A Probabilistic Adaptive Cerebral Cortex Segmentation Algorithm for Magnetic Resonance Human Head Scan Images

The total efficiency of Magnetic Resonance Imaging (MRI) results in the need for human involvement in order to appropriately detect information contained in the image. Currently, there has been a surge in interest in automated algorithms that can more precisely divide medical image structures into substructures than prior attempts. Instant segregation of cerebral cortex width from MRI scanned images is difficult due to noise, Intensity Non-Uniformity (INU), Partial Volume Effects (PVE), MRI's low resolution, and the very complicated architecture of the cortical folds. In this paper, a Probabilistic Adaptive Cerebral Cortex Segmentation (PACCS) approach is proposed for segmenting brain areas of T1 weighted MRI of human head images. Skull Stripping (SS), Brain Hemisphere Segmentation (BHS) and CCS are the three primary processes in the suggested technique. In step 1, Non-Brain Cells (NBC) is eliminated by a Contour-Based Two-Stage Brain Extraction Method (CTS-BEM). Step 2 details a basic BHS technique for Curve Fitting (CF) detection in MRI human head images. The left and right hemispheres are divided using the discovered Mid-Sagittal Plane (MSP). At last, to enhance a probabilistic CCS structure with adjustments such as prior facts change to remove segmentation bias; the creation of express direct extent training; and a segmentation version based on a regionally various Gaussian Mixture Model- Hidden Markov Random Field – Expectation Maximization (GMM-HMRF-EM). The underlying partial extent categorization and its interplay with found image intensities are represented as a spatially correlated HMRF within the GMM-HMRF-EM method. The proposed GMM-HMRF method estimates HMRF parameters using the EM technique. Finally, the outcomes of segmentation are evaluated in terms of precision, recall, specificity, Jaccard Similarity (JS), and Dice Similarity (DS). The proposed method works better and more consistently than the present locally Varying MRF (LV-MRF), according to the experimental findings obtained by using the suggested GMM-HMRF-EM methodology to 18 individuals' brain images

Brain MRI Segmentation with Multiphase Minimal Partitioning: A Comparative Study

This paper presents the implementation and quantitative evaluation of a multiphase three-dimensional deformable model in a level set framework for automated segmentation of brain MRIs. The segmentation algorithm performs an optimal partitioning of three-dimensional data based on homogeneity measures that naturally evolves to the extraction of different tissue types in the brain. Random seed initialization was used to minimize the sensitivity of the method to initial conditions while avoiding the need for a priori information. This random initialization ensures robustness of the method with respect to the initialization and the minimization set up. Postprocessing corrections with morphological operators were applied to refine the details of the global segmentation method. A clinical study was performed on a database of 10 adult brain MRI volumes to compare the level set segmentation to three other methods: “idealized” intensity thresholding, fuzzy connectedness, and an expectation maximization classification using hidden Markov random fields. Quantitative evaluation of segmentation accuracy was performed with comparison to manual segmentation computing true positive and false positive volume fractions. A statistical comparison of the segmentation methods was performed through a Wilcoxon analysis of these error rates and results showed very high quality and stability of the multiphase three-dimensional level set method

Development of Unsupervised Image Segmentation Schemes for Brain MRI using HMRF model

Image segmentation is a classical problem in computer vision and is of paramount importance to medical imaging. Medical image segmentation is an essential step for most subsequent image analysis task. The segmentation of anatomic structure in the brain plays a crucial role in neuro imaging analysis. The study of many brain disorders involves accurate tissue segmentation of brain magnetic resonance (MR) images. Manual segmentation of the brain tissues, namely white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) in MR images by an human expert is tedious for studies involving larger database. In addition, the lack of clearly defined edges between adjacent tissue classes deteriorates the significance of the analysis of the resulting segmentation. The segmentation is further complicated by the overlap of MR intensities of different tissue classes and by the presence of a spatially and smoothly varying intensity in-homogeneity. The prime objective of this dissertation is to develop strategies and methodologies for an automated brain MR image segmentation scheme

Validation of Tissue Modelization and Classification Techniques in T1-weighted MR Brain Images

We propose a deep study on tissue modelization and classification techniques on T1-weighted MR images. Six approaches have been taken into account to perform this validation study. We consider first the Finite Gaussian Mixture model (A-FGMM) and a Bayes classification. Second method is the same as A-FGMM but introducing a Hidden Markov Random Field (HMRF) model to encode spatial information and classification is then performed by Maximum a Posteriori (MAP). Third, we study a method that models mixture tissues as a linear combination Gaussian pure tissue distributions (C-GPV) and it also performs a Bayes classification. Fourth, method D-GPV-HMRF uses the same image model as method C-GPV but encode spatial information as done in method B-HMRF. Fifth algorithm do not parameterize the intensity distribution but they directly classifies from intensity probabilities (Error Probability, E-EP). Last method it is also non-parametric but uses a HMRF to introduce spatial information (F-NPHMRF). All methods have been tested on a Digital Brain Phantom image considered as the ground truth. Noise and intensity non-uniformities have been added to simulate real image conditions. Results demonstrate that methods relying in both intensity and spatial information are in general more robust to noise and inhomogeneities. We demonstrate also that partial volume (PV) is still not completely well-model even if methods that uses this mixture model perform less errors

