Plaque imaging volume analysis: technique and application

The prevention and management of atherosclerosis poses a tough challenge to public health organizations worldwide. Together with myocardial infarction, stroke represents its main manifestation, with up to 25% of all ischemic strokes being caused by thromboembolism arising from the carotid arteries. Therefore, a vast number of publications have focused on the characterization of the culprit lesion, the atherosclerotic plaque. A paradigm shift appears to be taking place at the current state of research, as the attention is gradually moving from the classically defined degree of stenosis to the identification of features of plaque vulnerability, which appear to be more reliable predictors of recurrent cerebrovascular events. The present review will offer a perspective on the present state of research in the field of carotid atherosclerotic disease, focusing on the imaging modalities currently used in the study of the carotid plaque and the impact that such diagnostic means are having in the clinical setting

Coronary CT Angiography and the Napkin-ring Sign Indicates High-Risk Atherosclerotic Lesions

Coronary computed tomography angiography (CCTA) is used extensively nowadays as a non-invasive imaging method for the evaluation of patients suspected of coronary artery disease, providing data on calcium burden, the presence of coronary artery stenoses, but also, more recently, on coronary atherosclerotic plaque morphology and composition. Plaque morphology analysis by CCTA aims to accurately identify vulnerable plaques, in an attempt to reduce the number of ischemic events triggered by high-risk atherosclerotic lesions. Recent research provides CCTA descriptions of vulnerable plaques and a particular radiological sign shows promising perspectives. The napkin-ring sign refers to a rupture-prone plaque in a coronary artery, comprising a necrotic core covered by a thin cap fibro-atheroma. The napkin-ring sign is described on CCTA in cross-sectional images of coronary arteries as a central low-attenuation area surrounded by an open ring area of high attenuation, having a high specificity and positive predictive value for the presence of advanced lesions. These lesions have been designated as vulnerable plaques, indicating an increased probability of rupture, and were shown to correlate with a higher incidence of cardiovascular events. In acute coronary syndromes, the location of the napkin-ring sign was shown to correspond to the culprit lesions. The aim of the current paper is to provide an overview of the current literature on available methods for quantitative measurement of atherosclerotic plaque features from CCTA and to discuss the clinical implications of the napkin-ring sign as detected by CCTA

A multiscale modelling approach to understand atherosclerosis formation: A patient-specific case study in the aortic bifurcation

Atherogenesis, the formation of plaques in the wall of blood vessels, starts as a result of lipid accumulation (low-density lipoprotein cholesterol) in the vessel wall. Such accumulation is related to the site of endothelial mechanotransduction, the endothelial response to mechanical stimuli and haemodynamics, which determines biochemical processes regulating the vessel wall permeability. This interaction between biomechanical and biochemical phenomena is complex, spanning different biological scales and is patient-specific, requiring tools able to capture such mathematical and biological complexity in a unified framework. Mathematical models offer an elegant and efficient way of doing this, by taking into account multifactorial and multiscale processes and mechanisms, in order to capture the fundamentals of plaque formation in individual patients. In this study, a mathematical model to understand plaque and calcification locations is presented: this model provides a strong interpretability and physical meaning through a multiscale, complex index or metric (the penetration site of low-density lipoprotein cholesterol, expressed as volumetric flux). Computed tomography scans of the aortic bifurcation and iliac arteries are analysed and compared with the results of the multifactorial model. The results indicate that the model shows potential to predict the majority of the plaque locations, also not predicting regions where plaques are absent. The promising results from this case study provide a proof of concept that can be applied to a larger patient population

The vulnerable coronary plaque: update on imaging technologies.?

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Role of computed tomography and magnetic resonance imaging in patients with cardiovascular disease

