Carotid Ultrasound Boundary Study (CUBS): An Open Multicenter Analysis of Computerized Intima–Media Thickness Measurement Systems and Their Clinical Impact

[Abstract] Common carotid intima–media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts’ manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan–Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.

Basic Science to Clinical Research: Segmentation of Ultrasound and Modelling in Clinical Informatics

The world of basic science is a world of minutia; it boils down to improving even a fraction of a percent over the baseline standard. It is a domain of peer reviewed fractions of seconds and the world of squeezing every last ounce of efficiency from a processor, a storage medium, or an algorithm. The field of health data is based on extracting knowledge from segments of data that may improve some clinical process or practice guideline to improve the time and quality of care. Clinical informatics and knowledge translation provide this information in order to reveal insights to the world of improving patient treatments, regimens, and overall outcomes. In my world of minutia, or basic science, the movement of blood served an integral role. The novel detection of sound reverberations map out the landscape for my research. I have applied my algorithms to the various anatomical structures of the heart and artery system. This serves as a basis for segmentation, active contouring, and shape priors. The algorithms presented, leverage novel applications in segmentation by using anatomical features of the heart for shape priors and the integration of optical flow models to improve tracking. The presented techniques show improvements over traditional methods in the estimation of left ventricular size and function, along with plaque estimation in the carotid artery. In my clinical world of data understanding, I have endeavoured to decipher trends in Alzheimer’s disease, Sepsis of hospital patients, and the burden of Melanoma using mathematical modelling methods. The use of decision trees, Markov models, and various clustering techniques provide insights into data sets that are otherwise hidden. Finally, I demonstrate how efficient data capture from providers can achieve rapid results and actionable information on patient medical records. This culminated in generating studies on the burden of illness and their associated costs. A selection of published works from my research in the world of basic sciences to clinical informatics has been included in this thesis to detail my transition. This is my journey from one contented realm to a turbulent one

Carotid Ultrasound Boundary Study (CUBS): An Open Multicenter Analysis of Computerized Intima–Media Thickness Measurement Systems and Their Clinical Impact

Common carotid intima–media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts’ manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan–Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.1

Quantifying atherosclerosis in vasculature using ultrasound imaging

Cerebrovascular disease accounts for approximately 30% of the global burden associated with cardiovascular diseases [1]. According to the World Stroke Organisation, there are approximately 13.7 million new stroke cases annually, and just under six million people will die from stroke each year [2]. The underlying cause of this disease is atherosclerosis – a vascular pathology which is characterised by thickening and hardening of blood vessel walls. When fatty substances such as cholesterol accumulate on the inner linings of an artery, they cause a progressive narrowing of the lumen referred to as a stenosis. Localisation and grading of the severity of a stenosis, is important for practitioners to assess the risk of rupture which leads to stroke. Ultrasound imaging is popular for this purpose. It is low cost, non-invasive, and permits a quick assessment of vessel geometry and stenosis by measuring the intima media thickness. Research is showing that 3D monitoring of plaque progression may provide a better indication of sites which are at risk of rupture. Various metrics have been proposed. From these, the quantification of plaques by measuring vessel wall volume (VWV) using the segmented media-adventitia boundaries (MAB) and lumen-intima boundaries (LIB) has been shown to be sensitive to temporal changes in carotid plaque burden. Thus, methods to segment these boundaries are required to help generate VWV measurements with high accuracy, less user interaction and increased robustness to variability in di↵erent user acquisition protocols.ii This work proposes three novel methods to address these requirements, to ultimately produce a highly accurate, fully automated segmentation algorithm which works on intensity-invariant data. The first method proposed was that of generating a novel, intensity-invariant representation of ultrasound data by creating phase-congruency maps from raw unprocessed radio-frequency ultrasound information. Experiments carried out showed that this representation retained the necessary anatomical structural information to facilitate segmentation, while concurrently being invariant to changes in amplitude from the user. The second method proposed was the novel application of Deep Convolutional Networks (DCN) to carotid ultrasound images to achieve fully automatic delineation of the MAB boundaries, in addition to the use of a novel fusion of amplitude and phase congruency data as an image source. Experiments carried out showed that the DCN produces highly accurate and automated results, and that the fusion of amplitude and phase yield superior results to either one alone. The third method proposed was a new geometrically constrained objective function for the network's Stochastic Gradient Descent optimisation, thus tuning it to the segmentation problem at hand, while also developing the network further to concurrently delineate both the MAB and LIB to produce vessel wall contours. Experiments carried out here also show that the novel geometric constraints improve the segmentation results on both MAB and LIB contours. In conclusion, the presented work provides significant novel contributions to field of Carotid Ultrasound segmentation, and with future work, this could lead to implementations which facilitate plaque progression analysis for the end�user

