Background The debate regarding the lower age limit for mammography service screening is old and lively; a product in part of the lower breast cancer risk in younger ages as well as the limited data available for studies of the younger age group. Recently the idea of inviting only high risk groups has gained momentum, however high risk might not be equivalent to greater benefit from screening. Therefore, there is a need for information on effectiveness of screening as it relates to young women and to specific risk groups. To this end, this thesis evaluates mammography screening for the age group – 40 to 49 year old women – in terms of breast cancer mortality reduction in total and in subgroups based on breast cancer risk factors. Overdiagnosis of mammography screening is also evaluated for women 40 to 49 years old. In addition, this thesis presents a statistical method to estimate this effectiveness and to test for differences in effectiveness between subgroups adjusted for non-compliance and contamination. Methods The studies of this thesis are based on data from the Screening of Young Women (SCRY) database. The SCRY database consists of detailed information on diagnosis, death, screening exposure and risk factors for breast cancer cases and population size by year (between 1986 and 2005) and municipality for women in Sweden between 40 and 49 years old. The material was divided into a study group consisting of the counties that invited women in the age group 40-49 years to mammography screening, and a contemporaneous control group consisting of the counties that did not. Effectiveness was estimated in terms of rate ratios for two different exposures (invitation to and participation in screening), and overdiagnosis for subsequent screening was estimated adjusting for lead time bias. Defining a reference period enabled adjustment for possible underlying differences in breast cancer mortality and incidence. A statistical model for adjusting for non-compliance and contamination in randomised controlled trials was further developed to allow for adjustment in cohort studies using a Poisson model with log-linear structure for exposure and background risk. Results During the study period (1986-2005), there were 619 and 1205 breast cancer deaths and 6047 and 7790 breast cancer cases in the study group and the control groups, respectively. For women between 40 and 49 years old, the breast cancer mortality reduction was estimated at 26% [95% CI, 17 to 34%] for invited to screening and 29% [95% CI, 20 to 38%] for attending screening. The RR estimates for the high-risk groups based on the risk factors parity, age at birth of first child, and socio-economic status were equal to or higher than that of the low risk groups. The new statistical method showed that the decrease in effectiveness with parity was not a statistically significant trend. The overdiagnosis from subsequent screening for 40 to 49 year old women was estimated at 1% [95 % CI, -6 to 8 %] (i.e., not statistically significant). Conclusion Subgroup specific effectiveness was also estimated. The relative effectiveness of screening for breast cancer with mammography for women age 40 to 49 years appears to be comparable to that for older women. These findings and the fact that there was no statistically significant overdiagnosis from subsequent screening speak for inviting women 40 to 49 years old to screening. High-risk screening for nulliparous women aged 40 to 49 years, for example, might be an alternative in countries where population-based screening for all women between 40 and 49 years old is not possible. However, the matter of risk factors and the effect of their combinations is complex and risk group screening presents ethical and practical difficulties. The new statistical model is a useful tool for analysing cohorts with exposed and non-exposed populations where non-compliance and contamination is a potential source of bias.

The first part of this thesis is concerned with trend modelling of breast cancer mortality rates. By using an age-period-cohort model, the relative contributions of period and cohort effects are evaluated once the unquestionable existence of the age effect is controlled for. The result of such a modelling gives indications in the search for explanatory factors. While this type of modelling is usually performed with 5-year period intervals, the use of 1-year period data, as in Paper I, may be more appropriate. The main theme of the thesis is the evaluation of the ability to detect signals in x-ray images of breasts. Early detection is the most important tool to achieve a reduction in breast cancer mortality rates, and computer-aided detection systems can be an aid for the radiologist in the diagnosing process. The evaluation of computer-aided detection systems includes the estimation of distributions. One way of obtaining estimates of distributions when no assumptions are at hand is kernel density estimation, or the adaptive version thereof that smoothes to a greater extent in the tails of the distribution, thereby reducing spurious effects caused by outliers. The technique is described in the context of econometrics in Paper II and then applied together with the bootstrap in the breast cancer research area in Papers III-V. Here, estimates of the sampling distributions of different parameters are used in a new model for free-response receiver operating characteristic (FROC) curve analysis. Compared to earlier work in the field, this model benefits from the advantage of not assuming independence of detections in the images, and in particular, from the incorporation of the sampling distribution of the system's operating point. Confidence intervals obtained from the proposed model with different approaches with respect to the estimation of the distributions and the confidence interval extraction methods are compared in terms of coverage and length of the intervals by simulations of lifelike data.

