Caracterización de Patrones Anormales en Mamografías

Abstract. Computer-guided image interpretation is an extensive research area whose main purpose is to provide tools to support decision-making, for which a large number of automatic techniques have been proposed, such as, feature extraction, pattern recognition, image processing, machine learning, among others. In breast cancer, the results obtained at this area, they have led to the development of diagnostic support systems, which have even been approved by the FDA (Federal Drug Administration). However, the use of those systems is not widely extended in clinic scenarios, mainly because their performance is unstable and poorly reproducible. This is due to the high variability of the abnormal patterns associated with this neoplasia. This thesis addresses the main problem associated with the characterization and interpretation of breast masses and architectural distortion, mammographic findings directly related to the presence of breast cancer with higher variability in their form, size and location. This document introduces the design, implementation and evaluation of strategies to characterize abnormal patterns and to improve the mammographic interpretation during the diagnosis process. The herein proposed strategies allow to characterize visual patterns of these lesions and the relationship between them to infer their clinical significance according to BI-RADS (Breast Imaging Reporting and Data System), a radiologic tool used for mammographic evaluation and reporting. The obtained results outperform some obtained by methods reported in the literature both tasks classification and interpretation of masses and architectural distortion, respectively, demonstrating the effectiveness and versatility of the proposed strategies.Resumen. La interpretación de imágenes guiada por computador es una área extensa de investigación cuyo objetivo principal es proporcionar herramientas para el soporte a la toma de decisiones, para lo cual se han usado un gran número de técnicas de extracción de características, reconocimiento de patrones, procesamiento de imágenes, aprendizaje de máquina, entre otras. En el cáncer de mama, los resultados obtenidos en esta área han dado lugar al desarrollo de sistemas de apoyo al diagnóstico que han sido incluso aprobados por la FDA (Federal Drug Administration). Sin embargo, el uso de estos sistemas no es ampliamente extendido, debido principalmente, a que su desempeño resulta inestable y poco reproducible frente a la alta variabilidad de los patrones anormales asociados a esta neoplasia. Esta tesis trata el principal problema asociado a la caracterización y análisis de masas y distorsión de la arquitectura debido a que son hallazgos directamente relacionados con la presencia de cáncer y que usualmente presentan mayor variabilidad en su forma, tamaño y localización, lo que altera los resultados diagnósticos. Este documento introduce el diseño, implementación y evaluación de un conjunto de estrategias para caracterizar patrones anormales relacionados con este tipo de hallazgos para mejorar la interpretación y soportar el diagnóstico mediante la imagen mamaria. Los modelos aquí propuestos permiten caracterizar patrones visuales y la relación entre estos para inferir su significado clínico según el estándar BI-RADS (Breast Imaging Reporting and Data System) usado para la evaluación y reporte mamográfico. Los resultados obtenidos han demostrado mejorar a los resultados obtenidos por los métodos reportados en la literatura en tareas como clasificación e interpretación de masas y distorsión arquitectural, demostrando la efectividad y versatilidad de las estrategia propuestas.Doctorad

Developing and Applying CAD-generated Image Markers to Assist Disease Diagnosis and Prognosis Prediction

