Breast Cancer : automatic detection and risk analysis through machine learning algorithms, using mammograms

Tese de Mestrado Integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica), 2021, Universidade de Lisboa, Faculdade de CiênciasCom 2.3 milhões de casos diagnosticados em todo o Mundo, durante o ano de 2020, o cancro da mama tornou-se aquele com maior incidência, nesse mesmo ano, considerando ambos os sexos. Anualmente, em Portugal, são diagnosticados aproximadamente sete mil (7000) novos casos de cancro da mama, com mil oitocentas (1800) mulheres a morrerem, todos os anos, devido a esta doença - indicando uma taxa de mortalidade de aproximadamente 5 mulheres por dia. A maior parte dos diagnósticos de cancro da mama ocorrem ao nível de programas de rastreio, que utilizam mamografia. Esta técnica de imagem apresenta alguns problemas: o facto de ser uma imagem a duas dimensões leva a que haja sobreposição de tecidos, o que pode mascarar a presença de tumores; e a fraca sensibilidade a mamas mais densas, sendo estas caraterísticas de mulheres com risco de cancro da mama mais elevado. Como estes dois problemas dificultam a leitura das mamografias, grande parte deste trabalhou focou-se na verificação do desempenho de métodos computacionais na tarefa de classificar mamografias em duas classes: cancro e não-cancro. No que diz respeito à classe “não cancro” (N = 159), esta foi constituída por mamografias saudáveis (N=84), e por mamografias que continham lesões benignas (N=75). Já a classe “cancro” continha apenas mamografias com lesões malignas (N = 73). A discriminação entre estas duas classes foi feita com recurso a algoritmos de aprendizagem automática. Múltiplos classificadores foram otimizados e treinados (Ntreino=162, Nteste = 70), recorrendo a um conjunto de características previamente selecionado, que descreve a textura de toda a mamografia, em vez de apenas uma única Região de Interesse. Estas características de textura baseiam-se na procura de padrões: sequências de pixéis com a mesma intensidade, ou pares específicos de pixéis. O classificador que apresentou uma performance mais elevada foi um dos Support Vector Machine (SVM) treinados – AUC= 0.875, o que indica um desempenho entre o bom e o excelente. A Percent Mammographic Density (%PD) é um importante fator de risco no que diz respeito ao desenvolvimento da doença, pelo que foi estudado se a sua adição ao set de features selecionado resultaria numa melhor performance dos classificadores. O classificador, treinado e otimizado utilizando as features de textura e os cálculos de %PD, com maior capacidade discriminativa foi um Linear Discriminant Analysis (LDA) – AUC = 0.875. Uma vez que a performance é igual à obtida com o classificador que utiliza apenas features de textura, conclui-se que a %PD parece não contribuir com informação relevante. Tal pode ocorrer porque as próprias características de textura já têm informação sobre a densidade da mama. De forma a estudar-se de que modo o desempenho destes métodos computacionais pode ser afetado por piores condições de aquisição de imagem, foi simulado ruído gaussiano, e adicionado ao set de imagens utilizado para testagem. Este ruído, adicionado a cada imagem com quatro magnitudes diferentes, resultou numa AUC de 0.765 para o valor mais baixo de ruído, e numa AUC de 0.5 para o valor de ruído mais elevado. Tais resultados indicam que, para níveis de ruído mais baixo, o classificador consegue, ainda assim, manter uma performance satisfatória – o que deixa de se verificar para valores mais elevados de ruído. Estudou-se, também, se a aplicação de técnicas de filtragem – com um filtro mediana – poderia ajudar a recuperar informação perdida aquando da adição de ruído. A aplicação do filtro a todas as imagens ruidosas resultou numa AUC de 0.754 para o valor mais elevado de ruído, atingindo assim um desempenho similar ao set de imagens menos ruidosas, antes do processo de filtragem (AUC=0.765). Este resultados parecem indicar que, na presença de más condições de aquisição, a aplicação de um filtro mediana pode ajudar a recuperar informação, conduzindo assim a um melhor desempenho dos métodos computacionais. No entanto, esta mesma conclusão parece não se verificar para valores de ruído mais baixo onde a AUC após filtragem acaba por ser mais reduzida. Tal resultado poderá indicar que, em situações onde o nível de ruído é mais baixo, a técnica de filtragem não só remove o ruído, como acaba também por, ela própria, remover informação ao nível da textura da imagem. De modo a verificar se mamas com diferentes densidades afetavam a performance do classificador, foram criados três sets de teste diferentes, cada um deles contendo imagens de mamas com a mesma densidade (1, 2, e 3). Os resultados obtidos indicam-nos que um aumento na densidade das mamas analisadas não resulta, necessariamente, numa diminuição da capacidade em discriminar as classes definidas (AUC = 0.864, AUC = 0.927, AUC= 0.905; para as classes 1, 2, e 3 respetivamente). A utilização da imagem integral para analisar de textura, e a utilização de imagens de datasets diferentes (com dimensões de imagem diferentes), poderiam introduzir um viés na classificação, especialmente no que diz respeito às diferentes áreas da mama. Para verificar isso mesmo, utilizando o coeficiente de correlação de Pearson, ρ = 0.3, verificou-se que a área da mama (e a percentagem de ocupação) tem uma fraca correlação com a classificação dada a cada imagem. A construção do classificador, para além de servir de base a todos os testes apresentados, serviu também o propósito de criar uma interface interativa, passível de ser utilizada como ficheiro executável, sem necessidade de instalação de nenhum software. Esta aplicação permite que o utilizador carregue imagens de mamografia, exclua background desnecessário para a análise da