imagerie médicale incontournable grâce à son excellente performance pour le diagnostic de nombreuses pathologies. Toutefois, le scanner est un examen d’imagerie irradiant. Compte-tenu des risques potentiels de cancer radio-induit liés aux faibles doses de rayons X, la réduction de la dose d’irradiation au scanner est primordiale. Dans ce travail, nous avons étudié plusieurs facteurs techniques et comportementaux qui permettent d’optimiser et de réduire la dose d’irradiation au scanner, tout en préservant une excellente performance diagnostique. Du côté des facteurs comportementaux, la sensibilisation des équipes médicales et paramédicales est fondamentale dans une démarche d’optimisation de la dose d’irradiation au scanner. De même, la limitation du nombre de phases d’acquisition et la réduction de la couverture d’acquisition sont deux manières simples pour réduire les doses délivrées. Du côté des facteurs techniques, nous avons montrés que l’utilisation des reconstructions itératives, par rapport aux reconstructions standards en rétroprojection filtrée, permet de réduire de moitié la dose d’irradiation des scanners, à qualité d’image équivalente. L’acquisition en mode volumique pour les scanners avec une faible couverture d’acquisition et l’utilisation de la modulation automatique du milliampérage permettent aussi de réduire et d’optimiser les doses. Enfin, nous nous sommes intéressés à l’optimisation de protocoles de scanner en pratique clinique courante en se focalisant sur les scanners réalisés pour la recherche d’une colique néphrétique et pour les scanners en imagerie ostéo-articulaire. Dans ce dernier domaine, nous avons aussi proposé des protocoles de scanner pour des applications cliniques avancées comme le scanner dynamique des articulations ou le scanner de perfusion tumorale / Since its introduction in the 1970s, computed tomography (CT) has become the technique of reference in medical imaging for many diseases due to its high diagnostic performance. Its main limitation is the radiation dose delivered to the patient. Considering the potential risks of radiation-induced cancer caused even with low dose exposure, dose reduction in CT is essential. In this work, we studied several technical and behavioral factors that allow for CT radiation dose reduction and optimization, without modifying the diagnostic performance. Among the behavioral factors studied, education and awareness of radiologists and radiology technicians are important elements for CT radiation dose reduction. Limiting CT scan coverage and the number of acquisition phases is also a straightforward and effective way to reduce dose exposure. Regarding technical factors, we have shown that iterative reconstruction algorithms can reduce in half the radiation dose in comparison with standard filtered back projection, while maintaining equivalent image quality. The use of wide volume mode for acquisitions with a short coverage and the use of the automatic tube current modulation can also be used to reduce and optimize CT radiation dose. Finally, we provide guidelines to optimize CT radiation dose in some clinical settings such as renal colic and musculoskeletal CT. We also propose practical guidelines for advanced clinical applications of joint dynamic CT and perfusion CT in musculoskeletal disease

Este trabalho tem por objetivo a composição e caracterização de um dosímetro à base de DL-Alanina e Ferro-ll em forma de gel para aplicações em dosimetría para campos de doses da radiação gama do Co-60 experimentadas em procedimentos de radioterapia. O aminoácido DL-Alanina é dissolvido em solução ácida contendo o Fe-ll e adicionado o gel. Procedeu-se a uma série de ensaios variando reagente a reagente e realizando procedimentos para avaliar o comportamento em função do tempo do gel dosimétrico obtido. Os espectros de absorção antes e após a irradiação apresentam máximos em 457 nm e 588 nm, respectivamente. Esses dois picos correspondem aos comprimentos de onda de absorção das espécies Fe-ll e Fe-lll, respectivamente; estando ambas as espécies em equilíbrio. Com a irradiação, ocorre a formação de radicais que oxidam o Fe-ll em Fe-lll, alterando com isso o balanço entre as duas espécies - daí o aumento da concentração de Fe-lll - fazendo com que mude a tonalidade do gel, sendo, portanto, possível de ser determinada a dose absorvida. Nas análises dos espectros e respectivas curvas dose-resposta observou-se que o gel dosimétrico apresenta linearidade no intervalo de doses entre 0,5 e 40 Gy. A partir dos resultados obtidos de linearidade, estabilidade e menor dose detectável - 0,3 Gy - conclui-se que o presente Gel Dosimétrico à base de DL-Alanina e Fe-ll apresenta excelente potencial para a finalidade que é proposto, qual seja a determinação do campo de doses em radioterapia e futura aplicação como padrão na determinação desses campos, em 3D, utilizando-se a técnica de Imagem por Ressonância Magnética - IRM. / The aim of this work is to develop a DL-Alanine, Fe-ll based gel dosimeter to be applied in the dosimetry of the Co-60 gamma-radiation fields in the dose range of radiation therapy procedures. The aminoacid DL-Alanine is dissolved in an acid solution containing the Fe-ll and added to the gel. A series of essays was performed with different chemicals and different procedures were made to evaluate the behavior of the obtained dosimetric gel as function of the time. The absorption spectra, before and after the irradiation, present maximum in 457 nm and 588 nm, respectively. These two peaks correspond to absorption wavelengths of the chemical species Fe-ll and Fe-lll, respectively, both species being in equilibrium. With the irradiation, the formation of the radicals that oxide the Fe-ll into Fe-lll occurs, altering the chemical balance of both species - hence the increase of the Fe-lll - and causing the gel to change its tonality, in such a way that it is possible to determine the absorved dose. In the analysis of the spectra and respective dose-response curves it was observed that the dosimetric gel shows linearity in dose range of 0.5 to 40 Gy. From the obtained linearity results, stability and lower detectable dose - 0,3 Gy - it is possible to conclude that the present DL-Alanine, Fe-ll based dosimetric gel presents an excellent potential to the application to which it is proposed, namely, the determination of the dose fields in radiation therapy and its future application as a standard in the determination of these fields, in 3D, using the Magnetic Resonance Imaging.