Developing computer-aided detection and/or diagnosis (CAD) schemes has been an active research topic in medical imaging informatics (MII) with promising results in assisting clinicians in making better diagnostic and/or clinical decisions in the last two decades. To build robust CAD schemes, we need to develop state-of-the-art image processing and machine learning (ML) algorithms to optimize each step in the CAD pipeline, including detection and segmentation of the region of interest, optimal feature generation, followed by integration to ML classifiers. In my dissertation, I conducted multiple studies investigating the feasibility of developing several novel CAD schemes in the field of medicine concerning different purposes. The first study aims to investigate how to optimally develop a CAD scheme of contrast-enhanced digital mammography (CEDM) images to classify breast masses. CEDM includes both low energy (LE) and dual-energy subtracted (DES) images. A CAD scheme was applied to segment mass regions depicting LE and DES images separately. Optimal segmentation results generated from DES images were also mapped to LE images or vice versa. After computing image features, multilayer perceptron-based ML classifiers integrated with a correlation-based feature subset evaluator and leave-one-case-out cross-validation method were built to classify mass regions. The study demonstrated that DES images eliminated the overlapping effect of dense breast tissue, which helps improve mass segmentation accuracy. By mapping mass regions segmented from DES images to LE images, CAD yields significantly improved performance. The second study aims to develop a new quantitative image marker computed from the pre-intervention computed tomography perfusion (CTP) images and evaluate its feasibility to predict clinical outcome among acute ischemic stroke (AIS) patients undergoing endovascular mechanical thrombectomy after diagnosis of large vessel occlusion. A CAD scheme is first developed to pre-process CTP images of different scanning series for each study case, perform image segmentation, quantify contrast-enhanced blood volumes in bilateral cerebral hemispheres, and compute image features related to asymmetrical cerebral blood flow patterns based on the cumulative cerebral blood flow curves of two hemispheres. Next, image markers based on a single optimal feature and ML models fused with multi-features are developed and tested to classify AIS cases into two classes of good and poor prognosis based on the Modified Rankin Scale. The study results show that ML model trained using multiple features yields significantly higher classification performance than the image marker using the best single feature (p<0.01). This study demonstrates the feasibility of developing a new CAD scheme to predict the prognosis of AIS patients in the hyperacute stage, which has the potential to assist clinicians in optimally treating and managing AIS patients. The third study aims to develop and test a new CAD scheme to predict prognosis in aneurysmal subarachnoid hemorrhage (aSAH) patients using brain CT images. Each patient had two sets of CT images acquired at admission and prior to discharge. CAD scheme was applied to segment intracranial brain regions into four subregions, namely, cerebrospinal fluid (CSF), white matter (WM), gray matter (GM), and extraparenchymal blood (EPB), respectively. CAD then computed nine image features related to 5 volumes of the segmented sulci, EPB, CSF, WM, GM, and four volumetrical ratios to sulci. Subsequently, 16 ML models were built using multiple features computed either from CT images acquired at admission or prior to discharge to predict eight prognosis related parameters. The results show that ML models trained using CT images acquired at admission yielded higher accuracy to predict short-term clinical outcomes, while ML models trained using CT images acquired prior to discharge had higher accuracy in predicting long-term clinical outcomes. Thus, this study demonstrated the feasibility of predicting the prognosis of aSAH patients using new ML model-generated quantitative image markers. The fourth study aims to develop and test a new interactive computer-aided detection (ICAD) tool to quantitatively assess hemorrhage volumes. After loading each case, the ICAD tool first segments intracranial brain volume, performs CT labeling of each voxel. Next, contour-guided image-thresholding techniques based on CT Hounsfield Unit are used to estimate and segment hemorrhage-associated voxels (ICH). Next, two experienced neurology residents examine and correct the markings of ICH categorized into either intraparenchymal hemorrhage (IPH) or intraventricular hemorrhage (IVH) to obtain the true markings. Additionally, volumes and maximum two-dimensional diameter of each sub-type of hemorrhage are also computed for understanding ICH prognosis. The performance to segment hemorrhage regions between semi-automated ICAD and the verified neurology residents’ true markings is evaluated using dice similarity coefficient (DSC). The data analysis results in the study demonstrate that the new ICAD tool enables to segment and quantify ICH and other hemorrhage volumes with higher DSC. Finally, the fifth study aims to bridge the gap between traditional radiomics and deep learning systems by comparing and assessing these two technologies in classifying breast lesions. First, one CAD scheme is applied to segment lesions and compute radiomics features. In contrast, another scheme applies a pre-trained residual net architecture (ResNet50) as a transfer learning model to extract automated features. Next, the principal component algorithm processes both initially computed radiomics and automated features to create optimal feature vectors. Then, several support vector machine (SVM) classifiers are built using the optimized radiomics or automated features. This study indicates that (1) CAD built using only deep transfer learning yields higher classification performance than the traditional radiomic-based model, (2) SVM trained using the fused radiomics and automated features does not yield significantly higher AUC, and (3) radiomics and automated features contain highly correlated information in lesion classification. In summary, in all these studies, I developed and investigated several key concepts of CAD pipeline, including (i) pre-processing algorithms, (ii) automatic detection and segmentation schemes, (iii) feature extraction and optimization methods, and (iv) ML and data analysis models. All developed CAD models are embedded with interactive and visually aided graphical user interfaces (GUIs) to provide user functionality. These techniques present innovative approaches for building quantitative image markers to build optimal ML models. The study results indicate the underlying CAD scheme's potential application to assist radiologists in clinical settings for their assessments in diagnosing disease and improving their overall performance