imagem, extraia features, teste o classificador construído e dê como output, no ecrã, a classe correspondente à imagem carregada. A análise de risco de desenvolvimento da doença foi conseguida através da análise visual da variação dos valores das features de textura ao longo dos anos para um pequeno set (N=11) de mulheres. Esta mesma análise permitiu descortinar aquilo que parece ser uma tendência apresentada apenas por mulheres doentes, na mamografia imediatamente anterior ao diagnóstico da doença. Todos os resultados obtidos são descritos profundamente ao longo deste documento, onde se faz, também, uma referência pormenorizada a todos os métodos utilizados para os obter. O resultado da classificação feita apenas com as features de textura encontra-se dentro dos valores referenciados no estado-da-arte, indicando que o uso de features de textura, por si só, demonstrou ser profícuo. Para além disso, tal resultado serve também de indicação que o recurso a toda a imagem de mamografia, sem o trabalho árduo de definição de uma Região de Interesse, poderá ser utilizado com relativa segurança. Os resultados provenientes da análise do efeito da densidade e da área da mama, dão também confiança no uso do classificador. A interface interativa que resultou desta primeira fase de trabalho tem, potencialmente, um diferenciado conjunto de aplicações: no campo médico, poderá servir de auxiliar de diagnóstico ao médico; já no campo da análise computacional, poderá servir para a definição da ground truth de potenciais datasets que não tenham legendas definidas. No que diz respeito à análise de risco, a utilização de um dataset de dimensões reduzidas permitiu, ainda assim, compreender que existem tendências nas variações das features ao longo dos anos, que são especificas de mulheres que desenvolveram a doença. Os resultados obtidos servem, então, de indicação que a continuação desta linha de trabalho, procurando avaliar/predizer o risco, deverá ser seguida, com recurso não só a datasets mais completos, como também a métodos computacionais de aprendizagem automática.Two million and three hundred thousand Breast Cancer (BC) cases were diagnosed in 2020, making it the type of cancer with the highest incidence that year, considering both sexes. Breast Cancer diagnosis usually occurs during screening programs using mammography, which has some downsides: the masking effect due to its 2-D nature, and its poor sensitivity concerning dense breasts. Since these issues result in difficulties reading mammograms, the main part of this work aimed to verify how a computer vision method would perform in classifying mammograms into two classes: cancer and non-cancer. The ‘non-cancer group’ (N=159) was composed by images with healthy tissue (N=84) and images with benign lesions (N=75), while the cancer group (N=73) contained malignant lesions. To achieve this, multiple classifiers were optimized and trained (Ntrain = 162, Ntest = 70) with a previously selected ideal sub-set of features that describe the texture of the entire image, instead of just one small Region of Interest (ROI). The classifier with the best performance was Support Vector Machine (SVM), (AUC = 0.875), which indicates a good-to-excellent capability discriminating the two defined groups. To assess if Percent Mammographic Density (%PD), an important risk factor, added important information, a new classifier was optimized and trained using the selected sub-set of texture features plus the %PD calculation. The classifier with the best performance was a Linear Discriminant Analysis (LDA), (AUC=0.875), which seems to indicate, once it achieves the same performance as the classifier using only texture features, that there is no relevant information added from %PD calculations. This happens because texture already includes information on breast density. To understand how the classifier would perform in worst image acquisition conditions, gaussian noise was added to the test images (N=70), with four different magnitudes (AUC= 0.765 for the lowest noise value vs. AUC ≈ 0.5 for the highest). A median filter was applied to the noised images towards evaluating if information could be recovered. For the highest noise value, after filtering, the AUC was very close to the one obtained for the lowest noise value before filtering (0.754 vs 0.765), which indicates information recovery. The effect of density in classifier performance was evaluated by constructing three different test sets, each containing images from a density class (1,2,3). It was seen that an increase in density did not necessarily resulted in a decrease in performance, which indicates that the classifier is robust to density variation (AUC = 0.864, AUC= 0.927, AUC= 0.905 ; for class 1, 2, and 3 respectively). Since the entire image is being analyzed, and images come from different datasets, it was verified if breast area was adding bias to classification. Pearson correlation coefficient provided an output of ρ = 0.22, showing that there is a weak correlation between these two variables. Finally, breast cancer risk was assessed by visual texture feature analysis through the years, for a small set of women (N=11). This visual analysis allowed to unveil what seems to be a pattern amongst women who developed the disease, in the mammogram immediately before diagnosis. The details of each phase, as well as the associated final results are deeply described throughout this document. The work done in the first classification task resulted in a state-of-the-art performance, which may serve as foundation for new research in the area, without the laborious work of ROI definition. Besides that, the use of texture features alone proved to be fruitful. Results concerning risk may serve as basis for future work in the area, with larger datasets and the incorporation of Computer Vision methods

