A knowledge of the fundamental optical properties of breast tissues is necessary in order to optimize transillumination imaging techniques for the diagnosis of breast disease. The optical absorption and scattering coefficients have been measured in normal and diseased breast tissues, over the range of wavelengths from 500 to 1100 nm. The tissues were obtained from surgical specimens, and consisted of normal glandular and adipose tissues, fibrocystic disease, fibroadenoma, and ductal carcinoma. Total attenuation coefficients were measured for thin slices of tissue obtained on a microtome. The diffuse reflectance and transmittance were measured for 1.0 mm thick samples of these tissues, using standard integrating sphere techniques. Monte Carlo simulations were performed to derive the scattering and absorption coefficients, as well as the mean cosine of the scattering angle. The results indicate that scatter exceeds absorption by at least two orders of magnitude. The absorption coefficients are strongly affected by the presence of blood, particularly at wavelengths below 600nm. The scattering coefficients lie in the range 30 mm to 90 mm-1 at 500 nm, and fall smoothly with increasing wavelength to between 10 mm and 50 mm at 1100 nm. The scatter coefficient for adipose tissue differs, in that it is invariant with wavelength over this spectral range. The scattered light, for all tissues examined, is highly forward peaked, with the mean cosine of the scattering angle in the range 0.945 to 0.985. This value remains constant with wavelength to within +/-0.01 for any given tissue. The absorption coefficients and scattering properties of each tissue type fall within distinct ranges at each wavelength. Fibrocystic disease and adipose tissue appear to be the most clearly distinguishable groups. The optical properties of carcinoma do not differ significantly from those of normal glandular tissues, although both groups differ from other tissue types. The implications of these results for imaging are yet to be determined. / Thesis / Master of Science (MS)

A radiação espalhada em radiodiagnóstico, como em mamografia, é usualmente considerada um problema, uma vez que degrada o contraste da imagem. No entanto, pesquisas recentes mostram que a distribuição angular de fótons espalhados (perfil de espalhamento) pode fornecer informações sobre as estruturas que compõem um tecido biológico, permitindo, a partir da análise desta, identificar a presença de anormalidades no tecido. Neste estudo, foram utilizadas as técnicas de espalhamento de raios X em médio (WAXS) e baixo (SAXS) ângulo para determinar o perfil de espalhamento de tecidos mamários previamente classificados como: tecidos normais (adiposo e fibroglandular), neoplasias benignas e malignas, usando um tubo de raios X e radiação síncrotron. Através das informações de cada perfil foi possível identificar algumas estruturas moleculares e supramoleculares presentes nos tecidos estudados. Além disso, foi construído um modelo de classificação baseado na análise de discriminante dos perfis de espalhamento, o qual permitiu classificar corretamente todas as amostras analisadas neste estudo, quando combinadas as informações das regiões de médio e baixo ângulo. Portanto, os resultados obtidos neste trabalho sugerem a possibilidade do desenvolvimento de novas técnicas radiológicas que permitiriam ampliar a capacidade de diagnóstico do câncer mamário. / Scattering radiation in diagnostic radiology, such as mammography, is usually considered a problem, since it degrades the image contrast. However, recent investigations show that the angular distribution of scattered photons (scattering profile) can provide information about the structures that compose a biological tissue, allowing, from the analysis of the scattering profile, identify the presence of abnormalities in the tissue. In this study, we have used the wide angle x-ray scattering (WAXS) and small angle x-ray scattering (SAXS) techniques to determine the scattering profiles of human breast tissues previously classified as: normal tissue (adipose and fibroglandular), benign or malignant neoplasia, using a x-ray tube and synchrotron radiation. Through the information provide by each profile was possible to identify some molecular and supramolecular structures present in these tissues. In addition, we built a classification model based on discriminant analysis of scattering profiles, which enabled the correct classification of all samples analyzed in this study, when combined information from WAXS and SAXS regions. Therefore, the results obtained in this work suggest the possibility of developing new radiological techniques would expand the capability of breast cancer diagnosis.

