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

Open-source virtual bronchoscopy for image guided navigation

This thesis describes the development of an open-source system for virtual bronchoscopy used in combination with electromagnetic instrument tracking. The end application is virtual navigation of the lung for biopsy of early stage cancer nodules. The open-source platform 3D Slicer was used for creating freely available algorithms for virtual bronchscopy. Firstly, the development of an open-source semi-automatic algorithm for prediction of solitary pulmonary nodule malignancy is presented. This approach may help the physician decide whether to proceed with biopsy of the nodule. The user-selected nodule is segmented in order to extract radiological characteristics (i.e., size, location, edge smoothness, calcification presence, cavity wall thickness) which are combined with patient information to calculate likelihood of malignancy. The overall accuracy of the algorithm is shown to be high compared to independent experts' assessment of malignancy. The algorithm is also compared with two different predictors, and our approach is shown to provide the best overall prediction accuracy. The development of an airway segmentation algorithm which extracts the airway tree from surrounding structures on chest Computed Tomography (CT) images is then described. This represents the first fundamental step toward the creation of a virtual bronchoscopy system. Clinical and ex-vivo images are used to evaluate performance of the algorithm. Different CT scan parameters are investigated and parameters for successful airway segmentation are optimized. Slice thickness is the most affecting parameter, while variation of reconstruction kernel and radiation dose is shown to be less critical. Airway segmentation is used to create a 3D rendered model of the airway tree for virtual navigation. Finally, the first open-source virtual bronchoscopy system was combined with electromagnetic tracking of the bronchoscope for the development of a GPS-like system for navigating within the lungs. Tools for pre-procedural planning and for helping with navigation are provided. Registration between the lungs of the patient and the virtually reconstructed airway tree is achieved using a landmark-based approach. In an attempt to reduce difficulties with registration errors, we also implemented a landmark-free registration method based on a balanced airway survey. In-vitro and in-vivo testing showed good accuracy for this registration approach. The centreline of the 3D airway model is extracted and used to compensate for possible registration errors. Tools are provided to select a target for biopsy on the patient CT image, and pathways from the trachea towards the selected targets are automatically created. The pathways guide the physician during navigation, while distance to target information is updated in real-time and presented to the user. During navigation, video from the bronchoscope is streamed and presented to the physician next to the 3D rendered image. The electromagnetic tracking is implemented with 5 DOF sensing that does not provide roll rotation information. An intensity-based image registration approach is implemented to rotate the virtual image according to the bronchoscope's rotations. The virtual bronchoscopy system is shown to be easy to use and accurate in replicating the clinical setting, as demonstrated in the pre-clinical environment of a breathing lung method. Animal studies were performed to evaluate the overall system performance

A Survey on Deep Learning in Medical Image Analysis

Deep learning algorithms, in particular convolutional networks, have rapidly become a methodology of choice for analyzing medical images. This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year. We survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks and provide concise overviews of studies per application area. Open challenges and directions for future research are discussed.Comment: Revised survey includes expanded discussion section and reworked introductory section on common deep architectures. Added missed papers from before Feb 1st 201

