25 research outputs found
Computer-aided detection and diagnosis of breast cancer in 2D and 3D medical imaging through multifractal analysis
This Thesis describes the research work performed in the scope of a doctoral research program
and presents its conclusions and contributions. The research activities were carried on in the
industry with Siemens S.A. Healthcare Sector, in integration with a research team.
Siemens S.A. Healthcare Sector is one of the world biggest suppliers of products, services and
complete solutions in the medical sector. The company offers a wide selection of diagnostic
and therapeutic equipment and information systems. Siemens products for medical imaging and
in vivo diagnostics include: ultrasound, computer tomography, mammography, digital breast tomosynthesis,
magnetic resonance, equipment to angiography and coronary angiography, nuclear
imaging, and many others.
Siemens has a vast experience in Healthcare and at the beginning of this project it was strategically
interested in solutions to improve the detection of Breast Cancer, to increase its competitiveness
in the sector.
The company owns several patents related with self-similarity analysis, which formed the background
of this Thesis. Furthermore, Siemens intended to explore commercially the computer-
aided automatic detection and diagnosis eld for portfolio integration. Therefore, with the
high knowledge acquired by University of Beira Interior in this area together with this Thesis,
will allow Siemens to apply the most recent scienti c progress in the detection of the breast
cancer, and it is foreseeable that together we can develop a new technology with high potential.
The project resulted in the submission of two invention disclosures for evaluation in Siemens
A.G., two articles published in peer-reviewed journals indexed in ISI Science Citation Index,
two other articles submitted in peer-reviewed journals, and several international conference
papers. This work on computer-aided-diagnosis in breast led to innovative software and novel
processes of research and development, for which the project received the Siemens Innovation
Award in 2012.
It was very rewarding to carry on such technological and innovative project in a socially sensitive
area as Breast Cancer.No cancro da mama a deteção precoce e o diagnóstico correto são de extrema importância na
prescrição terapêutica e caz e e ciente, que potencie o aumento da taxa de sobrevivência à
doença. A teoria multifractal foi inicialmente introduzida no contexto da análise de sinal e a
sua utilidade foi demonstrada na descrição de comportamentos siológicos de bio-sinais e até
na deteção e predição de patologias. Nesta Tese, três métodos multifractais foram estendidos
para imagens bi-dimensionais (2D) e comparados na deteção de microcalci cações em mamogramas.
Um destes métodos foi também adaptado para a classi cação de massas da mama, em
cortes transversais 2D obtidos por ressonância magnética (RM) de mama, em grupos de massas
provavelmente benignas e com suspeição de malignidade. Um novo método de análise multifractal
usando a lacunaridade tri-dimensional (3D) foi proposto para classi cação de massas da
mama em imagens volumétricas 3D de RM de mama. A análise multifractal revelou diferenças
na complexidade subjacente às localizações das microcalci cações em relação aos tecidos normais,
permitindo uma boa exatidão da sua deteção em mamogramas. Adicionalmente, foram
extraídas por análise multifractal características dos tecidos que permitiram identi car os casos
tipicamente recomendados para biópsia em imagens 2D de RM de mama. A análise multifractal
3D foi e caz na classi cação de lesões mamárias benignas e malignas em imagens 3D de RM de
mama. Este método foi mais exato para esta classi cação do que o método 2D ou o método
padrão de análise de contraste cinético tumoral. Em conclusão, a análise multifractal fornece
informação útil para deteção auxiliada por computador em mamogra a e diagnóstico auxiliado
por computador em imagens 2D e 3D de RM de mama, tendo o potencial de complementar a
interpretação dos radiologistas
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When the machine does not know measuring uncertainty in deep learning models of medical images
This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonRecently, Deep learning (DL), which involves powerful black box predictors, has outperformed
human experts in several medical diagnostic problems. However, these methods focus
exclusively on improving the accuracy of point predictions without assessing their outputs’
quality and ignore the asymmetric cost involved in different types of misclassification errors.
Neural networks also do not deliver confidence in predictions and suffer from over and
under confidence, i.e. are not well calibrated. Knowing how much confidence there is in a
prediction is essential for gaining clinicians’ trust in the technology.