Comprehensive Brain MRI Segmentation in High Risk Preterm Newborns

Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes

Enhancement Techniques and Methods for Brain MRI Imaging

In this paper, it is planned to review and compare the different methods of enhancing a DICOM of brain MRIused in preprocessing and segmentation techniques. Image segmentation is the process of partitioning an image into multiple segments, so as to change the representation of an image into something that is more meaningful and easier to analyze. Several general-purpose algorithms and techniques have been developed for image segmentation. This paper describes the different segmentation techniques used in the field of ultrasound, MR image and SAR Image Processing. In preprocessing and enhancement stage is used to eliminate the noise and high frequency components from DICOM image. In this paper, various Preprocessing and Enhancement Technique, Segmentation Algorithm and their compared

Automated Segmentation of Cerebral Aneurysm Using a Novel Statistical Multiresolution Approach

Cerebral Aneurysm (CA) is a vascular disease that threatens the lives of many adults. It a ects almost 1:5 - 5% of the general population. Sub- Arachnoid Hemorrhage (SAH), resulted by a ruptured CA, has high rates of morbidity and mortality. Therefore, radiologists aim to detect it and diagnose it at an early stage, by analyzing the medical images, to prevent or reduce its damages. The analysis process is traditionally done manually. However, with the emerging of the technology, Computer-Aided Diagnosis (CAD) algorithms are adopted in the clinics to overcome the traditional process disadvantages, as the dependency of the radiologist's experience, the inter and intra observation variability, the increase in the probability of error which increases consequently with the growing number of medical images to be analyzed, and the artifacts added by the medical images' acquisition methods (i.e., MRA, CTA, PET, RA, etc.) which impedes the radiologist' s work. Due to the aforementioned reasons, many research works propose di erent segmentation approaches to automate the analysis process of detecting a CA using complementary segmentation techniques; but due to the challenging task of developing a robust reproducible reliable algorithm to detect CA regardless of its shape, size, and location from a variety of the acquisition methods, a diversity of proposed and developed approaches exist which still su er from some limitations. This thesis aims to contribute in this research area by adopting two promising techniques based on the multiresolution and statistical approaches in the Two-Dimensional (2D) domain. The rst technique is the Contourlet Transform (CT), which empowers the segmentation by extracting features not apparent in the normal image scale. While the second technique is the Hidden Markov Random Field model with Expectation Maximization (HMRF-EM), which segments the image based on the relationship of the neighboring pixels in the contourlet domain. The developed algorithm reveals promising results on the four tested Three- Dimensional Rotational Angiography (3D RA) datasets, where an objective and a subjective evaluation are carried out. For the objective evaluation, six performance metrics are adopted which are: accuracy, Dice Similarity Index (DSI), False Positive Ratio (FPR), False Negative Ratio (FNR), speci city, and sensitivity. As for the subjective evaluation, one expert and four observers with some medical background are involved to assess the segmentation visually. Both evaluations compare the segmented volumes against the ground truth data

Doctor of Philosophy

dissertationFunctional magnetic resonance imaging (fMRI) measures the change of oxygen consumption level in the blood vessels of the human brain, hence indirectly detecting the neuronal activity. Resting-state fMRI (rs-fMRI) is used to identify the intrinsic functional patterns of the brain when there is no external stimulus. Accurate estimation of intrinsic activity is important for understanding the functional organization and dynamics of the brain, as well as differences in the functional networks of patients with mental disorders. This dissertation aims to robustly estimate the functional connectivities and networks of the human brain using rs-fMRI data of multiple subjects. We use Markov random field (MRF), an undirected graphical model to represent the statistical dependency among the functional network variables. Graphical models describe multivariate probability distributions that can be factorized and represented by a graph. By defining the nodes and the edges along with their weights according to our assumptions, we build soft constraints into the graph structure as prior information. We explore various approximate optimization methods including variational Bayesian, graph cuts, and Markov chain Monte Carlo sampling (MCMC). We develop the random field models to solve three related problems. In the first problem, the goal is to detect the pairwise connectivity between gray matter voxels in a rs-fMRI dataset of the single subject. We define a six-dimensional graph to represent our prior information that two voxels are more likely to be connected if their spatial neighbors are connected. The posterior mean of the connectivity variables are estimated by variational inference, also known as mean field theory in statistical physics. The proposed method proves to outperform the standard spatial smoothing and is able to detect finer patterns of brain activity. Our second work aims to identify multiple functional systems. We define a Potts model, a special case of MRF, on the network label variables, and define von Mises-Fisher distribution on the normalized fMRI signal. The inference is significantly more difficult than the binary classification in the previous problem. We use MCMC to draw samples from the posterior distribution of network labels. In the third application, we extend the graphical model to the multiple subject scenario. By building a graph including the network labels of both a group map and the subject label maps, we define a hierarchical model that has richer structure than the flat single-subject model, and captures the shared patterns as well as the variation among the subjects. All three solutions are data-driven Bayesian methods, which estimate model parameters from the data. The experiments show that by the regularization of MRF, the functional network maps we estimate are more accurate and more consistent across multiple sessions

