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

Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Automatic 3D pulmonary nodule detection in CT images: a survey

This work presents a systematic review of techniques for the 3D automatic detection of pulmonary nodules in computerized-tomography (CT) images. Its main goals are to analyze the latest technology being used for the development of computational diagnostic tools to assist in the acquisition, storage and, mainly, processing and analysis of the biomedical data. Also, this work identifies the progress made, so far, evaluates the challenges to be overcome and provides an analysis of future prospects. As far as the authors know, this is the first time that a review is devoted exclusively to automated 3D techniques for the detection of pulmonary nodules from lung CT images, which makes this work of noteworthy value. The research covered the published works in the Web of Science, PubMed, Science Direct and IEEEXplore up to December 2014. Each work found that referred to automated 3D segmentation of the lungs was individually analyzed to identify its objective, methodology and results. Based on the analysis of the selected works, several studies were seen to be useful for the construction of medical diagnostic aid tools. However, there are certain aspects that still require attention such as increasing algorithm sensitivity, reducing the number of false positives, improving and optimizing the algorithm detection of different kinds of nodules with different sizes and shapes and, finally, the ability to integrate with the Electronic Medical Record Systems and Picture Archiving and Communication Systems. Based on this analysis, we can say that further research is needed to develop current techniques and that new algorithms are needed to overcome the identified drawbacks

Medical imaging analysis with artificial neural networks

Given that neural networks have been widely reported in the research community of medical imaging, we provide a focused literature survey on recent neural network developments in computer-aided diagnosis, medical image segmentation and edge detection towards visual content analysis, and medical image registration for its pre-processing and post-processing, with the aims of increasing awareness of how neural networks can be applied to these areas and to provide a foundation for further research and practical development. Representative techniques and algorithms are explained in detail to provide inspiring examples illustrating: (i) how a known neural network with fixed structure and training procedure could be applied to resolve a medical imaging problem; (ii) how medical images could be analysed, processed, and characterised by neural networks; and (iii) how neural networks could be expanded further to resolve problems relevant to medical imaging. In the concluding section, a highlight of comparisons among many neural network applications is included to provide a global view on computational intelligence with neural networks in medical imaging

Lung nodule diagnosis and cancer histology classification from computed tomography data by convolutional neural networks: A survey

Lung cancer is among the deadliest cancers. Besides lung nodule classification and diagnosis, developing non-invasive systems to classify lung cancer histological types/subtypes may help clinicians to make targeted treatment decisions timely, having a positive impact on patients' comfort and survival rate. As convolutional neural networks have proven to be responsible for the significant improvement of the accuracy in lung cancer diagnosis, with this survey we intend to: show the contribution of convolutional neural networks not only in identifying malignant lung nodules but also in classifying lung cancer histological types/subtypes directly from computed tomography data; point out the strengths and weaknesses of slice-based and scan-based approaches employing convolutional neural networks; and highlight the challenges and prospective solutions to successfully apply convolutional neural networks for such classification tasks. To this aim, we conducted a comprehensive analysis of relevant Scopus-indexed studies involved in lung nodule diagnosis and cancer histology classification up to January 2022, dividing the investigation in convolutional neural network-based approaches fed with planar or volumetric computed tomography data. Despite the application of convolutional neural networks in lung nodule diagnosis and cancer histology classification is a valid strategy, some challenges raised, mainly including the lack of publicly-accessible annotated data, together with the lack of reproducibility and clinical interpretability. We believe that this survey will be helpful for future studies involved in lung nodule diagnosis and cancer histology classification prior to lung biopsy by means of convolutional neural networks

An Enhanced Texture-Based Feature Extraction Approach for Classification of Biomedical Images of CT-Scan of Lungs

Content Based Image Retrieval (CBIR) techniques based on texture have gained a lot of popularity in recent times. In the proposed work, a feature vector is obtained by concatenation of features extracted from local mesh peak valley edge pattern (LMePVEP) technique; a dynamic threshold based local mesh ternary pattern technique and texture of the image in five different directions. The concatenated feature vector is then used to classify images of two datasets viz. Emphysema dataset and Early Lung Cancer Action Program (ELCAP) lung database. The proposed framework has improved the accuracy by 12.56%, 9.71% and 7.01% in average for data set 1 and 9.37%, 8.99% and 7.63% in average for dataset 2 over three popular algorithms used for image retrieval

