Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Computational Anatomy for Multi-Organ Analysis in Medical Imaging: A Review

The medical image analysis field has traditionally been focused on the development of organ-, and disease-specific methods. Recently, the interest in the development of more 20 comprehensive computational anatomical models has grown, leading to the creation of multi-organ models. Multi-organ approaches, unlike traditional organ-specific strategies, incorporate inter-organ relations into the model, thus leading to a more accurate representation of the complex human anatomy. Inter-organ relations are not only spatial, but also functional and physiological. Over the years, the strategies 25 proposed to efficiently model multi-organ structures have evolved from the simple global modeling, to more sophisticated approaches such as sequential, hierarchical, or machine learning-based models. In this paper, we present a review of the state of the art on multi-organ analysis and associated computation anatomy methodology. The manuscript follows a methodology-based classification of the different techniques 30 available for the analysis of multi-organs and multi-anatomical structures, from techniques using point distribution models to the most recent deep learning-based approaches. With more than 300 papers included in this review, we reflect on the trends and challenges of the field of computational anatomy, the particularities of each anatomical region, and the potential of multi-organ analysis to increase the impact of 35 medical imaging applications on the future of healthcare.Comment: Paper under revie

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

Development of advanced 3D medical analysis tools for clinical training, diagnosis and treatment

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The objective of this PhD research was the development of novel 3D interactive medical platforms for medical image analysis, simulation and visualisation, with a focus on oncology images to support clinicians in managing the increasing amount of data provided by several medical image modalities. DoctorEye and Automatic Tumour Detector platforms were developed through constant interaction and feedback from expert clinicians, integrating a number of innovations in algorithms and methods, concerning image handling, segmentation, annotation, visualisation and plug-in technologies. DoctorEye is already being used in a related tumour modelling EC project (ContraCancrum) and offers several robust algorithms and tools for fast annotation, 3D visualisation and measurements to assist the clinician in better understanding the pathology of the brain area and define the treatment. It is free to use upon request and offers a user friendly environment for clinicians as it simplifies the implementation of complex algorithms and methods. It integrates a sophisticated, simple-to-use plug-in technology allowing researchers to add algorithms and methods (e.g. tumour growth and simulation algorithms for improving therapy planning) and interactively check the results. Apart from diagnostic and research purposes, it supports clinical training as it allows an expert clinician to evaluate a clinical delineation by different clinical users. The Automatic Tumour Detector focuses on abdominal images, which are more complex than those of the brain. It supports full automatic 3D detection of kidney pathology in real-time as well as 3D advanced visualisation and measurements. This is achieved through an innovative method implementing Templates. They contain rules and parameters for the Automatic Recognition Framework defined interactively by engineers based on clinicians’ 3D Golden Standard models. The Templates enable the automatic detection of kidneys and their possible abnormalities (tumours, stones and cysts). The system also supports the transmission of these Templates to another expert for a second opinion. Future versions of the proposed platforms could integrate even more sophisticated algorithms and tools and offer fully computer-aided identification of a variety of other organs and their dysfunctions

Computational methods to predict and enhance decision-making with biomedical data.

The proposed research applies machine learning techniques to healthcare applications. The core ideas were using intelligent techniques to find automatic methods to analyze healthcare applications. Different classification and feature extraction techniques on various clinical datasets are applied. The datasets include: brain MR images, breathing curves from vessels around tumor cells during in time, breathing curves extracted from patients with successful or rejected lung transplants, and lung cancer patients diagnosed in US from in 2004-2009 extracted from SEER database. The novel idea on brain MR images segmentation is to develop a multi-scale technique to segment blood vessel tissues from similar tissues in the brain. By analyzing the vascularization of the cancer tissue during time and the behavior of vessels (arteries and veins provided in time), a new feature extraction technique developed and classification techniques was used to rank the vascularization of each tumor type. Lung transplantation is a critical surgery for which predicting the acceptance or rejection of the transplant would be very important. A review of classification techniques on the SEER database was developed to analyze the survival rates of lung cancer patients, and the best feature vector that can be used to predict the most similar patients are analyzed

Atlas-based segmentation of medical images

Atlas-Based Segmentation of medical images is an image analysis task which involves labelling a desired anatomy or set of anatomy from images generated by medical imaging modalities. The overall goal of atlas-based segmentation is to assist radiologists in the detection and diagnosis of diseases. By extracting the relevant anatomy from medical images and presenting it in an appropriate view, their work-flow can be optimised. This portfolio-style thesis discusses the research projects carried out in order to evaluate the applicability of atlas-based methods to a variety of medical imaging problems. The thesis describes how atlas-based methods have been applied to heart segmentation, to extract the heart for further cardiac analysis from cardiac CT images, to kidney segmentation, to prepare the kidney for automated perfusion measurements, and to coronary vessel tracking, in order to improve on the quality of tracking algorithms. This thesis demonstrates how state of the art atlas-based segmentation techniques can be applied successfully to a range of clinical problems in different imaging modalities. Each application has been tested using not only standard experimentation principles, but also by clinically-trained personnel to evaluate its efficacy. The success of these methods is such that some of the described applications have since been deployed in commercial products. While exploring these applications, several techniques based on published literature were explored and tailored to suit each individual application. This thesis describes in detail the methods used for each application in turn, recognising the state of the art, and outlines the author's contribution in every application