Background: Although there have been recent advances, cardiovascular disease remains the commonest cause of premature death in the United Kingdom. There is a need to develop safe non-invasive techniques to aid the diagnosis and treatment of patients with cardiovascular disease.Objectives: The aims of this thesis are: (i) to establish whether coronary artery calcification can be measured reproducibly by helical computed tomography; (ii) to establish the effect of lipid lowering therapy on the progression of coronary calcification; (iii) to determine whether multidetector computed tomography can predict graft patency in patients who have undergone coronary artery bypass grafting; and (iv), to investigate the role of magnetic resonance imaging to assess plaque characteristics following acute carotid plaque rupture.Methods: In 16 patients, coronary artery calcification was assessed twice within 4 weeks by helical computed tomography. As part of a randomised controlled trial, patients received atorvastatin 80 mg daily or matching placebo, and had coronary calcification assessed annually. Fifty patients with previous coronary artery bypass surgery who were listed for diagnostic coronary angiography underwent contrast enhanced computed tomography angiography using a 16-slice multidetector computed tomography scanner. Finally, 15 patients with recent symptoms and signs of an acute transient ischaemic attack, amaurosis fugax or stroke underwent magnetic resonance angiography of the carotid arteries using dedicated surface coils. Plaque volume, regional plaque densities and neovascularisation were determined before and after gadolinium enhancement.Results: Quantification of coronary artery calcification demonstrated good reproducibility in patients with scores > 100 AU. Despite reducing systemic inflammation and halving serum low-density lipoprotein cholesterol concentrations, atorvastatin therapy did not affect the rate of progression of coronary artery calcification. Computed tomography angiography was found to be highly specific for the detection of graft patency. Assessment of plaque characteristics by magnetic resonance scanning in patients with recent acute carotid plaque was feasible and reproducible.Conclusions: Coronary artery calcium scores can be determined in a reproducible manner. Although they correlate well with the presence of atherosclerosis and predict future coronary risk. there is little role for monitoring progression of coronary artery calcification in order to assess the response to lipid lowering therapy. Computed tomography can be used reliably to predict graft patency in patients who have undergone coronary artery bypass grafting, and is an acceptable non-invasive alternative to invasive coronary angiography. Magnetic resonance imaging techniques ' can be employed in a feasible, timely and reproducible manner to detect plaque characteristics associated with acute atherothrombotic disease

Reproducibility of computed tomography angiography data analysis using semiautomated plaque quantification software: Implications for the design of longitudinal studies

Reproducibility of the quantitative assessment of atherosclerosis by computed tomography coronary angiography (CTCA) is paramount for the design of longitudinal studies. The purpose of this study was to assess the inter- and intra-observer reproducibility using semiautomated CT plaque analysis software in symptomatic individuals. CTCA was performed in 10 symptomatic patients after percutaneous treatment of the culprit lesions and was repeated after 3 years. The plaque quantitative analysis was performed in untreated vessels with mild-tomoderate atherosclerosis and included geometrical and compositional characteristics using semiautomated CT plaque analysis software. A total of 945 matched crosssections from 21 segments were analyzed independently by a second reviewer to assess inter-observer variability; the first observer repeated all the analyses after 3 months to assess intra-observer variability. The observer variability was also compared to the absolute plaque changes detected over time. Agreement was evaluated by Bland-Altman analysis and co

Validation and application of intravascular ultrasound in the study of percutaneous coronary intervention

Intravascular ultrasound (IVUS) is a relatively new method of imaging coronary arteries which has several advantages over contrast angiography in the accurate quantification of coronary lumen and vessel dimensions and assessment of atherosclerotic plaque. Experimentally, IVUS has so far provided detailed insights into the distribution and composition of atheroma in the coronary circulation and its behaviour when subjected, particularly, to balloon dilatation. The technique is now regarded as a useful adjunct to angiography in the routine assessment of patients with atherosclerotic coronary disease as well as in the guidance of percutaneous coronary interventional techniques such as balloon angioplasty and intracoronary stent implantation. Additionally, the concept of three-dimensional reconstruction of IVUS images has recently been realized providing the opportunity for longitudinal as well as tomographic analysisDespite the wealth of information so far provided by IVUS most in vitro studies require cautious interpretation due to well-recognised limitations of studying animal models of atherosclerosis or human coronary disease in circumstances that do not accurately reflect the clinical setting. This thesis is based upon the development of a pulsatile flow system which is capable of accurately reproducing some of the important physiological properties of in-vivo flow in normal and diseased coronary arteries. Some characteristics of in-vivo coronary blood flow cannot be met, such as the effect of blood viscosity and extrinsic compression of the vessel by the beating heart. However, the system is designed to enable the study of human coronary atherosclerotic disease by IVUS in conditions which closely resemble those seen in the clinical setting. The initial chapters provide an overview of IVUS, including methods and rationale for three-dimensional reconstruction, and describe the development and validation of the flow system. Chapters 3 and 4 assess the qualitative accuracy of IVUS in the assessment of the composition of atherosclerotic plaque and also the reproducibility of IVUS assessments of vessel and lumen dimensions in diseased coronary arteries. There follows a study of coronary balloon angioplasty designed to assess the influence of procedural factors, such as balloon calibre and inflation pressure selection, and IVUS guidance on the initial success of the procedure. In the remaining chapters two studies examine three-dimensional reconstruction of IVUS images and the influence of technical factors, which are inherent in IVUS imaging, on the accuracy of atherosclerotic plaque volume measurement and its use in assessing vascular injury following coronary balloon angioplasty. It should be emphasized that all patient donors died from causes other than cardiovascular disease such that the histopathological studies involved the use of coronary artery specimens which were not required for diagnostic purposes. The studies adhered to strict ethical standards of the day. Harvesting of specimens received ethical approval as part of the overall IVUS research programme being undertaken at the time. All specimens were retained by the Department of Pathology during the study period and disposed of appropriately following the final analysesTaken together these studies have helped to provide further insights into the quantitative and qualitative accuracy of IVUS in the assessment of coronary atherosclerosis and the technical factors which may confound these analyses. Furthermore, the value of IVUS in guiding, and assessing the outcome of, coronary balloon angioplasty is clearly demonstrated. Given the close correlation of the studies to the clinical setting the findings should be expected to influence our approach to clinical IVUS studies and utilize the technique more frequently in the guidance of percutaneous coronary intervention

