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

Segmentation of Pulmonary Nodules in Computed Tomography Using a Regression Neural Network Approach and Its Application to the Lung Image Database Consortium and Image Database Resource Initiative Dataset

We present new pulmonary nodule segmentation algorithms for computed tomography (CT). These include a fully-automated (FA) system, a semi-automated (SA) system, and a hybrid system. Like most traditional systems, the new FA system requires only a single user-supplied cue point. On the other hand, the SA system represents a new algorithm class requiring 8 user-supplied control points. This does increase the burden on the user, but we show that the resulting system is highly robust and can handle a variety of challenging cases. The proposed hybrid system starts with the FA system. If improved segmentation results are needed, the SA system is then deployed. The FA segmentation engine has 2 free parameters, and the SA system has 3. These parameters are adaptively determined for each nodule in a search process guided by a regression neural network (RNN). The RNN uses a number of features computed for each candidate segmentation. We train and test our systems using the new Lung Image Database Consortium and Image Database Resource Initiative (LIDC–IDRI) data. To the best of our knowledge, this is one of the first nodule-specific performance benchmarks using the new LIDC–IDRI dataset. We also compare the performance of the proposed methods with several previously reported results on the same data used by those other methods. Our results suggest that the proposed FA system improves upon the state-of-the-art, and the SA system offers a considerable boost over the FA system

Segmentation of Pulmonary Nodules in Computed Tomography using a Regression Neural Network Approach and its Application to the Lung Image Database Consortium and Image Database Resource Initiative Dataset

We present new pulmonary nodule segmentation algorithms for computed tomography (CT). These include a fully-automated (FA) system, a semi-automated (SA) system, and a hybrid system. Like most traditional systems, the new FA system requires only a single user-supplied cue point. On the other hand, the SA system represents a new algorithm class requiring 8 user-supplied control points. This does increase the burden on the user, but we show that the resulting system is highly robust and can handle a variety of challenging cases. The proposed hybrid system starts with the FA system. If improved segmentation results are needed, the SA system is then deployed. The FA segmentation engine has 2 free parameters, and the SA system has 3. These parameters are adaptively determined for each nodule in a search process guided by a regression neural network (RNN). The RNN uses a number of features computed for each candidate segmentation. We train and test our systems using the new Lung Image Database Consortium and Image Database Resource Initiative (LIDC–IDRI) data. To the best of our knowledge, this is one of the first nodule-specific performance benchmarks using the new LIDC–IDRI dataset. We also compare the performance of the proposed methods with several previously reported results on the same data used by those other methods. Our results suggest that the proposed FA system improves upon the state-of-the-art, and the SA system offers a considerable boost over the FA system

Segmentation of Pulmonary Nodules in Computed Tomography using a Regression Neural Network Approach and its Application to the Lung Image Database Consortium and Image Database Resource Initiative Dataset

We present new pulmonary nodule segmentation algorithms for computed tomography (CT). These include a fully-automated (FA) system, a semi-automated (SA) system, and a hybrid system. Like most traditional systems, the new FA system requires only a single user-supplied cue point. On the other hand, the SA system represents a new algorithm class requiring 8 user-supplied control points. This does increase the burden on the user, but we show that the resulting system is highly robust and can handle a variety of challenging cases. The proposed hybrid system starts with the FA system. If improved segmentation results are needed, the SA system is then deployed. The FA segmentation engine has 2 free parameters, and the SA system has 3. These parameters are adaptively determined for each nodule in a search process guided by a regression neural network (RNN). The RNN uses a number of features computed for each candidate segmentation. We train and test our systems using the new Lung Image Database Consortium and Image Database Resource Initiative (LIDC–IDRI) data. To the best of our knowledge, this is one of the first nodule-specific performance benchmarks using the new LIDC–IDRI dataset. We also compare the performance of the proposed methods with several previously reported results on the same data used by those other methods. Our results suggest that the proposed FA system improves upon the state-of-the-art, and the SA system offers a considerable boost over the FA system

CAD system for lung nodule analysis.

