3D Ultrasound in the Management of Post Hemorrhagic Ventricle Dilatation

Enlargement of the cerebral ventricles is relatively common among extremely preterm neonates born before 28 weeks gestational age. One common cause of ventricle dilatation is post hemorrhagic ventricle dilatation following a bleed in the cerebral ventricles. While many neonates with PHVD will have spontaneous resolution of the condition, severe, persistent PHVD is associated with a greater risk of brain injury and morbidity later in life and left untreated can cause death. The current clinical management strategy consists of daily measurements of head circumference and qualitative interpretation of two-dimensional US images to detect ventricular enlargement and monitoring vital signs for indications increased intracranial pressure (i.e. apnea, bradycardia). Despite the widespread clinical use of these indicators, they do not have the specificity to reliably indicate when an intervention to remove some CSF is required to prevent brain damage. Early recognition of interventional necessity using quantitative measurements could help with the management of the disease, and could lead to better care in the future. Our objective was to develop and validate a three-dimensional ultrasound system for use within an incubator of neonates with PHVD in order to accurately measure the cerebral ventricle volume. This system was validated against known geometric phantoms as well as a custom ventricle-like phantom. Once validated, the system was used in a clinical study of 70 neonates with PHVD to measure the ventricle size. In addition to three-dimensional ultrasound, clinical ultrasound images, and MRIs were attained. Clinical measurements of the ventricles and three-dimensional ultrasound ventricle volumes were used to determine thresholds between neonates with PHVD who did and did not receive interventions based on current clinical management. We determined image based thresholds for intervention for both neonates who will receive an initial intervention, as well as those who will receive multiple interventions. Three-dimensional ultrasound based ventricle volume measurements had high sensitivity and specificity as patients with persistent PHVD have ventricles that increase in size faster than those who undergo resolution. This allowed for delineation between interventional and non-interventional patients within the first week of life. While this is still a small sample size study, these results can give rise to larger studies that would be able to determine if earlier intervention can result in better neurodevelopmental outcomes later in life

Automated Morphometric Characterization of the Cerebral Cortex for the Developing and Ageing Brain

Morphometric characterisation of the cerebral cortex can provide information about patterns of brain development and ageing and may be relevant for diagnosis and estimation of the progression of diseases such as Alzheimer's, Huntington's, and schizophrenia. Therefore, understanding and describing the differences between populations in terms of structural volume, shape and thickness is of critical importance. Methodologically, due to data quality, presence of noise, PV effects, limited resolution and pathological variability, the automated, robust and time-consistent estimation of morphometric features is still an unsolved problem. This thesis focuses on the development of tools for robust cross-sectional and longitudinal morphometric characterisation of the human cerebral cortex. It describes techniques for tissue segmentation, structural and morphometric characterisation, cross-sectional and longitudinally cortical thickness estimation from serial MRI images in both adults and neonates. Two new probabilistic brain tissue segmentation techniques are introduced in order to accurately and robustly segment the brain of elderly and neonatal subjects, even in the presence of marked pathology. Two other algorithms based on the concept of multi-atlas segmentation propagation and fusion are also introduced in order to parcelate the brain into its multiple composing structures with the highest possible segmentation accuracy. Finally, we explore the use of the Khalimsky cubic complex framework for the extraction of topologically correct thickness measurements from probabilistic segmentations without explicit parametrisation of the edge. A longitudinal extension of this method is also proposed. The work presented in this thesis has been extensively validated on elderly and neonatal data from several scanners, sequences and protocols. The proposed algorithms have also been successfully applied to breast and heart MRI, neck and colon CT and also to small animal imaging. All the algorithms presented in this thesis are available as part of the open-source package NiftySeg

