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

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

Unsupervised learning for vascular heterogeneity assessment of glioblastoma based on magnetic resonance imaging: The Hemodynamic Tissue Signature

[ES] El futuro de la imagen médica está ligado a la inteligencia artificial. El análisis manual de imágenes médicas es hoy en día una tarea ardua, propensa a errores y a menudo inasequible para los humanos, que ha llamado la atención de la comunidad de Aprendizaje Automático (AA). La Imagen por Resonancia Magnética (IRM) nos proporciona una rica variedad de representaciones de la morfología y el comportamiento de lesiones inaccesibles sin una intervención invasiva arriesgada. Sin embargo, explotar la potente pero a menudo latente información contenida en la IRM es una tarea muy complicada, que requiere técnicas de análisis computacional inteligente. Los tumores del sistema nervioso central son una de las enfermedades más críticas estudiadas a través de IRM. Específicamente, el glioblastoma representa un gran desafío, ya que, hasta la fecha, continua siendo un cáncer letal que carece de una terapia satisfactoria. Del conjunto de características que hacen del glioblastoma un tumor tan agresivo, un aspecto particular que ha sido ampliamente estudiado es su heterogeneidad vascular. La fuerte proliferación vascular del glioblastoma, así como su robusta angiogénesis han sido consideradas responsables de la alta letalidad de esta neoplasia. Esta tesis se centra en la investigación y desarrollo del método Hemodynamic Tissue Signature (HTS): un método de AA no supervisado para describir la heterogeneidad vascular de los glioblastomas mediante el análisis de perfusión por IRM. El método HTS se basa en el concepto de hábitat, que se define como una subregión de la lesión con un perfil de IRM que describe un comportamiento fisiológico concreto. El método HTS delinea cuatro hábitats en el glioblastoma: el hábitat HAT, como la región más perfundida del tumor con captación de contraste; el hábitat LAT, como la región del tumor con un perfil angiogénico más bajo; el hábitat IPE, como la región adyacente al tumor con índices de perfusión elevados; y el hábitat VPE, como el edema restante de la lesión con el perfil de perfusión más bajo. La investigación y desarrollo de este método ha originado una serie de contribuciones enmarcadas en esta tesis. Primero, para verificar la fiabilidad de los métodos de AA no supervisados en la extracción de patrones de IRM, se realizó una comparativa para la tarea de segmentación de gliomas de grado alto. Segundo, se propuso un algoritmo de AA no supervisado dentro de la familia de los Spatially Varying Finite Mixture Models. El algoritmo propone una densidad a priori basada en un Markov Random Field combinado con la función probabilística Non-Local Means, para codificar la idea de que píxeles vecinos tienden a pertenecer al mismo objeto. Tercero, se presenta el método HTS para describir la heterogeneidad vascular del glioblastoma. El método se ha aplicado a casos reales en una cohorte local de un solo centro y en una cohorte internacional de más de 180 pacientes de 7 centros europeos. Se llevó a cabo una evaluación exhaustiva del método para medir el potencial pronóstico de los hábitats HTS. Finalmente, la tecnología desarrollada en la tesis se ha integrado en la plataforma online ONCOhabitats (https://www.oncohabitats.upv.es). La plataforma ofrece dos servicios: 1) segmentación de tejidos de glioblastoma, y 2) evaluación de la heterogeneidad vascular del tumor mediante el método HTS. Los resultados de esta tesis han sido publicados en diez contribuciones científicas, incluyendo revistas y conferencias de alto impacto en las áreas de Informática Médica, Estadística y Probabilidad, Radiología y Medicina Nuclear y Aprendizaje Automático. También se emitió una patente industrial registrada en España, Europa y EEUU. Finalmente, las ideas originales concebidas en esta tesis dieron lugar a la creación de ONCOANALYTICS CDX, una empresa enmarcada en el modelo de negocio de los companion diagnostics de compuestos farmacéuticos.