Heterogeneidad tumoral en imágenes PET-CT

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Físicas, Departamento de Estructura de la Materia, Física Térmica y Electrónica, leída el 28/01/2021Cancer is a leading cause of morbidity and mortality [1]. The most frequent cancers worldwide are non–small cell lung carcinoma (NSCLC) and breast cancer [2], being their management a challenging task [3]. Tumor diagnosis is usually made through biopsy [4]. However, medical imaging also plays an important role in diagnosis, staging, response to treatment, and recurrence assessment [5]. Tumor heterogeneity is recognized to be involved in cancer treatment failure, with worse clinical outcomes for highly heterogeneous tumors [6,7]. This leads to the existence of tumor sub-regions with different biological behavior (some more aggressive and treatment-resistant than others) [8-10]. Which are characterized by a different pattern of vascularization, vessel permeability, metabolism, cell proliferation, cell death, and other features, that can be measured by modern medical imaging techniques, including positron emission tomography/computed tomography (PET/CT) [10-12]. Thus, the assessment of tumor heterogeneity through medical images could allow the prediction of therapy response and long-term outcomes of patients with cancer [13]. PET/CT has become essential in oncology [14,15] and is usually evaluated through semiquantitative metabolic parameters, such as maximum/mean standard uptake value (SUVmax, SUVmean) or metabolic tumor volume (MTV), which are valuables as prognostic image-based biomarkers in several tumors [16-17], but these do not assess tumor heterogeneity. Likewise, fluorodeoxyglucose (18F-FDG) PET/CT is important to differentiate malignant from benign solitary pulmonary nodules (SPN), reducing so the number of patients who undergo unnecessary surgical biopsies. Several publications have shown that some quantitative image features, extracted from medical images, are suitable for diagnosis, tumor staging, the prognosis of treatment response, and long-term evolution of cancer patients [18-20]. The process of extracting and relating image features with clinical or biological variables is called “Radiomics” [9,20-24]. Radiomic parameters, such as textural features have been related directly to tumor heterogeneity [25]. This thesis investigated the relationships of the tumor heterogeneity, assessed by 18F-FDG-PET/CT texture analysis, with metabolic parameters and pathologic staging in patients with NSCLC, and explored the diagnostic performance of different metabolic, morphologic, and clinical criteria for classifying (malignant or not) of solitary pulmonary nodules (SPN). Furthermore, 18F-FDG-PET/CT radiomic features of patients with recurrent/metastatic breast cancer were used for constructing predictive models of response to the chemotherapy, based on an optimal combination of several feature selection and machine learning (ML) methods...El cáncer es una de las principales causas de morbilidad y mortalidad. Los más frecuentes son el carcinoma de pulmón de células no pequeñas (NSCLC) y el cáncer de mama, siendo su tratamiento un reto. El diagnóstico se suele realizar mediante biopsia. La heterogeneidad tumoral (HT) está implicada en el fracaso del tratamiento del cáncer, con peores resultados clínicos para tumores muy heterogéneos. Esta conduce a la existencia de subregiones tumorales con diferente comportamiento biológico (algunas más agresivas y resistentes al tratamiento); las cuales se caracterizan por diferentes patrones de vascularización, permeabilidad de los vasos sanguíneos, metabolismo, proliferación y muerte celular, que se pueden medir mediante imágenes médicas, incluida la tomografía por emisión de positrones/tomografía computarizada con fluorodesoxiglucosa (18F-FDG-PET/CT). La evaluación de la HT a través de imágenes médicas, podría mejorar la predicción de la respuesta al tratamiento y de los resultados a largo plazo, en pacientes con cáncer. La 18F-FDG-PET/CT es esencial en oncología, generalmente se evalúa con parámetros metabólicos semicuantitativos, como el valor de captación estándar máximo/medio (SUVmáx, SUVmedio) o el volumen tumoral metabólico (MTV), que tienen un gran valor pronóstico en varios tumores, pero no evalúan la HT. Asimismo, es importante para diferenciar los nódulos pulmonares solitarios (NPS) malignos de los benignos, reduciendo el número de pacientes que van a biopsias quirúrgicas innecesarias. Publicaciones recientes muestran que algunas características cuantitativas, extraídas de las imágenes médicas, son robustas para diagnóstico, estadificación, pronóstico de la respuesta al tratamiento y la evolución, de pacientes con cáncer. El proceso de extraer y relacionar estas características con variables clínicas o biológicas se denomina “Radiomica”. Algunos parámetros radiómicos, como la textura, se han relacionado directamente con la HT. Esta tesis investigó las relaciones entre HT, evaluada mediante análisis de textura (AT) de imágenes 18F-FDG-PET/CT, con parámetros metabólicos y estadificación patológica en pacientes con NSCLC, y exploró el rendimiento diagnóstico de diferentes criterios metabólicos, morfológicos y clínicos para la clasificación de NPS. Además, se usaron características radiómicas de imágenes 18F-FDG-PET/CT de pacientes con cáncer de mama recurrente/metastásico, para construir modelos predictivos de la respuesta a la quimioterapia, combinándose varios métodos de selección de características y aprendizaje automático (ML)...Fac. de Ciencias FísicasTRUEunpu

Advanced machine learning methods for oncological image analysis

Cancer is a major public health problem, accounting for an estimated 10 million deaths worldwide in 2020 alone. Rapid advances in the field of image acquisition and hardware development over the past three decades have resulted in the development of modern medical imaging modalities that can capture high-resolution anatomical, physiological, functional, and metabolic quantitative information from cancerous organs. Therefore, the applications of medical imaging have become increasingly crucial in the clinical routines of oncology, providing screening, diagnosis, treatment monitoring, and non/minimally- invasive evaluation of disease prognosis. The essential need for medical images, however, has resulted in the acquisition of a tremendous number of imaging scans. Considering the growing role of medical imaging data on one side and the challenges of manually examining such an abundance of data on the other side, the development of computerized tools to automatically or semi-automatically examine the image data has attracted considerable interest. Hence, a variety of machine learning tools have been developed for oncological image analysis, aiming to assist clinicians with repetitive tasks in their workflow. This thesis aims to contribute to the field of oncological image analysis by proposing new ways of quantifying tumor characteristics from medical image data. Specifically, this thesis consists of six studies, the first two of which focus on introducing novel methods for tumor segmentation. The last four studies aim to develop quantitative imaging biomarkers for cancer diagnosis and prognosis. The main objective of Study I is to develop a deep learning pipeline capable of capturing the appearance of lung pathologies, including lung tumors, and integrating this pipeline into the segmentation networks to leverage the segmentation accuracy. The proposed pipeline was tested on several comprehensive datasets, and the numerical quantifications show the superiority of the proposed prior-aware DL framework compared to the state of the art. Study II aims to address a crucial challenge faced by supervised segmentation models: dependency on the large-scale labeled dataset. In this study, an unsupervised segmentation approach is proposed based on the concept of image inpainting to segment lung and head- neck tumors in images from single and multiple modalities. The proposed autoinpainting pipeline shows great potential in synthesizing high-quality tumor-free images and outperforms a family of well-established unsupervised models in terms of segmentation accuracy. Studies III and IV aim to automatically discriminate the benign from the malignant pulmonary nodules by analyzing the low-dose computed tomography (LDCT) scans. In Study III, a dual-pathway deep classification framework is proposed to simultaneously take into account the local intra-nodule heterogeneities and the global contextual information. Study IV seeks to compare the discriminative power of a series of carefully selected conventional radiomics methods, end-to-end Deep Learning (DL) models, and deep features-based radiomics analysis on the same dataset. The numerical analyses show the potential of fusing the learned deep features into radiomic features for boosting the classification power. Study V focuses on the early assessment of lung tumor response to the applied treatments by proposing a novel feature set that can be interpreted physiologically. This feature set was employed to quantify the changes in the tumor characteristics from longitudinal PET-CT scans in order to predict the overall survival status of the patients two years after the last session of treatments. The discriminative power of the introduced imaging biomarkers was compared against the conventional radiomics, and the quantitative evaluations verified the superiority of the proposed feature set. Whereas Study V focuses on a binary survival prediction task, Study VI addresses the prediction of survival rate in patients diagnosed with lung and head-neck cancer by investigating the potential of spherical convolutional neural networks and comparing their performance against other types of features, including radiomics. While comparable results were achieved in intra- dataset analyses, the proposed spherical-based features show more predictive power in inter-dataset analyses. In summary, the six studies incorporate different imaging modalities and a wide range of image processing and machine-learning techniques in the methods developed for the quantitative assessment of tumor characteristics and contribute to the essential procedures of cancer diagnosis and prognosis

