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Carotid Disease
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Book description

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.

Reviews

'This is a very useful book. … an excellent monograph on a rapidly developing topic which it covers well.'

Source: Neuroradiology

'Another quality of the book is the adequate balance among the 35 chapters. The editors should be praised for producing a pleasing consistency of style. Production is excellent with helpful tables and good illustrations. A welcome list of abbreviations used through the work can be found at the beginning of the book.'

Source: Pediatric Radiology

'This book provides a comprehensive review of the current state of imaging both for the assessment of carotid stenosis, and particularly of the methods and rationale for plaque imaging. The reviews are well-written and up to date with comprehensive references. … I think this book is of particular value to departments and practitioners that have a large carotid practice, particularly those who want to develop or research imaging of plaque morphology.'

Source: Clinical Radiology

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Contents


Page 1 of 2


  • Background
  • View abstract

    Summary

    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.
  • 2 - Epidemiology of carotid artery atherosclerosis
    pp 22-34
    • By Christopher J. O'Donnell, National Heart, Lung and Blood Institute and its Framingham Heart Study, Bethesda, MD, and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • View abstract

    Summary

    The totality of epidemiologic evidence demonstrates a high burden of subclinical carotid disease in middle-aged and elderly men and women. This chapter reviews the epidemiology of carotid artery atherosclerosis, including its distribution, determinants and risks conferred by its presence. High-resolution imaging modalities are now available to provide reproducible, quantitative assessment of the degree of luminal obstruction or wall disease of the carotid artery. High-resolution B-mode imaging ultrasonography is useful for detection of the degree of luminal stenosis or of intimal medial thickness (IMT) of the common carotid artery, carotid bulb, and the internal carotid artery. Carotid stenosis as well as internal carotid IMT and common carotid IMT are each associated with prevalent cardiovascular disease. Elegant clinical-pathological studies have been performed on humans with carotid artery segments that were first imaged by magnetic resonance and subsequently removed by carotid endarterectomy.
  • 3 - Genetics of carotid atherosclerosis
    pp 35-44
    • By Stephen S. Rich, Wake Forest University School of Medicine, Winston-Salem, NC, USA, Donna K. Arnett, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA
  • View abstract

    Summary

    Carotid atherosclerosis is a multifactorial pheno-type that is the end product of an array of genetic and environmental causes. Genetic analyses of common carotid artery (CCA) intima media thickness (IMT) and ICA IMT measurements with models incorporating cardiovascular risk factors resulted in significant estimates of heritability for CCA IMT and ICA IMT. The role of MMPs and atherosclerosis are determined on the basis of gene function, rather than gene discovery. Expression of matrix metalloproteinases (MMPs) interstitial collagenase (MMP-1) gelatinases (MMP-2 and MMP-9) and stromelysin (MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) were studied in human atherosclerotic plaques and in uninvolved arterial specimens. There are numerous candidate genes that could feasibly contribute to carotid atherosclerosis. The purpose of the genomewide linkage scan is to conduct a systematic evaluation of the entire human genome using families to examine the similarity of phenotype with sharing of alleles at polymorphic genetic markers.
  • 4 - Hematological processes in emboli formation
    pp 45-58
  • View abstract

    Summary

    This chapter outlines the hemostatic response to vascular damage in the carotid artery and considers the endogenous hemostatic factors that may determine the likelihood of embolization in patients. It discusses the mechanisms involved in thrombus formation and stabilization. Platelets provide a reinforced loop in the generation of a thrombus, providing a source of thrombin to recruit new platelets and propagate clot formation. The mechanism of stabilization of a thrombus by P-selectin appears to be partly stabilization of platelet-platelet aggregates but mostly through recruitment of leucocytes via interaction of P-selectin with PSGL-1. Many factors are involved in forming a stable thrombus and consequently there are many candidates for regulating the risk of embolization. Antiplatelet and antithrombotic therapies are of benefit in limiting the growth of thrombus within the carotid vessel. In particular, adenosine diphosphate (ADP) seems to have a very specific role in regulating embolization.
  • 5 - Medical treatment for carotid stenosis
    pp 59-71
    • By Matthew F. Giles, University Department of Clinical Neurology, Radcliffe Infirmary, Oxford, OX2 6HE, UK, Peter M. Rothwell, University Department of Clinical Neurology, Radcliffe Infirmary, Oxford, OX2 6HE, UK
  • View abstract