Mammography Techniques and Review

Mammography remains at the backbone of medical tools to examine the human breast. The early detection of breast cancer typically uses adjunct tests to mammogram such as ultrasound, positron emission mammography, electrical impedance, Computer-aided detection systems and others. In the present digital era it is even more important to use the best new techniques and systems available to improve the correct diagnosis and to prevent mortality from breast cancer. The first part of this book deals with the electrical impedance mammographic scheme, ultrasound axillary imaging, position emission mammography and digital mammogram enhancement. A detailed consideration of CBR CAD System and the availability of mammographs in Brazil forms the second part of this book. With the up-to-date papers from world experts, this book will be invaluable to anyone who studies the field of mammography

Information Fusion of Magnetic Resonance Images and Mammographic Scans for Improved Diagnostic Management of Breast Cancer

Medical imaging is critical to non-invasive diagnosis and treatment of a wide spectrum of medical conditions. However, different modalities of medical imaging employ/apply di erent contrast mechanisms and, consequently, provide different depictions of bodily anatomy. As a result, there is a frequent problem where the same pathology can be detected by one type of medical imaging while being missed by others. This problem brings forward the importance of the development of image processing tools for integrating the information provided by different imaging modalities via the process of information fusion. One particularly important example of clinical application of such tools is in the diagnostic management of breast cancer, which is a prevailing cause of cancer-related mortality in women. Currently, the diagnosis of breast cancer relies mainly on X-ray mammography and Magnetic Resonance Imaging (MRI), which are both important throughout different stages of detection, localization, and treatment of the disease. The sensitivity of mammography, however, is known to be limited in the case of relatively dense breasts, while contrast enhanced MRI tends to yield frequent 'false alarms' due to its high sensitivity. Given this situation, it is critical to find reliable ways of fusing the mammography and MRI scans in order to improve the sensitivity of the former while boosting the specificity of the latter. Unfortunately, fusing the above types of medical images is known to be a difficult computational problem. Indeed, while MRI scans are usually volumetric (i.e., 3-D), digital mammograms are always planar (2-D). Moreover, mammograms are invariably acquired under the force of compression paddles, thus making the breast anatomy undergo sizeable deformations. In the case of MRI, on the other hand, the breast is rarely constrained and imaged in a pendulous state. Finally, X-ray mammography and MRI exploit two completely di erent physical mechanisms, which produce distinct diagnostic contrasts which are related in a non-trivial way. Under such conditions, the success of information fusion depends on one's ability to establish spatial correspondences between mammograms and their related MRI volumes in a cross-modal cross-dimensional (CMCD) setting in the presence of spatial deformations (+SD). Solving the problem of information fusion in the CMCD+SD setting is a very challenging analytical/computational problem, still in need of efficient solutions. In the literature, there is a lack of a generic and consistent solution to the problem of fusing mammograms and breast MRIs and using their complementary information. Most of the existing MRI to mammogram registration techniques are based on a biomechanical approach which builds a speci c model for each patient to simulate the effect of mammographic compression. The biomechanical model is not optimal as it ignores the common characteristics of breast deformation across different cases. Breast deformation is essentially the planarization of a 3-D volume between two paddles, which is common in all patients. Regardless of the size, shape, or internal con guration of the breast tissue, one can predict the major part of the deformation only by considering the geometry of the breast tissue. In contrast with complex standard methods relying on patient-speci c biomechanical modeling, we developed a new and relatively simple approach to estimate the deformation and nd the correspondences. We consider the total deformation to consist of two components: a large-magnitude global deformation due to mammographic compression and a residual deformation of relatively smaller amplitude. We propose a much simpler way of predicting the global deformation which compares favorably to FEM in terms of its accuracy. The residual deformation, on the other hand, is recovered in a variational framework using an elastic transformation model. The proposed algorithm provides us with a computational pipeline that takes breast MRIs and mammograms as inputs and returns the spatial transformation which establishes the correspondences between them. This spatial transformation can be applied in different applications, e.g., producing 'MRI-enhanced' mammograms (which is capable of improving the quality of surgical care) and correlating between different types of mammograms. We investigate the performance of our proposed pipeline on the application of enhancing mammograms by means of MRIs and we have shown improvements over the state of the art