A radiação espalhada em radiodiagnóstico, como em mamografia, é usualmente considerada um problema, uma vez que degrada o contraste da imagem. No entanto, pesquisas recentes mostram que a distribuição angular de fótons espalhados (perfil de espalhamento) pode fornecer informações sobre as estruturas que compõem um tecido biológico, permitindo, a partir da análise desta, identificar a presença de anormalidades no tecido. A proposta deste trabalho foi desenvolver medidas do perfil de espalhamento a médio (WAXS) e baixo ângulo (SAXS) de tecidos mamários previamente classificados, como tecidos normais, alterações benignas ou malignas, usando um tubo de raios X e radiação Síncrotron e, posteriormente, identificar as estruturas moleculares e supramoleculares presentes nos tecidos estudados e verificar estatisticamente se as informações contidas conjuntamente nos perfis de espalhamento a médio e baixo ângulo permitem diferenciar tecidos normais de alterados. Este tipo de estudo é potencialmente importante na área da Saúde por estar associado ao desenvolvimento de novas técnicas radiológicas que permitiriam ampliar a capacidade de diagnóstico do câncer mamário. / Scattering radiation in diagnostic radiology, such as mammography, is usually considered a problem, since it degrades the image contrast. However, recent research shows that the angular distribution of scattered photons (scattering profile) can provide information on the structures that compose a biological tissue, allowing, from the analysis of this, identify the presence of abnormalities in the tissue. The purpose of this study was to develop measurements of scattering profile at wide angle x-ray scattering (WAXS) and small angle x-ray scattering (SAXS) from breast tissue previously classified as normal tissue, benign or malignant disease, using a x-ray tube and synchrotron radiation and, subsequently, identify molecular and supra-molecular structures present in these tissues studied and verify statistically, if the information contained in both scattering profiles at wide and small angle allow differentiate normal tissues of changed. This type of study is potentially important in the health area, since to be associated with the development of new radiological techniques that would allow to expand the ability of breast cancer diagnosis.

A radiação espalhada em radiodiagnóstico, como em mamografia, é usualmente considerada um problema, uma vez que degrada o contraste da imagem. No entanto, pesquisas recentes mostram que a distribuição angular de fótons espalhados (perfil de espalhamento) pode fornecer informações sobre as estruturas que compõem um tecido biológico, permitindo, a partir da análise desta, identificar a presença de anormalidades no tecido. A proposta deste trabalho foi desenvolver medidas do perfil de espalhamento a médio (WAXS) e baixo ângulo (SAXS) de tecidos mamários previamente classificados, como tecidos normais, alterações benignas ou malignas, usando um tubo de raios X e radiação Síncrotron e, posteriormente, identificar as estruturas moleculares e supramoleculares presentes nos tecidos estudados e verificar estatisticamente se as informações contidas conjuntamente nos perfis de espalhamento a médio e baixo ângulo permitem diferenciar tecidos normais de alterados. Este tipo de estudo é potencialmente importante na área da Saúde por estar associado ao desenvolvimento de novas técnicas radiológicas que permitiriam ampliar a capacidade de diagnóstico do câncer mamário. / Scattering radiation in diagnostic radiology, such as mammography, is usually considered a problem, since it degrades the image contrast. However, recent research shows that the angular distribution of scattered photons (scattering profile) can provide information on the structures that compose a biological tissue, allowing, from the analysis of this, identify the presence of abnormalities in the tissue. The purpose of this study was to develop measurements of scattering profile at wide angle x-ray scattering (WAXS) and small angle x-ray scattering (SAXS) from breast tissue previously classified as normal tissue, benign or malignant disease, using a x-ray tube and synchrotron radiation and, subsequently, identify molecular and supra-molecular structures present in these tissues studied and verify statistically, if the information contained in both scattering profiles at wide and small angle allow differentiate normal tissues of changed. This type of study is potentially important in the health area, since to be associated with the development of new radiological techniques that would allow to expand the ability of breast cancer diagnosis.

