Sistemas de ayuda al diagnóstico y reconocimiento de microcalcificaciones en mamografía mediante descriptores de escala y redes jerárquicas

La presente Tesis investiga el campo del reconocimiento automático de imágenes mediante ordenador aplicado al análisis de imágenes médicas en mamografía digital. Hay un interés por desarrollar sistemas de aprendizaje que asistan a los radiólogos en el reconocimiento de las microcalcificaciones para apoyarles en los programas de cribado y prevención del cáncer de mama. Para ello el análisis de las microcalcificaciones se ha revelado como técnica clave de diagnóstico precoz, pero sin embargo el diseño de sistemas automáticos para reconocerlas es complejo por la variabilidad y condiciones de las imágenes mamográficas. En este trabajo se analizan los planteamientos teóricos de diseño de sistemas de reconocimiento de imágenes, con énfasis en los problemas específicos de detección y clasificación de microcalcificaciones. Se ha realizado un estudio que incluye desde las técnicas de operadores morfológicos, redes neuronales, máquinas de vectores soporte, hasta las más recientes de aprendizaje profundo mediante redes neuronales convolucionales, contemplando la importancia de los conceptos de escala y jerarquía a la hora del diseño y sus implicaciones en la búsqueda de la arquitectura de conexiones y capas de la red. Con estos fundamentos teóricos y elementos de diseño procedentes de otros trabajos en este área realizados por el autor, se implementan tres sistemas de reconocimiento de mamografías que reflejan una evolución tecnológica, culminando en un sistema basado en Redes Neuronales Convolucionales (CNN) cuya arquitectura se diseña gracias al análisis teórico anterior y a los resultados prácticos de análisis de escalas llevados a cabo en nuestra base de datos de imágenes. Los tres sistemas se entrenan y validan con la base de datos de mamografías DDSM, con un total de 100 muestras de entrenamiento y 100 de prueba escogidas para evitar sesgos y reflejar fielmente un programa de cribado. La validez de las CNN para el problema que nos ocupa queda demostrada y se propone un camino de investigación para el diseño de su arquitectura. ABSTRACT This Dissertation investigates the field of computer image recognition applied to medical imaging in mammography. There is an interest in developing learning systems to assist radiologists in recognition of microcalcifications to help them in screening programs for prevention of breast cancer. Analysis of microcalcifications has emerged as a key technique for early diagnosis of breast cancer, but the design of automatic systems to recognize them is complicated by the variability and conditions of mammographic images. In this Thesis the theoretical approaches to design image recognition systems are discussed, with emphasis on the specific problems of detection and classification of microcalcifications. Our study includes techniques ranging from morphological operators, neural networks and support vector machines, to the most recent deep convolutional neural networks. We deal with learning theory by analyzing the importance of the concepts of scale and hierarchy at the design stage and its implications in the search for the architecture of connections and network layers. With these theoretical facts and design elements coming from other works in this area done by the author, three mammogram recognition systems which reflect technological developments are implemented, culminating in a system based on Convolutional Neural Networks (CNN), whose architecture is designed thanks to the previously mentioned theoretical study and practical results of analysis conducted on scales in our image database. All three systems are trained and validated against the DDSM mammographic database, with a total of 100 training samples and 100 test samples chosen to avoid bias and stand for a real screening program. The validity of the CNN approach to the problem is demonstrated and a research way to help in designing the architecture of these networks is proposed.

Sistemas de ayuda al diagnóstico y a la terapia funcional en enfermedades neurodegenerativas