Image Registration Workshop Proceedings

Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research

Comparative Analysis of Segment Anything Model and U-Net for Breast Tumor Detection in Ultrasound and Mammography Images

In this study, the main objective is to develop an algorithm capable of identifying and delineating tumor regions in breast ultrasound (BUS) and mammographic images. The technique employs two advanced deep learning architectures, namely U-Net and pretrained SAM, for tumor segmentation. The U-Net model is specifically designed for medical image segmentation and leverages its deep convolutional neural network framework to extract meaningful features from input images. On the other hand, the pretrained SAM architecture incorporates a mechanism to capture spatial dependencies and generate segmentation results. Evaluation is conducted on a diverse dataset containing annotated tumor regions in BUS and mammographic images, covering both benign and malignant tumors. This dataset enables a comprehensive assessment of the algorithm's performance across different tumor types. Results demonstrate that the U-Net model outperforms the pretrained SAM architecture in accurately identifying and segmenting tumor regions in both BUS and mammographic images. The U-Net exhibits superior performance in challenging cases involving irregular shapes, indistinct boundaries, and high tumor heterogeneity. In contrast, the pretrained SAM architecture exhibits limitations in accurately identifying tumor areas, particularly for malignant tumors and objects with weak boundaries or complex shapes. These findings highlight the importance of selecting appropriate deep learning architectures tailored for medical image segmentation. The U-Net model showcases its potential as a robust and accurate tool for tumor detection, while the pretrained SAM architecture suggests the need for further improvements to enhance segmentation performance

Advanced Computational Methods for Oncological Image Analysis

[Cancer is the second most common cause of death worldwide and encompasses highly variable clinical and biological scenarios. Some of the current clinical challenges are (i) early diagnosis of the disease and (ii) precision medicine, which allows for treatments targeted to specific clinical cases. The ultimate goal is to optimize the clinical workflow by combining accurate diagnosis with the most suitable therapies. Toward this, large-scale machine learning research can define associations among clinical, imaging, and multi-omics studies, making it possible to provide reliable diagnostic and prognostic biomarkers for precision oncology. Such reliable computer-assisted methods (i.e., artificial intelligence) together with clinicians’ unique knowledge can be used to properly handle typical issues in evaluation/quantification procedures (i.e., operator dependence and time-consuming tasks). These technical advances can significantly improve result repeatability in disease diagnosis and guide toward appropriate cancer care. Indeed, the need to apply machine learning and computational intelligence techniques has steadily increased to effectively perform image processing operations—such as segmentation, co-registration, classification, and dimensionality reduction—and multi-omics data integration.

