Modeling small objects under uncertainties : novel algorithms and applications.

Active Shape Models (ASM), Active Appearance Models (AAM) and Active Tensor Models (ATM) are common approaches to model elastic (deformable) objects. These models require an ensemble of shapes and textures, annotated by human experts, in order identify the model order and parameters. A candidate object may be represented by a weighted sum of basis generated by an optimization process. These methods have been very effective for modeling deformable objects in biomedical imaging, biometrics, computer vision and graphics. They have been tried mainly on objects with known features that are amenable to manual (expert) annotation. They have not been examined on objects with severe ambiguities to be uniquely characterized by experts. This dissertation presents a unified approach for modeling, detecting, segmenting and categorizing small objects under uncertainty, with focus on lung nodules that may appear in low dose CT (LDCT) scans of the human chest. The AAM, ASM and the ATM approaches are used for the first time on this application. A new formulation to object detection by template matching, as an energy optimization, is introduced. Nine similarity measures of matching have been quantitatively evaluated for detecting nodules less than 1 em in diameter. Statistical methods that combine intensity, shape and spatial interaction are examined for segmentation of small size objects. Extensions of the intensity model using the linear combination of Gaussians (LCG) approach are introduced, in order to estimate the number of modes in the LCG equation. The classical maximum a posteriori (MAP) segmentation approach has been adapted to handle segmentation of small size lung nodules that are randomly located in the lung tissue. A novel empirical approach has been devised to simultaneously detect and segment the lung nodules in LDCT scans. The level sets methods approach was also applied for lung nodule segmentation. A new formulation for the energy function controlling the level set propagation has been introduced taking into account the specific properties of the nodules. Finally, a novel approach for classification of the segmented nodules into categories has been introduced. Geometric object descriptors such as the SIFT, AS 1FT, SURF and LBP have been used for feature extraction and matching of small size lung nodules; the LBP has been found to be the most robust. Categorization implies classification of detected and segmented objects into classes or types. The object descriptors have been deployed in the detection step for false positive reduction, and in the categorization stage to assign a class and type for the nodules. The AAMI ASMI A TM models have been used for the categorization stage. The front-end processes of lung nodule modeling, detection, segmentation and classification/categorization are model-based and data-driven. This dissertation is the first attempt in the literature at creating an entirely model-based approach for lung nodule analysis

Co-Segmentation Methods for Improving Tumor Target Delineation in PET-CT Images

Positron emission tomography (PET)-Computed tomography (CT) plays an important role in cancer management. As a multi-modal imaging technique it provides both functional and anatomical information of tumor spread. Such information improves cancer treatment in many ways. One important usage of PET-CT in cancer treatment is to facilitate radiotherapy planning, for the information it provides helps radiation oncologists to better target the tumor region. However, currently most tumor delineations in radiotherapy planning are performed by manual segmentation, which consumes a lot of time and work. Most computer-aided algorithms need a knowledgeable user to locate roughly the tumor area as a starting point. This is because, in PET-CT imaging, some tissues like heart and kidney may also exhibit a high level of activity similar to that of a tumor region. In order to address this issue, a novel co-segmentation method is proposed in this work to enhance the accuracy of tumor segmentation using PET-CT, and a localization algorithm is developed to differentiate and segment tumor regions from normal regions. On a combined dataset containing 29 patients with lung tumor, the combined method shows good segmentation results as well as good tumor recognition rate

Computer-Aided Assessment of Tuberculosis with Radiological Imaging: From rule-based methods to Deep Learning

