Semi-Supervised Deep Learning for Multi-Tissue Segmentation from Multi-Contrast MRI

Segmentation of thigh tissues (muscle, fat, inter-muscular adipose tissue (IMAT), bone, and bone marrow) from magnetic resonance imaging (MRI) scans is useful for clinical and research investigations in various conditions such as aging, diabetes mellitus, obesity, metabolic syndrome, and their associated comorbidities. Towards a fully automated, robust, and precise quantification of thigh tissues, herein we designed a novel semi-supervised segmentation algorithm based on deep network architectures. Built upon Tiramisu segmentation engine, our proposed deep networks use variational and specially designed targeted dropouts for faster and robust convergence, and utilize multi-contrast MRI scans as input data. In our experiments, we have used 150 scans from 50 distinct subjects from the Baltimore Longitudinal Study of Aging (BLSA). The proposed system made use of both labeled and unlabeled data with high efficacy for training, and outperformed the current state-of-the-art methods with dice scores of 97.52%, 94.61%, 80.14%, 95.93%, and 96.83% for muscle, fat, IMAT, bone, and bone marrow tissues, respectively. Our results indicate that the proposed system can be useful for clinical research studies where volumetric and distributional tissue quantification is pivotal and labeling is a significant issue. To the best of our knowledge, the proposed system is the first attempt at multi-tissue segmentation using a single end-to-end semi-supervised deep learning framework for multi-contrast thigh MRI scans.Comment: 20 pages, 9 figures, Journal of Signal Processing System

Prostate cancer biochemical recurrence prediction using bpMRI radiomics, clinical and histopathological data

Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), Universidade de Lisboa, Faculdade de Ciências, 2021O cancro da próstata é a segunda doença oncológica mais frequente nos homens, sendo frequentemente tratado com remoção cirúrgica total do órgão, denominada prostatectomia radical. Apesar dos avanços no diagnóstico e da evolução das terapias cirúrgicas, 20–35% dos candidatos a prostatectomia radical com intuito curativo sofrem de recidiva bioquímica, uma condição que representa o insucesso do tratamento inicial e também o primeiro sinal de progressão da doença. Em particular, dois terços dos casos de recidiva bioquímica ocorrem dentro de um período de dois anos. Ocorrendo cedo, este estado implica uma maior agressividade biológica da doença e um pior prognóstico, uma vez que pode dever-se `a presença de doença oculta, localmente avançada ou metastática. Apesar de o prognóstico devido ao desenvolvimento de recidiva bioquímica variar, em geral está associado a um risco acrescido de desenvolvimento de doença metastática e de mortalidade específica por cancro da próstata, representando assim uma importante preocupação clínica após terapia definitiva. Contudo, os modelos preditivos de recidiva bioquímica actuais não só falham na explicação da variabilidade dos resultados pós-cirúrgicos, como não têm habilidade para intervir cedo no processo de decisão de tratamento, uma vez que dependem de informação provinda da avaliação histopatológica da peça cirúrgica da prostatectomia ou da biópsia. Actualmente, o exame padrão para diagnóstico e para estadiamento do cancro da próstata é a ressonância magnética multiparamétrica, e as características provindas da avaliação dessas imagens têm mostrado potencial na caracterização do(s) tumor(es) e para predição de recidiva bioquímica. “Radiomics”, a recente metodologia aplicada à análise quantitativa de imagens médicas tem mostrado ter capacidade de quantificar objectivamente a heterogeneidade macroscópica de tecidos biológicos como tumores. Esta heterogeneidade detectada tem vindo a sugerir associação a heterogeneidade genómica que, por sua vez, tem demonstrado correlação com resistência a tratamento e propensão metastática. Porém, o potencial da análise radiómica das imagens de ressonância magnética (MRI) multiparamétrica da próstata para previsão de recidiva bioquímica pós-prostatectomia radical ainda não foi totalmente aprofundado. Esta dissertação propôs explorar o potencial da análise radiómica aplicada a imagens pré-cirúrgicas de ressonância magnética biparamétrica da próstata para previsão de recidiva bioquímica, no período de dois anos após prostatectomia radical. Este potencial foi avaliado através de modelos predictivos com base em dados radiómicos e parâmetros clínico-histopatológicos comummente adquiridos em três fases clínicas: pré-biópsia, pré- e pós-cirúrgica. 93 pacientes, de um total de 250, foram eleitos para este estudo retrospectivo, dos quais 20 verificaram recidiva bioquímica. 33 parâmetros clínico-histopatológicos foram recolhidos e 2715 variáveis radiómicas baseadas em intensidade, forma e textura, foram extraídas de todo o volume da próstata caracterizado em imagens originais e filtradas de ressonância magnética biparamétrica, nomeadamente, ponderadas em T2, ponderadas em Difusão, e mapas de coeficiente de difusão aparente (ADC). Embora os pacientes elegíveis tenham sido examinados na mesma instituição, as características do conjunto de imagens eram heterogéneas, sendo necessário aplicar vários passos de processamento para possibilitar uma comparação mais justa. Foi feita correção do campo tendencial (do inglês, “bias”) e segmentação manual das imagens T2, registo tanto para transposição das delineações do volume de interesse entre as várias modalidades imagiológicas como para correção de movimento, cálculo de mapas ADC, regularização do campo de visão, quantização personalizada em tons cinza e reamostragem. Tendo os dados recolhidos uma alta dimensionalidade (número de variáveis maior que o número de observações), foi escolhida a regressão logística com penalização L1 (LASSO) para resolver o problema de classificação. O uso da penalização aliada à regressão logística, um método simples e commumente usado em estudos de classificação, permite impedir o sobreajuste provável neste cenário de alta dimensionalidade. Além do popular LASSO, recorremos também ao algoritmo Priority-LASSO, um método recente para lidar com dados “ómicos” e desenvolvido com base no LASSO. O Priority-LASSO tem como princípio a definição da hierarquia ou prioridade das variáveis de estudo, através do agrupamento dessas mesmas variáveis em blocos sequenciais. Neste trabalho explorámos duas maneiras de agrupar as variáveis (Clínico-histopatológicas vs. Radiómicas e Clínico-histopatológicas vs. T2 vs. Difusão vs. ADC). Além disso, quisemos perceber qual o impacto da ordem destes mesmos blocos no desempenho do modelo. Para tal, testámos todas as permutações de blocos possíveis (2 e 24, respectivamente) em cada um dos casos. Assim, uma estrutura de aprendizagem automática, composta por métodos de classificação, validação-cruzada k-fold estratificada e repetida, e análises estatísticas, foi desenvolvida para identificar os melhores classificadores, dentro um conjunto de configura¸c˜oes testado para cada um dos três cenários clínicos simulados. Os algoritmos de regressão logística penalizada com LASSO e o Priority-LASSO efectuaram conjuntamente a seleção de características e o ajuste de modelos. Os modelos foram desenvolvidos de forma a optimizar o n´umero de casos positivos de recidiva bioquímica através da maximização das métricas área sob a curva (AUC) e medida-F (Fmax), derivadas da análise de curva característica de operação do receptor (ROC). Além da comparação das implementações Priority-LASSO com o caso em que não houve agrupamento de variáveis (isto é, LASSO), foram também comparados dois métodos de normalização de imagens com base no desempenho dos modelos (avaliado por Fmax). Um dos métodos tinha em conta o sinal de intensidade proveniente da próstata e de tecidos imediatamente circundantes, e outro apenas da próstata. Paralelamente, também o efeito do método de amostragem SMOTE, que permite equilibrar o número de casos positivos e negativos