[EN] The future of medical imaging is linked to Artificial Intelligence (AI). The manual analysis of medical images is nowadays an arduous, error-prone and often unaffordable task for humans, which has caught the attention of the Machine Learning (ML) community. Magnetic Resonance Imaging (MRI) provides us with a wide variety of rich representations of the morphology and behavior of lesions completely inaccessible without a risky invasive intervention. Nevertheless, harnessing the powerful but often latent information contained in MRI acquisitions is a very complicated task, which requires computational intelligent analysis techniques. Central nervous system tumors are one of the most critical diseases studied through MRI. Specifically, glioblastoma represents a major challenge, as it remains a lethal cancer that, to date, lacks a satisfactory therapy. Of the entire set of characteristics that make glioblastoma so aggressive, a particular aspect that has been widely studied is its vascular heterogeneity. The strong vascular proliferation of glioblastomas, as well as their robust angiogenesis and extensive microvasculature heterogeneity have been claimed responsible for the high lethality of the neoplasm. This thesis focuses on the research and development of the Hemodynamic Tissue Signature (HTS) method: an unsupervised ML approach to describe the vascular heterogeneity of glioblastomas by means of perfusion MRI analysis. The HTS builds on the concept of habitats. A habitat is defined as a sub-region of the lesion with a particular MRI profile describing a specific physiological behavior. The HTS method delineates four habitats within the glioblastoma: the HAT habitat, as the most perfused region of the enhancing tumor; the LAT habitat, as the region of the enhancing tumor with a lower angiogenic profile; the potentially IPE habitat, as the non-enhancing region adjacent to the tumor with elevated perfusion indexes; and the VPE habitat, as the remaining edema of the lesion with the lowest perfusion profile. The research and development of the HTS method has generated a number of contributions to this thesis. First, in order to verify that unsupervised learning methods are reliable to extract MRI patterns to describe the heterogeneity of a lesion, a comparison among several unsupervised learning methods was conducted for the task of high grade glioma segmentation. Second, a Bayesian unsupervised learning algorithm from the family of Spatially Varying Finite Mixture Models is proposed. The algorithm integrates a Markov Random Field prior density weighted by the probabilistic Non-Local Means function, to codify the idea that neighboring pixels tend to belong to the same semantic object. Third, the HTS method to describe the vascular heterogeneity of glioblastomas is presented. The HTS method has been applied to real cases, both in a local single-center cohort of patients, and in an international retrospective cohort of more than 180 patients from 7 European centers. A comprehensive evaluation of the method was conducted to measure the prognostic potential of the HTS habitats. Finally, the technology developed in this thesis has been integrated into an online open-access platform for its academic use. The ONCOhabitats platform is hosted at https://www.oncohabitats.upv.es, and provides two main services: 1) glioblastoma tissue segmentation, and 2) vascular heterogeneity assessment of glioblastomas by means of the HTS method. The results of this thesis have been published in ten scientific contributions, including top-ranked journals and conferences in the areas of Medical Informatics, Statistics and Probability, Radiology & Nuclear Medicine and Machine Learning. An industrial patent registered in Spain, Europe and EEUU was also issued. Finally, the original ideas conceived in this thesis led to the foundation of ONCOANALYTICS CDX, a company framed into the business model of companion diagnostics for pharmaceutical compounds.