CT diagnosis of early stroke : the initial approach to the new CAD tool based on multiscale estimation of ischemia

Background: Computer aided diagnosis (CAD) becomes one of the most important diagnostic tools for urgent states in cerebral stroke and other life-threatening conditions where time plays a crucial role. Routine CT is still diagnostically insufficient in hyperacute stage of stroke that is in the therapeutic window for thrombolytic therapy. Authors present computer assistant of early ischemic stroke diagnosis that supports the radiologic interpretations. A new semantic-visualization system of ischemic symptoms applied to noncontrast, routine CT examination was based on multiscale image processing and diagnostic content estimation. Material/Methods: Evaluation of 95 sets of examinations in patients admitted to a hospital with symptoms suggesting stroke was undertaken by four radiologists from two medical centers unaware of the final clinical findings. All of the consecutive cases were considered as having no CT direct signs of hyperacute ischemia. At the first test stage only the CTs performed at the admission were evaluated independently by radiologists. Next, the same early scans were evaluated again with additional use of multiscale computer-assistant of stroke (MulCAS). Computerized suggestion with increased sensitivity to the subtle image manifestations of cerebral ischemia was constructed as additional view representing estimated diagnostic content with enhanced stroke symptoms synchronized to routine CT data preview. Follow-up CT examinations and clinical features confirmed or excluded the diagnosis of stroke constituting 'gold standard' to verify stroke detection performance. Results: Higher AUC (area under curve) values were found for MulCAS -aided radiological diagnosis for all readers and the differences were statistically significant for random readers-random cases parametric and non-parametric DBM MRMC analysis. Sensitivity and specificity of acute stroke detection for the readers was increased by 30% and 4%, respectively. Conclusions: Routine CT completed with proposed method of computer assisted diagnosis provided noticeable better diagnosis efficiency of acute stroke according to the rates and opinions of all test readers. Further research includes fully automatic detection of hypodense regions to complete assisted indications and formulate the suggestions of stroke cases more objectively. Planned prospective studies will let evaluate more accurately the impact of this CAD tool on diagnosis and further treatment in patients suffered from stroke. It is necessary to determine whether this method is possible to be applied widely

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

Deep generative models for medical image synthesis and strategies to utilise them

Medical imaging has revolutionised the diagnosis and treatments of diseases since the first medical image was taken using X-rays in 1895. As medical imaging became an essential tool in a modern healthcare system, more medical imaging techniques have been invented, such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT), Ultrasound, etc. With the advance of medical imaging techniques, the demand for processing and analysing these complex medical images is increasing rapidly. Efforts have been put on developing approaches that can automatically analyse medical images. With the recent success of deep learning (DL) in computer vision, researchers have applied and proposed many DL-based methods in the field of medical image analysis. However, one problem with data-driven DL-based methods is the lack of data. Unlike natural images, medical images are more expensive to acquire and label. One way to alleviate the lack of medical data is medical image synthesis. In this thesis, I first start with pseudo healthy synthesis, which is to create a ‘healthy’ looking medical image from a pathological one. The synthesised pseudo healthy images can be used for the detection of pathology, segmentation, etc. Several challenges exist with this task. The first challenge is the lack of ground-truth data, as a subject cannot be healthy and diseased at the same time. The second challenge is how to evaluate the generated images. In this thesis, I propose a deep learning method to learn to generate pseudo healthy images with adversarial and cycle consistency losses to overcome the lack of ground-truth data. I also propose several metrics to evaluate the quality of synthetic ‘healthy’ images. Pseudo healthy synthesis can be viewed as transforming images between discrete domains, e.g. from pathological domain to healthy domain. However, there are some changes in medical data that are continuous, e.g. brain ageing progression. Brain changes as age increases. With the ageing global population, research on brain ageing has attracted increasing attention. In this thesis, I propose a deep learning method that can simulate such brain ageing progression. Specifically, longitudinal brain data are not easy to acquire; if some exist, they only cover several years. Thus, the proposed method focuses on learning subject-specific brain ageing progression without training on longitudinal data. As there are other factors, such as neurodegenerative diseases, that can affect brain ageing, the proposed model also considers health status, i.e. the existence of Alzheimer’s Disease (AD). Furthermore, to evaluate the quality of synthetic aged images, I define several metrics and conducted a series of experiments. Suppose we have a pre-trained deep generative model and a downstream tasks model, say a classifier. One question is how to make the best of the generative model to improve the performance of the classifier. In this thesis, I propose a simple procedure that can discover the ‘weakness’ of the classifier and guide the generator to synthesise counterfactuals (synthetic data) that are hard for the classifier. The proposed procedure constructs an adversarial game between generative factors of the generator and the classifier. We demonstrate the effectiveness of this proposed procedure through a series of experiments. Furthermore, we consider the application of generative models in a continual learning context and investigate the usefulness of them to alleviate spurious correlation. This thesis creates new avenues for further research in the area of medical image synthesis and how to utilise the medical generative models, which we believe could be important for future studies in medical image analysis with deep learning

Hierarchical clustering-based segmentation (HCS) aided diagstic image interpretation monitoring.