durante o processo de aprendizagem do algoritmo, foi avaliado no desempenho dos modelos. Com este método, gerámos casos sintéticos para a classe positiva (classe minoritária) para recidiva bioquímica, a partir dos casos já existentes. O modelo de regressão logística com Priority-LASSO com a sequência de blocos de variáveis Clínico-histopatológicas, T2, Difusão, ADC e com restrição de esparsidade de cada bloco com o parâmetro pmax = (1,7,0,1), foi seleccionada como a melhor configuração em cada um dos cenários clínicos testados, superando os modelos de regressão logística LASSO. Durante o desenvolvimento dos modelos, e em todos os cenários clínicos, os modelos com melhor desempenho obtiveram bons valor médios de Fmax (mínimo–máximo: 0.702–0.754 e 0.910–0.925 para classe positiva e negativa de recidiva bioquímica, respectivamente). Contudo, na validação final com um conjunto de dados independentes, os modelos obtiveram valores Fmax muito baixos para a classe positiva (0.297–0.400), revelando um sobreajuste, apesar do uso de métodos de penalização. Também se verificou grande instabilidade nos atributos seleccionados. Contudo, os modelos obtiveram razoáveis valores de medida-F (0.779–0.833) e de Precisão (0.821–0.873) para a classe de recidiva bioquímica negativa durante as fases de treino e de validação, pelo que estes modelos poderão ter valor a ser explorado. Os modelos pré-biópsia tiveram desempenho inferior no treino, mas sofreram menos de sobreajuste. Os classificadores pré-operatórios foram excessivamente optimistas, e os modelos pós-operatórios foram os melhores a detectar correctamente casos negativos de recidiva bioquímica. Outros resultados observados incluem a superioridade no desempenho dos modelos baseados em imagens que usaram o método de normalização realizado apenas com o volume da próstata, e o inesperado resultado de que o uso método de amostragem SMOTE não ter trazido melhoria na classificação de casos positivos de recorrência bioquímica, nem nos casos negativos, durante a validação dos modelos. Tendo em contas às variáveis seleccionadas e a sequência de prioridade dos melhores modelos Priority-LASSO, concluímos que os atributos radiómicos provindos da análise de textura de imagens MRI ponderadas em T2 poderão ter potencial para distinguir pacientes que não irão sofrer recidiva bioquímica inicial, conjuntamente com níveis iniciais de antigénio específico da próstata, num cenário pré-biópsia. A inclusão de parâmetros pré- ou pós-operatórios não adicionou valor substancial para a classificação de casos positivos de recidiva bioquímica em conjunto com variáveis radiómicos de MRI biparamétrica. Estudos com alto poder estatístico serão necessários para elucidar acerca do papel de atributos de radiómica baseados em imagens de bpMRI como predictores de recidiva bioquímica.Primary prostate cancer is often treated with radical prostatectomy (RP). Yet, 20–35% of males undergoing RP with curative intent will experience biochemical recurrence (BCR). Of those, two-thirds happen within two years, implying a more aggressive disease and poorer prognosis. Current BCR risk stratification tools are bounded to biopsy- or to surgery-derived histopathological evaluation, having limited ability for early treatment decision-making. Magnetic resonance imaging (MRI) is acquired as part of the diagnostic procedure and imaging derived features have shown promise in tumour characterisation and BCR prediction. We investigated the value of imaging features extracted from preoperative biparametric MRI (bpMRI) combined with clinic-histopathological data to develop models to predict two-year post-prostatectomy BCR in three simulated clinical scenarios: pre-biopsy, pre- and postoperative. In a cohort of 20 BCR positive and 73 BCR negative RP-treated patients examined in the same institution, 33 clinico-histopathological variables were retrospectively collected, and 2715 radiomic features (based on intensity, shape and texture) were extracted from the whole-prostate volume imaged in original and filtered T2- and Diffusion-weighted MRI and ADC maps scans. A systematic machine-learning framework comprised of classification, stratified k-fold cross validation and statistical analyses was developed to identify the top performing BCR classifiers’ configurations within three clinical scenarios. LASSO and Priority-LASSO logistic regression algorithms were used for feature selection and model fitting, optimising the amount of correctly classified BCR positive cases through AUC and F-score maximisation (Fmax) derived from ROC curve analysis. We also investigated the impact of two image normalisation methods and SMOTE-based minority oversampling on model performance. Priority-LASSO logistic regression with four-block priority sequence Clinical, T2w, DWI, ADC, with block sparsity restriction pmax = (1,7,0,1) was selected as the best performing model configuration across all clinical scenarios, outperforming LASSO logistic regression models. During development and across the simulated clinical scenarios, top models achieved good median Fmax values (range: 0.702–0.754 and 0.910–0.925 for BCR positive and negative classes, respectively); yet, during validation with an independent set, the models obtained very low Fmax for the target BCR positive class (0.297–0.400), revealing model overfitting. We also observed instability in the selected features. However, models attained reasonably good F-score (0.779–0.833) and Precision (0.821–0.873) for BCR negative class during training and validation phases, making these models worth exploring. Pre-biopsy models had lower performances in training but suffered less from overfitting. Preoperative classifiers were overoptimistic, and postoperative models were the most successful in detecting BCR negative cases. T2w-MRI textured-based radiomic features may have potential to distinguish negative BCR patients together with baseline prostate-specific antigen (PSA) levels in a pre-biopsy scenario. The inclusion of pre- or postoperative variables did not substantially add value to BCR positive cases classification with bpMRI radiomic features. Highly powered studies with curated imaging data are needed to elucidate the role of bpMRI radiomic features as predictors of BCR