Calibrated uncertainty quantification is a challenging problem as no ground truth is
available. To address this, we make two observations: (i) cost-sensitive deep neural networks
with Dropweights models better quantify calibrated predictive uncertainty, and (ii) estimated
uncertainty with point predictions in Deep Ensembles Bayesian Neural Networks with
DropWeights can lead to a more informed decision and improve prediction quality.
This dissertation focuses on quantifying uncertainty using concepts from cost-sensitive
neural networks, calibration of confidence, and Dropweights ensemble method. First, we
show how to improve predictive uncertainty by deep ensembles of neural networks with Dropweights
learning an approximate distribution over its weights in medical image segmentation
and its application in active learning. Second, we use the Jackknife resampling technique
to correct bias in quantified uncertainty in image classification and propose metrics to measure
uncertainty performance. The third part of the thesis is motivated by the discrepancy
between the model predictive error and the objective in quantified uncertainty when costs for
misclassification errors or unbalanced datasets are asymmetric. We develop cost-sensitive
modifications of the neural networks in disease detection and propose metrics to measure the
quality of quantified uncertainty. Finally, we leverage an adaptive binning strategy to measure
uncertainty calibration error that directly corresponds to estimated uncertainty performance
and address problematic evaluation methods.
We evaluate the effectiveness of the tools on nuclei images segmentation, multi-class
Brain MRI image classification, multi-level cell type-specific protein expression prediction in
ImmunoHistoChemistry (IHC) images and cost-sensitive classification for Covid-19 detection
from X-Rays and CT image dataset. Our approach is thoroughly validated by measuring the
quality of uncertainty. It produces an equally good or better result and paves the way for the
future that addresses the practical problems at the intersection of deep learning and Bayesian
decision theory.
In conclusion, our study highlights the opportunities and challenges of the application of
estimated uncertainty in deep learning models of medical images, representing the confidence of the model’s prediction, and the uncertainty quality metrics show a significant improvement
when using Deep Ensembles Bayesian Neural Networks with DropWeights
Radiomic and Artificial Intelligence Analysis with Textural Metrics, Morphological and Dynamic Perfusion Features Extracted by Dynamic Contrast-Enhanced Magnetic Resonance Imaging in the Classification of Breast Lesions
The aim of the study was to estimate the diagnostic accuracy of textural, morpho- logical and dynamic features, extracted by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images, by carrying out univariate and multivariate statistical analyses including artificial intelligence approaches. Methods: In total, 85 patients with known breast lesion were enrolled in this retrospective study according to regulations issued by the local Institutional Review Board. All patients underwent DCE-MRI examination. The reference standard was pathology from a surgical specimen for malignant lesions and pathology from a surgical specimen or fine needle aspiration cytology, core or Tru-Cut needle biopsy for benign lesions. In total, 91 samples of 85 patients were ana- lyzed. Furthermore, 48 textural metrics, 15 morphological and 81 dynamic parameters were extracted by manually segmenting regions of interest. Statistical analyses including univariate and multivari- ate approaches were performed: non-parametric Wilcoxon–Mann–Whitney test; receiver operating characteristic (ROC), linear classifier (LDA), decision tree (DT), k-nearest neighbors (KNN), and support vector machine (SVM) were utilized. A balancing approach and feature selection methods were used. Results: The univariate analysis showed low accuracy and area under the curve (AUC) for all considered features. Instead, in the multivariate textural analysis, the best performance (accuracy (ACC) = 0.78; AUC = 0.78) was reached with all 48 metrics and an LDA trained with balanced data. The best performance (ACC = 0.75; AUC = 0.80) using morphological features was reached with an SVM trained with 10-fold cross-variation (CV) and balanced data (with adaptive synthetic (ADASYN) function) and a subset of five robust morphological features (circularity, rectangularity, sphericity, gleaning and surface). The best performance (ACC = 0.82; AUC = 0.83) using dynamic features was reached with a trained SVM and balanced data (with ADASYN function). Conclusion: Multivariate analyses using pattern recognition approaches, including all morphological, textural and dynamic features, optimized by adaptive synthetic sampling and feature selection operations obtained the best results and showed the best performance in the discrimination of benign and malignant lesions