    Summary

    Patients with carotid stenosis are at high risk of stroke and acute ischemic events in other vascular territories and require intensive medical treatment. This chapter reviews the evidence for specific medical treatments in patients with carotid stenosis. Antiplatelet agents, cholesterol-lowering drugs and blood-pressure-lowering drugs should be considered in all patients with carotid stenosis. The use of drug combinations has the theoretical advantage of inhibiting platelet activity through more than one pharmacological mechanism, hence potentially conferring a greater antiplatelet effect. Loss of the normal autoregulatory capacity of the cerebral circulation such that cerebral blood flow is directly dependent on perfusion pressure, is common and there has been concern that blood pressure lowering may reduce cerebral perfusion and increase the risk of stroke. Intima-media thickness (IMT) is correlated with the presence of cardiovascular risk factors and possibly with the future risk of vascular events including stroke and myocardial infarction.
  • 6 - Surgical management of symptomatic carotid disease: carotid endarterectomy and extracranial-intracranial bypass
    pp 72-85
  • View abstract

    Summary

    This chapter reviews the major clinical trials on carotid endarterectomy and carotid angioplasty, and summarizes the technique used by the authors for carotid endarterectomy. The evolution of carotid endarterectomy, carotid angioplasty, and stenting and extracranial-intracranial (EC-IC) has been predicated on the results of clinical trials. The EC-IC bypass trial introduced the concept of multicenter prospective randomized trials to the neurosurgical community. The ongoing carotid revascularization endarterectomy versus stent trial (CREST) is prospectively randomizing patients with symptomatic carotid stenosis to either carotid endarterectomy or carotid angioplasty, and stenting with distal embolic protection (DEP), regardless of perioperative risk stratification. Assessing perioperative risk is essential in the evaluation of patients in whom carotid endarterectomy, carotid angioplasty and stenting or EC-IC bypass is being considered. Patients with symptomatic carotid occlusions may benefit from EC-IC revascularization provided they suffer from diminished cerebrovascular reserve.
  • 7 - Surgery for asymptomatic carotid stenosis
    pp 86-93
    • By Stella Vig, Mayday University Hospital, London Road, Croydon, CR7 7YE, UK, Alison Halliday, St George's Hospital Medical School, Blackshaw Road, Tooting, London, SW17 0PT, UK
  • View abstract

    Summary

    The US asymptomatic carotid atherosclerosis study first reported reduction in stroke rate after prophylactic carotid endarterectomy. Four large randomized trials have now been reported suggesting that carotid endarterectomy for asymptomatic disease can prevent stroke. The US Veterans Administration hospitals' trial reported that 4 years after prophylactic carotid endarterectomy patients with asymptomatic carotid stenosis of 50-99% had significantly fewer transient ischemic attacks (TIA) and strokes than controls. The asymptomatic carotid surgery trial (ACST) is the largest vascular trial to date. Trials suggest that selected patients with asymptomatic disease will benefit from carotid endarterectomy. Appropriate screening populations could include patients attending vascular clinics, patients with contralateral symptomatic stenoses or disease in another vascular bed. A more recent study of combined or staged carotid endarterectomy and coronary artery bypass graft (CABG) in patients with asymptomatic carotid disease suggests that the perioperative stroke risk compares favorably with CABG alone.
  • 8 - Interventional management of carotid disease
    pp 94-104
  • View abstract

    Summary

    The NASCET showed that stroke risk was significantly reduced by carotid surgery in suitable patients with recent symptoms and carotid stenosis narrowing the vessel by more than 70%. For asymptomatic stenosis the risks and benefits of surgery are finely balanced and two recent trials, the asymptomatic carotid atherosclerosis study (ACAS) trial and the recent Medical Research Council (MRC) asymptomatic carotid surgery trial (ACST) have looked at this in great detail. Two new trials are in the process of commencing: the asymptomatic carotid surgery trial II (ACST II), and also the transatlantic asymptomatic carotid interventional trial (TACIT). Data on carotid angioplasty available from several small series show the risks of procedural related stroke or death are similar to those reported in NASCET and ECST. Carotid stenting is now a mature technique and is being rapidly used by many centers as a first-line treatment for symptomatic and asymptomatic carotid stenosis.
  • Luminal imaging techniques
  • View abstract

    Summary

    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.
  • 10 - Conventional digital subtraction angiography for carotid disease
    pp 126-139
  • View abstract