[CA] El futur de la imatge mèdica està lligat a la intel·ligència artificial. L'anàlisi manual d'imatges mèdiques és hui dia una tasca àrdua, propensa a errors i sovint inassequible per als humans, que ha cridat l'atenció de la comunitat d'Aprenentatge Automàtic (AA). La Imatge per Ressonància Magnètica (IRM) ens proporciona una àmplia varietat de representacions de la morfologia i el comportament de lesions inaccessibles sense una intervenció invasiva arriscada. Tanmateix, explotar la potent però sovint latent informació continguda a les adquisicions de IRM esdevé una tasca molt complicada, que requereix tècniques d'anàlisi computacional intel·ligent. Els tumors del sistema nerviós central són una de les malalties més crítiques estudiades a través de IRM. Específicament, el glioblastoma representa un gran repte, ja que, fins hui, continua siguent un càncer letal que manca d'una teràpia satisfactòria. Del conjunt de característiques que fan del glioblastoma un tumor tan agressiu, un aspecte particular que ha sigut àmpliament estudiat és la seua heterogeneïtat vascular. La forta proliferació vascular dels glioblastomes, així com la seua robusta angiogènesi han sigut considerades responsables de l'alta letalitat d'aquesta neoplàsia. Aquesta tesi es centra en la recerca i desenvolupament del mètode Hemodynamic Tissue Signature (HTS): un mètode d'AA no supervisat per descriure l'heterogeneïtat vascular dels glioblastomas mitjançant l'anàlisi de perfusió per IRM. El mètode HTS es basa en el concepte d'hàbitat, que es defineix com una subregió de la lesió amb un perfil particular d'IRM, que descriu un comportament fisiològic concret. El mètode HTS delinea quatre hàbitats dins del glioblastoma: l'hàbitat HAT, com la regió més perfosa del tumor amb captació de contrast; l'hàbitat LAT, com la regió del tumor amb un perfil angiogènic més baix; l'hàbitat IPE, com la regió adjacent al tumor amb índexs de perfusió elevats, i l'hàbitat VPE, com l'edema restant de la lesió amb el perfil de perfusió més baix. La recerca i desenvolupament del mètode HTS ha originat una sèrie de contribucions emmarcades a aquesta tesi. Primer, per verificar la fiabilitat dels mètodes d'AA no supervisats en l'extracció de patrons d'IRM, es va realitzar una comparativa en la tasca de segmentació de gliomes de grau alt. Segon, s'ha proposat un algorisme d'AA no supervisat dintre de la família dels Spatially Varying Finite Mixture Models. L'algorisme proposa un densitat a priori basada en un Markov Random Field combinat amb la funció probabilística Non-Local Means, per a codificar la idea que els píxels veïns tendeixen a pertànyer al mateix objecte semàntic. Tercer, es presenta el mètode HTS per descriure l'heterogeneïtat vascular dels glioblastomas. El mètode HTS s'ha aplicat a casos reals en una cohort local d'un sol centre i en una cohort internacional de més de 180 pacients de 7 centres europeus. Es va dur a terme una avaluació exhaustiva del mètode per mesurar el potencial pronòstic dels hàbitats HTS. Finalment, la tecnologia desenvolupada en aquesta tesi s'ha integrat en una plataforma online ONCOhabitats (https://www.oncohabitats.upv.es). La plataforma ofereix dos serveis: 1) segmentació dels teixits del glioblastoma, i 2) avaluació de l'heterogeneïtat vascular dels glioblastomes mitjançant el mètode HTS. Els resultats d'aquesta tesi han sigut publicats en deu contribucions científiques, incloent revistes i conferències de primer nivell a les àrees d'Informàtica Mèdica, Estadística i Probabilitat, Radiologia i Medicina Nuclear i Aprenentatge Automàtic. També es va emetre una patent industrial registrada a Espanya, Europa i els EEUU. Finalment, les idees originals concebudes en aquesta tesi van donar lloc a la creació d'ONCOANALYTICS CDX, una empresa emmarcada en el model de negoci dels companion diagnostics de compostos farmacèutics.En este sentido quiero agradecer a las diferentes instituciones y estructuras de financiación de investigación que han contribuido al desarrollo de esta tesis. En especial quiero agradecer a la Universitat Politècnica de València, donde he desarrollado toda mi carrera acadèmica y científica, así como al Ministerio de Ciencia e Innovación, al Ministerio de Economía y Competitividad, a la Comisión Europea, al EIT Health Programme y a la fundación Caixa ImpulseJuan Albarracín, J. (2020). Unsupervised learning for vascular heterogeneity assessment of glioblastoma based on magnetic resonance imaging: The Hemodynamic Tissue Signature [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/149560TESI