A radiação espalhada em radiodiagnóstico, como em mamografia, é usualmente considerada um problema, uma vez que degrada o contraste da imagem. No entanto, pesquisas recentes mostram que a distribuição angular de fótons espalhados (perfil de espalhamento) pode fornecer informações sobre as estruturas que compõem um tecido biológico, permitindo, a partir da análise desta, identificar a presença de anormalidades no tecido. Neste estudo, foram utilizadas as técnicas de espalhamento de raios X em médio (WAXS) e baixo (SAXS) ângulo para determinar o perfil de espalhamento de tecidos mamários previamente classificados como: tecidos normais (adiposo e fibroglandular), neoplasias benignas e malignas, usando um tubo de raios X e radiação síncrotron. Através das informações de cada perfil foi possível identificar algumas estruturas moleculares e supramoleculares presentes nos tecidos estudados. Além disso, foi construído um modelo de classificação baseado na análise de discriminante dos perfis de espalhamento, o qual permitiu classificar corretamente todas as amostras analisadas neste estudo, quando combinadas as informações das regiões de médio e baixo ângulo. Portanto, os resultados obtidos neste trabalho sugerem a possibilidade do desenvolvimento de novas técnicas radiológicas que permitiriam ampliar a capacidade de diagnóstico do câncer mamário. / Scattering radiation in diagnostic radiology, such as mammography, is usually considered a problem, since it degrades the image contrast. However, recent investigations show that the angular distribution of scattered photons (scattering profile) can provide information about the structures that compose a biological tissue, allowing, from the analysis of the scattering profile, identify the presence of abnormalities in the tissue. In this study, we have used the wide angle x-ray scattering (WAXS) and small angle x-ray scattering (SAXS) techniques to determine the scattering profiles of human breast tissues previously classified as: normal tissue (adipose and fibroglandular), benign or malignant neoplasia, using a x-ray tube and synchrotron radiation. Through the information provide by each profile was possible to identify some molecular and supramolecular structures present in these tissues. In addition, we built a classification model based on discriminant analysis of scattering profiles, which enabled the correct classification of all samples analyzed in this study, when combined information from WAXS and SAXS regions. Therefore, the results obtained in this work suggest the possibility of developing new radiological techniques would expand the capability of breast cancer diagnosis.

Bilateral breast augmentation is one of the most common cosmetic surgical procedures carried out on women in the western world. Breast augmentation involves increasing the volume of a woman‘s breasts through surgery by placing a silicone implant in the subglandular or subpectoral cavity. Although a capsule forms inevitably around breast implants as a natural part of healing, it can cause significant morbidity if the capsule becomes firm and contracted, a condition known as breast capsular contracture (BCC). The aetiology of BCC remains unknown however it is characterised by dense fibrocollagenous connective tissue with a local inflammatory response. Host response is influenced by several factors including implant surface texture, chemistry and interactions between cells and the extracellular matrix. Texturing holds the implant in place, thus preventing micromotion at the host prosthesis interface. While in smooth surfaces, the implant moves inside the breast, making the fibroblasts repeatedly produce collagen in response to this host-prosthesis shearing motion. In this thesis, the effect of surface characteristics and specific coatings on the cell-surface interaction has been examined on smooth compared to textured surfaces using commercially available breast implants. The properties of breast implants shells have been characterised using confocal laser microscopy, contact angle measurements, confocal Raman spectroscopy and tensile testing. Confocal laser microscopy was used to evaluate the topographical features and surface roughness of the implant surfaces. Contact angle measurements were carried out to determine the hydrophobicity of the implant surfaces. Chemical characterisation was carried out recording Raman images and spectra of the implants using confocal Raman spectrometer. The mechanical properties of the breast implant shells were measured via tensile testing. Adhesive interactions of breast-derived fibroblasts with breast implant surfaces were examined in-vitro. For this purpose, the effect of four molecule coatings (aggrecan, collagen I, fibronectin, and hyaluronic acid) was evaluated on fibroblast attachment, proliferation, fibroblast morphology, spreading, cytotoxicity and gene expression. Results from in-vitro assays demonstrated cell susceptibility to topography and protein coatings and further showed cytoskeletal re-organisation and modification with specific cell adhesion patterns. Combination of diverse topographies and specific coatings induced differential regulation of the expression of adhesion related genes, such as focal adhesion kinase, paxillin, vinculin, and α-actinin on breast fibroblasts. In conclusion, this thesis has demonstrated the extent and strength of cell adhesion and subsequent cell proliferation and differentiation. This is based on the physical interactions between cells and the extracellular environment in the form of topography and on the chemical interactions mediated by specific coatings. Precise characterisation of the silicone breast implant surfaces was achieved. This may play an important role in the development of improved breast implant surfaces with improved qualities leading the development of surfaces that may be less prone to capsular contracture.