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

Learning Algorithms for Fat Quantification and Tumor Characterization

Obesity is one of the most prevalent health conditions. About 30% of the world\u27s and over 70% of the United States\u27 adult populations are either overweight or obese, causing an increased risk for cardiovascular diseases, diabetes, and certain types of cancer. Among all cancers, lung cancer is the leading cause of death, whereas pancreatic cancer has the poorest prognosis among all major cancers. Early diagnosis of these cancers can save lives. This dissertation contributes towards the development of computer-aided diagnosis tools in order to aid clinicians in establishing the quantitative relationship between obesity and cancers. With respect to obesity and metabolism, in the first part of the dissertation, we specifically focus on the segmentation and quantification of white and brown adipose tissue. For cancer diagnosis, we perform analysis on two important cases: lung cancer and Intraductal Papillary Mucinous Neoplasm (IPMN), a precursor to pancreatic cancer. This dissertation proposes an automatic body region detection method trained with only a single example. Then a new fat quantification approach is proposed which is based on geometric and appearance characteristics. For the segmentation of brown fat, a PET-guided CT co-segmentation method is presented. With different variants of Convolutional Neural Networks (CNN), supervised learning strategies are proposed for the automatic diagnosis of lung nodules and IPMN. In order to address the unavailability of a large number of labeled examples required for training, unsupervised learning approaches for cancer diagnosis without explicit labeling are proposed. We evaluate our proposed approaches (both supervised and unsupervised) on two different tumor diagnosis challenges: lung and pancreas with 1018 CT and 171 MRI scans respectively. The proposed segmentation, quantification and diagnosis approaches explore the important adiposity-cancer association and help pave the way towards improved diagnostic decision making in routine clinical practice

Machine Intelligence for Advanced Medical Data Analysis: Manifold Learning Approach

In the current work, linear and non-linear manifold learning techniques, specifically Principle Component Analysis (PCA) and Laplacian Eigenmaps, are studied in detail. Their applications in medical image and shape analysis are investigated. In the first contribution, a manifold learning-based multi-modal image registration technique is developed, which results in a unified intensity system through intensity transformation between the reference and sensed images. The transformation eliminates intensity variations in multi-modal medical scans and hence facilitates employing well-studied mono-modal registration techniques. The method can be used for registering multi-modal images with full and partial data. Next, a manifold learning-based scale invariant global shape descriptor is introduced. The proposed descriptor benefits from the capability of Laplacian Eigenmap in dealing with high dimensional data by introducing an exponential weighting scheme. It eliminates the limitations tied to the well-known cotangent weighting scheme, namely dependency on triangular mesh representation and high intra-class quality of 3D models. In the end, a novel descriptive model for diagnostic classification of pulmonary nodules is presented. The descriptive model benefits from structural differences between benign and malignant nodules for automatic and accurate prediction of a candidate nodule. It extracts concise and discriminative features automatically from the 3D surface structure of a nodule using spectral features studied in the previous work combined with a point cloud-based deep learning network. Extensive experiments have been conducted and have shown that the proposed algorithms based on manifold learning outperform several state-of-the-art methods. Advanced computational techniques with a combination of manifold learning and deep networks can play a vital role in effective healthcare delivery by providing a framework for several fundamental tasks in image and shape processing, namely, registration, classification, and detection of features of interest