A graph-based approach for the retrieval of multi-modality medical images

Medical imaging has revolutionised modern medicine and is now an integral aspect of diagnosis and patient monitoring. The development of new imaging devices for a wide variety of clinical cases has spurred an increase in the data volume acquired in hospitals. These large data collections offer opportunities for search-based applications in evidence-based diagnosis, education, and biomedical research. However, conventional search methods that operate upon manual annotations are not feasible for this data volume. Content-based image retrieval (CBIR) is an image search technique that uses automatically derived visual features as search criteria and has demonstrable clinical benefits. However, very few studies have investigated the CBIR of multi-modality medical images, which are making a monumental impact in healthcare, e.g., combined positron emission tomography and computed tomography (PET-CT) for cancer diagnosis. In this thesis, we propose a new graph-based method for the CBIR of multi-modality medical images. We derive a graph representation that emphasises the spatial relationships between modalities by structurally constraining the graph based on image features, e.g., spatial proximity of tumours and organs. We also introduce a graph similarity calculation algorithm that prioritises the relationships between tumours and related organs. To enable effective human interpretation of retrieved multi-modality images, we also present a user interface that displays graph abstractions alongside complex multi-modality images. Our results demonstrated that our method achieved a high precision when retrieving images on the basis of tumour location within organs. The evaluation of our proposed UI design by user surveys revealed that it improved the ability of users to interpret and understand the similarity between retrieved PET-CT images. The work in this thesis advances the state-of-the-art by enabling a novel approach for the retrieval of multi-modality medical images

A robust framework for medical image segmentation through adaptable class-specific representation

Medical image segmentation is an increasingly important component in virtual pathology, diagnostic imaging and computer-assisted surgery. Better hardware for image acquisition and a variety of advanced visualisation methods have paved the way for the development of computer based tools for medical image analysis and interpretation. The routine use of medical imaging scans of multiple modalities has been growing over the last decades and data sets such as the Visible Human Project have introduced a new modality in the form of colour cryo section data. These developments have given rise to an increasing need for better automatic and semiautomatic segmentation methods. The work presented in this thesis concerns the development of a new framework for robust semi-automatic segmentation of medical imaging data of multiple modalities. Following the specification of a set of conceptual and technical requirements, the framework known as ACSR (Adaptable Class-Specific Representation) is developed in the first case for 2D colour cryo section segmentation. This is achieved through the development of a novel algorithm for adaptable class-specific sampling of point neighbourhoods, known as the PGA (Path Growing Algorithm), combined with Learning Vector Quantization. The framework is extended to accommodate 3D volume segmentation of cryo section data and subsequently segmentation of single and multi-channel greyscale MRl data. For the latter the issues of inhomogeneity and noise are specifically addressed. Evaluation is based on comparison with previously published results on standard simulated and real data sets, using visual presentation, ground truth comparison and human observer experiments. ACSR provides the user with a simple and intuitive visual initialisation process followed by a fully automatic segmentation. Results on both cryo section and MRI data compare favourably to existing methods, demonstrating robustness both to common artefacts and multiple user initialisations. Further developments into specific clinical applications are discussed in the future work section

Novel Approaches to the Representation and Analysis of 3D Segmented Anatomical Districts