El incremento de la esperanza de vida en los países desarrollados (más de 80 años en 2013), está suponiendo un crecimiento considerable en la incidencia y prevalencia de enfermedades discapacitantes, que si bien pueden aparecer a edades tempranas, son más frecuentes en la tercera edad, o en sus inmediaciones. Enfermedades neuro-degenerativas que suponen un gran hándicap funcional, pues algunas de ellas están asociadas a movimientos involuntarios de determinadas partes del cuerpo, sobre todo de las extremidades. Tareas cotidianas como la ingesta de alimento, vestirse, escribir, interactuar con el ordenador, etc… pueden llegar a ser grandes retos para las personas que las padecen. El diagnóstico precoz y certero resulta fundamental para la prescripción de la terapia o tratamiento óptimo. Teniendo en cuenta incluso que en muchos casos, por desgracia la mayoría, sólo se puede actuar para mitigar los síntomas, y no para sanarlos, al menos de momento. Aun así, acertar de manera temprana en el diagnóstico supone proporcionar al enfermo una mayor calidad de vida durante mucho más tiempo, por lo cual el esfuerzo merece, y mucho, la pena. Los enfermos de Párkinson y de temblor esencial suponen un porcentaje importante de la casuística clínica en los trastornos del movimiento que impiden llevar una vida normal, que producen una discapacidad física y una no menos importante exclusión social. Las vías de tratamiento son dispares de ahí que sea crítico acertar en el diagnóstico lo antes posible. Hasta la actualidad, los profesionales y expertos en medicina, utilizan unas escalas cualitativas para diferenciar la patología y su grado de afectación. Dichas escalas también se utilizan para efectuar un seguimiento clínico y registrar la historia del paciente. En esta tesis se propone una serie de métodos de análisis y de identificación/clasificación de los tipos de temblor asociados a la enfermedad de Párkinson y el temblor esencial. Empleando técnicas de inteligencia artificial basadas en clasificadores inteligentes: redes neuronales (MLP y LVQ) y máquinas de soporte vectorial (SVM), a partir del desarrollo e implantación de un sistema para la medida y análisis objetiva del temblor: DIMETER. Dicho sistema además de ser una herramienta eficaz para la ayuda al diagnóstico, presenta también las capacidades necesarias para proporcionar un seguimiento riguroso y fiable de la evolución de cada paciente. ABSTRACT The increase in life expectancy in developed countries in more than 80 years (data belongs to 2013), is assuming considerable growth in the incidence and prevalence of disabling diseases. Although they may appear at an early age, they are more common in the elderly ages or in its vicinity. Nuero-degenerative diseases that are a major functional handicap, as some of them are associated with involuntary movements of certain body parts, especially of the limbs. Everyday tasks such as food intake, dressing, writing, interact with the computer, etc ... can become large debris for people who suffer. Early and accurate diagnosis is crucial for prescribing optimal therapy or treatment. Even taking into account that in many cases, unfortunately the majority, can only act to mitigate the symptoms, not to cure them, at least for now. Nevertheless, early diagnosis may provide the patient a better quality of life for much longer time, so the effort is worth, and much, grief. Sufferers of Parkinson's and essential tremor represent a significant percentage of clinical casuistry in movement disorders that prevent a normal life, leading to physical disability and not least social exclusion. There are various treatment methods, which makes it necessary the immediate diagnosis. Up to date, professionals and medical experts, use a qualitative scale to differentiate the disease and degree of involvement. Therefore, those scales are used in clinical follow-up. In this thesis, several methods of analysis and identification / classification of types of tremor associated with Parkinson's disease and essential tremor are proposed. Using artificial intelligence techniques based on intelligent classification: neural networks (MLP and LVQ) and support vector machines (SVM), starting from the development and implementation of a system for measuring and objective analysis of the tremor: DIMETER. This system besides being an effective tool to aid diagnosis, it also has the necessary capabilities to provide a rigorous and reliable monitoring of the evolution of each patient.

Human-computer interaction based on visual hand-gesture recognition using volumetric spatiograms of local binary patterns

A more natural, intuitive, user-friendly, and less intrusive Human–Computer interface for controlling an application by executing hand gestures is presented. For this purpose, a robust vision-based hand-gesture recognition system has been developed, and a new database has been created to test it. The system is divided into three stages: detection, tracking, and recognition. The detection stage searches in every frame of a video sequence potential hand poses using a binary Support Vector Machine classifier and Local Binary Patterns as feature vectors. These detections are employed as input of a tracker to generate a spatio-temporal trajectory of hand poses. Finally, the recognition stage segments a spatio-temporal volume of data using the obtained trajectories, and compute a video descriptor called Volumetric Spatiograms of Local Binary Patterns (VS-LBP), which is delivered to a bank of SVM classifiers to perform the gesture recognition. The VS-LBP is a novel video descriptor that constitutes one of the most important contributions of the paper, which is able to provide much richer spatio-temporal information than other existing approaches in the state of the art with a manageable computational cost. Excellent results have been obtained outperforming other approaches of the state of the art.

