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

Highly accurate model for prediction of lung nodule malignancy with CT scans

Computed tomography (CT) examinations are commonly used to predict lung nodule malignancy in patients, which are shown to improve noninvasive early diagnosis of lung cancer. It remains challenging for computational approaches to achieve performance comparable to experienced radiologists. Here we present NoduleX, a systematic approach to predict lung nodule malignancy from CT data, based on deep learning convolutional neural networks (CNN). For training and validation, we analyze >1000 lung nodules in images from the LIDC/IDRI cohort. All nodules were identified and classified by four experienced thoracic radiologists who participated in the LIDC project. NoduleX achieves high accuracy for nodule malignancy classification, with an AUC of ~0.99. This is commensurate with the analysis of the dataset by experienced radiologists. Our approach, NoduleX, provides an effective framework for highly accurate nodule malignancy prediction with the model trained on a large patient population. Our results are replicable with software available at http://bioinformatics.astate.edu/NoduleX

Development and application in clinical practice of Computer-aided Diagnosis systems for the early detection of lung cancer

Lung cancer is the main cause of cancer-related deaths both in Europe and United States, because often it is diagnosed at late stages of the disease, when the survival rate is very low if compared to first asymptomatic stage. Lung cancer screening using annual low-dose Computed Tomography (CT) reduces lung cancer 5-year mortality by about 20% in comparison to annual screening with chest radiography. However, the detection of pulmonary nodules in low-dose chest CT scans is a very difficult task for radiologists, because of the large number (300/500) of slices to be analyzed. In order to support radiologists, researchers have developed Computer aided Detection (CAD) algorithms for the automated detection of pulmonary nodules in chest CT scans. Despite proved benefits of those systems on the radiologists detection sensitivity, the usage of CADs in clinical practice has not spread yet. The main objective of this thesis is to investigate and tackle the issues underlying this inconsistency. In particular, in Chapter 2 we introduce M5L, a fully automated Web and Cloud-based CAD for the automated detection of pulmonary nodules in chest CT scans. This system introduces a new paradigm in clinical practice, by making available CAD systems without requiring to radiologists any additional software and hardware installation. The proposed solution provides an innovative cost-effective approach for clinical structures. In Chapter 3 we present our international challenge aiming at a large-scale validation of state-of-the-art CAD systems. We also investigate and prove how the combination of different CAD systems reaches performances much higher than any best stand-alone system developed so far. Our results open the possibility to introduce in clinical practice very high-performing CAD systems, which miss a tiny fraction of clinically relevant nodules. Finally, we tested the performance of M5L on clinical data-sets. In chapter 4 we present the results of its clinical validation, which prove the positive impact of CAD as second reader in the diagnosis of pulmonary metastases on oncological patients with extra-thoracic cancers. The proposed approaches have the potential to exploit at best the features of different algorithms, developed independently, for any possible clinical application, setting a collaborative environment for algorithm comparison, combination, clinical validation and, if all of the above were successful, clinical practice

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

Machine learning approaches for lung cancer diagnosis.

The enormity of changes and development in the field of medical imaging technology is hard to fathom, as it does not just represent the technique and process of constructing visual representations of the body from inside for medical analysis and to reveal the internal structure of different organs under the skin, but also it provides a noninvasive way for diagnosis of various disease and suggest an efficient ways to treat them. While data surrounding all of our lives are stored and collected to be ready for analysis by data scientists, medical images are considered a rich source that could provide us with a huge amount of data, that could not be read easily by physicians and radiologists, with valuable information that could be used in smart ways to discover new knowledge from these vast quantities of data. Therefore, the design of computer-aided diagnostic (CAD) system, that can be approved for use in clinical practice that aid radiologists in diagnosis and detecting potential abnormalities, is of a great importance. This dissertation deals with the development of a CAD system for lung cancer diagnosis, which is the second most common cancer in men after prostate cancer and in women after breast cancer. Moreover, lung cancer is considered the leading cause of cancer death among both genders in USA. Recently, the number of lung cancer patients has increased dramatically worldwide and its early detection doubles a patient’s chance of survival. Histological examination through biopsies is considered the gold standard for final diagnosis of pulmonary nodules. Even though resection of pulmonary nodules is the ideal and most reliable way for diagnosis, there is still a lot of different methods often used just to eliminate the risks associated with the surgical procedure. Lung nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. A pulmonary nodule is the first indication to start diagnosing lung cancer. Lung nodules can be benign (normal subjects) or malignant (cancerous subjects). Large (generally defined as greater than 2 cm in diameter) malignant nodules can be easily detected with traditional CT scanning techniques. However, the diagnostic options for small indeterminate nodules are limited due to problems associated with accessing small tumors. Therefore, additional diagnostic and imaging techniques which depends on the nodules’ shape and appearance are needed. The ultimate goal of this dissertation is to develop a fast noninvasive diagnostic system that can enhance the accuracy measures of early lung cancer diagnosis based on the well-known hypotheses that malignant nodules have different shape and appearance than benign nodules, because of the high growth rate of the malignant nodules. The proposed methodologies introduces new shape and appearance features which can distinguish between benign and malignant nodules. To achieve this goal a CAD system is implemented and validated using different datasets. This CAD system uses two different types of features integrated together to be able to give a full description to the pulmonary nodule. These two types are appearance features and shape features. For the appearance features different texture appearance descriptors are developed, namely the 3D histogram of oriented gradient, 3D spherical sector isosurface histogram of oriented gradient, 3D adjusted local binary pattern, 3D resolved ambiguity local binary pattern, multi-view analytical local binary pattern, and Markov Gibbs random field. Each one of these descriptors gives a good description for the nodule texture and the level of its signal homogeneity which is a distinguishable feature between benign and malignant nodules. For the shape features multi-view peripheral sum curvature scale space, spherical harmonics expansions, and different group of fundamental geometric features are utilized to describe the nodule shape complexity. Finally, the fusion of different combinations of these features, which is based on two stages is introduced. The first stage generates a primary estimation for every descriptor. Followed by the second stage that consists of an autoencoder with a single layer augmented with a softmax classifier to provide us with the ultimate classification of the nodule. These different combinations of descriptors are combined into different frameworks that are evaluated using different datasets. The first dataset is the Lung Image Database Consortium which is a benchmark publicly available dataset for lung nodule detection and diagnosis. The second dataset is our local acquired computed tomography imaging data that has been collected from the University of Louisville hospital and the research protocol was approved by the Institutional Review Board at the University of Louisville (IRB number 10.0642). These frameworks accuracy was about 94%, which make the proposed frameworks demonstrate promise to be valuable tool for the detection of lung cancer