Optimization Algorithms for Deep Learning Based Medical Image Segmentations

Medical image segmentation is one of the fundamental processes to understand and assess the functionality of different organs and tissues as well as quantifying diseases and helping treatment planning. With ever increasing number of medical scans, the automated, accurate, and efficient medical image segmentation is as unmet need for improving healthcare. Recently, deep learning has emerged as one the most powerful methods for almost all image analysis tasks such as segmentation, detection, and classification and so in medical imaging. In this regard, this dissertation introduces new algorithms to perform medical image segmentation for different (a) imaging modalities, (b) number of objects, (c) dimensionality of images, and (d) under varying labeling conditions. First, we study dimensionality problem by introducing a new 2.5D segmentation engine that can be used in single and multi-object settings. We propose new fusion strategies and loss functions for deep neural networks to generate improved delineations. Later, we expand the proposed idea into 3D and 4D medical images and develop a budget (computational) friendly architecture search algorithm to make this process self-contained and fully automated without scarifying accuracy. Instead of manual architecture design, which is often based on plug-in and out and expert experience, the new algorithm provides an automated search of successful segmentation architecture within a short period of time. Finally, we study further optimization algorithms on label noise issue and improve overall segmentation problem by incorporating prior information about label noise and object shape information. We conclude the thesis work by studying different network and hyperparameter optimization settings that are fine-tuned for varying conditions for medical images. Applications are chosen from cardiac scans (images) and efficacy of the proposed algorithms are demonstrated on several data sets publicly available, and independently validated by blind evaluations

Tune your brown clustering, please

Brown clustering, an unsupervised hierarchical clustering technique based on ngram mutual information, has proven useful in many NLP applications. However, most uses of Brown clustering employ the same default configuration; the appropriateness of this configuration has gone predominantly unexplored. Accordingly, we present information for practitioners on the behaviour of Brown clustering in order to assist hyper-parametre tuning, in the form of a theoretical model of Brown clustering utility. This model is then evaluated empirically in two sequence labelling tasks over two text types. We explore the dynamic between the input corpus size, chosen number of classes, and quality of the resulting clusters, which has an impact for any approach using Brown clustering. In every scenario that we examine, our results reveal that the values most commonly used for the clustering are sub-optimal

Understanding the Tonada Cordobesa from an Acoustic, Perceptual and Sociolinguistic Perspective

The goal of this dissertation is to gain a better understanding of a non-standard form of pretonic vowel lengthening or the tonada cordobesa, in Cordobese Spanish, an understudied dialect in Argentina. This phenomenon is analyzed in two different but complementary studies and perspectives, each of which contributes to a better understanding of the sociolinguistic factors that constrain its variation, as well as the social meanings of this feature in Argentina. Study 1 investigates whether position in the intonational phrase (IP), vowel concordance, and social class and gender condition pretonic vowel lengthening from informal conversations with native speakers (n=20). The results reveal that both linguistic and social factors affect the pretonic to tonic vowel duration ratio. That is, prenuclear position, vowel concordance, and lower social class favor a higher ratio, the nonstandard form. Study 2 examines language attitudes, ideologies, and perceptions towards the tonada cordobesa using an online adaptation of a matched-guise test and a questionnaire on ideologies about Spanish in Argentina. The results show that judges (n=263) most accurately recognize the Cordobese speakers, followed by the Buenos Aires (BA) speakers. This points to the saliency of the tonada. In addition, the matched-guise uncovers some stigmatization of Cordobese Spanish as these guises received lower ratings on status and even on solidarity than those from Buenos Aires as found in de los Heros (1999). An analysis of manifestations of popular culture shows that the tonada is also used to portray local pride, or what Woolard (2008, 2009) calls authenticity. Furthermore, some judges hold contradictory ideologies with regards to the standard language in Argentina and BA Spanish was not always positively valued, as shown in other research (Llull & Pinardi, 2014; Rodríguez Louro, 2013). This provides insight in how BA Spanish and Cordobese Spanish are valued in Argentina