Contributions of Continuous Max-Flow Theory to Medical Image Processing

Discrete graph cuts and continuous max-flow theory have created a paradigm shift in many areas of medical image processing. As previous methods limited themselves to analytically solvable optimization problems or guaranteed only local optimizability to increasingly complex and non-convex functionals, current methods based now rely on describing an optimization problem in a series of general yet simple functionals with a global, but non-analytic, solution algorithms. This has been increasingly spurred on by the availability of these general-purpose algorithms in an open-source context. Thus, graph-cuts and max-flow have changed every aspect of medical image processing from reconstruction to enhancement to segmentation and registration. To wax philosophical, continuous max-flow theory in particular has the potential to bring a high degree of mathematical elegance to the field, bridging the conceptual gap between the discrete and continuous domains in which we describe different imaging problems, properties and processes. In Chapter 1, we use the notion of infinitely dense and infinitely densely connected graphs to transfer between the discrete and continuous domains, which has a certain sense of mathematical pedantry to it, but the resulting variational energy equations have a sense of elegance and charm. As any application of the principle of duality, the variational equations have an enigmatic side that can only be decoded with time and patience. The goal of this thesis is to show the contributions of max-flow theory through image enhancement and segmentation, increasing incorporation of topological considerations and increasing the role played by user knowledge and interactivity. These methods will be rigorously grounded in calculus of variations, guaranteeing fuzzy optimality and providing multiple solution approaches to addressing each individual problem

Shape analysis of the human brain.

Autism is a complex developmental disability that has dramatically increased in prevalence, having a decisive impact on the health and behavior of children. Methods used to detect and recommend therapies have been much debated in the medical community because of the subjective nature of diagnosing autism. In order to provide an alternative method for understanding autism, the current work has developed a 3-dimensional state-of-the-art shape based analysis of the human brain to aid in creating more accurate diagnostic assessments and guided risk analyses for individuals with neurological conditions, such as autism. Methods: The aim of this work was to assess whether the shape of the human brain can be used as a reliable source of information for determining whether an individual will be diagnosed with autism. The study was conducted using multi-center databases of magnetic resonance images of the human brain. The subjects in the databases were analyzed using a series of algorithms consisting of bias correction, skull stripping, multi-label brain segmentation, 3-dimensional mesh construction, spherical harmonic decomposition, registration, and classification. The software algorithms were developed as an original contribution of this dissertation in collaboration with the BioImaging Laboratory at the University of Louisville Speed School of Engineering. The classification of each subject was used to construct diagnoses and therapeutic risk assessments for each patient. Results: A reliable metric for making neurological diagnoses and constructing therapeutic risk assessment for individuals has been identified. The metric was explored in populations of individuals having autism spectrum disorders, dyslexia, Alzheimers disease, and lung cancer. Conclusion: Currently, the clinical applicability and benefits of the proposed software approach are being discussed by the broader community of doctors, therapists, and parents for use in improving current methods by which autism spectrum disorders are diagnosed and understood

Coronary Artery Segmentation and Motion Modelling

Conventional coronary artery bypass surgery requires invasive sternotomy and the use of a cardiopulmonary bypass, which leads to long recovery period and has high infectious potential. Totally endoscopic coronary artery bypass (TECAB) surgery based on image guided robotic surgical approaches have been developed to allow the clinicians to conduct the bypass surgery off-pump with only three pin holes incisions in the chest cavity, through which two robotic arms and one stereo endoscopic camera are inserted. However, the restricted field of view of the stereo endoscopic images leads to possible vessel misidentification and coronary artery mis-localization. This results in 20-30% conversion rates from TECAB surgery to the conventional approach. We have constructed patient-specific 3D + time coronary artery and left ventricle motion models from preoperative 4D Computed Tomography Angiography (CTA) scans. Through temporally and spatially aligning this model with the intraoperative endoscopic views of the patient's beating heart, this work assists the surgeon to identify and locate the correct coronaries during the TECAB precedures. Thus this work has the prospect of reducing the conversion rate from TECAB to conventional coronary bypass procedures. This thesis mainly focus on designing segmentation and motion tracking methods of the coronary arteries in order to build pre-operative patient-specific motion models. Various vessel centreline extraction and lumen segmentation algorithms are presented, including intensity based approaches, geometric model matching method and morphology-based method. A probabilistic atlas of the coronary arteries is formed from a group of subjects to facilitate the vascular segmentation and registration procedures. Non-rigid registration framework based on a free-form deformation model and multi-level multi-channel large deformation diffeomorphic metric mapping are proposed to track the coronary motion. The methods are applied to 4D CTA images acquired from various groups of patients and quantitatively evaluated