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

A Modular Approach to Lung Nodule Detection from Computed Tomography Images Using Artificial Neural Networks and Content Based Image Representation

Lung cancer is one of the most lethal cancer types. Research in computer aided detection (CAD) and diagnosis for lung cancer aims at providing effective tools to assist physicians in cancer diagnosis and treatment to save lives. In this dissertation, we focus on developing a CAD framework for automated lung cancer nodule detection from 3D lung computed tomography (CT) images. Nodule detection is a challenging task that no machine intelligence can surpass human capability to date. In contrast, human recognition power is limited by vision capacity and may suffer from work overload and fatigue, whereas automated nodule detection systems can complement expert’s efforts to achieve better detection performance. The proposed CAD framework encompasses several desirable properties such as mimicking physicians by means of geometric multi-perspective analysis, computational efficiency, and the most importantly producing high performance in detection accuracy. As the central part of the framework, we develop a novel hierarchical modular decision engine implemented by Artificial Neural Networks. One advantage of this decision engine is that it supports the combination of spatial-level and feature-level information analysis in an efficient way. Our methodology overcomes some of the limitations of current lung nodule detection techniques by combining geometric multi-perspective analysis with global and local feature analysis. The proposed modular decision engine design is flexible to modifications in the decision modules; the engine structure can adopt the modifications without having to re-design the entire system. The engine can easily accommodate multi-learning scheme and parallel implementation so that each information type can be processed (in parallel) by the most adequate learning technique of its own. We have also developed a novel shape representation technique that is invariant under rigid-body transformation and we derived new features based on this shape representation for nodule detection. We implemented a prototype nodule detection system as a demonstration of the proposed framework. Experiments have been conducted to assess the performance of the proposed methodologies using real-world lung CT data. Several performance measures for detection accuracy are used in the assessment. The results show that the decision engine is able to classify patterns efficiently with very good classification performance

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

Automatic 3D pulmonary nodule detection in CT images: a survey

This work presents a systematic review of techniques for the 3D automatic detection of pulmonary nodules in computerized-tomography (CT) images. Its main goals are to analyze the latest technology being used for the development of computational diagnostic tools to assist in the acquisition, storage and, mainly, processing and analysis of the biomedical data. Also, this work identifies the progress made, so far, evaluates the challenges to be overcome and provides an analysis of future prospects. As far as the authors know, this is the first time that a review is devoted exclusively to automated 3D techniques for the detection of pulmonary nodules from lung CT images, which makes this work of noteworthy value. The research covered the published works in the Web of Science, PubMed, Science Direct and IEEEXplore up to December 2014. Each work found that referred to automated 3D segmentation of the lungs was individually analyzed to identify its objective, methodology and results. Based on the analysis of the selected works, several studies were seen to be useful for the construction of medical diagnostic aid tools. However, there are certain aspects that still require attention such as increasing algorithm sensitivity, reducing the number of false positives, improving and optimizing the algorithm detection of different kinds of nodules with different sizes and shapes and, finally, the ability to integrate with the Electronic Medical Record Systems and Picture Archiving and Communication Systems. Based on this analysis, we can say that further research is needed to develop current techniques and that new algorithms are needed to overcome the identified drawbacks

Deep Lesion Graphs in the Wild: Relationship Learning and Organization of Significant Radiology Image Findings in a Diverse Large-scale Lesion Database

Radiologists in their daily work routinely find and annotate significant abnormalities on a large number of radiology images. Such abnormalities, or lesions, have collected over years and stored in hospitals' picture archiving and communication systems. However, they are basically unsorted and lack semantic annotations like type and location. In this paper, we aim to organize and explore them by learning a deep feature representation for each lesion. A large-scale and comprehensive dataset, DeepLesion, is introduced for this task. DeepLesion contains bounding boxes and size measurements of over 32K lesions. To model their similarity relationship, we leverage multiple supervision information including types, self-supervised location coordinates and sizes. They require little manual annotation effort but describe useful attributes of the lesions. Then, a triplet network is utilized to learn lesion embeddings with a sequential sampling strategy to depict their hierarchical similarity structure. Experiments show promising qualitative and quantitative results on lesion retrieval, clustering, and classification. The learned embeddings can be further employed to build a lesion graph for various clinically useful applications. We propose algorithms for intra-patient lesion matching and missing annotation mining. Experimental results validate their effectiveness.Comment: Accepted by CVPR2018. DeepLesion url adde