Lung cancer is the deadliest type of known cancer in the United States, claiming hundreds of thousands of lives each year. However, despite the high mortality rate, the 5-year survival rate after resection of Stage 1A non–small cell lung cancer is currently in the range of 62%– 82% and in recent studies even 90%. Patient survival is highly correlated with early detection. Computed Tomography (CT) technology services the early detection of lung cancer tremendously by offering a minimally invasive medical diagnostic tool. Some early types of lung cancer begin with a small mass of tissue within the lung, less than 3 cm in diameter, called a nodule. Most nodules found in a lung are benign, but a small population of them becomes malignant over time. Expert analysis of CT scans is the first step in determining whether a nodule presents a possibility for malignancy but, due to such low spatial support, many potentially harmful nodules go undetected until other symptoms motivate a more thorough search. Computer Vision and Pattern Recognition techniques can play a significant role in aiding the process of detecting and diagnosing lung nodules. This thesis outlines the development of a CAD system which, given an input CT scan, provides a functional and fast, second-opinion diagnosis to physicians. The entire process of lung nodule screening has been cast as a system, which can be enhanced by modern computing technology, with the hopes of providing a feasible diagnostic tool for clinical use. It should be noted that the proposed CAD system is presented as a tool for experts—not a replacement for them. The primary motivation of this thesis is the design of a system that could act as a catalyst for reducing the mortality rate associated with lung cancer

Lung nodule modeling and detection for computerized image analysis of low dose CT imaging of the chest.

From a computerized image analysis prospective, early diagnosis of lung cancer involves detection of doubtful nodules and classification into different pathologies. The detection stage involves a detection approach, usually by template matching, and an authentication step to reduce false positives, usually conducted by a classifier of one form or another; statistical, fuzzy logic, support vector machines approaches have been tried. The classification stage matches, according to a particular approach, the characteristics (e.g., shape, texture and spatial distribution) of the detected nodules to common characteristics (again, shape, texture and spatial distribution) of nodules with known pathologies (confirmed by biopsies). This thesis focuses on the first step; i.e., nodule detection. Specifically, the thesis addresses three issues: a) understanding the CT data of typical low dose CT (LDCT) scanning of the chest, and devising an image processing approach to reduce the inherent artifacts in the scans; b) devising an image segmentation approach to isolate the lung tissues from the rest of the chest and thoracic regions in the CT scans; and c) devising a nodule modeling methodology to enhance the detection rate and lend benefits for the ultimate step in computerized image analysis of LDCT of the lungs, namely associating a pathology to the detected nodule. The methodology for reducing the noise artifacts is based on noise analysis and examination of typical LDCT scans that may be gathered on a repetitive fashion; since, a reduction in the resolution is inevitable to avoid excessive radiation. Two optimal filtering methods are tested on samples of the ELCAP screening data; the Weiner and the Anisotropic Diffusion Filters. Preference is given to the Anisotropic Diffusion Filter, which can be implemented on 7x7 blocks/windows of the CT data. The methodology for lung segmentation is based on the inherent characteristics of the LDCT scans, shown as distinct bi-modal gray scale histogram. A linear model is used to describe the histogram (the joint probability density function of the lungs and non-lungs tissues) by a linear combination of weighted kernels. The Gaussian kernels were chosen, and the classic Expectation-Maximization (EM) algorithm was employed to estimate the marginal probability densities of the lungs and non-lungs tissues, and select an optimal segmentation threshold. The segmentation is further enhanced using standard shape analysis based on mathematical morphology, which improves the continuity of the outer and inner borders of the lung tissues. This approach (a preliminary version of it appeared in [14]) is found to be adequate for lung segmentation as compared to more sophisticated approaches developed at the CVIP Lab (e.g., [15][16]) and elsewhere. The methodology developed for nodule modeling is based on understanding the physical characteristics of the nodules in LDCT scans, as identified by human experts. An empirical model is introduced for the probability density of the image intensity (or Hounsfield units) versus the radial distance measured from the centroid – center of mass - of typical nodules. This probability density showed that the nodule spatial support is within a circle/square of size 10 pixels; i.e., limited to 5 mm in length; which is within the range that the radiologist specify to be of concern. This probability density is used to fill in the intensity (or Hounsfield units) of parametric nodule models. For these models (e.g., circles or semi-circles), given a certain radius, we calculate the intensity (or Hounsfield units) using an exponential expression for the radial distance with parameters specified from the histogram of an ensemble of typical nodules. This work is similar in spirit to the earlier work of Farag et al., 2004 and 2005 [18][19], except that the empirical density of the radial distance and the histogram of typical nodules provide a data-driven guide for estimating the intensity (or Hounsfield units) of the nodule models. We examined the sensitivity and specificity of parametric nodules in a template-matching framework for nodule detection. We show that false positives are inevitable problems with typical machine learning methods of automatic lung nodule detection, which invites further efforts and perhaps fresh thinking into automatic nodule detection. A new approach for nodule modeling is introduced in Chapter 5 of this thesis, which brings high promise in both the detection, and the classification of nodules. Using the ELCAP study, we created an ensemble of four types of nodules and generated a nodule model for each type based on optimal data reduction methods. The resulting nodule model, for each type, has lead to drastic improvements in the sensitivity and specificity of nodule detection. This approach may be used as well for classification. In conclusion, the methodologies in this thesis are based on understanding the LDCT scans and what is to be expected in terms of image quality. Noise reduction and image segmentation are standard. The thesis illustrates that proper nodule models are possible and indeed a computerized approach for image analysis to detect and classify lung nodules is feasible. Extensions to the results in this thesis are immediate and the CVIP Lab has devised plans to pursue subsequent steps using clinical data