Mención Internacional en el título de doctorTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb.) that produces pulmonary damage due to its airborne nature. This fact facilitates the disease fast-spreading, which, according to the World Health Organization (WHO), in 2021 caused 1.2 million deaths and 9.9 million new cases. Traditionally, TB has been considered a binary disease (latent/active) due to the limited specificity of the traditional diagnostic tests. Such a simple model causes difficulties in the longitudinal assessment of pulmonary affectation needed for the development of novel drugs and to control the spread of the disease. Fortunately, X-Ray Computed Tomography (CT) images enable capturing specific manifestations of TB that are undetectable using regular diagnostic tests, which suffer from limited specificity. In conventional workflows, expert radiologists inspect the CT images. However, this procedure is unfeasible to process the thousands of volume images belonging to the different TB animal models and humans required for a suitable (pre-)clinical trial. To achieve suitable results, automatization of different image analysis processes is a must to quantify TB. It is also advisable to measure the uncertainty associated with this process and model causal relationships between the specific mechanisms that characterize each animal model and its level of damage. Thus, in this thesis, we introduce a set of novel methods based on the state of the art Artificial Intelligence (AI) and Computer Vision (CV). Initially, we present an algorithm to assess Pathological Lung Segmentation (PLS) employing an unsupervised rule-based model which was traditionally considered a needed step before biomarker extraction. This procedure allows robust segmentation in a Mtb. infection model (Dice Similarity Coefficient, DSC, 94%±4%, Hausdorff Distance, HD, 8.64mm±7.36mm) of damaged lungs with lesions attached to the parenchyma and affected by respiratory movement artefacts. Next, a Gaussian Mixture Model ruled by an Expectation-Maximization (EM) algorithm is employed to automatically quantify the burden of Mtb.using biomarkers extracted from the segmented CT images. This approach achieves a strong correlation (R2 ≈ 0.8) between our automatic method and manual extraction. Consequently, Chapter 3 introduces a model to automate the identification of TB lesions and the characterization of disease progression. To this aim, the method employs the Statistical Region Merging algorithm to detect lesions subsequently characterized by texture features that feed a Random Forest (RF) estimator. The proposed procedure enables a selection of a simple but powerful model able to classify abnormal tissue. The latest works base their methodology on Deep Learning (DL). Chapter 4 extends the classification of TB lesions. Namely, we introduce a computational model to infer TB manifestations present in each lung lobe of CT scans by employing the associated radiologist reports as ground truth. We do so instead of using the classical manually delimited segmentation masks. The model adjusts the three-dimensional architecture, V-Net, to a multitask classification context in which loss function is weighted by homoscedastic uncertainty. Besides, the method employs Self-Normalizing Neural Networks (SNNs) for regularization. Our results are promising with a Root Mean Square Error of 1.14 in the number of nodules and F1-scores above 0.85 for the most prevalent TB lesions (i.e., conglomerations, cavitations, consolidations, trees in bud) when considering the whole lung. In Chapter 5, we present a DL model capable of extracting disentangled information from images of different animal models, as well as information of the mechanisms that generate the CT volumes. The method provides the segmentation mask of axial slices from three animal models of different species employing a single trained architecture. It also infers the level of TB damage and generates counterfactual images. So, with this methodology, we offer an alternative to promote generalization and explainable AI models. To sum up, the thesis presents a collection of valuable tools to automate the quantification of pathological lungs and moreover extend the methodology to provide more explainable results which are vital for drug development purposes. Chapter 6 elaborates on these conclusions.Programa de Doctorado en Multimedia y Comunicaciones por la Universidad Carlos III de Madrid y la Universidad Rey Juan CarlosPresidenta: María Jesús Ledesma Carbayo.- Secretario: David Expósito Singh.- Vocal: Clarisa Sánchez Gutiérre

Tumour grading and discrimination based on class assignment and quantitative texture analysis techniques