Contrast-enhanced mammography (CEM) relies on visualizing the growth of new blood vessels (i.e. tumor angiogenesis) to provide sufficient materials for cell proliferation during the development of cancer. Since cancers will accumulate an injected contrast agent more than other tissues, it is possible to use one of several methods to enhance the area of lesions in the x-ray image and remove the contrast of normal tissue. Large area flat panel detectors may be used for CEM wherein the subtraction of two acquired images is used to create the resulting enhanced image. There exist several methods to acquire the images to be subtracted, which include temporal subtraction (pre- and post-contrast images) and dual-energy subtraction (low- and high-energy images), however these methods suffer from artifacts due to patient motion between image acquisitions. In this research the use of a multilayer flat panel detector is examined for CEM that is designed to acquire both (low- and high-energy) images simultaneously, thus avoiding motion artifacts in the resulting subtracted image. For comparison, a dual-energy technique prone to motion artifacts that uses a single-layer detector is also investigated. Both detectors are evaluated and optimized using amorphous selenium as the x-ray to charge conversion material, however the theoretical analysis could be extended to other conversion materials. Experimental results of single pixel prototypes of both multilayer and single-layer detectors are also discussed and compared to theoretical results. For a more comprehensive analysis, the motion artifacts present in dual-exposure techniques are modeled and the performance degradation due to motion artifacts is estimated. The effects of noise reduction techniques are also evaluated to determine potential image quality improvements in CEM images.

Η παρούσα εργασία βασίστηκε πάνω στο λογισμικό προσομοίωσης BreastSimulator που αναπτύχθηκε στην μονάδα Βιοϊατρικής Τεχνολογίας του εργαστηρίου Ιατρικής Φυσικής στο Πανεπιστήμιο Πατρών. Το συγκεκριμένο πρόγραμμα προσομοίωσης αναφέρεται πρώτη φορά το 2002 και από τότε συνεχώς γίνονται προσπάθειες βελτίωσής του ως προς την ρεαλιστικότητα των μαστογραφικών εικόνων που αυτό παράγει. Η τελευταία έκδοση του εισάγει μια καινοτομία ως προς την παραγωγή του μαστογραφικού υποστρώματος με έναν νέο αλγόριθμο ο οποίος στην συγκεκριμένη εργασία συγκρίνεται και αξιολογείται από γιατρούς ακτινολόγους ως περισσότερο ρεαλιστικός σε σχέση με τον προηγούμενο. Η καινοτομία που εισάγει ο νέος αλγόριθμος σε σχέση με έναν προγενέστερο του εργαστηρίου μας οποία αφορά στο μαστογραφικό υπόστρωμα, το οποίο αποτελεί το σύνολο του λιπώδους, ινώδους και συνδετικού ιστού οι οποίοι δεν είναι σαφώς μοντελοποιημένοι όπως τα υπόλοιπα ανατομικά στοιχεία. Στον νέο αλγόριθμο το μαστογραφικό υπόστρωμα μοντελοποιείται εξαρχής ως τρισδιάστατο, στοιχείο ιδιαίτερα σημαντικό για την βελτίωση του αποτελέσματος προσομοίωσης μαστογραφικής εικόνας που πλέον είναι πολύ περισσότερο ρεαλιστική. Ο στόχος της εργασίας αυτής ήταν η παραγωγή ψηφιακών, «εικονικών» μοντέλων μαστού με τη χρήση του BreastSimulator με ρεαλιστικό αποτέλεσμα. Μετά την διαδικασία παραγωγής των μοντέλων μαστού, έγινε προσομοίωση της μαστογραφικής λήψης αυτών και είχε ως αποτέλεσμα την παραγωγή μαστογραφικών εικόνων χωρίς συμπίεση του μαστού. Με τον βελτιωμένο αλγόριθμο προσομοίωσης παρήχθησαν μοντέλα μαστού διαφόρων μεγεθών και πυκνοτήτων. Οι