Novel ultrasound features for the identification of the vulnerable carotid plaque

Background: The identification of the vulnerable carotid plaque is of paramount importance in order to prevent the significant stroke-related mortality and morbidity. Currently the clinical decision-making around this condition is based on the traditional ultrasound evaluation of the degree of stenosis. However, there is emerging evidence supporting that this is not sufficient for all patients. Aim of this thesis: The evaluation of novel carotid plaque features for the characterisation of plaque composition, volume and motion using 2 and 3 dimensional ultrasound technology. The ultimate goal is to identify novel sensitive imaging markers for carotid plaque characterisation and stroke-risk stratification. Methods: The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) Study was a large prospective multicentre trial that was recently completed. A post-hoc analysis of the sonographic and clinical data from this study was performed in order to evaluate the effectiveness of novel ultrasound texture features, such as second order statics, on stroke-risk prediction. In addition, the change of specific texture features and degree of stenosis during the ACSRS follow-up time (8 years) and their importance for stroke prediction was evaluated. In order to assess the potential of 3D ultrasound carotid imaging we also developed a special methodology using a 3D broadband, linear array probe and the Q-lab software. This methodology was then applied in a clinical, cross-sectional study of patients with symptomatic and asymptomatic carotid disease. Finally we developed a carotid plaque motion analysis methodology that we tested on a feasibility study. Results: The post-hoc analysis of more than 1, 000 patients from the ACSRS database showed that there are novel ultrasound features of plaque homogeneity that can contribute to plaque characterisation and improve stroke-risk prediction. Similarly our results suggest that the change of degree of stenosis or plaque’s composition through time might have significant predictive value when combined with the above novel features. The study in 3D ultrasound prospectively assessed more than 80 people with symptomatic and asymptomatic carotid disease with both 2 and 3D carotid ultrasound without, though, revealing any significant benefit from the use of 3D imaging in terms of stroke-risk prediction. Finally, our feasibility study on plaque motion analysis showed that it is possible to objectively characterise plaque motion, using ultrasound and dedicated software without complicated reconstructions. Conclusion: The use of novel 2D ultrasound texture features in combination with traditional ones can improve the stroke-risk stratification. 3D ultrasound is a promising new approach, however, the current technology does not appear to offer a significant benefit in comparison to cheaper traditional 2D ultrasound for carotid plaque evaluation. Further research is warranted on this issue.Open Acces

CAROTID THREE-DIMENSIONAL ULTRASOUND: LONGITUDINAL MEASUREMENT AND CARDIAC-GATED ACQUISITION

Carotid atherosclerosis is the main cause of stroke - the fourth leading cause of death in Canada - and can be quantified by ultrasound measurements. Intima-media thickness (IMT), total plaque area (TPA) and 3-dimensional ultrasound vessel wall volume (3DUS VWV) were compared in a longitudinal study of 71 patients with diabetic nephropathy randomized to vitamin B or placebo. Only 3DUS VWV was sensitive to a difference in change between treatment groups. We developed and tested cardiac-gated 3DUS acquisition for use in younger subjects with compliant arteries; images were acquired from 400 ms after the start of the cardiac cycle to the beginning of the next cardiac cycle. In healthy volunteers and rheumatoid arthritis patients, change in area over the cardiac cycle was reduced to below that seen in moderate atherosclerosis patients. 3DUS VWV can measure change in atherosclerosis and can now be used in younger patients at risk of atherosclerosis in future studies

Computer aided diagnosis of coronary artery disease, myocardial infarction and carotid atherosclerosis using ultrasound images: a review

The diagnosis of Coronary Artery Disease (CAD), Myocardial Infarction (MI) and carotid atherosclerosis is of paramount importance, as these cardiovascular diseases may cause medical complications and large number of death. Ultrasound (US) is a widely used imaging modality, as it captures moving images and image features correlate well with results obtained from other imaging methods. Furthermore, US does not use ionizing radiation and it is economical when compared to other imaging modalities. However, reading US images takes time and the relationship between image and tissue composition is complex. Therefore, the diagnostic accuracy depends on both time taken to read the images and experience of the screening practitioner. Computer support tools can reduce the inter-operator variability with lower subject specific expertise, when appropriate processing methods are used. In the current review, we analysed automatic detection methods for the diagnosis of CAD, MI and carotid atherosclerosis based on thoracic and Intravascular Ultrasound (IVUS). We found that IVUS is more often used than thoracic US for CAD. But for MI and carotid atherosclerosis IVUS is still in the experimental stage. Furthermore, thoracic US is more often used than IVUS for computer aided diagnosis systems

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

Area-preserving mapping of 3D ultrasound carotid artery images using density-equalizing reference map

Carotid atherosclerosis is a focal disease at the bifurcations of the carotid artery. To quantitatively monitor the local changes in the vessel-wall-plus-plaque thickness (VWT) and compare the VWT distributions for different patients or for the same patients at different ultrasound scanning sessions, a mapping technique is required to adjust for the geometric variability of different carotid artery models. In this work, we propose a novel method called density-equalizing reference map (DERM) for mapping 3D carotid surfaces to a standardized 2D carotid template, with an emphasis on preserving the local geometry of the carotid surface by minimizing the local area distortion. The initial map was generated by a previously described arc-length scaling (ALS) mapping method, which projects a 3D carotid surface onto a 2D non-convex L-shaped domain. A smooth and area-preserving flattened map was subsequently constructed by deforming the ALS map using the proposed algorithm that combines the density-equalizing map and the reference map techniques. This combination allows, for the first time, one-to-one mapping from a 3D surface to a standardized non-convex planar domain in an area-preserving manner. Evaluations using 20 carotid surface models show that the proposed method reduced the area distortion of the flattening maps by over 80% as compared to the ALS mapping method

Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors

Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk

Cardiovascular Risk Stratification in Diabetic Retinopathy via Atherosclerotic Pathway in COVID-19/non-COVID-19 Frameworks using Artificial Intelligence Paradigm: A Narrative Review

Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, is seen to be a powerful indicator of atherosclerosis. Further, the macrovascular complication of diabetes leads to coronary artery disease (CAD). Thus, the timely identification of cardiovascular disease (CVD) complications in DR patients is of utmost importance. Since CAD risk assessment is expensive for lowincome countries, it is important to look for surrogate biomarkers for risk stratification of CVD in DR patients. Due to the common genetic makeup between the coronary and carotid arteries, lowcost, high-resolution imaging such as carotid B-mode ultrasound (US) can be used for arterial tissue characterization and risk stratification in DR patients. The advent of artificial intelligence (AI) techniques has facilitated the handling of large cohorts in a big data framework to identify atherosclerotic plaque features in arterial ultrasound. This enables timely CVD risk assessment and risk stratification of patients with DR. Thus, this review focuses on understanding the pathophysiology of DR, retinal and CAD imaging, the role of surrogate markers for CVD, and finally, the CVD risk stratification of DR patients. The review shows a step-by-step cyclic activity of how diabetes and atherosclerotic disease cause DR, leading to the worsening of CVD. We propose a solution to how AI can help in the identification of CVD risk. Lastly, we analyze the role of DR/CVD in the COVID-19 framework

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on