    Summary

    This chapter reviews the current state of conventional digital subtraction angiography (DSA) in contemporary neurovascular imaging practice, including indications, techniques, complications and comparison with noninvasive techniques. The main indication for carotid DSA in current practice remains the evaluation of carotid atherosclerotic disease and accurate measurement of stenosis. Complications related to DSA can be classified as puncture-site-related, contrast-medium-related or neurological. More problematic complications such as pseudoaneurysms or large hematomas requiring surgical intervention are more infrequent. Several mechanisms have been postulated to account for the occurrence of neurological complications. Several established measurement methods are used to quantify the severity of internal carotid artery (ICA) stenosis prior to revascularization. The North American symptomatic carotid endarterectomy trial (NASCET) method is most widely used in North America, while the European carotid surgery trial (ECST) method tends to be frequently used in Europe.
  • 11 - Magnetic resonance angiography of the carotid artery
    pp 140-157
  • View abstract

    Summary

    This chapter summarizes the current state of carotid magnetic resonance angiography (MRA) and deals with the technical aspects of the various types of MRA, including time-of-flight (TOF), phase-contrast (PC) and contrast-enhanced MRA. TOF MRA can be performed as either multiple 2D single slice acquisitions or as a 3D volumetric flow compensated acquisition. Multiple overlapping thin slab acquisition (MOTSA) method aims to reduce the saturation effect by reducing the thickness of the 3D slabs, but maintains the volume coverage by using multiple slabs. Phase-contrast MRA relies on detecting changes in the phase of blood's transverse magnetization as it moves along a magnetic field gradient. Gadolinium-based contrast agents have been used with TOF MRA in order to improve the signal-to-noise ratio (SNR) of carotid angiograms. Amongst the various types of MRA available, 2D TOF and PC techniques are suitable for screening but they suffer from a number of technical limitations.
  • 12 - Computed tomographic angiography of carotid artery stenosis
    pp 158-165
  • View abstract

    Summary

    Computerized tomography angiography (CTA) is increasingly used in the diagnosis of carotid artery stenosis, along with other noninvasive tests such as duplex ultrasound (DUS) or magnetic resonance angiography (MRA). The use of intravenous iodinated contrast in CTA allows excellent images of the lumen of the arteries. CTA visualizes the wall of the arteries and the morphology of the atherosclerotic plaque. Each of the different postprocessing techniques used to construct a 3D angiographic display of the artery have their particular strengths and weaknesses in imaging carotid artery stenosis. Maximum intensity projection (MIP) reconstructions are often used in CTA because they can rapidly automatically be generated. The projection, lateral, posteroanterior, or oblique, which shows the most severe stenosis, is used for establishing the degree of stenosis. Multislice CT-scanning together with other technical developments will probably further improve the diagnostic accuracy of CTA.
  • 13 - Cost-effectiveness analysis for carotid imaging
    pp 166-179
  • View abstract

    Summary

    This chapter provides the basic cost-effectiveness decision analysis methodology and terminology for carotid imaging. The main focus of economic analyses has been the cost-effectiveness of screening programmes for more than 60% stenosis based on the results of the asymptomatic carotid atherosclerosis study (ACAS) trial. The cost-effectiveness analysis model typically starts with the reference case, which would usually be a typical hypothetical patient who has suffered from a minor stroke or a transient ischemic attack. A decision-tree model is essentially a horizontal flow chart that depicts all the decisions, chance events and outcomes that stem from an initial set of imaging options. There have been several studies reporting on the cost-effectiveness of carotid imaging modalities prior to surgery. In asymptomatic patients, cost-effectiveness analysis studies have generally focussed on the cost-effectiveness of screening for the identification of more than 60% stenosis based on the results of the ACAS trial.
  • Morphological plaque imaging
  • View abstract

    Summary

    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.
  • 15 - CT plaque imaging
    pp 191-207
  • View abstract

    Summary

    An atherosclerotic plaque with specific morphological features is more prone to rupture, and irregular luminal plaque surfaces are more prone to thrombus formation, thromboembolization and consequent acute events. Since computerized tomography angiography (CTA) can accurately grade the severity of carotid luminal stenosis, computerized tomography (CT) is increasingly used in the evaluation of stroke patients. CTA had a high degree of correlation with results of digital subtraction angiography (DSA) in the evaluation of carotid luminal stenosis. The main advantage of multidetector CT (MDCT) for carotid atherosclerotic plaque evaluation is the increased in-plane resolution, the decreased slice thickness and the subsequent ability to obtain near isotropic voxels. In MDCT the reconstructed slice thickness is independent of the detector collimation and is equal to or larger than the single detector collimation. MDCT can assess luminal surface morphology with the same or better accuracy than DSA.
  • 16 - Assessment of carotid plaque with conventional ultrasound
    pp 208-222
  • View abstract