Nowadays, image processing and 3D shape analysis are an integral part of clinical practice and have the potentiality to support clinicians with advanced analysis and visualization techniques. Both approaches provide visual and quantitative information to medical practitioners, even if from different points of view. Indeed, shape analysis is aimed at studying the morphology of anatomical structures, while image processing is focused more on the tissue or functional information provided by the pixels/voxels intensities levels. Despite the progress obtained by research in both fields, a junction between these two complementary worlds is missing. When working with 3D models analyzing shape features, the information of the volume surrounding the structure is lost, since a segmentation process is needed to obtain the 3D shape model; however, the 3D nature of the anatomical structure is represented explicitly. With volume images, instead, the tissue information related to the imaged volume is the core of the analysis, while the shape and morphology of the structure are just implicitly represented, thus not clear enough. The aim of this Thesis work is the integration of these two approaches in order to increase the amount of information available for physicians, allowing a more accurate analysis of each patient. An augmented visualization tool able to provide information on both the anatomical structure shape and the surrounding volume through a hybrid representation, could reduce the gap between the two approaches and provide a more complete anatomical rendering of the subject. To this end, given a segmented anatomical district, we propose a novel mapping of volumetric data onto the segmented surface. The grey-levels of the image voxels are mapped through a volume-surface correspondence map, which defines a grey-level texture on the segmented surface. The resulting texture mapping is coherent to the local morphology of the segmented anatomical structure and provides an enhanced visual representation of the anatomical district. The integration of volume-based and surface-based information in a unique 3D representation also supports the identification and characterization of morphological landmarks and pathology evaluations. The main research contributions of the Ph.D. activities and Thesis are: \u2022 the development of a novel integration algorithm that combines surface-based (segmented 3D anatomical structure meshes) and volume-based (MRI volumes) information. The integration supports different criteria for the grey-levels mapping onto the segmented surface; \u2022 the development of methodological approaches for using the grey-levels mapping together with morphological analysis. The final goal is to solve problems in real clinical tasks, such as the identification of (patient-specific) ligament insertion sites on bones from segmented MR images, the characterization of the local morphology of bones/tissues, the early diagnosis, classification, and monitoring of muscle-skeletal pathologies; \u2022 the analysis of segmentation procedures, with a focus on the tissue classification process, in order to reduce operator dependency and to overcome the absence of a real gold standard for the evaluation of automatic segmentations; \u2022 the evaluation and comparison of (unsupervised) segmentation methods, finalized to define a novel segmentation method for low-field MR images, and for the local correction/improvement of a given segmentation. The proposed method is simple but effectively integrates information derived from medical image analysis and 3D shape analysis. Moreover, the algorithm is general enough to be applied to different anatomical districts independently of the segmentation method, imaging techniques (such as CT), or image resolution. The volume information can be integrated easily in different shape analysis applications, taking into consideration not only the morphology of the input shape but also the real context in which it is inserted, to solve clinical tasks. The results obtained by this combined analysis have been evaluated through statistical analysis

Analysis of textural image features for content based retrieval

Digital archaelogy and virtual reality with archaeological artefacts have been quite hot research topics in the last years 55,56 . This thesis is a preperation study to build the background knowledge required for the research projects, which aim to computerize the reconstruction of the archaelogical data like pots, marbles or mosaic pieces by shape and ex ural features. Digitalization of the cultural heritage may shorten the reconstruction time which takes tens of years currently 61 ; it will improve the reconstruction robustness by incorporating with the literally available machine vision algorithms and experiences from remote experts working on a no-cost virtual object together. Digitalization can also ease the exhibition of the results for regular people, by multiuser media applications like internet based virtual museums or virtual tours. And finally, it will make possible to archive values with their original texture and shapes for long years far away from the physical risks that the artefacts currently face. On the literature 1,2,3,5,8,11,14,15,16 , texture analysis techniques have been throughly studied and implemented for the purpose of defect analysis purposes by image processing and machine vision scientists. In the last years, these algorithms have been started to be used for similarity analysis of content based image retrieval 1,4,10 . For retrieval systems, the concurrent problems seem to be building efficient and fast systems, therefore, robust image features haven't been focused enough yet. This document is the first performance review of the texture algorithms developed for retrieval and defect analysis together. The results and experiences gained during the thesis study will be used to support the studies aiming to solve the 2D puzzle problem using textural continuity methods on archaelogical artifects, Appendix A for more detail. The first chapter is devoted to learn how the medicine and psychology try to explain the solutions of similiarity and continuity analysis, which our biological model, the human vision, accomplishes daily. In the second chapter, content based image retrieval systems, their performance criterias, similiarity distance metrics and the systems available have been summarized. For the thesis work, a rich texture database has been built, including over 1000 images in total. For the ease of the users, a GUI and a platform that is used for content based retrieval has been designed; The first version of a content based search engine has been coded which takes the source of the internet pages, parses the metatags of images and downloads the files in a loop controlled by our texture algorithms. The preprocessing algorithms and the pattern analysis algorithms required for the robustness of the textural feature processing have been implemented. In the last section, the most important textural feature extraction methods have been studied in detail with the performance results of the codes written in Matlab and run on different databases developed