παράμετροι των πιο ρεαλιστικών μοντέλων συγκεντρώθηκαν σε μια βάση δεδομένων στην οποία μπορούν να ανατρέξουν μελλοντικοί χρήστες του λογισμικού για πειραματικές μελέτες. Τα αποτελέσματα της σύγκρισης δείχνουν ότι οι εικόνες που παρήχθησαν με τον νέο αλγόριθμο προσομοίωσης του μαστογραφικού υποστρώματος υπερέχουν σαφώς του προγενέστερου ως προς τη ρεαλιστικότητα. Οι εικόνες από τον νέο αλγόριθμο αξιολογήθηκαν συνολικά κατά μέσο όρο σε ποσοστό περίπου 80% ως ρεαλιστικές και πολύ ρεαλιστικές, ενώ σε ποσοστό 20% αξιολογήθηκαν ως μη ρεαλιστικές. Οι εικόνες του προηγούμενου αλγορίθμου αξιολογήθηκαν αντίστοιχα με ποσοστό 10% ως ρεαλιστικές και πολύ ρεαλιστικές και 90% ως μη ρεαλιστικές. Ακόμα αναλύεται το μοντέλο προσομοίωσης, η διαδικασία παραγωγής της βάσης δεδομένων, η διαδικασία αξιολόγησης από ομάδα γιατρών, ενώ αναφέρεται η σημασία της μαστογραφίας σαν κορυφαία προληπτική εξέταση για την έγκαιρη διάγνωση του καρκίνου του μαστού και η σημασία της προσομοίωσης αυτής της εξέτασης. / The current master thesis was based on the software simulation named BreastSimulator which was developed in the unit of Biomedical engineering of the Medical Physics laboratory at the University of Patras. This particular simulation program refers for the first time in 2002. Since then, there have been continuous improvements of the program in order to produce realistic mammographic images. The key improvement of the last edition of BreastSimulator is the development of a new algorithm for 3D background texture creation which was evaluated by radiologists as more realistic than the previous one. The innovation introduced by the new algorithm compared to a previous one of our laboratory is about the modeling of the mammographic background, which simulates the presence of adipose, fibrous and connective tissues as well as other non-glandular tissue types that are not explicitly modeled. The optimized methodology is an evolution of a previously presented 3D non compressed breast modeling method which now produces more realistic mammographic images. The objective of this work was the production of digital, ' virtual ' breast models using BreastSimulator with realistic outcome. After having modeled the breast phantoms, a simulation of irradiation was done and as a result of this process we produced mammographic images. Using the improved algorithm simulation we produced breast models of various size and composition. The optimum parameters of the most realistic models were collected in a database in which future users can refer for experimental studies. Comparing the images produced by the new algorithm to the images from the previous one shows that the new algorithm for mammographic texture is superior compared to the old approach in terms of similarity with real mammograms. The images from the new algorithm were evaluated from the experienced radiologists approximately 80% as a realistic and very realistic and 20% as unrealistic, while the images of the previous one were evaluated 10% as a realistic and very realistic and 90% as unrealistic. Additionally, there are some details about the breast model simulation, the process of creating the database and the evaluation process by a group of 5 doctors. The importance of mammography as the leading preventive examination for early detection of breast cancer is highlighted as well as the significance of the simulation of this medical imaging examination.