Multiclassificador inteligente de falhas no domínio do tempo em motores de indução trifásicos alimentados por inversores de frequência

Os motores de indução desempenham um importante papel na indústria, fato este que destaca a importância do correto diagnóstico e classificação de falhas ainda em fase inicial de sua evolução, possibilitando aumento na produtividade e, principalmente, eliminando graves danos aos processos e às máquinas. Assim, a proposta desta tese consiste em apresentar um multiclassificador inteligente para o diagnóstico de motor sem defeitos, falhas de curto-circuito nos enrolamentos do estator, falhas de rotor e falhas de rolamentos em motores de indução trifásicos acionados por diferentes modelos de inversores de frequência por meio da análise das amplitudes dos sinais de corrente de estator no domínio do tempo. Para avaliar a precisão de classificação frente aos diversos níveis de severidade das falhas, foram comparados os desempenhos de quatro técnicas distintas de aprendizado de máquina; a saber: (i) Rede Fuzzy Artmap, (ii) Rede Perceptron Multicamadas, (iii) Máquina de Vetores de Suporte e (iv) k-Vizinhos-Próximos. Resultados experimentais obtidos a partir de 13.574 ensaios experimentais são apresentados para validar o estudo considerando uma ampla faixa de frequências de operação, bem como regimes de conjugado de carga em 5 motores diferentes.

Aplicação de técnicas inteligentes com análise no domínio do tempo para reconhecimento de defeitos em motores de indução trifásicos

Os motores de indução trifásicos são os principais elementos de conversão de energia elétrica em mecânica motriz aplicados em vários setores produtivos. Identificar um defeito no motor em operação pode fornecer, antes que ele falhe, maior segurança no processo de tomada de decisão sobre a manutenção da máquina, redução de custos e aumento de disponibilidade. Nesta tese são apresentas inicialmente uma revisão bibliográfica e a metodologia geral para a reprodução dos defeitos nos motores e a aplicação da técnica de discretização dos sinais de correntes e tensões no domínio do tempo. É também desenvolvido um estudo comparativo entre métodos de classificação de padrões para a identificação de defeitos nestas máquinas, tais como: Naive Bayes, k-Nearest Neighbor, Support Vector Machine (Sequential Minimal Optimization), Rede Neural Artificial (Perceptron Multicamadas), Repeated Incremental Pruning to Produce Error Reduction e C4.5 Decision Tree. Também aplicou-se o conceito de Sistemas Multiagentes (SMA) para suportar a utilização de múltiplos métodos concorrentes de forma distribuída para reconhecimento de padrões de defeitos em rolamentos defeituosos, quebras nas barras da gaiola de esquilo do rotor e curto-circuito entre as bobinas do enrolamento do estator de motores de indução trifásicos. Complementarmente, algumas estratégias para a definição da severidade dos defeitos supracitados em motores foram exploradas, fazendo inclusive uma averiguação da influência do desequilíbrio de tensão na alimentação da máquina para a determinação destas anomalias. Os dados experimentais foram adquiridos por meio de uma bancada experimental em laboratório com motores de potência de 1 e 2 cv acionados diretamente na rede elétrica, operando em várias condições de desequilíbrio das tensões e variações da carga mecânica aplicada ao eixo do motor.