Quantification of atherosclerotic plaque in the elderly with positron emission tomography/computed tomography

L'athérosclérose est une maladie cardiovasculaire inflammatoire qui est devenue la première cause de morbidité et de mortalité dans les pays développés et parmi les principales causes d’invalidité au monde. Elle se caractérise par l’épaississement de la paroi vasculaire artérielle suite à l'accumulation de lipides et le dépôt d'autres substances au niveau de l’intima (endothélium) pour former la plaque d’athérome. Avec l'âge, cette plaque peut grossir, se calcifier et ainsi rétrécir le calibre de l'artère pour diminuer son débit et à un stade avancé de la maladie, elle peut se rompre et obstruer les petites artères dans n'importe quelle partie du corps causant des complications aigues, y compris la mort soudaine. L'objectif de cette thèse est de pouvoir détecter l'inflammation de la plaque athérosclérotique quantitativement avec la TEP/TDM dans le but de prévenir son détachement. Les mesures avec la TDM et la TEP avec le 18F-FDG ont été acquises chez des sujets humains âgés de 65 à 85 ans. Des analyses quantitatives ont été conduites sur les images de TDM en fonction de l'intensité et des étendues des calcifications, et sur les images de la TEP pour évaluer le métabolisme des plaques. L'effet des traitements par les statines a aussi été étudié. Au-delà la couverture de cette étude de façon détaillée au niveau physiologique en corrélant différents paramètres des plaques, et au niveau méthodologique en utilisant de nouvelles approches pour l'analyse pharmacocinétique, il en ressort principalement la suggestion de la détection de la vulnérabilité de la plaque artérielle par la TDM, plus disponible et moins coûteuse, en remplacement des analyses biochimiques, surtout la protéine C-réactive (CRP) considérée être la méthode standard.Abstract : Atherosclerosis is an inflammatory cardiovascular disease considered the leading cause of morbidity and mortality in developed countries and among the leading causes of disability worldwide. It is characterized by the thickening of the arterial vascular wall due to the accumulation of lipids and the deposition of other substances in the intima (endothelium) to form atheroma plaque. With age, this plaque can grow larger, calcify and thus narrow the size of the artery to decrease blood flow and at an advanced stage of the disease, it can rupture, be transported by blood and block the small arteries in any part of the body causing acute complications, including sudden death. The objective of this thesis was to be able to detect the inflammation of the atherosclerotic plaque quantitatively with PET/CT in order to prevent its detachment. Measurements with CT and PET with 18F-FDG were acquired in human subjects aged 65 to 85 years. Quantitative analyzes were performed on CT images based on the intensity and extent of calcifications, and on PET images to assess plaque metabolism. The effect of statin treatments has also been studied. Beyond the coverage of this study in a detailed manner at the physiological level by correlating different parameters of the plaques, and at the methodological level by using new approaches for pharmacokinetic analysis, it mainly emerges the suggestion for the detection of the vulnerability of the arterial plaque by CT alone, more available and less expensive, replacing biochemical analyzes, especially Creactive protein (CRP) considered to be the standard method