Representation learning for breast cancer lesion detection
Breast Cancer (BC) is the second type of cancer with a higher incidence in women, it is responsible for the death of hundreds of thousands of women every year. However, when detected in the early stages of the disease, treatment methods have proven to be very effective in increasing life expectancy and, in many cases, patients fully recover. Several medical image modalities, such as MG – Mammography (X-Rays), US - Ultrasound, CT - Computer Tomography, MRI - Magnetic Resonance Imaging, and Tomosynthesis have been explored to support radiologists/physicians in clinical decision-making work- flows for the detection and diagnosis of BC. MG is the imaging modality more used at the worldwide level, however, recent research results have demonstrated that breast MRI is more sensitive than mam- mography to find pathological lesions, and it is not limited/affected by breast density issues. Therefore, it is currently a trend to introduce MRI-based breast assessment into clinical workflows (screening and diagnosis), but when compared to MG the workload of radiologists/physicians increases, MRI assess- ment is a more time-consuming task, and its effectiveness is affected not only by the variety of morpho- logical characteristics of each specific tumor phenotype and its origin but also by human fatigue. Com- puter-Aided Detection (CADe) methods have been widely explored primarily in mammography screen- ing tasks, but it remains an unsolved problem in breast MRI settings.
This work aims to explore and validate BC detection models using Machine (Deep) Learning algorithms. As the main contribution, we have developed and validated an innovative method that improves the “breast MRI preprocessing phase” to select the patient’s image slices and bounding boxes representing pathological lesions. With this, it is possible to build a more robust training dataset to feed the deep learning models, reducing the computation time and the dimension of the dataset, and more importantly, to identify with high accuracy the specific regions (bounding boxes) for each of the patient images, in which a possible pathological lesion (tumor) has been identified. In experimental settings using a fully annotated (released for public domain) dataset comprising a total of 922 MRI-based BC patient cases, we have achieved, as the most accurate trained model, an accuracy rate of 97.83%, and subsequently, applying a ten-fold cross-validation method, a mean accuracy on the trained models of 94.46% and an associated standard deviation of 2.43%.O cancro da mama (CdM) é o segundo tipo de cancro com maior incidência nas mulheres. É respon- sável pela morte de centenas de milhares de mulheres todos os anos. Contudo, quando detetado nas fases iniciais da doença, os métodos de tratamento provaram ser muito eficazes aumentando a espe- rança de vida e, em muitos casos, os pacientes recuperam totalmente. Têm sido exploradas várias modalidades de imagem médica, tais como MG - Mamografia (Raios-X), US - Ultra-som, CT - Tomo- grafia Computadorizada, MRI - Ressonância Magnética e Tomossíntese, para apoiar radiologistas nos fluxos de trabalho clínico para a deteção e diagnóstico do CdM. A MG é a modalidade de imagem mais utilizada a nível mundial, contudo, resultados de pesquisas recentes demonstraram que o MRI é mais sensível do que a mamografia para encontrar lesões patológicas e, também, não é limitada ou afetada por questões de densidade mamária. Consequentemente, atualmente é uma tendência introduzir a avaliação mamográfica baseada em MRI nos fluxos de trabalho clínico - rastreio e diagnóstico -, mas quando comparada com a MG, a carga de trabalho dos radiologistas aumenta. A avaliação por MRI é uma tarefa mais demorada, e a sua eficácia é afetada não só pela variedade de características morfo- lógicas e origem de cada fenótipo tumoral específico, mas, também pela fadiga humana. Os métodos de deteção assistida por computador (CADe) têm sido amplamente explorados principalmente em ta- refas de rastreio mamográfico, mas continua a ser um problema por resolver em ambientes de resso- nância magnética mamária.
