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

Deep Learning with Limited Labels for Medical Imaging

Recent advancements in deep learning-based AI technologies provide an automatic tool to revolutionise medical image computing. Training a deep learning model requires a large amount of labelled data. Acquiring labels for medical images is extremely challenging due to the high cost in terms of both money and time, especially for the pixel-wise segmentation task of volumetric medical scans. However, obtaining unlabelled medical scans is relatively easier compared to acquiring labels for those images. This work addresses the pervasive issue of limited labels in training deep learning models for medical imaging. It begins by exploring different strategies of entropy regularisation in the joint training of labelled and unlabelled data to reduce the time and cost associated with manual labelling for medical image segmentation. Of particular interest are consistency regularisation and pseudo labelling. Specifically, this work proposes a well-calibrated semi-supervised segmentation framework that utilises consistency regularisation on different morphological feature perturbations, representing a significant step towards safer AI in medical imaging. Furthermore, it reformulates pseudo labelling in semi-supervised learning as an Expectation-Maximisation framework. Building upon this new formulation, the work explains the empirical successes of pseudo labelling and introduces a generalisation of the technique, accompanied by variational inference to learn its true posterior distribution. The applications of pseudo labelling in segmentation tasks are also presented. Lastly, this work explores unsupervised deep learning for parameter estimation of diffusion MRI signals, employing a hierarchical variational clustering framework and representation learning

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

수치 모델과 그래프 이론을 이용한 향상된 영상 분할 연구 -폐 영상에 응용-

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2016. 2. 김희찬.This dissertation presents a thoracic cavity segmentation algorithm and a method of pulmonary artery and vein decomposition from volumetric chest CT, and evaluates their performances. The main contribution of this research is to develop an automated algorithm for segmentation of the clinically meaningful organ. Although there are several methods to improve the organ segmentation accuracy such as the morphological method based on threshold algorithm or the object selection method based on the connectivity information our novel algorithm uses numerical algorithms and graph theory which came from the computer engineering field. This dissertation presents a new method through the following two examples and evaluates the results of the method. The first study aimed at the thoracic cavity segmentation. The thoracic cavity is the organ enclosed by the thoracic wall and the diaphragm surface. The thoracic wall has no clear boundary. Moreover since the diaphragm is the thin surface, this organ might have lost parts of its surface in the chest CT. As the previous researches, a method which found the mediastinum on the 2D axial view was reported, and a thoracic wall extraction method and several diaphragm segmentation methods were also informed independently. But the thoracic cavity volume segmentation method was proposed in this thesis for the first time. In terms of thoracic cavity volumetry, the mean±SD volumetric overlap ratio (VOR), false positive ratio on VOR (FPRV), and false negative ratio on VOR (FNRV) of the proposed method were 98.17±0.84%, 0.49±0.23%, and 1.34±0.83%, respectively. The proposed semi-automatic thoracic cavity segmentation method, which extracts multiple organs (namely, the rib, thoracic wall, diaphragm, and heart), performed with high accuracy and may be useful for clinical purposes. The second study proposed a method to decompose the pulmonary vessel into vessel subtrees for separation of the artery and vein. The volume images of the separated artery and vein could be used for a simulation support data in the lung cancer. Although a clinician could perform the separation in his imagination, and separate the vessel into the artery and vein in the manual, an automatic separation method is the better method than other methods. In the previous semi-automatic method, root marking of 30 to 40 points was needed while tracing vessels under 2D slice view, and this procedure needed approximately an hour and a half. After optimization of the feature value set, the accuracy of the arterial and venous decomposition was 89.71 ± 3.76% in comparison with the gold standard. This framework could be clinically useful for studies on the effects of the pulmonary arteries and veins on lung diseases.Chapter 1 General Introduction 2 1.1 Image Informatics using Open Source 3 1.2 History of the segmentation algorithm 5 1.3 Goal of Thesis Work 8 Chapter 2 Thoracic cavity segmentation algorithm using multi-organ extraction and surface fitting in volumetric CT 10 2.1 Introduction 11 2.2 Related Studies 13 2.3 The Proposed Thoracic Cavity Segmentation Method 16 2.4 Experimental Results 35 2.5 Discussion 41 2.6 Conclusion 45 Chapter 3 Semi-automatic decomposition method of pulmonary artery and vein using two level minimum spanning tree constructions for non-enhanced volumetric CT 46 3.1 Introduction 47 3.2 Related Studies 51 3.3 Artery and Vein Decomposition 55 3.4 An Efficient Decomposition Method 70 3.5 Evaluation 75 3.6 Discussion and Conclusion 85 References 88 Abstract in Korean 95Docto

Texture Analysis and Machine Learning to Predict Pulmonary Ventilation from Thoracic Computed Tomography