Estudo do espectro Laplaciano na categorização de imagens

Uma imagem engloba informação que precisa ser organizada para interpretar e compreender seu conteúdo. Existem diversas técnicas computacionais para extrair a principal informação de uma imagem e podem ser divididas em três áreas: análise de cor, textura e forma. Uma das principais delas é a análise de forma, por descrever características de objetos baseadas em seus pontos fronteira. Propomos um método de caracterização de imagens, por meio da análise de forma, baseada nas propriedades espectrais do laplaciano em grafos. O procedimento construiu grafos G baseados nos pontos fronteira do objeto, cujas conexões entre vértices são determinadas por limiares T_l. A partir dos grafos obtêm-se a matriz de adjacência A e a matriz de graus D, as quais definem a matriz Laplaciana L=D -A. A decomposição espectral da matriz Laplaciana (autovalores) é investigada para descrever características das imagens. Duas abordagens são consideradas: a) Análise do vetor característico baseado em limiares e a histogramas, considera dois parâmetros o intervalo de classes IC_l e o limiar T_l; b) Análise do vetor característico baseado em vários limiares para autovalores fixos; os quais representam o segundo e último autovalor da matriz L. As técnicas foram testada em três coleções de imagens: sintéticas (Genéricas), parasitas intestinais (SADPI) e folhas de plantas (CNShape), cada uma destas com suas próprias características e desafios. Na avaliação dos resultados, empregamos o modelo de classificação support vector machine (SVM), o qual avalia nossas abordagens, determinando o índice de separação das categorias. A primeira abordagem obteve um acerto de 90 % com a coleção de imagens Genéricas, 88 % na coleção SADPI, e 72 % na coleção CNShape. Na segunda abordagem, obtém-se uma taxa de acerto de 97 % com a coleção de imagens Genéricas; 83 % para SADPI e 86 % no CNShape. Os resultados mostram que a classificação de imagens a partir do espectro do Laplaciano, consegue categorizá-las satisfatoriamente.

GEOFIER: um sistema de anotação geográfica de textos com o uso de classificadores de aprendizagem de máquina.

A anotação geográfica de documentos consiste na adoção de metadados para a identificação de nomes de locais e a posição de suas ocorrências no texto. Esta informação é útil, por exemplo, para mecanismos de busca. A partir dos topônimos mencionados no texto é possível identificar o contexto espacial em que o assunto do texto está inserido, o que permite agrupar documentos que se refiram a um mesmo contexto, atribuindo ao documento um escopo geográfico. Esta Dissertação de Mestrado apresenta um novo método, batizado de Geofier, para determinação do escopo geográfico de documentos. A novidade apresentada pelo Geofier é a possibilidade da identificação do escopo geográfico de um documento por meio de classificadores de aprendizagem de máquina treinados sem o uso de um gazetteer e sem premissas quanto à língua dos textos analisados. A Wikipédia foi utilizada como fonte de um conjunto de documentos anotados geograficamente para o treinamento de uma hierarquia de Classificadores Naive Bayes e Support Vector Machines (SVMs). Uma comparação de desempenho entre o Geofier e uma reimplementação do sistema Web-a-Where foi realizada em relação à determinação do escopo geográfico dos textos da Wikipédia. A hierarquia do Geofier foi treinada e avaliada de duas formas: usando topônimos do mesmo gazetteer que o Web-a-Where e usando n-gramas extraídos dos documentos de treinamento. Como resultado, o Geofier manteve desempenho superior ao obtido pela reimplementação do Web-a-Where.

Electroencephalogram based Causality Graph Analysis in Behavior Tasks of Parkinson’s Disease Patients

Electroencephalographic (EEG) signals of the human brains represent electrical activities for a number of channels recorded over a the scalp. The main purpose of this thesis is to investigate the interactions and causality of different parts of a brain using EEG signals recorded during a performance subjects of verbal fluency tasks. Subjects who have Parkinson's Disease (PD) have difficulties with mental tasks, such as switching between one behavior task and another. The behavior tasks include phonemic fluency, semantic fluency, category semantic fluency and reading fluency. This method uses verbal generation skills, activating different Broca's areas of the Brodmann's areas (BA44 and BA45). Advanced signal processing techniques are used in order to determine the activated frequency bands in the granger causality for verbal fluency tasks. The graph learning technique for channel strength is used to characterize the complex graph of Granger causality. Also, the support vector machine (SVM) method is used for training a classifier between two subjects with PD and two healthy controls. Neural data from the study was recorded at the Colorado Neurological Institute (CNI). The study reveals significant difference between PD subjects and healthy controls in terms of brain connectivities in the Broca's Area BA44 and BA45 corresponding to EEG electrodes. The results in this thesis also demonstrate the possibility to classify based on the flow of information and causality in the brain of verbal fluency tasks. These methods have the potential to be applied in the future to identify pathological information flow and causality of neurological diseases.