Statistical shape analysis of neuroanatomical structures based on spherical wavelet transformation

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references.Evidence suggests that morphological changes of neuroanatomical structures may reflect abnormalities in neurodevelopment, or relate to a variety of disorders, such as schizophrenia and Alzheimer's disease (AD). Advances in high-resolution Magnetic Resonance Imaging (MRI) techniques allow us to study these alterations of brain structures in vivo. Previous work in studying the shape variations of brain structures has provided additional localized information compared with traditional volume-based study. However, challenges remain in finding an accurate shape presentation and conducting shape analysis with sound statistical principles. In this work, we develop methods for automatically extracting localized and multi-scale shape features and conducting statistical shape analysis of neuroanatomical structures obtained from MR images. We first develop a procedure to extract multi-scale shape features of brain structures using biorthogonal spherical wavelets. Using this wavelet-based shape representation, we build multi-scale shape models and study the localized cortical folding variations in a normal population using Principal Component Analysis (PCA). We then build a shape-based classification framework for detecting pathological changes of cortical surfaces using advanced classification methods, such as predictive Automatic Relevance Determination (pred-ARD), and demonstrate promising results in patient/control group comparison studies. Thirdly, we develop a nonlinear temporal model for studying the temporal order and regional difference of cortical folding development based on this shape representation. Furthermore, we develop a shape-guided segmentation method to improve the segmentation of sub-cortical structures, such as hippocampus, by using shape constraints obtained in the wavelet domain.(cont.) Finally, we improve upon the proposed wavelet-based shape representation by adopting a newly developed over-complete spherical wavelet transformation and demonstrate its utility in improving the accuracy and stability of shape representations. By using these shape representations and statistical analysis methods, we have demonstrated promising results in localizing shape changes of neuroanatomical structures related to aging, neurological diseases, and neurodevelopment at multiple spatial scales. Identification of these shape changes could potentially lead to more accurate diagnoses and improved understanding of neurodevelopment and neurological diseases.by Peng Yu.Ph.D

Automatic MRI segmentation of the developing neonatal brain

Detailed morphometric analysis of the neonatal brain is required to characterise normal brain development and investigate the neuroanatomical correlates of cognitive impairments. The segmentation of the brain in Magnetic Resonance Imaging (MRI) is a prerequisite to obtain quantitative measurements of regional brain structures. These measurements obtained at term-equivalent or early preterm age may lead to improved understanding of brain growth and may help evaluate long-term neurodevelopmental performance at an early stage. This thesis focuses on the development of an accurate segmentation algorithm for the neonatal brain MR images and its application in large cohorts of subjects. Neonatal brain segmentation is challenging due to the large anatomical variability as a result of the rapid brain development in the neonatal period. The lack of training data in the neonatal period, encoded in brain atlases, further hinders the development of automatic segmentation tools. A novel algorithm for the tissue segmentation of the neonatal brain is proposed. The algorithm is extended for the regional brain segmentation. This is the first segmentation method for the parcellation of the developing neonatal brain into multiple structures. A novel method is further proposed for the group-wise segmentation of the data that utilizes unlabelled data to complement the labelling information of brain atlases. Previous studies in the literature tended to overestimate the extent of the cortical region. A method based on the morphology of the cortex is introduced to correct for this over-segmentation. The segmentation method is applied on an extensive database of neonatal MR images. Regional volumetric, surface and diffusion tensor imaging measurements are derived from the early preterm period to term-equivalent age. These measurements allow characterisation of the regional brain development and the investigation of correlations with clinical factors. Finally, a spatio-temporal structural atlas is constructed for multiple regions of the neonatal brain.Open Acces