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

Informative sample generation using class aware generative adversarial networks for classification of chest Xrays

Training robust deep learning (DL) systems for disease detection from medical images is challenging due to limited images covering different disease types and severity. The problem is especially acute, where there is a severe class imbalance. We propose an active learning (AL) framework to select most informative samples for training our model using a Bayesian neural network. Informative samples are then used within a novel class aware generative adversarial network (CAGAN) to generate realistic chest xray images for data augmentation by transferring characteristics from one class label to another. Experiments show our proposed AL framework is able to achieve state-of-the-art performance by using about $35\%$ of the full dataset, thus saving significant time and effort over conventional methods

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

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

Radiogenomics Framework for Associating Medical Image Features with Tumour Genetic Characteristics

Significant progress has been made in the understanding of human cancers at the molecular genetics level and it is providing new insights into their underlying pathophysiology. This progress has enabled the subclassification of the disease and the development of targeted therapies that address specific biological pathways. However, obtaining genetic information remains invasive and costly. Medical imaging is a non-invasive technique that captures important visual characteristics (i.e. image features) of abnormalities and plays an important role in routine clinical practice. Advancements in computerised medical image analysis have enabled quantitative approaches to extract image features that can reflect tumour genetic characteristics, leading to the emergence of ‘radiogenomics’. Radiogenomics investigates the relationships between medical imaging features and tumour molecular characteristics, and enables the derivation of imaging surrogates (radiogenomics features) to genetic biomarkers that can provide alternative approaches to non-invasive and accurate cancer diagnosis. This thesis presents a new framework that combines several novel methods for radiogenomics analysis that associates medical image features with tumour genetic characteristics, with the main objectives being: i) a comprehensive characterisation of tumour image features that reflect underlying genetic information; ii) a method that identifies radiogenomics features encoding common pathophysiological information across different diseases, overcoming the dependence on large annotated datasets; and iii) a method that quantifies radiogenomics features from multi-modal imaging data and accounts for unique information encoded in tumour heterogeneity sub-regions. The present radiogenomics methods advance radiogenomics analysis and contribute to improving research in computerised medical image analysis

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

Evaluating and Improving 4D-CT Image Segmentation for Lung Cancer Radiotherapy

Lung cancer is a high-incidence disease with low survival despite surgical advances and concurrent chemo-radiotherapy strategies. Image-guided radiotherapy provides for treatment measures, however, significant challenges exist for imaging, treatment planning, and delivery of radiation due to the influence of respiratory motion. 4D-CT imaging is capable of improving image quality of thoracic target volumes influenced by respiratory motion. 4D-CT-based treatment planning strategies requires highly accurate anatomical segmentation of tumour volumes for radiotherapy treatment plan optimization. Variable segmentation of tumour volumes significantly contributes to uncertainty in radiotherapy planning due to a lack of knowledge regarding the exact shape of the lesion and difficulty in quantifying variability. As image-segmentation is one of the earliest tasks in the radiotherapy process, inherent geometric uncertainties affect subsequent stages, potentially jeopardizing patient outcomes. Thus, this work assesses and suggests strategies for mitigation of segmentation-related geometric uncertainties in 4D-CT-based lung cancer radiotherapy at pre- and post-treatment planning stages