Este trabalho tem como objetivo o desenvolvimento de um novo método para a simulação de redução da dose de radiação em imagens mamográficas clínicas. Assim, estudos sobre a influência da redução da dose de radiação no diagnóstico do câncer de mama podem ser realizados sem que o paciente se exponha a doses extras de radiação. Uma análise preliminar foi realizada para a caracterização do ruído produzido pelo equipamento mamográfico no processo de aquisição da imagem. Essa análise evidenciou a importância de um método local de simulação, uma vez que o ruído depende da posição ao longo do campo. O novo método proposto consiste em ajustar os níveis de cinza e adicionar uma máscara de ruído Poisson, dependente do sinal, nas imagens clínicas adquiridas com a dose de radiação padrão, simulando sua aquisição com doses de radiação reduzidas. A dependência entre ruído e sinal foi criada com o uso da transformada de Anscombe. O desempenho do método proposto foi avaliado utilizando-se imagens mamográficas de um phantom antropomórfico obtidas com diferentes doses de radiação. As imagens simuladas pelo método proposto foram comparadas com as imagens reais. A similaridade entre os espectros de ruído permitiu a comparação de métricas locais da imagem. O erro percentual entre os níveis de cinza das imagens reais e simuladas se manteve inferior a 1%. O ruído adicionado manteve um erro percentual inferior a 1%. Testes de t-Student mostraram que não existe diferença estatística significante (p < 0,05) entre as imagens reais e simuladas pelo método proposto. / This work aims to develop a new method for simulating reduction of the radiation dose in clinical digital mammography. Using such method, studies regarding the influence of dose reduction in cancer diagnosis can be performed without unnecessary exposure of patients to X-ray radiation. A preliminary study characterized the noise produced by the digital mammography equipment during the acquisition process. This analysis emphasized the importance of simulating noise locally, since noise is dependent on the spatial position of the pixel. Therefore, the proposed method consists of adjusting the gray levels and adding signal-dependent Poisson noise to images acquired at the standard radiation dose. Dependency between noise and signal was created using the Anscombe transformation. The performance of the proposed method was evaluated using mammographic images of an anthropomorphic phantom acquired at different radiation doses. Images simulated using the proposed method were compared to real images acquired using the clinical equipment. Similarity between noise power spectra and local metrics validated the similarity between images. The gray level of the simulated and real images were compared using local mean and reported averaged errors smaller than 1%. The added noise was also compared and the averaged error was smaller than 1%. Statistical Student\'s t-test tests showed no statistical difference (p < 0.05) between real images and the ones simulated using the proposed method.

Most breast cancer patients undergo radiation diagnostics and are also treated with radiotherapy. In addition to being an important treatment modality, ionizing radiation (IR) is a potent tumour-causing agent that has been linked to breast cancer development. However, the exact molecular etiology of IR-induced mammary gland carcinogenesis remains unknown. We set out to analyze the role of DNA methylation in mammary gland responses to low dose IR using a well-established rat model. We also studied low dose IR effects on global gene expression and microRNAome. We found that exposure to low, mammography-like dose of IR led to a significant loss of global DNA methylation in rat mammary gland tissue. Furthermore, low dose IR significantly affected rat mammary gland transcriptome and microRNAome. The datasets generated within the scope of this thesis may be used to identify novel predictive biomarkers for assessment of the magnitude of IR effects on mammary gland tissue. / xi, 120 leaves ; 29 cm