Breast cancer is the most common form of cancer among women, this type of cancer is diagnosed in around 9000 women every year in Sweden. The most common studies to find breast cancer is through mammography where the breast tissue is compressed and exposed by radiation. Not only does the technique expose the breast tissue for radiation, but it can also be very uncomfortable. There is research on a new kind of scanning where use of microwaves reduces the uncomfortable situation. The MDH research team that are working with this technology needs help to position a transmitter of microwaves to test their equipment. The purpose of this paper is to discover a way to mechanically position a transmitter so that it can be moved along a breast model. The investigation will be made through a product development process in order to review the research question: RQ: “How can a product be designed to position and adjust a microwave transmitter to various locations in order to help testing of cancer research equipment?” By using an agile working methodology in combination with a Design thinking process this thesis includes several sprints that involved continues improvement and feedback from the research team. The first sprint was mostly to discover and experiment on new design ideas as well as control if any of them could work. It resulted in need of measurement changes and redesigning. The second sprint involved measurement corrections. The model itself had the reasonable measurements and the functions worked as expected. However, some of the functions needed to be improved as well as a problem with clearing of the wires to the transmitter itself. The third sprint included changes where more freedom was given and more clearance was made for the wires, but this design turned out to be unpredictable. The fourth sprint included a completely new design to stabilizing the prototype as a result from the researchers’ feedback. To answer the research question, the final design resulted in a 3D printed stand designed to move the transmitter along x-axis as well as rotate around y-axis to adjust to different breast diameters and forms. The stand also includes a rack and pinion design that makes it possible to adjust to different breast lengths. Lastly, the stand makes it possible to gradually move the transmitter around the breast model. However, the final design does not only answer the research question it also fulfils stability and functionality requirements set by the research team. This clarifies why the first iterations needed redesigning. Therefore, the stand is ready for preliminary tests of the researcher’s equipment. To conclude, there are many different design solutions that can answer the research question. However, the design requires stability which reduce the number of design solutions.

Diagnostic methods to effectively image dense breast tissue (DBT) can pose challenges for breast cancer screening. While conventional mammography is the gold standard for breast cancer screening, this technique has a low sensitivity to DBT and can miss about 78% of cancers in DBT, but magnetic resonance imaging (MRI) has a high sensitivity for imaging DBT, and produces a smaller number of false positives. The purpose of this study was to determine the extent to which conventional mammograms can miss breast cancer in women with DBT and to determine if an adjunct method of imaging DBT might detect breast cancers that are missed by mammography alone. Quantitative data were collected from a sample of 300 randomly selected participants using surveys. SPSS statistical software was used to analyze the data with the factor analysis method. Qualitative data were collected by telephone interviews from 10 women who were patients of a breast cancer center. NVivo software was used to analyze the data with the thematic analysis method. All analyses were guided by theoretical framework of von Bertalanffy's general systems theory, Miller's living systems theory, and the theory of intelligent medical diagnosis. Key results determined that a significant number of women with DBT had breast cancer that was undetected by mammograms; results also showed that women with DBT can benefit from breast cancer screening by adding an adjunct screening method (e.g., MRI). This study may contribute to social change by making the breast cancer screening community aware of the potential benefit of adding MRI as an adjunct to conventional screening so that more breast cancers are detected in the early stages of the disease.