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

A patch-based approach for the segmentation of pathologies: Application to glioma labelling

International audienceIn this paper, we describe a novel and generic approach to address fully-automatic segmentation of brain tumors by using multi-atlas patch-based voting techniques. In addition to avoiding the local search window assumption, the conventional patch-based framework is enhanced through several simple procedures: an improvement of the training dataset in terms of both label purity and intensity statistics, augmented features to implicitly guide the nearest-neighbor-search, multi-scale patches, invariance to cube isometries, stratification of the votes with respect to cases and labels. A probabilistic model automatically delineates regions of interest enclosing high-probability tumor volumes, which allows the algorithm to achieve highly competitive running time despite minimal processing power and resources. This method was evaluated on Multimodal Brain Tumor Image Segmentation challenge datasets. State-of-the-art results are achieved, with a limited learning stage thus restricting the risk of overfit. Moreover, segmentation smoothness does not involve any post-processing

Extended Modality Propagation: Image Synthesis of Pathological Cases

International audienceThis paper describes a novel generative model for the synthesis of multi-modal medical images of pathological cases based on a single label map. Our model builds upon i) a generative model commonly used for label fusion and multi-atlas patch-based segmentation of healthy anatomical structures, ii) the Modality Propagation iterative strategy used for a spatially-coherent synthesis of subject-specific scans of desired image modalities. The expression Extended Modality Propagation is coined to refer to the extension of Modality Propagation to the synthesis of images of pathological cases. Moreover, image synthesis uncertainty is estimated. An application to Magnetic Resonance Imaging synthesis of glioma-bearing brains is i) validated on the training dataset of a Multimodal Brain Tumor Image Segmentation challenge, ii) compared to the state-of-the-art in glioma image synthesis, and iii) illustrated using the output of two different tumor growth models. Such a generative model allows the generation of a large dataset of synthetic cases, which could prove useful for the training, validation, or benchmarking of image processing algorithms

Neural Responses to Naturalistic Clips of Behaving Animals Under Two Different Task Contexts

The human brain rapidly deploys semantic information during perception to facilitate our interaction with the world. These semantic representations are encoded in the activity of distributed populations of neurons (Haxby et al., 2001; McClelland and Rogers, 2003; Kriegeskorte et al., 2008b) and command widespread cortical real estate (Binder et al., 2009; Huth et al., 2012). The neural representation of a stimulus can be described as a location (i.e., response vector) in a high-dimensional neural representational space (Kriegeskorte and Kievit, 2013; Haxby et al., 2014). This resonates with behavioral and theoretical work describing mental representations of objects and actions as being organized in a multidimensional psychological space (Attneave, 1950; Shepard, 1958, 1987; Edelman, 1998; Gärdenfors and Warglien, 2012). Current applications of this framework to neural representation (e.g., Kriegeskorte et al., 2008b) often implicitly assume that these neural representational spaces are relatively fixed and context-invariant. In contrast, earlier work emphasized the importance of attention and task demands in actively reshaping representational space (Shepard, 1964; Tversky, 1977; Nosofsky, 1986; Kruschke, 1992). A growing body of work in both electrophysiology (e.g., Sigala and Logothetis, 2002; Sigala, 2004; Cohen and Maunsell, 2009; Reynolds and Heeger, 2009) and human neuroimaging (e.g., Hon et al., 2009; Jehee et al., 2011; Brouwer and Heeger, 2013; Çukur et al., 2013; Sprague and Serences, 2013; Harel et al., 2014; Erez and Duncan, 2015; Nastase et al., 2017) has suggested mechanisms by which behavioral goals dynamically alter neural representation