Este trabalho visa explorar e validar modelos de deteção de CdM usando algoritmos de Machine (Deep) Learning. Como contributo principal, desenvolvemos e validámos um método inovador que me- lhora a "fase de pré-processamento das imagens de ressonância magnética mamária" para selecionar as fatias de imagem do paciente e as respetivas caixas de contorno que representam as lesões pato- lógicas. Com isto, é possível construir um conjunto de dados de treino mais robusto para alimentar os modelos de deep learning, reduzir o tempo de computação, reduzir a dimensão do conjunto de dados e, mais importante, para identificar com alta precisão as regiões específicas para cada uma das ima- gens do paciente nas quais foi identificada uma possível lesão patológica (tumor). Os resultados expe- rimentais, num conjunto de imagens de ressonância magnética de domínio público totalmente anotado com 922 casos de doentes com CdM, mostram no melhor modelo uma taxa de exatidão de 97.83%. Foi aplicado um método de validação cruzada de 10 folds do qual resultou uma exatidão média de 94,46% com um desvio padrão de 2,43% nos modelos treinados
Three-Dimensional Local Energy-Based Shape Histogram (3D-LESH): A Novel Feature Extraction Technique
In this paper, we present a novel feature extraction technique, termed Three-Dimensional Local Energy-Based Shape Histogram (3D-LESH), and exploit it to detect breast cancer in volumetric medical images. The technique is incorporated as part of an intelligent expert system that can aid medical practitioners making diagnostic decisions. Analysis of volumetric images, slice by slice, is cumbersome and inefficient. Hence, 3D-LESH is designed to compute a histogram-based feature set from a local energy map, calculated using a phase congruency (PC) measure of volumetric Magnetic Resonance Imaging (MRI) scans in 3D space. 3D-LESH features are invariant to contrast intensity variations within different slices of the MRI scan and are thus suitable for medical image analysis.The contribution of this article is manifold. First, we formulate a novel 3D-LESH feature extraction technique for 3D medical images to analyse volumetric images. Further, the proposed 3D-LESH algorithmis, for the first time, applied to medical MRI images. The final contribution is the design of an intelligent clinical decision support system (CDSS) as a multi-stage approach, combining novel 3D-LESH feature extraction with machine learning classifiers, to detect cancer from breast MRI scans. The proposed system applies contrast-limited adaptive histogram equalisation (CLAHE) to the MRI images before extracting 3D-LESH features. Furthermore, a selected subset of these features is fed into a machine-learning classifier, namely, a support vector machine (SVM), an extreme learning machine (ELM) or an echo state network (ESN) classifier, to detect abnormalities and distinguish between different stages of abnormality. We demonstrate the performance of the proposed technique by its application to benchmark breast cancer MRI images. The results indicate high-performance accuracy of the proposed system (98%±0.0050, with an area under a receiver operating charactertistic curve value of 0.9900 ± 0.0050) with multiple classifiers. When compared with the state-of-the-art wavelet-based feature extraction technique, statistical analysis provides conclusive evidence of the significance of our proposed 3D-LESH algorithm
Breast cancer detection using deep convolutional neural networks and support vector machines
It is important to detect breast cancer as early as possible. In this manuscript, a new methodology for classifying breast cancer using deep learning and some segmentation techniques are introduced. A new computer aided detection (CAD) system is proposed for classifying benign and malignant mass tumors in breast mammography images. In this CAD system, two segmentation approaches are used. The first approach involves determining the region of interest (ROI) manually, while the second approach uses the technique of threshold and region based. The deep convolutional neural network (DCNN) is used for feature extraction. A well-known DCNN architecture named AlexNet is used and is fine-tuned to classify two classes instead of 1,000 classes. The last fully connected (fc) layer is connected to the support vector machine (SVM) classifier to obtain better accuracy. The results are obtained using the following publicly available datasets (1) the digital database for screening mammography (DDSM); and (2) the Curated Breast Imaging Subset of DDSM (CBIS-DDSM). Training on a large number of data gives high accuracy rate. Nevertheless, the biomedical datasets contain a relatively small number of samples due to limited patient volume. Accordingly, data augmentation is a method for increasing the size of the input data by generating new data from the original input data. There are many forms for the data augmentation; the one used here is the rotation. The accuracy of the new-trained DCNN architecture is 71.01% when cropping the ROI manually from the mammogram. The highest area under the curve (AUC) achieved was 0.88 (88%) for the samples obtained from both segmentation techniques. Moreover, when using the samples obtained from the CBIS-DDSM, the accuracy of the DCNN is increased to 73.6%. Consequently, the SVM accuracy becomes 87.2% with an AUC equaling to 0.94 (94%). This is the highest AUC value compared to previous work using the same conditions
Exploring variability in medical imaging
Although recent successes of deep learning and novel machine learning techniques improved the perfor-
mance of classification and (anomaly) detection in computer vision problems, the application of these
methods in medical imaging pipeline remains a very challenging task. One of the main reasons for this
is the amount of variability that is encountered and encapsulated in human anatomy and subsequently
reflected in medical images. This fundamental factor impacts most stages in modern medical imaging
processing pipelines.