Cartilage tissue engineering has been emerging as a promising therapeutic approach, where engineered constructs or scaffolds are used as temporary supports to promote regeneration of functional cartilage tissue. Hybrid constructs fabricated from cells, hydrogels, and solid polymeric materials show the most potential for their enhanced biological and mechanical properties. However, fabrication of customized hybrid constructs with impregnated cells is still in its infancy and many issues related to their structural integrity and the cell functions need to be addressed by research. Meanwhile, it is noticed that nowadays monitoring the success of tissue engineered constructs must rely on animal models, which have to be sacrificed for subsequent examination based on histological techniques. This becomes a critical issue as tissue engineering advances from animal to human studies, thus raising a great need for non-invasive assessments of engineered constructs in situ. To address the aforementioned issues, this research is aimed to (1) develop novel fabrication processes to fabricate hybrid constructs incorporating living cells (hereafter referred as “construct biofabrication”) for cartilage tissue regeneration and (2) develop non-invasive monitoring methods based on synchrotron X-ray imaging techniques for examining cartilage tissue constructs in situ. Based on three-dimensional (3D) printing techniques, novel biofabrication processes were developed to create constructs from synthetic polycaprolactone (PCL) polymer framework and cell-impregnated alginate hydrogel, so as to provide both structural and biological properties as desired in cartilage tissue engineering. To ensure the structural integrity of the constructs, the influence of both PCL polymer and alginate was examined, thus forming a basis to prepare materials for subsequent construct biofabrication. To ensure the biological properties, three types of cells, i.e., two primary cell populations from embryonic chick sternum and an established chondrocyte cell line of ATDC5 were chosen to be incorporated in the construct biofabrication. The biological performance of the cells in the construct were examined along with the influence of the polymer melting temperature on them. The promising results of cell viability and proliferation as well as cartilage matrix production demonstrate that the developed processes are appropriate for fabricating hybrid constructs for cartilage tissue engineering. To develop non-invasive in situ assessment methods for cartilage and other soft tissue engineering applications, synchrotron phase-based X-ray imaging techniques of diffraction enhanced imaging (DEI), analyzer based imaging (ABI), and inline phase contrast imaging (PCI) were investigated, respectively, with samples prepared from pig knees implanted with low density scaffolds. The results from the computed-tomography (CT)-DEI, CT-ABI, and extended-distance CT-PCI showed the scaffold implanted in pig knee cartilage in situ with structural properties more clearly than conventional PCI and clinical MRI, thus providing information and means for tracking the success of scaffolds in tissue repair and remodeling. To optimize the methods for live animal and eventually for human patients, strategies with the aim to reduce the radiation dose during the imaging process were developed by reducing the number of CT projections, region of imaging, and imaging resolution. The results of the developed strategies illustrate that effective dose for CT-DEI, CT-ABI, and extended-distance CT-PCI could be reduced to 0.3-10 mSv, comparable to the dose for clinical X-ray scans, without compromising the image quality. Taken together, synchrotron X-ray imaging techniques were illustrated promising for developing non-invasive monitoring methods for examining cartilage tissue constructs in live animals and eventually in human patients.

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Orientador: Marco Antônio Rodrigues Fernandes / Resumo: Este trabalho apresenta um estudo de planos radioterápicos realizados com o Sistema de Planejamento de Tratamento (TPS) XiO 5.10, utilizados em centros de radioterapia. Foram analisados os protocolos clínicos de radioterapia através de pesquisa bibliográfica em artigos científicos e textos produzidos pelas sociedades especializadas da área da radioncologia. Foram realizadas visitas técnicas junto a serviços de radioterapia para melhor entendimento das diferenças entre os distintos sistemas de planejamentos radioterápicos aplicados. A pesquisa verificou a resposta de três diferentes algoritmos computacionais de cálculo de dose de radiação: Superposition, Convolution e Fast Superposition, disponíveis no TPS XiO® da Elekta Medical Systems. Para isto foram analisados os parâmetros de distribuição de dose para 22 planejamentos radioterápicos realizados em uma clínica de radioterapia privada, sendo: 1 paciente com metástase cerebral, 3 pacientes com tumores de cabeça e pescoço, 9 com câncer de mama e 9 com tumores da próstata. Também foi quantificada a influência da heterogeneidade do tecido irradiado, através dos métodos de correção de heterogeneidade do XiO. Independentemente da correção de heterogeneidade do tecido, de um modo geral, o algoritmo de Convolution tendeu a subestimar a dose no PTV quando comparado com os outros dois algoritmos de cálculo de dose. Não foram percebidas diferenças significativas nos valores de dose de radiação calculados para o PTV, determinadas com os... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This paper bring forward a study of radiotherapeutic planning accomplished by XiO 5.10 treatment planning systems utilized in radiotherapic centers. The clinical protocols of radiotherapy were analyzed through bibliographic research in scientific articles and texts produced by societies related to the area of radioncology. . Technical reconnaissance visits were performed in radiotherapy services for a better understanding of the differences between the systems of radiotherapy planning applied. The research verified the response of three distinct computational algorithms of calculation of dose radiation: Superposition, Convolution and Fast Superposition, available in the Tps XiO® of Elekta Medical Systems. For this purpose, were analyzed the dose distribution parameters for 22 radiotherapy plans performed in a private radiotherapy clinic: 1 patient with cerebral metastasis, 3 patients with head and neck tumors, 9 with breast cancer and 9 with prostate tumors . The influence of the heterogeneity of the irradiated tissue was also quantified through the XiO heterogeneity correction methods. Regardless of the correction of tissue heterogeneity, the Convolution algorithm tended to, in general, underestimate the dose in the PTV when compared to the other two dose calculation algorithms. No significant differences were observed in the radiation dose values calculated for the PTV, determined with the other two algorithms, however, the Superposition method provides a slight reduction o... (Complete abstract click electronic access below) / Mestre

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