Breast cancer is the most common form of cancer in female population in the Czech Republic. In 2002 the Czech Republic joined most European countries and launched nation-wide mammography screening, enabling women to attend regular preventive examinations when they reach 45 years of age. In January 2014 they started to address women to invite them for preventive breast cancer examinations, as part of a nationwide information campaign. Mortality of this cancer has been decreasing in recent years, which can be explained by the increasing quality of treatment and earlier detection of the disease. Therefore, knowledge of primary and secondary prevention is very important. The theoretical part briefly describes the anatomy of female breasts, defines a malignant tumor, as well as epidemiological aspects of breast cancer. Another chapter is about prevention itself. In the secondary prevention I describe self-examination of breasts and the history and nature of mammography screening. I also present organizations implementing preventive programs aimed at breast cancer. The practical part includes research results, which were obtained through quantitative research questionnaires. The research group consisted of women who live in the Ústí region. The questionnaire consisted of 27 questions and was answered by a group of 150 women between 18 and 44 years old and 150 women over 45 years. I handed out these questionnaires in Ústí healthcare center and I also created an electronic questionnaire which I sent across social networks. Out of the 150 (100 %) questionnaires distributed in Ústí healthcare center, I got only 60 back and 58 of them were sufficiently completed for the needs of the research, the return was only 38.7 %. I received the remaining 242 questionnaires electronically. The aim of the study was to explore the awareness of risk factors of breast cancer of women in the Ústí Region and also to find out whether women in the Ústí region carried out self-examination of breasts and if women over 45 attended regular mammography screening. Based on my research aim I set out four hypotheses. Hypothesis 1: Women in the Ústí region are informed about the risk factors of breast cancer. Hypothesis 2: Women at the age of 18 to 44 in the Usti region are more informed about the risk factors of breast cancer than women in the age group over 45. Hypothesis 3: The difference in the frequency of breast self-examination among women in the age group 18 to 44 is statistically more significant than in women in the over 45 age group. Hypothesis 4: Attending mammography examination of women over 45 in the Ústí region rises according to their level of education. The results of testing my hypotheses show that women in the Ústí region are not informed about the risk factors of breast cancer. I assumed that awareness is higher among women in the 18 to 44 age group, but even this hypothesis wasn't proven. Awareness of risk factors is on the same level in category of 18 to 44 years as in women over 45 years of age. Regarding breast self-examination, women in the above 45 years old age group carry out self-examination more often than women 18 to 44 years old. Even the last hypothesis was not confirmed, attendance of mammography doesn't appear to depend on the education of women. Awareness of women needs to increase, especially in case of risk factors of breast cancer. Awareness increase could be achieved by greater information campaign on television, in newspapers, in businesses with high numbers of working women, or in secondary and higher education through various public lectures. Over 90% of women attend Mammography screening according to my research, which are laudable results. The fact that the actual self-examination of breasts isn't carried out at all by more than half of the women in the age group 18 to 44 is serious. This work could serve as teaching or study material to improve general knowledge of this topic.

O trabalho buscou conhecer os motivos que levaram mulheres do município de Piraí, estado do Rio de Janeiro, agendadas para realizar o exame de mamografia, a não comparecer ao mesmo / The study sougth to know the reasons why women Piraí

O trabalho buscou avaliar as dificuldades e limites da gestão municipal na incorporação de serviços de mamografia em sete municípios selecionados na região do Médio Paraíba. Utilizando abordagem metodológica qualiquantitativa, se desenvolveu a partir do levantamento de dados secundários sobre o parque tecnológico de serviços e a produção de mamografias nos municípios selecionados e da realização de entrevistas semi-estruturadas aplicadas junto aos gestores municipais e aos responsáveis pelos setores de Controle, Avaliação e Auditoria das localidades. A análise das entrevistas identificou sete categorias temáticas principais: (1) o conhecimento do nível local sobre o problema de saúde em tela, onde se pode constatar dificuldades para uma análise mais precisa da situação de saúde relacionada ao câncer de mama nas localidades; (2) o conhecimento dos processos de tomada de decisão, onde se pode perceber que a gestão municipal esbarra em uma série de dificuldades que impossibilitam, em muitos casos, a incorporação de tecnologias nos serviços próprios, trazendo como única alternativa a compra dos serviços mamográficos; (3) a oferta e acesso aos exames mamográficos, evidenciando precariedade, pois é facilitada