Expert System with an Embedded Imaging Module for Diagnosing Lung Diseases

Lung diseases are one of the major causes of suffering and death in the world. Improved survival rate could be obtained if the diseases can be detected at its early stage. Specialist doctors with the expertise and experience to interpret medical images and diagnose complex lung diseases are scarce. In this work, a rule-based expert system with an embedded imaging module is developed to assist the general physicians in hospitals and clinics to diagnose lung diseases whenever the services of specialist doctors are not available. The rule-based expert system contains a large knowledge base of data from various categories such as patient's personal and medical history, clinical symptoms, clinical test results and radiological information. An imaging module is integrated into the expert system for the enhancement of chest X-Ray images. The goal of this module is to enhance the chest X-Ray images so that it can provide details similar to more expensive methods such as MRl and CT scan. A new algorithm which is a modified morphological grayscale top hat transform is introduced to increase the visibility of lung nodules in chest X-Rays. Fuzzy inference technique is used to predict the probability of malignancy of the nodules. The output generated by the expert system was compared with the diagnosis made by the specialist doctors. The system is able to produce results\ud which are similar to the diagnosis made by the doctors and is acceptable by clinical standards

Computed tomography image analysis for the detection of obstructive lung diseases

Damage to the small airways resulting from direct lung injury or associated with many systemic disorders is not easy to identify. Non-invasive techniques such as chest radiography or conventional tests of lung function often cannot reveal the pathology. On Computed Tomography (CT) images, the signs suggesting the presence of obstructive airways disease are subtle, and inter- and intra-observer variability can be considerable. The goal of this research was to implement a system for the automated analysis of CT data of the lungs. Its function is to help clinicians establish a confident assessment of specific obstructive airways diseases and increase the precision of investigation of structure/function relationships. To help resolve the ambiguities of the CT scans, the main objectives of our system were to provide a functional description of the raster images, extract semi-quantitative measurements of the extent of obstructive airways disease and propose a clinical diagnosis aid using a priori knowledge of CT image features of the diseased lungs. The diagnostic process presented in this thesis involves the extraction and analysis of multiple findings. Several novel low-level computer vision feature extractors and image processing algorithms were developed for extracting the extent of the hypo-attenuated areas, textural characterisation of the lung parenchyma, and morphological description of the bronchi. The fusion of the results of these extractors was achieved with a probabilistic network combining a priori knowledge of lung pathology. Creating a CT lung phantom allowed for the initial validation of the proposed methods. Performance of the techniques was then assessed with clinical trials involving other diagnostic tests and expert chest radiologists. The results of the proposed system for diagnostic decision-support demonstrated the feasibility and importance of information fusion in medical image interpretation.Open acces

Lung Cancer Detection through TYDWT Algorithm

Lung cancer is one of the leading causes of cancer-related deaths worldwide. Early detection of lung cancer plays a critical role in its treatment and survival rates. In recent years, computer-aided diagnosis systems have been developed to assist radiologists in detecting lung nodules in computed tomography (CT) images. This paper proposes a novel approach for lung cancer detection using Transverse Dyadic Wavelet Transform (TDWT) for feature extraction and classification. TDWT is a multi-resolution analysis technique that can capture both time and frequency information of the input images. The TYDWT algorithm is applied to the lung CT scan images to decompose the images into different sub-bands at multiple scales. The extracted features from these sub-bands are then used to train a machine learning model for lung cancer detection. The performance of the proposed method is evaluated on a publicly available dataset, achieving an accuracy of 95.6% and a sensitivity of 95.2%. The proposed method shows promising results for automated lung cancer detection, which can improve the accuracy and efficiency of the diagnosis process. The results demonstrate that the proposed approach using TDWT can be an effective method for early detection of lung cancer