Collaborative Artificial Intelligence Algorithms for Medical Imaging Applications

In this dissertation, we propose novel machine learning algorithms for high-risk medical imaging applications. Specifically, we tackle current challenges in radiology screening process and introduce cutting-edge methods for image-based diagnosis, detection and segmentation. We incorporate expert knowledge through eye-tracking, making the whole process human-centered. This dissertation contributes to machine learning, computer vision, and medical imaging research by: 1) introducing a mathematical formulation of radiologists level of attention, and sparsifying their gaze data for a better extraction and comparison of search patterns. 2) proposing novel, local and global, image analysis algorithms. Imaging based diagnosis and pattern analysis are high-risk Artificial Intelligence applications. A standard radiology screening procedure includes detection, diagnosis and measurement (often done with segmentation) of abnormalities. We hypothesize that having a true collaboration is essential for a better control mechanism, in such applications. In this regard, we propose to form a collaboration medium between radiologists and machine learning algorithms through eye-tracking. Further, we build a generic platform consisting of novel machine learning algorithms for each of these tasks. Our collaborative algorithm utilizes eye tracking and includes an attention model and gaze-pattern analysis, based on data clustering and graph sparsification. Then, we present a semi-supervised multi-task network for local analysis of image in radiologists\u27 ROIs, extracted in the previous step. To address missing tumors and analyze regions that are completely missed by radiologists during screening, we introduce a detection framework, S4ND: Single Shot Single Scale Lung Nodule Detection. Our proposed detection algorithm is specifically designed to handle tiny abnormalities in lungs, which are easy to miss by radiologists. Finally, we introduce a novel projective adversarial framework, PAN: Projective Adversarial Network for Medical Image Segmentation, for segmenting complex 3D structures/organs, which can be beneficial in the screening process by guiding radiologists search areas through segmentation of desired structure/organ

Development, Implementation and Pre-clinical Evaluation of Medical Image Computing Tools in Support of Computer-aided Diagnosis: Respiratory, Orthopedic and Cardiac Applications

