Variational inference for medical image segmentation

Variational inference techniques are powerful methods for learning probabilistic models and provide significant advantages over maximum likelihood (ML) or maximum a posteriori (MAP) approaches. Nevertheless they have not yet been fully exploited for image processing applications. In this paper we present a variational Bayes (VB) approach for image segmentation. We aim to show that VB provides a framework for generalising existing segmentation algorithms that rely on an expectation–maximisation formulation, while increasing their robustness and computational stability. We also show how optimal model complexity can be automatically determined in a variational setting, as opposed to ML frameworks which are intrinsically prone to overfitting. Finally, we demonstrate how suitable intensity priors, that can be used in combination with the presented algorithm, can be learned from large imaging data sets by adopting an empirical Bayes approach

An Information Theoretic Approach For Feature Selection And Segmentation In Posterior Fossa Tumors

Posterior Fossa (PF) is a type of brain tumor located in or near brain stem and cerebellum. About 55% - 70 % pediatric brain tumors arise in the posterior fossa, compared with only 15% - 20% of adult tumors. For segmenting PF tumors we should have features to study the characteristics of tumors. In literature, different types of texture features such as Fractal Dimension (FD) and Multifractional Brownian Motion (mBm) have been exploited for measuring randomness associated with brain and tumor tissues structures, and the varying appearance of tissues in magnetic resonance images (MRI). For selecting best features techniques such as neural network and boosting methods have been exploited. However, neural network cannot descirbe about the properties of texture features. We explore methods such as information theroetic methods which can perform feature selection based on properties of texture features. The primary contribution of this dissertation is investigating efficacy of different image features such as intensity, fractal texture, and level - set shape in segmentation of PF tumor for pediatric patients. We explore effectiveness of using four different feature selection and three different segmentation techniques respectively to discriminate tumor regions from normal tissue in multimodal brain MRI. Our research suggest that Kullback - Leibler Divergence (KLD) measure for feature ranking and selection and Expectation Maximization (EM) algorithm for feature fusion and tumor segmentation offer the best performance for the patient data in this study. To improve segmentation accuracy, we need to consider abnormalities such as cyst, edema and necrosis which surround tumors. In this work, we exploit features which describe properties of cyst and technique which can be used to segment it. To achieve this goal, we extend the two class KLD techniques to multiclass feature selection techniques, so that we can effectively select features for tumor, cyst and non tumor tissues. We compute segemntation accuracy by computing number of pixels segemented to total number of pixels for the best features. For automated process we integrate the inhomoheneity correction, feature selection using KLD and segmentation in an integrated EM framework. To validate results we have used similarity coefficients for computing the robustness of segmented tumor and cyst

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Computational methods to predict and enhance decision-making with biomedical data.

The proposed research applies machine learning techniques to healthcare applications. The core ideas were using intelligent techniques to find automatic methods to analyze healthcare applications. Different classification and feature extraction techniques on various clinical datasets are applied. The datasets include: brain MR images, breathing curves from vessels around tumor cells during in time, breathing curves extracted from patients with successful or rejected lung transplants, and lung cancer patients diagnosed in US from in 2004-2009 extracted from SEER database. The novel idea on brain MR images segmentation is to develop a multi-scale technique to segment blood vessel tissues from similar tissues in the brain. By analyzing the vascularization of the cancer tissue during time and the behavior of vessels (arteries and veins provided in time), a new feature extraction technique developed and classification techniques was used to rank the vascularization of each tumor type. Lung transplantation is a critical surgery for which predicting the acceptance or rejection of the transplant would be very important. A review of classification techniques on the SEER database was developed to analyze the survival rates of lung cancer patients, and the best feature vector that can be used to predict the most similar patients are analyzed

Bayesian generative learning of brain and spinal cord templates from neuroimaging datasets

In the field of neuroimaging, Bayesian modelling techniques have been largely adopted and recognised as powerful tools for the purpose of extracting quantitative anatomical and functional information from medical scans. Nevertheless the potential of Bayesian inference has not yet been fully exploited, as many available tools rely on point estimation techniques, such as maximum likelihood estimation, rather than on full Bayesian inference. The aim of this thesis is to explore the value of approximate learning schemes, for instance variational Bayes, to perform inference from brain and spinal cord MRI data. The applications that will be explored in this work mainly concern image segmentation and atlas construction, with a particular emphasis on the problem of shape and intensity prior learning, from large training data sets of structural MR scans. The resulting computational tools are intended to enable integrated brain and spinal cord morphometric analyses, as opposed to the approach that is most commonly adopted in neuroimaging, which consists in optimising separate tools for brain and spine morphometrics

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

Detection of brain tumour in 2d MRI: implementation and critical review of clustering-based image segmentation methods

Image segmentation can be defined as segregation or partitioning of images into multiple regions with the same predefined homogeneity criterion. Image segmentation is a crucial process in medical image analysis. This paper explores and investigates several unsupervised image segmentation approaches and their viability and performances in delineating tumour region in contrast enhanced T1-weighted brain MRI (Magnetic Resonance Imaging) scans. First and foremost, raw CE T1-weighted brain MR images are downloaded from a free online database. The images are then pre-processed and undergo an important process called skull stripping. Then, image segmentation techniques such as k-means clustering, Gaussian mixture model segmentation and fuzzy c-means are applied to the pre-processed MR images. The image segmentation results are evaluated using several performance measures, such as precision, recall, Tanimoto coefficient and Dice similarity index in reference to ground truth images. The highest average Dice coefficient is achieved by k-means (0.189) before post-processing and GMM (0.208) after post-processing. Unsupervised clustering-based brain tumour segmentation based on just image pixel intensity in single-spectral brain MRI without adaptive post-processing algorithm cannot achieve efficient and robust segmentation results

Methodological challenges and analytic opportunities for modeling and interpreting Big Healthcare Data

Abstract Managing, processing and understanding big healthcare data is challenging, costly and demanding. Without a robust fundamental theory for representation, analysis and inference, a roadmap for uniform handling and analyzing of such complex data remains elusive. In this article, we outline various big data challenges, opportunities, modeling methods and software techniques for blending complex healthcare data, advanced analytic tools, and distributed scientific computing. Using imaging, genetic and healthcare data we provide examples of processing heterogeneous datasets using distributed cloud services, automated and semi-automated classification techniques, and open-science protocols. Despite substantial advances, new innovative technologies need to be developed that enhance, scale and optimize the management and processing of large, complex and heterogeneous data. Stakeholder investments in data acquisition, research and development, computational infrastructure and education will be critical to realize the huge potential of big data, to reap the expected information benefits and to build lasting knowledge assets. Multi-faceted proprietary, open-source, and community developments will be essential to enable broad, reliable, sustainable and efficient data-driven discovery and analytics. Big data will affect every sector of the economy and their hallmark will be ‘team science’.http://deepblue.lib.umich.edu/bitstream/2027.42/134522/1/13742_2016_Article_117.pd