Machines are good at operations which require precision and computing objective measures. In contrast, humans are good at generalisation and making decisions based on their past experience and heuristics. Hence, to solve any problem with a solution involving human-machine interaction, it is imperative that the tasks are shared appropriately. However, the boundary which divides these two different set of tasks is not well defined in domains such as medical image interpretation. Therefore, one needs a versatile tool which is flexible enough to accommodate the varied requirements of the user. The aim of this study is to design and implement such a software tool to aid the radiologists in the interpretation of diagnostic images.Tissue abnormality in a medical image is usually related to a dissimilar part of an otherwise homogeneous image. The dissimilarity may be subtle or strong depending on the medical modality and the type of abnormal tissue. Hierarchical Clustering-based Segmentation (HCS) process is a dissimilarity highlighting process that yields a hierarchy of segmentation results. In this study, the HCS process was investigated for offering the user a versatile and flexible environment to perceive the varied dissimilarities that might be present in diagnostic images. Consequently, the user derives the maximum benefit from the computational capability (perception) of the machine and at the same time incorporate their own decision process (interpretation) at the appropriate places.As a result of the above investigation, this study demonstrates how HCS process can be used to aid radiologists in their interpretive tasks. Specifically this study has designed the following HCS process aided diagnostic image interpretation applications: interpretation of computed tomography (CT) images of the lungs to quantitatively measure the dimensions of the airways and the accompanying blood vessels; Interpretation of X-ray mammograms to quantitatively differentiate benign from malignant abnormalities. One of the major contribution of this study is to demonstrate how the above HCS process aided interpretation of diagnostic images can be used to monitor disease conditions. This thesis details the development and evaluation of the novel computer aided monitoring (CAM) system. The designed CAM system is used to objectively measure the properties of suspected abnormal areas in the CT images of the lungs and in X-ray mammogram. Thus, the CAM system can be used to assist the clinician to objectively monitor the abnormality. For instance, its response to treatment and consequently its prognosis. The implemented CAM system to monitor abnormalities in X-ray mammograms is briefly described below. Using the approximate location and size of the abnormality, obtained from the user, the HCS process automatically identifies the more appropriate boundaries of the different regions within a region of interest (ROI), centred at the approximate location. From the set of, HCS process segmented, regions the user identifies the regions which most likely represent the abnormality and the healthy areas. Subsequently, the CAM system compares the characteristics of the user identified abnormal region with that of the healthy region; to differentiate malignant from benign abnormality. In processing sixteen mammograms, the designed CAM system demonstrated the possibility of successfully differentiating malignant from benign abnormalities

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

Advances in Clinical Neurophysiology

Including some of the newest advances in the field of neurophysiology, this book can be considered as one of the treasures that interested scientists would like to collect. It discusses many disciplines of clinical neurophysiology that are, currently, crucial in the practice as they explain methods and findings of techniques that help to improve diagnosis and to ensure better treatment. While trying to rely on evidence-based facts, this book presents some new ideas to be applied and tested in the clinical practice. Advances in Clinical Neurophysiology is important not only for the neurophysiologists but also for clinicians interested or working in wide range of specialties such as neurology, neurosurgery, intensive care units, pediatrics and so on. Generally, this book is written and designed to all those involved in, interpreting or requesting neurophysiologic tests

Novel mathematical modeling approaches to assess ischemic stroke lesion evolution on medical imaging