somente a porta de entrada nos serviços de Atenção Básica; (4) a produção dos procedimentos, revelando que, de uma forma geral, os gestores têm se esforçado por cumprir com as metas pactuadas, ainda que o exame das informações disponíveis mostrem que seu alcance encontra-se, via de regra, distante do pretendido; (5) a regulação e monitoramento dos serviços mamográficos, onde pode se perceber a baixa adesão ao Sistema de Regulação nas gestões locais; (6) a satisfação quanto à prestação dos serviços contratados, usualmente avaliadas de forma subjetiva e ancorada tão somente na falta de reclamações; e, por fim, (7) dificuldades na tomada de decisão relativa à incorporação de um serviço mamográfico próprio, que esbarram em impedimentos políticos, administrativos e financeiros. Pode-se concluir que o estudo permitiu extrair subsídios capazes de contribuir para o conhecimento e reflexão sobre as práticas de incorporação tecnológica e monitoramento dos serviços mamográficos na região. / The study aimed to evaluate the difficulties and limits of the municipal administration in the incorporation of mammography services in seven selected cities in the Middle Paraíba. Using qualitative-quantitative methodological approach, developed from the data collection side of the park service and the production technology of mammography in selected cities and conducting semi-structured interviews with the managers applied and municipal sectors responsible for monitoring, evaluation and Audit of locations. The analysis of interviews identified seven major themes: (1) knowledge of local health problem on the screen, where you can see difficulties in a more precise analysis of the health situation related to breast cancer in the localities, (2 ) knowledge of the processes of decision making, where you can see that the municipal administration was hampered by a number of difficulties that make it impossible in many cases, the incorporation of technologies in their own service, bringing only alternative to the purchase of mammography services, ( 3) the supply and access to mammographic studies, showing insecurity, it is facilitated only port of entry to primary care services, (4) the production procedures, revealing that, in general, managers have been struggling to meet with the agreed targets, in considering the available information shows that their power is as a rule, far from being attained; (5) the regulation and monitoring of mammography services, which can realize low compliance with the Regulatory System the local administrations, (6) satisfaction regarding the provision of contracted services, usually evaluated on a subjective s and anchored solely in the absence of complaints, and, finally, (7) difficulties in making a decision on the incorporation of a service mammography itself, which runs into political impediments, administrative and financial. It can be concluded that the study allowed to extract subsidies can contribute to knowledge and reflection on practices in technological and monitoring of mammography services in the region.

Made available in DSpace on 2015-05-14T12:36:57Z (GMT). No. of bitstreams: 1 parte1.pdf: 2544032 bytes, checksum: 308f2d618965be3ff9596eb650c5db50 (MD5) Previous issue date: 2010-10-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In order to assure a quality control in mammography, according to the rules of the Brazilian Ministry of Health, the use of a mamma s radiographic simulator, called phantom is used to test the mammography device in a consistent daily, monthly and annual basis. In this context, this paper aims to research and develop a computerized system for mammographers quality control using digital image processing and analysis techniques over the phantom images. Initially an analysis was made of the structures that make up the image of the phantom and observing its features is an elaborated study of what are the possible techniques that best fit its processing. From this study, we have a better understanding about the techniques used and what are the difficulties of its applications in image phantom. The results are presented and based on them, there is a discussion about the used techniques. Finally, we describe the advantages of using a computerized system to perform mammographers quality control. / O emprego de um simulador radiográfico de mama, denominado phantom, permite aplicar os testes de aceitação do mamógrafo e realizar os testes de constância diários, mensais e anuais do programa de controle de qualidade em mamografia, de acordo com as normas do Ministério da Saúde. Neste contexto, o presente trabalho tem como objetivo pesquisar e desenvolver um sistema computadorizado de controle de qualidade em mamografias, através do processamento e análise de imagens digitais de phantoms. Inicialmente é realizada uma análise das estruturas que compõem a imagem do phantom e observando-se suas características é elaborado um estudo sobre quais são as possíveis técnicas que melhor se adéquam ao seu processamento. A partir desse estudo, tem-se um entendimento melhor sobre as técnicas utilizadas e quais as dificuldades de suas aplicações na imagem de phantom. Os resultados são apresentados e com base neles, há uma discussão a respeito das técnicas abordadas. Por fim, são descritas as vantagens da utilização de um sistema computadorizado para efetuar o controle de qualidade em mamografias.