Chronic obstructive pulmonary disease (COPD) leads to persistent airflow limitation, causing a large burden to patients and the health care system. Thoracic CT provides an opportunity to observe the structural pathophysiology of COPD, whereas hyperpolarized gas MRI provides images of the consequential ventilation heterogeneity. However, hyperpolarized gas MRI is currently limited to research centres, due to the high cost of gas and polarization equipment. Therefore, I developed a pipeline using texture analysis and machine learning methods to create predicted ventilation maps based on non-contrast enhanced, single-volume thoracic CT. In a COPD cohort, predicted ventilation maps were qualitatively and quantitatively related to ground-truth MRI ventilation, and both maps were related to important patient lung function and quality-of-life measures. This study is the first to demonstrate the feasibility of predicting hyperpolarized MRI-based ventilation from single-volume, breath-hold thoracic CT, which has potential to translate pulmonary ventilation information to widely available thoracic CT imaging

Quantitative Evaluation of Pulmonary Emphysema Using Magnetic Resonance Imaging and x-ray Computed Tomography

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality affecting at least 600 million people worldwide. The most widely used clinical measurements of lung function such as spirometry and plethysmography are generally accepted for diagnosis and monitoring of the disease. However, these tests provide only global measures of lung function and they are insensitive to early disease changes. Imaging tools that are currently available have the potential to provide regional information about lung structure and function but at present are mainly used for qualitative assessment of disease and disease progression. In this thesis, we focused on the application of quantitative measurements of lung structure derived from 1H magnetic resonance imaging (MRI) and high resolution computed tomography (CT) in subjects diagnosed with COPD by a physician. Our results showed that significant and moderately strong relationship exists between 1H signal intensity (SI) and 3He apparent diffusion coefficient (ADC), as well as between 1H SI and CT measurements of emphysema. This suggests that these imaging methods may be quantifying the same tissue changes in COPD, and that pulmonary 1H SI may be used effectively to monitor emphysema as a complement to CT and noble gas MRI. Additionally, our results showed that objective multi-threshold analysis of CT images for emphysema scoring that takes into account the frequency distribution of each Hounsfield unit (HU) threshold was effective in correctly classifying the patient into COPD and healthy subgroups. Finally, we found a significant correlation between whole lung average subjective and objective emphysema scores with high inter-observer agreement. It is concluded that 1H MRI and high resolution CT can be used to quantitatively evaluate lung tissue alterations in COPD subjects

Artificial Intelligence in Image-Based Screening, Diagnostics, and Clinical Care of Cardiopulmonary Diseases

Cardiothoracic and pulmonary diseases are a significant cause of mortality and morbidity worldwide. The COVID-19 pandemic has highlighted the lack of access to clinical care, the overburdened medical system, and the potential of artificial intelligence (AI) in improving medicine. There are a variety of diseases affecting the cardiopulmonary system including lung cancers, heart disease, tuberculosis (TB), etc., in addition to COVID-19-related diseases. Screening, diagnosis, and management of cardiopulmonary diseases has become difficult owing to the limited availability of diagnostic tools and experts, particularly in resource-limited regions. Early screening, accurate diagnosis and staging of these diseases could play a crucial role in treatment and care, and potentially aid in reducing mortality. Radiographic imaging methods such as computed tomography (CT), chest X-rays (CXRs), and echo ultrasound (US) are widely used in screening and diagnosis. Research on using image-based AI and machine learning (ML) methods can help in rapid assessment, serve as surrogates for expert assessment, and reduce variability in human performance. In this Special Issue, “Artificial Intelligence in Image-Based Screening, Diagnostics, and Clinical Care of Cardiopulmonary Diseases”, we have highlighted exemplary primary research studies and literature reviews focusing on novel AI/ML methods and their application in image-based screening, diagnosis, and clinical management of cardiopulmonary diseases. We hope that these articles will help establish the advancements in AI

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

Image processing in medicine advances for phenotype characterization, computer-assisted diagnosis and surgical planning