Stroke is a major cause of disability and death worldwide. Although different clinical studies and trials used Magnetic Resonance Imaging (MRI) to examine patterns of change in different imaging modalities (eg: perfusion and diffusion), we still lack a clear and definite answer to the question: “How does an acute ischemic stroke lesion grow?” The inability to distinguish viable and dead tissue in abnormal MR regions in stroke patients weakens the evidence accumulated to answer this question, and relying on static snapshots of patient scans to fill in the spatio-temporal gaps by “thinking/guessing” make it even harder to tackle. Different opposing observations undermine our understanding of ischemic stroke evolution, especially at the acute stage: viable tissue transiting into dead tissue may be clear and intuitive, however, “visibly” dead tissue restoring to full recovery is still unclear. In this thesis, we search for potential answers to these raised questions from a novel dynamic modelling perspective that would fill in some of the missing gaps in the mechanisms of stroke evolution. We divided our thesis into five parts. In the first part, we give a clinical and imaging background on stroke and state the objectives of this thesis. In the second part, we summarize and review the literature in stroke and medical imaging. We specifically spot gaps in the literature mainly related to medical image analysis methods applied to acute-subacute ischemic stroke. We emphasize studies that progressed the field and point out what major problems remain. Noticeably, we have discovered that macroscopic (imaging-based) dynamic models that simulate how stroke lesion evolves in space and time were completely overlooked: an untapped potential that may alter and hone our understanding of stroke evolution. Progress in the dynamic simulation of stroke was absent –if not inexistent. In the third part, we answer this new call and apply a novel current-based dynamic model âpreviously applied to compare the evolution of facial characteristics between Chimpanzees and Bonobos [Durrleman 2010] – to ischemic stroke. This sets a robust numerical framework and provides us with mathematical tools to fill in the missing gaps between MR acquisition time points and estimate a four-dimensional evolution scenario of perfusion and diffusion lesion surfaces. We then detect two characteristics of patterns of abnormal tissue boundary change: spatial, describing the direction of change –outward as tissue boundary expands or inward as it contracts–; and kinetic, describing the intensity (norm) of the speed of contracting and expanding ischemic regions. Then, we compare intra- and inter-patients estimated patterns of change in diffusion and perfusion data. Nevertheless, topology change limits this approach: it cannot handle shapes with different parts that vary in number over time (eg: fragmented stroke lesions, especially in diffusion scans, which are common). In the fourth part, we suggest a new mathematical dynamic model to increase rigor in the imaging-based dynamic modeling field as a whole by overcoming the topology-change hurdle. Metamorphosis. It morphs one source image into a target one [Trouvé 2005]. In this manuscript, we extend it into dealing with more than two time-indexed images. We propose a novel extension of image-to-image metamorphosis into longitudinal metamorphosis for estimating an evolution scenario of both scattered and solitary ischemic lesions visible on serial MR. It is worth noting that the spatio-temporal metamorphosis we developed is a generic model that can be used to examine intensity and shape changes in time-series imaging and study different brain diseases or disorders. In the fifth part, we discuss our main findings and investigate future directions to explore to sharpen our understanding of ischemia evolution patterns

Non-communicable Diseases, Big Data and Artificial Intelligence

This reprint includes 15 articles in the field of non-communicable Diseases, big data, and artificial intelligence, overviewing the most recent advances in the field of AI and their application potential in 3P medicine

EXplainable Artificial Intelligence: enabling AI in neurosciences and beyond

The adoption of AI models in medicine and neurosciences has the potential to play a significant role not only in bringing scientific advancements but also in clinical decision-making. However, concerns mounts due to the eventual biases AI could have which could result in far-reaching consequences particularly in a critical field like biomedicine. It is challenging to achieve usable intelligence because not only it is fundamental to learn from prior data, extract knowledge and guarantee generalization capabilities, but also to disentangle the underlying explanatory factors in order to deeply understand the variables leading to the final decisions. There hence has been a call for approaches to open the AI `black box' to increase trust and reliability on the decision-making capabilities of AI algorithms. Such approaches are commonly referred to as XAI and are starting to be applied in medical fields even if not yet fully exploited. With this thesis we aim at contributing to enabling the use of AI in medicine and neurosciences by taking two fundamental steps: (i) practically pervade AI models with XAI (ii) Strongly validate XAI models. The first step was achieved on one hand by focusing on XAI taxonomy and proposing some guidelines specific for the AI and XAI applications in the neuroscience domain. On the other hand, we faced concrete issues proposing XAI solutions to decode the brain modulations in neurodegeneration relying on the morphological, microstructural and functional changes occurring at different disease stages as well as their connections with the genotype substrate. The second step was as well achieved by firstly defining four attributes related to XAI validation, namely stability, consistency, understandability and plausibility. Each attribute refers to a different aspect of XAI ranging from the assessment of explanations stability across different XAI methods, or highly collinear inputs, to the alignment of the obtained explanations with the state-of-the-art literature. We then proposed different validation techniques aiming at practically fulfilling such requirements. With this thesis, we contributed to the advancement of the research into XAI aiming at increasing awareness and critical use of AI methods opening the way to real-life applications enabling the development of personalized medicine and treatment by taking a data-driven and objective approach to healthcare