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This chapter outlines the basic principles of nuclear imaging as applied to imaging of the atherosclerotic plaque. The small size of most atherosclerotic lesions and their anatomical proximity to other structures places exacting demands on nuclear imaging systems. In single photon emission computed tomography (SPECT) and PET the detected photon emission is corrected to account for errors due to attenuation, scatter, random decay events and dead time, following which 2D and 3D topographical images can be reconstructed. Vulnerable lesions are characterized by high levels of low density lipoprotein (LDL) accumulation, oxidation and phagocytosis by plaque macrophages and foam cells. The recognition that fluorine-18 labelled deoxyglucose (FDG)-PET might have a role in imaging inflammation led to its use in diagnosing and following patients with systemic vasculitides. Vulnerable plaques provide a highly thrombogenic substrate and have often gone through both symptomatic and asymptomatic episodes of rupture, thrombosis and repair.
Magnetic resonance imaging (MRI) detects significant changes in the morphology of atherosclerotic plaque during the course of lipid-lowering therapy, and demonstrates the promise of this noninvasive imaging modality for use in clinical trials. Images obtained from the placebo-control arm of a five-site carotid MRI study were analyzed to assess the variability of MRI for measuring lesion size and composition, and to provide sample size calculations for a variety of imaging endpoints. MRI is capable of quantifying atherosclerotic lesion size and plaque composition in the setting of a multicenter trial with low interscan variability. Sample-size calculations based on reproducibility data for carotid MRI indicate that clinical trials involving approximately 150 subjects per treatment arm would be sufficiently powered to detect a 5% difference in treatment effect. MRI may provide valuable insight into pathophysiology and mechanisms of pharmacologic activity.
This chapter provides the traditional and evolving criteria used for grading carotid artery stenosis as well as the clinical relevance of sonography in the management of symptomatic and asymptomatic carotid disease. Doppler diagnosis of carotid stenosis focuses on three areas: the prestenotic region, the stenosis itself, and the poststenotic region. Color-flow imaging permits rapid identification of the carotid vessels and allows for easier recognition of flow abnormalities that suggest the presence of stenosis. There are numerous spectral criteria for classifying stenosis in the internal carotid artery (ICA). Some focus on categories of stenosis, while others focus on threshold levels of stenosis. Carotid duplex studies have been used as the noninvasive standard to evaluate for carotid stenosis. Standardized criteria evaluating peak systolic velocities, end diastolic velocities, and the ICA/common carotid artery (CCA) ratio have been set and correlate to specific percentages of stenosis.
Stroke is a major cause of morbidity and mortality, with carotid disease representing an important contributory risk factor. This book is about the pathogenesis and management of carotid disease with specific focus on the role imaging has to play in the early recognition of symptomatic and asymptomatic disease as well as the treatment of the developed condition. Technological advances in imaging modalities now allow detailed analysis of the disease progression, the prediction of critical events leading to a stroke, as well as the identification of the most effective surgical or other interventional treatments. This book should be read by neurologists, cardiologists, vascular surgeons, neurosurgeons and radiologists involved in the care of patients with carotid disease, and also by researchers involved in the development of new therapeutic techniques and drugs.
Atherosclerosis, regardless of the arterial location, shares common features of intimal smooth muscle cells, inflammation, thrombosis, and extracellular accumulation of matrix, lipid, and calcification. This chapter characterizes atherosclerotic carotid disease in light of our knowledge of coronary atherosclerosis, and relates carotid plaque morphology to cerebral ischemic syndromes with special focus on features of plaque instability. It is difficult to correlate carotid, aortic and cerebrovascular plaque morphology at autopsy, for technical reasons. High flow rates and the shear forces caused by the bifurcation of the common carotid artery into the internal and external carotids result in unique features of carotid plaque morphology as compared to the coronary circulation. The reduction of stroke risk after carotid endarterectomy is attributed to removal of the cerebral embolic source in most patients. The chapter also provides a comparison of the histomorphometric features of unstable coronary and carotid atherosclerotic plaques.