Variability of human anatomy makes it virtually impossible to build large datasets for each disease
with labels and annotation for fully supervised machine learning. An efficient way to cope with this is
to try and learn only from normal samples. Such data is much easier to collect. A case study of such
an automatic anomaly detection system based on normative learning is presented in this work. We
present a framework for detecting fetal cardiac anomalies during ultrasound screening using generative
models, which are trained only utilising normal/healthy subjects.
However, despite the significant improvement in automatic abnormality detection systems, clinical
routine continues to rely exclusively on the contribution of overburdened medical experts to diagnosis
and localise abnormalities. Integrating human expert knowledge into the medical imaging processing
pipeline entails uncertainty which is mainly correlated with inter-observer variability. From the per-
spective of building an automated medical imaging system, it is still an open issue, to what extent
this kind of variability and the resulting uncertainty are introduced during the training of a model
and how it affects the final performance of the task. Consequently, it is very important to explore the
effect of inter-observer variability both, on the reliable estimation of model’s uncertainty, as well as
on the model’s performance in a specific machine learning task. A thorough investigation of this issue
is presented in this work by leveraging automated estimates for machine learning model uncertainty,
inter-observer variability and segmentation task performance in lung CT scan images.
Finally, a presentation of an overview of the existing anomaly detection methods in medical imaging
was attempted. This state-of-the-art survey includes both conventional pattern recognition methods
and deep learning based methods. It is one of the first literature surveys attempted in the specific
research area.Open Acces
Cancer Outcome Prediction with Multiform Medical Data using Deep Learning
This thesis illustrated the work done for my PhD project, which aims to develop personalised cancer outcome prediction models using various types of medical data. A predictive modelling workflow that can analyse data with different forms and generate comprehensive outcome prediction was designed and implemented on a variety of datasets. The model development was accompanied by applying deep learning techniques for multivariate survival analysis, medical image analysis and sequential data processing.
The modelling workflow was applied to three different tasks:
1. Deep learning models were developed for estimating the progression probability of patients with colorectal cancer after resection and after different lines of chemotherapy, which got significantly better predictive performance than the Cox regression models. Besides, CT-based models were developed for predicting the tumour local response after chemotherapy of patients with lung metastasis, which got an AUC of 0. 769 on disease progression detection and 0.794 on treatment response classification.
2. Deep learning models were developed for predicting the survival state of patients with non-small cell lung cancer after radiotherapy using CT scans, dose distribution and disease and treatment variables. The eventual model obtained by ensemble voting got an AUC of 0.678, which is significantly higher than the score achieved by the radiomics model (0.633).
3. Deep-learning-aided approaches were used for estimating the progression risk for patients with solitary fibrous tumours using digital pathology slides. The deep learning architecture was able to optimise the WHO risk assessment model using automatically identified levels of mitotic activity. Compared to manual counting given by pathologists, deep-learning-aided mitosis counting can re-grade the patients whose risks were underestimated.
The applications proved that the predictive models based on hybrid neural networks were able to analyse multiform medical data for generating data-based cancer outcome prediction. The results can be used for realising personalised treatment planning, evaluating treatment quality, and aiding clinical decision-making