Morphological classification of microtidal sand and gravel beaches

A new classification of microtidal sand and gravel beaches with very different morphologies is presented below. In 557 studied transects, 14 variables were used. Among the variables to be emphasized is the depth of the Posidonia oceanica. The classification was performed for 9 types of beaches: Type 1: Sand and gravel beaches, Type 2: Sand and gravel separated beaches, Type 3: Gravel and sand beaches, Type 4: Gravel and sand separated beaches, Type 5: Pure gravel beaches, Type 6: Open sand beaches, Type 7: Supported sand beaches, Type 8: Bisupported sand beaches and Type 9: Enclosed beaches. For the classification, several tools were used: discriminant analysis, neural networks and Support Vector Machines (SVM), the results were then compared. As there is no theory for deciding which is the most convenient neural network architecture to deal with a particular data set, an experimental study was performed with different numbers of neuron in the hidden layer. Finally, an architecture with 30 neurons was chosen. Different kernels were employed for SVM (Linear, Polynomial, Radial basis function and Sigmoid). The results obtained for the discriminant analysis were not as good as those obtained for the other two methods (ANN and SVM) which showed similar success.

Computational Methods for Identifying Hypertrophic Cardiomyopathy using 12-lead ECG

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease where the heart muscle is partially thickened and blood flow is - potentially fatally - obstructed. It is one of the leading causes of sudden cardiac death in young people. Electrocardiography (ECG) and Echocardiography (Echo) are the standard tests for identifying HCM and other cardiac abnormalities. The American Heart Association has recommended using a pre-participation questionnaire for young athletes instead of ECG or Echo tests due to considerations of cost and time involved in interpreting the results of these tests by an expert cardiologist. Initially we set out to develop a classifier for automated prediction of young athletes’ heart conditions based on the answers to the questionnaire. Classification results and further in-depth analysis using computational and statistical methods indicated significant shortcomings of the questionnaire in predicting cardiac abnormalities. Automated methods for analyzing ECG signals can help reduce cost and save time in the pre-participation screening process by detecting HCM and other cardiac abnormalities. Therefore, the main goal of this dissertation work is to identify HCM through computational analysis of 12-lead ECG. ECG signals recorded on one or two leads have been analyzed in the past for classifying individual heartbeats into different types of arrhythmia as annotated primarily in the MIT-BIH database. In contrast, we classify complete sequences of 12-lead ECGs to assign patients into two groups: HCM vs. non-HCM. The challenges and issues we address include missing ECG waves in one or more leads and the dimensionality of a large feature-set. We address these by proposing imputation and feature-selection methods. We develop heartbeat-classifiers by employing Random Forests and Support Vector Machines, and propose a method to classify full 12-lead ECGs based on the proportion of heartbeats classified as HCM. The results from our experiments show that the classifiers developed using our methods perform well in identifying HCM. Thus the two contributions of this thesis are the utilization of computational and statistical methods for discovering shortcomings in a current screening procedure and the development of methods to identify HCM through computational analysis of 12-lead ECG signals.

Inference of binding affinity from neuronal receptors in humans

Tese de mestrado, Bioinformática e Biologia Computacional (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2016

Optimization and Machine Learning Frameworks for Complex Network Analysis

Thesis (Ph.D.)--University of Washington, 2016-06

Microarray expression profiling in melanoma reveals a BRAF mutation signature

We have used microarray gene expression pro. ling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase ( MAPK) activation ( either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.

Prediction of subcellular localization using sequence-biased recurrent networks

Motivation: Targeting peptides direct nascent proteins to their specific subcellular compartment. Knowledge of targeting signals enables informed drug design and reliable annotation of gene products. However, due to the low similarity of such sequences and the dynamical nature of the sorting process, the computational prediction of subcellular localization of proteins is challenging. Results: We contrast the use of feed forward models as employed by the popular TargetP/SignalP predictors with a sequence-biased recurrent network model. The models are evaluated in terms of performance at the residue level and at the sequence level, and demonstrate that recurrent networks improve the overall prediction performance. Compared to the original results reported for TargetP, an ensemble of the tested models increases the accuracy by 6 and 5% on non-plant and plant data, respectively.

Genes for the majority of group A streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease

Background. The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. Methods. In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. Results. Virulence gene profiles of individual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. Conclusions. Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/ or host factors.