Echocardiography

The book "Echocardiography - New Techniques" brings worldwide contributions from highly acclaimed clinical and imaging science investigators, and representatives from academic medical centers. Each chapter is designed and written to be accessible to those with a basic knowledge of echocardiography. Additionally, the chapters are meant to be stimulating and educational to the experts and investigators in the field of echocardiography. This book is aimed primarily at cardiology fellows on their basic echocardiography rotation, fellows in general internal medicine, radiology and emergency medicine, and experts in the arena of echocardiography. Over the last few decades, the rate of technological advancements has developed dramatically, resulting in new techniques and improved echocardiographic imaging. The authors of this book focused on presenting the most advanced techniques useful in today's research and in daily clinical practice. These advanced techniques are utilized in the detection of different cardiac pathologies in patients, in contributing to their clinical decision, as well as follow-up and outcome predictions. In addition to the advanced techniques covered, this book expounds upon several special pathologies with respect to the functions of echocardiography

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

Speckle Detection in Ultrasonic Images Using Unsupervised Clustering Techniques

Research for the improvement of the quality of clinical ultrasound images has been a topic of interest for researchers and physicians. One of the challenges is the presence of speckle artifacts. This dissertation reviews the speckle phenomena in such images, and develops algorithms to better identify this artifact in sonographic images. Speckle artifact is categorized into two groups: partially developed speckles and fully developed speckles (FDS). This concept has been used, along with the classification techniques, to segment the ultrasound images into patches and classify the patches in the image as FDS or non-FDS. The proposed algorithms and the results of the experiments have been validated using simulation, phantom and real data that were created for the purposes of this study or taken from other research groups. Current speckle detection methods do not optimize statistical features and they are not based on machine learning techniques. For the first time this work introduces a novel method for searching and extracting the best features for optimizing speckle detection rate using statistical machine learning and ensemble classification. Potential applications include strain imaging by tracking speckle displacement, elastography, speckle tracking and suppression applications, and needle-tracking applications.Ph.D., Biomedical Engineering -- Drexel University, 201

Quantitative Analysis of Ultrasound Images of the Preterm Brain

In this PhD new algorithms are proposed to better understand and diagnose white matter damage in the preterm Brain. Since Ultrasound imaging is the most suited modality for the inspection of brain pathologies in very low birth weight infants we propose multiple techniques to assist in what is called Computer-Aided Diagnosis. As a main result we are able to increase the qualitative diagnosis from a 70% detectability to a 98% quantitative detectability

Carotid Ultrasound for Stroke Prediction

Introduction: The aims of this thesis were to identify if carotid endarterectomy was cost-effective and affordable in the United Kingdom and secondly to explore the potential of contrast enhanced ultrasound and plaque texture analysis for risk stratification in asymptomatic patients with carotid atherosclerosis. Methods: A cost-utility analysis based on results from the Asymptomatic Carotid Surgery Trial was performed using a Markov transition state model. Three cross-sectional studies of symptomatic and asymptomatic individuals with 50-99% carotid stenosis were performed for late phase and dynamic phase contrast enhanced ultrasound, followed by plaque texture analysis. Results: There was a high probability of surgical endarterectomy lying under the £20-30, 000 per quality adjusted life year National Institute for Health and Clinical Excellence acceptability threshold in the United Kingdom. In men under 75 years of age, the cost per quality adjusted life year gained was lower and in women there was improved effectiveness with reduced long-term costs. Late phase contrast enhanced ultrasound imaging of carotid atherosclerosis suffered from a tissue suppression artefact which limited its ability to image microbubble retention. Quantification of plaque perfusion using low mechanical index imaging demonstrated a pseudoenhancement phenomenon from non-linear propagation, which artificially increased far wall intensity, again limiting its use for quantification of plaque perfusion. Semi-quantitative grading of plaque perfusion revealed no significant difference in generalised plaque perfusion between symptomatic and asymptomatic individuals, however detection of ulceration using dynamic contrast enhanced ultrasound showed a trend towards an association with symptomatic status. Type II plaque showed a significant independent association with symptomatic status. Conclusion: Carotid endarterectomy is likely to be cost-effective in those under 75 years of age, particularly women. However, without further selection, the upfront costs and high number needed to treat with endarterectomy limit its potential as a large scale strategy. Improvements in non-linear pulse sequencing are required before quantitative contrast enhanced ultrasound can reliably be used for functional imaging of carotid atherosclerosis. Qualitative assessment of plaque perfusion is unlikely to gain widespread use due to its high subjectivity. However assessment of plaque type and to a lesser extent imaging of ulceration using contrast enhanced ultrasound are promising and reproducible imaging biomarkers for further study. Validation of these markers with histology and then prospective study of individuals with these plaque phenotypes is proposed. In the future individuals with a recent transient ischaemic attack and moderate (50-69%) stenosis may prove to be an ideal group for risk stratification