Over the last decade, image processing tools have become crucial components of all clinical and research efforts involving medical imaging and associated applications. The imaging data available to the radiologists continue to increase their workload, raising the need for efficient identification and visualization of the required image data necessary for clinical assessment. Computer-aided diagnosis (CAD) in medical imaging has evolved in response to the need for techniques that can assist the radiologists to increase throughput while reducing human error and bias without compromising the outcome of the screening, diagnosis or disease assessment. More intelligent, but simple, consistent and less time-consuming methods will become more widespread, reducing user variability, while also revealing information in a more clear, visual way. Several routine image processing approaches, including localization, segmentation, registration, and fusion, are critical for enhancing and enabling the development of CAD techniques. However, changes in clinical workflow require significant adjustments and re-training and, despite the efforts of the academic research community to develop state-of-the-art algorithms and high-performance techniques, their footprint often hampers their clinical use. Currently, the main challenge seems to not be the lack of tools and techniques for medical image processing, analysis, and computing, but rather the lack of clinically feasible solutions that leverage the already developed and existing tools and techniques, as well as a demonstration of the potential clinical impact of such tools. Recently, more and more efforts have been dedicated to devising new algorithms for localization, segmentation or registration, while their potential and much intended clinical use and their actual utility is dwarfed by the scientific, algorithmic and developmental novelty that only result in incremental improvements over already algorithms. In this thesis, we propose and demonstrate the implementation and evaluation of several different methodological guidelines that ensure the development of image processing tools --- localization, segmentation and registration --- and illustrate their use across several medical imaging modalities --- X-ray, computed tomography, ultrasound and magnetic resonance imaging --- and several clinical applications: Lung CT image registration in support for assessment of pulmonary nodule growth rate and disease progression from thoracic CT images. Automated reconstruction of standing X-ray panoramas from multi-sector X-ray images for assessment of long limb mechanical axis and knee misalignment. Left and right ventricle localization, segmentation, reconstruction, ejection fraction measurement from cine cardiac MRI or multi-plane trans-esophageal ultrasound images for cardiac function assessment. When devising and evaluating our developed tools, we use clinical patient data to illustrate the inherent clinical challenges associated with highly variable imaging data that need to be addressed before potential pre-clinical validation and implementation. In an effort to provide plausible solutions to the selected applications, the proposed methodological guidelines ensure the development of image processing tools that help achieve sufficiently reliable solutions that not only have the potential to address the clinical needs, but are sufficiently streamlined to be potentially translated into eventual clinical tools provided proper implementation. G1: Reducing the number of degrees of freedom (DOF) of the designed tool, with a plausible example being avoiding the use of inefficient non-rigid image registration methods. This guideline addresses the risk of artificial deformation during registration and it clearly aims at reducing complexity and the number of degrees of freedom. G2: The use of shape-based features to most efficiently represent the image content, either by using edges instead of or in addition to intensities and motion, where useful. Edges capture the most useful information in the image and can be used to identify the most important image features. As a result, this guideline ensures a more robust performance when key image information is missing. G3: Efficient method of implementation. This guideline focuses on efficiency in terms of the minimum number of steps required and avoiding the recalculation of terms that only need to be calculated once in an iterative process. An efficient implementation leads to reduced computational effort and improved performance. G4: Commence the workflow by establishing an optimized initialization and gradually converge toward the final acceptable result. This guideline aims to ensure reasonable outcomes in consistent ways and it avoids convergence to local minima, while gradually ensuring convergence to the global minimum solution. These guidelines lead to the development of interactive, semi-automated or fully-automated approaches that still enable the clinicians to perform final refinements, while they reduce the overall inter- and intra-observer variability, reduce ambiguity, increase accuracy and precision, and have the potential to yield mechanisms that will aid with providing an overall more consistent diagnosis in a timely fashion