DEFORM'06 - Proceedings of the Workshop on Image Registration in Deformable Environments

Preface These are the proceedings of DEFORM'06, the Workshop on Image Registration in Deformable Environments, associated to BMVC'06, the 17th British Machine Vision Conference, held in Edinburgh, UK, in September 2006. The goal of DEFORM'06 was to bring together people from different domains having interests in deformable image registration. In response to our Call for Papers, we received 17 submissions and selected 8 for oral presentation at the workshop. In addition to the regular papers, Andrew Fitzgibbon from Microsoft Research Cambridge gave an invited talk at the workshop. The conference website including online proceedings remains open, see http://comsee.univ-bpclermont.fr/events/DEFORM06. We would like to thank the BMVC'06 co-chairs, Mike Chantler, Manuel Trucco and especially Bob Fisher for is great help in the local arrangements, Andrew Fitzgibbon, and the Programme Committee members who provided insightful reviews of the submitted papers. Special thanks go to Marc Richetin, head of the CNRS Research Federation TIMS, which sponsored the workshop. August 2006 Adrien Bartoli Nassir Navab Vincent Lepeti

Frequency Domain Ultrasound Waveform Tomography Breast Imaging

Ultrasound tomography is an emerging modality for imaging breast tissue for the detection of disease. Using the principles of full waveform inversion, high-resolution quantitative sound speed and attenuation maps of the breast can be created. In this thesis, we introduce some basic principles of imaging breast disease and the formalism of sound wave propagation. We present numerical methods to model acoustic wave propagation as well methods to solve the corresponding inverse problem. Numerical simulations of sound speed and attenuation reconstructions are used to assess the efficacy of the algorithm. A careful review of the preprocessing techniques needed for the successful inversion of acoustic data is presented. Ex vivo and in vivo sound speed reconstructions highlight the significant improvements that are made upon commonly used travel time sound speed reconstruction methods. Note that we do not present ex vivo or in vivo attenuation reconstructions in this thesis. For the sound speed images, the higher resolution and contrast of the waveform method will hopefully allow a radiologist to make a more informed diagnosis of breast disease. A comparison of full waveform sound speed imaging to MRI shows a great deal of concordant findings. Lastly, we give examples of the use of full waveform inversion sound speed imaging in a clinical setting

Noise-Enhanced and Human Visual System-Driven Image Processing: Algorithms and Performance Limits

This dissertation investigates the problem of image processing based on stochastic resonance (SR) noise and human visual system (HVS) properties, where several novel frameworks and algorithms for object detection in images, image enhancement and image segmentation as well as the method to estimate the performance limit of image segmentation algorithms are developed. Object detection in images is a fundamental problem whose goal is to make a decision if the object of interest is present or absent in a given image. We develop a framework and algorithm to enhance the detection performance of suboptimal detectors using SR noise, where we add a suitable dose of noise into the original image data and obtain the performance improvement. Micro-calcification detection is employed in this dissertation as an illustrative example. The comparative experiments with a large number of images verify the efficiency of the presented approach. Image enhancement plays an important role and is widely used in various vision tasks. We develop two image enhancement approaches. One is based on SR noise, HVS-driven image quality evaluation metrics and the constrained multi-objective optimization (MOO) technique, which aims at refining the existing suboptimal image enhancement methods. Another is based on the selective enhancement framework, under which we develop several image enhancement algorithms. The two approaches are applied to many low quality images, and they outperform many existing enhancement algorithms. Image segmentation is critical to image analysis. We present two segmentation algorithms driven by HVS properties, where we incorporate the human visual perception factors into the segmentation procedure and encode the prior expectation on the segmentation results into the objective functions through Markov random fields (MRF). Our experimental results show that the presented algorithms achieve higher segmentation accuracy than many representative segmentation and clustering algorithms available in the literature. Performance limit, or performance bound, is very useful to evaluate different image segmentation algorithms and to analyze the segmentability of the given image content. We formulate image segmentation as a parameter estimation problem and derive a lower bound on the segmentation error, i.e., the mean square error (MSE) of the pixel labels considered in our work, using a modified Cramér-Rao bound (CRB). The derivation is based on the biased estimator assumption, whose reasonability is verified in this dissertation. Experimental results demonstrate the validity of the derived bound

Characterising pattern asymmetry in pigmented skin lesions

Abstract. In clinical diagnosis of pigmented skin lesions asymmetric pigmentation is often indicative of melanoma. This paper describes a method and measures for characterizing lesion symmetry. The estimate of mirror symmetry is computed first for a number of axes at different degrees of rotation with respect to the lesion centre. The statistics of these estimates are the used to assess the overall symmetry. The method is applied to three different lesion representations showing the overall pigmentation, the pigmentation pattern, and the pattern of dermal melanin. The best measure is a 100% sensitive and 96% specific indicator of melanoma on a test set of 33 lesions, with a separate training set consisting of 66 lesions