Medical imaging represents the utilisation of technology in biology for the purpose of noninvasively revealing the internal structure of the organs of the human body. It is a way to improve the quality of the patient's life through a more precise and rapid diagnosis, and with limited side-effects, leading to an effective overall treatment procedure. The main objective of this thesis is to propose novel tumour discrimination techniques that cover both micro and macro-scale textures encountered in computed tomography (CI') and digital microscopy (DM) modalities, respectively. Image texture can provide significant information on the (ab)normality of tissue, and this thesis expands this idea to tumour texture grading and classification. The fractal dimension (FO) as a texture measure was applied to contrast enhanced CT lung tumour images in an aim to improve tumour grading accuracy from conventional CI' modality, and quantitative performance analysis showed an accuracy of 83.30% in distinguishing between advanced (aggressive) and early stage (non-aggressive) malignant tumours. A different approach was adopted for subtype discrimination of brain tumour OM images via a set of statistical and model-based texture analysis algorithms. The combined Gaussian Markov random field and run-length matrix texture measures outperformed all other combinations, achieving an overall class assignment classification accuracy of 92.50%. Also two new histopathological multi resolution approaches based on applying the FO as the best bases selection for discrete wavelet packet transform, and when fused with the Gabor filters' energy output improved the accuracy to 91.25% and 95.00%, respectively. While noise is quite common in all medical imaging modalities, the impact of noise on the applied texture measures was assessed as well. The developed lung and brain texture analysis techniques can improve the physician's ability to detect and analyse pathologies leading for a more reliable diagnosis and treatment of disease

A review of algorithms for medical image segmentation and their applications to the female pelvic cavity

This paper aims to make a review on the current segmentation algorithms used for medical images. Algorithms are classified according to their principal methodologies, namely the ones based on thresholds, the ones based on clustering techniques and the ones based on deformable models. The last type is focused on due to the intensive investigations into the deformable models that have been done in the last few decades. Typical algorithms of each type are discussed and the main ideas, application fields, advantages and disadvantages of each type are summarised. Experiments that apply these algorithms to segment the organs and tissues of the female pelvic cavity are presented to further illustrate their distinct characteristics. In the end, the main guidelines that should be considered for designing the segmentation algorithms of the pelvic cavity are proposed

Computer aided assessment of CT scans of traumatic brain injury patients

A thesis submitted in partial fulfilment for the degree of Doctor of PhilosophyOne of the serious public health problems is the Traumatic Brain Injury, also known as silent epidemic, affecting millions every year. Management of these patients essentially involves neuroimaging and noncontrast CT scans are the first choice amongst doctors. Significant anatomical changes identified on the neuroimages and volumetric assessment of haemorrhages and haematomas are of critical importance for assessing the patients’ condition for targeted therapeutic and/or surgical interventions. Manual demarcation and annotation by experts is still considered gold standard, however, the interpretation of neuroimages is fraught with inter-observer variability and is considered ’Achilles heel’ amongst radiologists. Errors and variability can be attributed to factors such as poor perception, inaccurate deduction, incomplete knowledge or the quality of the image and only a third of doctors confidently report the findings. The applicability of computer aided dianosis in segmenting the apposite regions and giving ’second opinion’ has been positively appraised to assist the radiologists, however, results of the approaches vary due to parameters of algorithms and manual intervention required from doctors and this presents a gap for automated segmentation and estimation of measurements of noncontrast brain CT scans. The Pattern Driven, Content Aware Active Contours (PDCAAC) Framework developed in this thesis provides robust and efficient segmentation of significant anatomical landmarks, estimations of their sizes and correlation to CT rating to assist the radiologists in establishing the diagnosis and prognosis more confidently. The integration of clinical profile of the patient into image segmentation algorithms has significantly improved their performance by highlighting characteristics of the region of interest. The modified active contour method in the PDCAAC framework achieves Jaccard Similarity Index (JI) of 0.87, which is a significant improvement over the existing methods of active contours achieving JI of 0.807 with Simple Linear Iterative Clustering and Distance Regularized Level Set Evolution. The Intraclass Correlation Coefficient of intracranial measurements is >0.97 compared with radiologists. Automatic seeding of the initial seed curve within the region of interest is incorporated into the method which is a novel approach and alleviates limitation of existing methods. The proposed PDCAAC framework can be construed as a contribution towards research to formulate correlations between image features and clinical variables encompassing normal development, ageing, pathological and traumatic cases propitious to improve management of such patients. Establishing prognosis usually entails survival but the focus can also be extended to functional outcomes, residual disability and quality of life issues