En esta Tesis presentamos nuestras contribuciones al estado del arte en procesamiento digital de imágenes médicas, articulando nuestra exposición en torno a los tres principales objetivos de la adquisición de imágenes en medicina: la prevención, el diagnóstico y el tratamiento de las enfermedades. La prevención de la enfermedad se puede conseguir a veces mediante una caracterización cuidadosa de los fenotipos propios de la misma. Tal caracterización a menudo se alcanza a partir de imágenes. Presentamos nuestro trabajo en caracterización del enfisema pulmonar a partir de imágenes TAC (Tomografía Axial Computerizada) de tórax en alta resolución, a través del análisis de las texturas locales de la imagen. Nos proponemos llenar el vacío existente entre la práctica clínica actual, y las sofisticadas pero costosas técnicas de caracterización de regiones texturadas, disponibles en la literatura. Lo hacemos utilizando la distribución local de intensidades como un descriptor adecuado para determinar el grado de destrucción de tejido en pulmones enfisematosos. Se presentan interesantes resultados derivados del análisis de varios cientos de imágenes para niveles variables de severidad de la enfermedad, sugiriendo tanto la validez de nuestras hipótesis, como la pertinencia de este tipo de análisis para la comprensión de la enfermedad pulmonar obstructiva crónica. El procesado de imágenes médicas también puede asistir en el diagnóstico y detección de enfermedades. Presentamos nuestras contribuciones a este campo, que consisten en técnicas de segmentación y cuantificación de imágenes dermatoscópicas de lesiones de la piel. La segmentación se obtiene mediante un novedoso algoritmo basado en contornos activos que explota al máximo el contenido cromático de las imágenes, gracias a la maximización de la discrepancia mediante comparaciones cross-bin. La cuantificación de texturas en lesiones melanocíticas se lleva a cabo utilizando un modelado de los patrones de pigmentación basado en campos aleatorios de Markov, en un esfuerzo por adoptar la tendencia emergente en dermatología: la detección de la malignidad mediante el análisis de la irregularidad de la textura. Los resultados para ambas técnicas son validados con un conjunto significativo de imágenes dermatológicas, sugiriendo líneas interesantes para la detección automática del melanoma maligno. Cuando la enfermedad ya está presente, el tratamiento digital de imágenes puede asistir en la planificación quirúrgica y la intervención guiada por imagen. La planificación terapeútica, ejemplicada por la planificación de cirugía plástica usando realidad virtual, se aborda en nuestro trabajo en segmentación de hueso/grasa/músculo en imágenes TAC. Usando un abordaje interactivo e incremental, nuestro sistema permite obtener segmentaciones precisas a partir de unos cuantos clics de ratón para una gran variedad de condiciones de adquisición y frente a anatomícas anormales. Presentamos nuestra metodología, y nuestra validación experimental profusa basada tanto en segmentaciones manuales como en valoraciones subjetivas de los usuarios, e indicamos referencias al lector que detallan los beneficios obtenidos con el uso de la plataforma de planifificación que utiliza nuestro algoritmo. Como conclusión presentamos una disertación final sobre la importancia de nuestros resultados y las líneas probables de trabajo futuro hacía el objetivo último de mejorar el cuidado de la salud mediante técnicas de tratamiento digital de imágenes médicas.In this Thesis we present our contributions to the state-of-the-art in medical image processing, articulating our exposition around the three main roles of medical imaging: disease prevention, diagnosis and treatment. Disease prevention can sometimes be achieved by proper characterization of disease phenotypes. Such characterization is often attained from the standpoint of imaging. We present our work in characterization of emphysema from highresolution computed-tomography images via quanti_cation of local texture. We propose to _ll the gap between current clinical practice and sophisticated texture approaches by the use of local intensity distributions as an adequate descriptor for the degree of tissue destruction in the emphysematous lung. Interesting results are presented from the analysis of several hundred datasets of lung CT for varying disease severity, suggesting both the correctness of our hypotheses and the pertinence of _ne emphysema quanti_cation for understanding of chronic obstructive pulmonary disease. Medical image processing can also assist in the diagnosis and detection of disease. We introduce our contributions to this_eld, consisting of segmentation and quanti_cation techniques in application to dermatoscopy images of skin lesions. Segmentation is achieved via a novel active contour algorithm that fully exploits the color content of the images, via cross-bin histogram dissimilarity maximization. Texture quanti_cation in the context of melanocytic lesions is performed using modelization of the pigmentation patterns via Markov random elds, in an e_ort to embrace the emerging trend in dermatology: malignancy assessment based on texture irregularity analysis. Experimental results for both, the segmentation and quanti_cation proposed techniques, will be validated on a signi_cant set of dermatoscopy images, suggesting interesting pathways towards automatic detection and diagnosis of malignant melanoma. Once disease has occurred, image processing can assist in therapeutical planning and image-guided intervention. Therapeutical planning, exempli_ed by virtual reality surgical planning, is tackled by our work in segmentation of bone/fat/muscle in CT images for plastic surgery planning. Using an interactive, incremental approach, our system is able to provide accurate segmentations based on a couple of mouse-clicks for a wide variety of imaging conditions and abnormal anatomies. We present our methodology, and provide profuse experimental validation based on manual segmentations and subjective assessment, and refer the reader to related work reporting on the clinical bene_ts obtained using the virtual reality platform hosting our algorithm. As a conclusion we present a _nal dissertation on the signi_cance of our results and the probable lines of future work towards fully bene_tting healthcare using medical image processing