This chapter concentrates on computational simulation based on magnetic resonance imaging (MRI) and ultrasound imaging. It explores the flow structure and wall shear stress distributions, and describes the relationship with arterial disease patterns. An accurate description of 3D vessel geometry is essential for accurate modelling of blood flow using computational fluid dynamics (CFD), and magnetic resonance angiography (MRA) has been the most popular technique for obtaining the information in vivo. However, for superficial vessels such as the carotid and femoral arteries, extravascular 3D ultrasound can be a cost-effective alternative to MRA. Extravascular 3D ultrasound has potential to become a relatively inexpensive, fast and accurate alternative to MRI for CFD-based hemodynamics studies of superficial arteries. Standardized imaging protocols with high quality images will certainly help to reduce the manpower needed for model reconstruction and preparation, and to minimize operator dependence of the reconstruction process.
This chapter discusses the use of vascular imaging data to advance the development of new therapies from the perspective of the pharmaceutical industry. It discusses the technologies currently used in large phase-3 studies, and addresses the technical, clinical, and regulatory considerations for the purpose of drug development and regulatory approval. M. A. Espeland reviewed the utility of carotid ultrasound as a clinical research tool to monitor atherosclerosis progression, and discussed the concept of surrogacy with respect to imaging data, and using the clinical and statistical criteria that are required for research data to be considered clinically meaningful. The chapter presents the angiography and intra- and extravascular ultrasound, to support their use in clinical trials for the development of antiatherosclerotic therapies. The technical validation elements to be addressed in a regulatory submission should have background information on the hardware, analytical software, training, data processing, data transfer, and quality control.
Developments in both magnetic resonance imaging (MRI) technology, computer software and a huge array of potential cellular and molecular targets are a step toward the identification of high-risk carotid disease. This chapter covers the recent advances with particular respect to MRI. The carotid artery plaque is ideally suited for imaging by multicontrast MRI. The chapter discusses a variety of molecular targets that may provide improved imaging of carotid atherosclerotic plaque using MRI. The presence of neovessels is strongly associated with plaque inflammation and likelihood of rupture, presumably by allowing an alternative route for entry of monocytes and lymphocytes into the plaque. Histological studies have demonstrated that superficial thrombus superimposed on a ruptured atherosclerotic plaque characterizes those plaques at high risk of ischemic events. The chapter describes the role of matrix metalloproteinases (MMPs) in plaque instability and matrix remodeling in atherosclerotic plaques.
Transcranial Doppler (TCD) utilizes the Doppler principle to determine the direction and velocity of blood flow. Most TCDs use long sample volumes in order to improve the signal-to-noise ratio and ease the detection of the basal cerebral arteries. Most TCDs use the fast Fourier transform (FFT) method of spectral analysis which produces the typical visual representation of blood flow velocity. The FFT method of spectral analysis is used in most TCD systems because it allows almost instantaneous detection and display of information in a form which is understandable to most observers. Pulsatility and resistance indices reflect characteristics of the Doppler shift velocity waveforms, and indicate the degree of pulsatility of the waveform. TCD is able to detect two of the major causes of neurological deficits that are abnormalities in blood flow and cerebral embolization. These have made it a valuable practical tool for treating patients in diverse clinical disciplines.
This chapter introduces the state-of-the-art noninvasive magnetic resonance imaging (MRI) techniques that are used to monitor atherosclerosis of the carotid artery. High-resolution MRI is an ideal plaque imaging technique because it is noninvasive and able to create excellent soft tissue contrast and distinguish flowing blood from surrounding stationary tissues. Multicontrast weighted imaging protocol provides an oblique view of the carotid artery to better visualize the location of the carotid bifurcation and to demonstrate plaque distribution. The objective of the American Heart Association (AHA) histological classification of atherosclerosis, first published in 1995, was to provide a clinically relevant categorization of human atherosclerotic lesions based on their histological composition and structure. Major plaque components include fibrous connective tissue, the lipid-rich necrotic core, intraplaque hemorrhage, and calcification. MRI is capable of identifying many of the key vulnerable plaque features defined by the expert panel with a high level of accuracy and reproducibility.
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