Différentes techniques d'imagerie par contraste de phase des rayons X ont été récemment développées. Contrairement aux méthodes conventionnelles, qui mesurent les propriétés d'absorption des tissus, ces techniques donnent aussi le contraste du déphasage introduit par l'échantillon. Puisque le changement dans la phase peut être important même quand les différences en atténuation sont faibles ou absentes, le contraste d'image obtenable peut être considérablement augmenté, notamment pour les tissus mous biologiques. Ces méthodes sont donc très prometteuses pour une application dans le domaine médical. Cette Thèse a le but de contribuer à une compréhension plus profonde de ces techniques, en particulier la propagation-based imaging (PBI), la analyzer-based imaging (ABI) et la grating interferometry (GIFM), et d'étudier leur potentiel et la meilleure implémentation pratique pour les applications médicales. Une partie importante de cette Thèse est dédiée à l'utilisation d'algorithmes mathématiques pour l'extraction, à partir des images acquises, d'informations quantitatives (absorption, réfraction et diffusion) concernant l'échantillon. En particulier, cinq parmi les algorithmes les plus connus pour la technique ABI sont analysés théoriquement et comparés expérimentalement, dans les modalités planaire et tomographique, en utilisant des fantômes et des échantillons de tissu mammaire et d'os-cartilage. Une méthode semi-quantitative pour l'acquisition et la reconstruction d'images tomographiques dans les techniques ABI et GIFM est aussi proposée. Les conditions de validité sont analysées en détail et la méthode, permettant une simplification considérable de l'implémentation pratique, est vérifiée expérimentalement sur des fantômes et des échantillons humains. Enfin, une comparaison théorique et expérimentale des techniques PBI, ABI et GIFM est présentée. Les avantages et les désavantages de chacune des techniques sont mis en évidence. Les résultats obtenus par cette analyse peuvent être très utiles pour déterminer quelle technique est la plus adaptée à une application donnée. / Several X-ray phase-contrast techniques have recently been developed. Unlike conventional X-ray methods, which measure the absorption properties of the tissues, these techniques derive contrast also from the modulation of the phase produced by the sample. Since the phase shift can be significant even for small details characterized by weak or absent absorption, the achievable image contrast can be greatly increased, notably for the soft biological tissues. These methods are therefore very promising for applications in the medical domain. The aim of this Thesis is to contribute to a deeper understanding of these techniques, in particular propagation-based imaging (PBI), analyzer-based imaging (ABI) and grating interferometry (GIFM), and to study their potential and the best practical implementation for medical imaging applications. An important part of this Thesis is dedicated to the use of mathematical algorithms for the extraction, from the acquired images, of quantitative sample information (the absorption, refraction and scattering sample properties). In particular, five among the most known algorithms based on the geometrical optics approximation have been theoretically analysed and experimentally compared, in planar and tomographic modalities, by using geometrical phantoms and human bone-cartilage and breast samples. A semi-quantitative method for the acquisition and reconstruction of tomographic images in the ABI and GIFM techniques has also been proposed. The validity conditions are analyzed in detail and the method, enabling a considerable simplification of the imaging procedure, is experimentally verified on phantoms and human samples. Finally, a theoretical and experimental comparison of the PBI, ABI and GIFM techniques is presented. The advantages and drawbacks of each of these techniques are discussed. The results obtained from this analysis can be very useful for determining the most adapted technique for a given application.