Attitudes towards Finnish-accented English

The thesis opens with a discussion of what attitudes are, and develops with a review of studies of attitudes towards pronunciation error, attitudes towards foreign accents and perception of foreign-accented speakers. The empirical part of the thesis attempts to identify how native (British) and Finnish listeners of English react to and evaluate typical segmental features of mispronunciation in the English speech of Finnish men and women of various ages. Two experiments using modifications of the matched-guise technique were conducted, one to consider error evaluation and to establish a hierarchy of segmental mispronunciation, the other to examine speaker evaluation, the image of the speaker created by the mispronunciation. Recordings of Finnish-accented English were presented to male and female listeners of various ages, and reactions collected. Statistical analyses of the results were carried out and the following general conclusions were drawn: the English labiodental lenis fricative /v/ when mispronounced in the typical Finnish manner as a labiodental frictionless continuant [u] is not tolerated by native English listeners at all, though it is highly tolerated by Finnish-speaking listeners (and Swedish-speaking Finns) themselves; the degree of mispronunciation in Finnish-accented English seriously affects listeners' estimations of the speaker's age, bad mispronunciation prompting under-estimation of age and good pronunciation over-estimation; both Finnish-speaking listeners and English-speaking listeners have almost identical clear pre-set standards about what constitutes `good' and `bad' pronunciation; a Finnish speaker's phonemically `better' and `worse' pronunciation affects the image listeners have of the speaker, status/competence traits in particular being up-graded for better pronunciation, solidarity/benevolence traits remaining broadly unaffected, and Englishspeaking listeners generally being more positive towards the Finnish-accented speakers than compatriot Finns

Sociophonetics and class differentiation: A study of working- and middle- class English in Cape Town's coloured community

Includes bibliographical references.This thesis provides a detailed acoustic description of the phonetic variation and changes evident in the monophthongal vowel system of Coloured South African English in Cape Town. The changes are largely a result of South Africa's post-apartheid socio-educational reform. A detailed acoustic description highlights the most salient changes (compared with earlier reports of the variety), indicating the extent of the change amongst working-class and middle-class speakers. The fieldwork conducted for this study consists of sociolinguistic interviews, conducted with a total of 40 Coloured speakers (half male, half female) from both working-class and middle-class backgrounds. All speakers were young adults, born between 1983 and 1993, thus raised and schooled in a period of transition from apartheid to democracy. Each of the middle-class speakers had some experience of attending formerly exclusively White schools, giving them significant contact with White peers and teachers, while the educational careers of the working-class speakers exposed them almost solely to Coloured peers and educators. The acoustic data were processed using methods of Forced Alignment and automatic formant extraction – methods applied for the first time to any variety of South African English. The results of the analysis were found generally to support the findings of scholars who have documented this variety previously, with some notable exceptions amongst middle-class speakers. The changes are attributable to socio-educational change in the post-apartheid setting and the directionality of the changes approximate trends amongst White South African English speakers. The TRAP, GOOSE and FOOT lexical sets show most change: TRAP is lowering, while GOOSE and FOOT are fronting. Although the changes approximate the vowel quality used by White speakers, middle-class Coloured speakers use an intermediate value between White speakers and working-class Coloured speakers i.e. they have not fully adopted White norms for any of the vowel classes. Working-class speakers were found to have maintained the monophthongal vowel system traditionally used by Coloured speakers