    Summary

    This chapter discusses the clinical merits and limitations of conventional ultrasound (US) techniques for evaluation of both early and advanced carotid disease. A number of complementary ultrasonographic techniques such as B-mode scanning, duplex sonography, and contrast harmonic imaging are available for imaging of the carotid arteries. The first morphological abnormalities of arterial walls can be imaged by B-mode ultrasonography. This technique is one of the best methods for detection of early stages of atherosclerotic disease, because it is easily applicable, readily available, and demonstrates the wall structure with better resolution than magnetic resonance angiography or conventional angiography. In the initial period of cerebrovascular ultrasonographic insonation, the ophthalmic artery was used as an indirect test for detection of significant carotid artery stenosis. Targeted US techniques combine US imaging technology with specific contrast agents for the assessment of molecular or genetic signatures for disease.
  • 17 - Assessment of carotid plaque with intravascular ultrasound
    pp 223-234
  • View abstract

    Summary

    Intravascular ultrasound (IVUS) is a catheter-based diagnostic tool that provides a real-time, high-resolution, tomographic view of coronary arteries. There are basically two types of commercially available IVUS imaging catheters: a single-element mechanically rotated transducer and a phased-array electronic system. Mechanical systems comprise a flexible cable with a single rotation transducer that revolves at 30 revolutions per second emitting and receiving ultrasound signals every 1º increment. Phased-array catheters contain a 64-element annular array that enables a coordinated emission of the ultrasound signal. Quantitative angiographic measurements can be misleading since this technique only allows the evaluation of the profile of the lumen. A meta-analysis of angiographic studies has concluded that the magnitude of the antiatherosclerotic effects is small compared with the effects of statins on the prevention of cardiovascular events. The relation between shear stress and plaque vulnerability is currently the subject of intensive research efforts.
  • 18 - Image postprocessing
    pp 235-250
  • View abstract

    Summary

    This chapter focuses on the algorithms implemented in CASCADE to perform the four principal processing steps in carotid plaque characterization. It presents an overall framework for measuring the volumes of atherosclerotic plaque components in the carotid artery. To evaluate the effects of plaque composition on outcome, noninvasive imaging techniques must be paired with algorithms to segment the plaque into its constituent components and quantify the relative amounts of each. The extent of high-density regions in computed tomography (CT) images of vessel walls is associated with the extent of calcification, and can be used as a risk factor for heart attack and stroke. The image processing challenge for measuring morphological indices of atherosclerotic plaque is one of boundary detection. From the lumen and wall boundaries, a number of morphological indices can be derived. These include the minimal lumen area, maximal wall area, total wall volume, and maximal wall thickness.
  • Functional plaque imaging
  • View abstract

    Summary

    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.
  • 20 - USPIO – enhanced magnetic resonance imaging of carotid atheroma
    pp 272-287
  • View abstract

    Summary

    Ultrasmall paramagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) imaging is a promising noninvasive method to identify high-risk atheromatous plaques. Iron oxide particles function as contrast-enhancing agents by creating a large dipolar magnetic field gradient that acts on the water molecules that diffuse close to the particles. Howarth reported that USPIO appeared to show a dual contrast effect with signal enhancement being seen in plaques with little inflammation and large fibrous caps. The contralateral side of symptomatic patients given USPIO were also analyzed. It was found that 95% patients showed bilateral USPIO uptake suggesting an inflammatory burden within their carotid atheroma bilaterally. Three different approaches have been adopted to make the seemly impossible task a reality: ultrashort echo times (uTE), inversion recovery on-resonance water suppression (IRON) imaging, and Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP).
  • 21 - Gadolinium-enhanced plaque imaging
    pp 288-301
  • View abstract

    Summary

    This chapter overviews clinically available and developmental contrast agents used in plaque imaging. The majority of plaque imaging experiments in humans has utilized small molecular weight gadolinium agents such as Gd-DTPA and Gd-DTPA-BMA. A target of molecular contrast agents in the investigation of atherosclerosis is factors influencing angiogenesis. A major alternative to gadolinium-based agents are ultrasmall particles of superparamagnetic iron oxides. Contrast-enhanced (CE)-magnetic resonance imaging (MRI) of atherosclerosis using gadolinium agents requires special considerations in the method of image acquisition. Although late phase enhancement has been shown to provide additional information for characterizing plaque composition, the major contributions of CE MRI were expected to be in quantification and identification of inflammation. Although standard gadolinium agents produce non-specific enhancement, they still provide considerable useful information for gauging atherosclerotic plaque. Contrast-enhanced T1-weighted images can serve as additional weightings in a comprehensive multicontrast evaluation of plaque composition.

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