Dada a dificuldade de avaliação das imagens mamográficas no rastreamento do câncer de mama e a necessidade de precisão diagnóstica, tornou-se estimulante a luta pelo desenvolvimento de ferramentas computacionais que auxiliam esse processo, denominadas de esquemas de Computer-aided detection/diagnosis (CADe/CADx). Apresenta-se como um desafio para a comunidade científica a padronização dos critérios de avaliação destes esquemas a partir de bancos de imagens amplos e diversificados que representem casos tanto de benignidade quanto os de malignidade. Considerando este aspecto, o presente trabalho consiste no desenvolvimento de um objeto simulador (phantom) de mama capaz de gerar diversos padrões de imagens obtidos pela variação aleatória de tamanho, forma, contraste e distribuição de lesões. Para garantir imagens mais realistas, o phantom foi confeccionado em camadas compostas por filme de PVC submerso em parafina gel em uma distribuição não uniforme. Essa distribuição permite simular regiões heterogeneamente densas, de acordo com a concentração do material. A estimativa da densidade percentual da mama simulada foi obtida com a ajuda do software LIBRA®, para gerar imagens nas quatro categorias de classificação de densidades BI-RADS®. Os nódulos foram simulados usando dois modelos tridimensionais impressos em 3D, um para lesões circunscritas e outro para espiculadas. Para as microcalcificações, foi utilizada a hidroxiapatita granulada distribuída em quatro clusters que representam casos comumente encontrados em mamas reais. Alternativamente, uma ferramenta computacional foi desenvolvida para a inserção das lesões nas imagens, de acordo com a localização e intensidade escolhidas. As características do phantom foram estudadas comparando os coeficientes de atenuação dos materiais utilizados e dos tecidos mamários. Também textura e ruído das imagens do phantom foram comparados em relação aos das imagens clínicas. A partir da base de imagens formada, um protótipo de esquema CADx foi avaliado. Os resultados foram analisados estatisticamente a partir de curvas ROC e comparados com os obtidos nos testes realizados com imagens clínicas. Concluiu-se que o phantom desenvolvido neste trabalho permitiu gerar um padrão de imagem próximo ao obtido em mamografias reais e apropriado ao suprimento da base de imagens para validação dos sistemas CADx. / The need for diagnostic accuracy in breast cancer screening has motivated the use of computational schemes known as computer-aided detection/diagnosis (CAD/CADx). However, standardization of the evaluation criteria regarding these schemes is still a challenge, since they depend on the access to large and diversified image databases representing both benign and malignant cases. With this feature in view, this work aimed at the development of a structured breast phantom able to generate many images patterns achieved not only by the variation of size, shape, contrast but also by mainly the distribution of simulated lesions. To guarantee the realism of the images, the phantom was made in layers composed by PVC film submerged in paraffin gel with a non-uniform distribution. Such distribution allowed simulating more or less dense regions, according to the material concentration. The percent density estimative of the simulated breast was determined with the LIBRA® software, resulting in the four categories of BIRADS® density classification. Nodules were simulated using two 3D printed models, one for circumscribed and another for spiculated lesions. For simulating microcalcifications, granulated hydroxyapatite was used distributed in four clusters. Alternatively, a computational tool was developed for the insertion of lesions into the images, according to the location and intensity chosen. Phantom characteristics were studied comparing attenuation coefficients of the materials used and breast tissues. The texture and noise of the phantom images were also compared in relation to the clinical ones. From the image database created, a CADx system was evaluated considering its modules of nodule classification and detection of microcalcifications. The results were analyzed statistically from ROC curves and compared with those usually obtained in clinical imaging tests. We concluded that the phantom developed in this work allowed to generate an image pattern similar to that obtained in real mammograms and suitable for supplying an image database to be used as a ground truth for CAD and CADx schemes validation/evaluation.