O trabalho buscou conhecer os motivos que levaram mulheres do município de Piraí, estado do Rio de Janeiro, agendadas para realizar o exame de mamografia, a não comparecer ao mesmo / The study sougth to know the reasons why women Piraí

O trabalho buscou avaliar as dificuldades e limites da gestão municipal na incorporação de serviços de mamografia em sete municípios selecionados na região do Médio Paraíba. Utilizando abordagem metodológica qualiquantitativa, se desenvolveu a partir do levantamento de dados secundários sobre o parque tecnológico de serviços e a produção de mamografias nos municípios selecionados e da realização de entrevistas semi-estruturadas aplicadas junto aos gestores municipais e aos responsáveis pelos setores de Controle, Avaliação e Auditoria das localidades. A análise das entrevistas identificou sete categorias temáticas principais: (1) o conhecimento do nível local sobre o problema de saúde em tela, onde se pode constatar dificuldades para uma análise mais precisa da situação de saúde relacionada ao câncer de mama nas localidades; (2) o conhecimento dos processos de tomada de decisão, onde se pode perceber que a gestão municipal esbarra em uma série de dificuldades que impossibilitam, em muitos casos, a incorporação de tecnologias nos serviços próprios, trazendo como única alternativa a compra dos serviços mamográficos; (3) a oferta e acesso aos exames mamográficos, evidenciando precariedade, pois é facilitada somente a porta de entrada nos serviços de Atenção Básica; (4) a produção dos procedimentos, revelando que, de uma forma geral, os gestores têm se esforçado por cumprir com as metas pactuadas, ainda que o exame das informações disponíveis mostrem que seu alcance encontra-se, via de regra, distante do pretendido; (5) a regulação e monitoramento dos serviços mamográficos, onde pode se perceber a baixa adesão ao Sistema de Regulação nas gestões locais; (6) a satisfação quanto à prestação dos serviços contratados, usualmente avaliadas de forma subjetiva e ancorada tão somente na falta de reclamações; e, por fim, (7) dificuldades na tomada de decisão relativa à incorporação de um serviço mamográfico próprio, que esbarram em impedimentos políticos, administrativos e financeiros. Pode-se concluir que o estudo permitiu extrair subsídios capazes de contribuir para o conhecimento e reflexão sobre as práticas de incorporação tecnológica e monitoramento dos serviços mamográficos na região. / The study aimed to evaluate the difficulties and limits of the municipal administration in the incorporation of mammography services in seven selected cities in the Middle Paraíba. Using qualitative-quantitative methodological approach, developed from the data collection side of the park service and the production technology of mammography in selected cities and conducting semi-structured interviews with the managers applied and municipal sectors responsible for monitoring, evaluation and Audit of locations. The analysis of interviews identified seven major themes: (1) knowledge of local health problem on the screen, where you can see difficulties in a more precise analysis of the health situation related to breast cancer in the localities, (2 ) knowledge of the processes of decision making, where you can see that the municipal administration was hampered by a number of difficulties that make it impossible in many cases, the incorporation of technologies in their own service, bringing only alternative to the purchase of mammography services, ( 3) the supply and access to mammographic studies, showing insecurity, it is facilitated only port of entry to primary care services, (4) the production procedures, revealing that, in general, managers have been struggling to meet with the agreed targets, in considering the available information shows that their power is as a rule, far from being attained; (5) the regulation and monitoring of mammography services, which can realize low compliance with the Regulatory System the local administrations, (6) satisfaction regarding the provision of contracted services, usually evaluated on a subjective s and anchored solely in the absence of complaints, and, finally, (7) difficulties in making a decision on the incorporation of a service mammography itself, which runs into political impediments, administrative and financial. It can be concluded that the study allowed to extract subsidies can contribute to knowledge and reflection on practices in technological and monitoring of mammography services in the region.