Atlas-based segmentation and classification of magnetic resonance brain images

A wide range of different image modalities can be found today in medical imaging. These modalities allow the physician to obtain a non-invasive view of the internal organs of the human body, such as the brain. All these three dimensional images are of extreme importance in several domains of medicine, for example, to detect pathologies, follow the evolution of these pathologies, prepare and realize surgical planning with, or without, the help of robot systems or for statistical studies. Among all the medical image modalities, Magnetic Resonance (MR) imaging has become of great interest in many research areas due to its great spatial and contrast image resolution. It is therefore perfectly suited for anatomic visualization of the human body such as deep structures and tissues of the brain. Medical image analysis is a complex task because medical images usually involve a large amount of data and they sometimes present some undesirable artifacts, as for instance the noise. However, the use of a priori knowledge in the analysis of these images can greatly simplify this task. This prior information is usually represented by the reference images or atlases. Modern brain atlases are derived from high resolution cryosections or in vivo images, single subject-based or population-based, and they provide detailed images that may be interactively and easily examined in their digital format in computer assisted diagnosis or intervention. Then, in order to efficiently combine all this information, a battery of registration techniques is emerging based on transformations that bring two medical images into voxel-to-voxel correspondence. One of the main aims of this thesis is to outline the importance of including prior knowledge in the medical image analysis framework and the indispensable role of registration techniques in this task. In order to do that, several applications using atlas information are presented. First, the atlas-based segmentation in normal anatomy is shown as it is a key application of medical image analysis using prior knowledge. It consists of registering the brain images derived from different subjects and modalities within the atlas coordinate system to improve the localization and delineation of the structures of interest. However, the use of an atlas can be problematic in some particular cases where some structures, for instance a tumor or a sulcus, exists in the subject and not in the atlas. In order to solve this limitation of the atlases, a new atlas-based segmentation method for pathological brains is proposed in this thesis as well as a validation method to assess this new approach. Results show that deep structures of the brain can still be efficiently segmented using an anatomic atlas even if they are largely deformed because of a lesion. The importance of including a priori knowledge is also presented in the application of brain tissue classification. The prior information represented by the tissue templates can be included in a brain tissue segmentation approach thanks to the registration techniques. This is another important issue presented in this thesis and it is analyzed through a comparative study of several non-supervised classification techniques. These methods are selected to represent the whole range of prior information that can be used in the classification process: the image intensity, the local spatial model, and the anatomical priors. Results show that the registration between the subject and the tissue templates allows the use of prior information but the accuracy of both the prior information and the registration highly influence the performance of the classification techniques. Another aim of this thesis is to present the concept of dynamic medical image analysis, in which the prior knowledge and the registration techniques are also of main importance. Actually, many medical image applications have the objective of statically analyzing one single image, as for instance in the case of atlas-based segmentation or brain tissue classification. But in other cases the implicit idea of changes detection is present. Intuitively, since the human body is changing continuously, we would like to do the image analysis from a dynamic point of view by detecting these changes, and by comparing them afterwards with templates to know if they are normal. The need of such approaches is even more evident in the case of many brain pathologies such as tumors, multiple sclerosis or degenerative diseases. In these cases, the key point is not only to detect but also to quantify and even characterize the evolving pathology. The evaluation of lesion variations over time can be very useful, for instance in the pharmaceutical research and clinical follow up. Of course, a sequence of images is needed in order to do such an analysis. Two approaches dealing with the idea of change detection are proposed as the last (but not least) issue presented in this work. The first one consists of performing a static analysis of each image forming the data set and, then, of comparing them. The second one consists of analyzing the non-rigid transformation between the sequence images instead of the images itself. Finally, both static and dynamic approaches are illustrated with a potential application: the cortical degeneration study is done using brain tissue segmentation, and the study of multiple sclerosis lesion evolution is performed by non-rigid deformation analysis. In conclusion, the importance of including a priori information encoded in the brain atlases in medical image analysis has been put in evidence with a wide range of possible applications. In the same way, the key role of registration techniques is shown not only as an efficient way to combine all the medical image modalities but also as a main element in the dynamic medical image analysis

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