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

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

Convolutional Neural Network based Malignancy Detection of Pulmonary Nodule on Computer Tomography

Without performing biopsy that could lead physical damages to nerves and vessels, Computerized Tomography (CT) is widely used to diagnose the lung cancer due to the high sensitivity of pulmonary nodule detection. However, distinguishing pulmonary nodule in-between malignant and benign is still not an easy task. As the CT scans are mostly in relatively low resolution, it is not easy for radiologists to read the details of the scan image. In the past few years, the continuing rapid growth of CT scan analysis system has generated a pressing need for advanced computational tools to extract useful features to assist the radiologist in reading progress. Computer-aided detection (CAD) systems have been developed to reduce observational oversights by identifying the suspicious features that a radiologist looks for during case review. Most previous CAD systems rely on low-level non-texture imaging features such as intensity, shape, size or volume of the pulmonary nodules. However, the pulmonary nodules have a wide variety in shapes and sizes, and also the high visual similarities between benign and malignant patterns, so relying on non-texture imaging features is difficult for diagnosis of the nodule types. To overcome the problem of non-texture imaging features, more recent CAD systems adopted the supervised or unsupervised learning scheme to translate the content of the nodules into discriminative features. Such features enable high-level imaging features highly correlated with shape and texture. Convolutional neural networks (ConvNets), supervised methods related to deep learning, have been improved rapidly in recent years. Due to their great success in computer vision tasks, they are also expected to be helpful in medical imaging. In this thesis, a CAD based on a deep convolutional neural network (ConvNet) is designed and evaluated for malignant pulmonary nodules on computerized tomography. The proposed ConvNet, which is the core component of the proposed CAD system, is trained on the LUNGx challenge database to classify benign and malignant pulmonary nodules on CT. The architecture of the proposed ConvNet consists of 3 convolutional layers with maximum pooling operations and rectified linear units (ReLU) activations, followed by 2 denser layers with full-connectivities, and the architecture is carefully tailored for pulmonary nodule classification by considering the problems of over-fitting, receptive field, and imbalanced data. The proposed CAD system achieved the sensitivity of 0.896 and specificity of 8.78 at the optimal cut-off point of the receiver operating characteristic curve (ROC) with the area under the curve (AUC) of 0.920. The testing results showed that the proposed ConvNet achieves 10% higher AUC compared to the state-of-the-art work related to the unsupervised method. By integrating the proposed highly accurate ConvNet, the proposed CAD system also outperformed the other state-of-the-art ConvNets explicitly designed for diagnosis of pulmonary nodules detection or classification

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 Diagnosis of Pulmonary Nodules in Thoracic Computed Tomography.

Lung cancer is the leading cause of cancer death in the United States. The five-year survival rate is 15% because most patients present with advanced disease. If lung cancer is detected and treated at its earliest stage, the five-year survival rate has been reported as high as 92%. Computed tomography (CT) has been shown to be more sensitive than chest radiography in detecting abnormal lung lesions (nodules), especially when they are small. However, each thin-slice thoracic CT scan can contain hundreds of images. Large amounts of image data, radiologist fatigue, and diagnostic uncertainty may lead to missed cancers or unnecessary biopsies. We address these issues by developing a computer-aided diagnosis (CAD) system that would serve as a second reader for radiologists by analyzing nodules and providing a malignancy estimate using computer vision and machine learning techniques. To segment the nodules, we extended the active contour (AC) model to 3D by adding new energy terms. The classification accuracy, quantified by the area (Az) under the receiver operating characteristic curve, was used as the figure-of-merit to guide segmentation parameter optimization. The effect of CT acquisition parameters on 3DAC segmentation was systematically studied by imaging simulated nodules in chest phantoms. We conducted simulation studies to compare the relative performance of feature selection and classification methods and to examine the bias and variance introduced due to limited training sample sizes. We also designed new feature descriptors to describe the nodule surface, which were combined with texture and morphological features extracted from the nodule volume and the surrounding tissue to characterize the nodule. Stepwise feature selection was used to search for the subset of most effective features to be used in the linear discriminant analysis classifier. The CAD system achieved a test Az of 0.86±0.02 in a leave-one-case-out resampling scheme for 256 nodules from 152 patients. We conducted an observer study with six thoracic radiologists and found that their average Az in assessing nodule malignancy increased significantly (p<0.05) from 0.83±0.03 without CAD to 0.85±0.04 with CAD. These results indicate the potential usefulness of CAD as a second reader for radiologists in characterizing lung nodules.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60814/1/tway_1.pd

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

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

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