From Case Study to Prospective Study

Abstract

Atherosclerosis remains a major cause of death in industrialized countries. Our understanding of the natural course of the disease and of the effects of intervention is mainly based on autopsy studies and on studies in animal models. This has primarily been because of the lack of good tools to image plaque components in vivo. Indeed, even in animal studies, analysis of plaque components has occurred for the most part ex vivo by histologic sections and dedicated staining techniques. In vivo visualization of the atherosclerotic plaque and its components (calcifications, fibrocellular tissue, lipid core, hemorrhage, and thrombus), particularly in humans, will further elucidate the disease process and the effect of various types of interventions, and subsequently will have important clinical implications. The severity of stenosis in the carotid artery is a wellknown predictor of cerebral infarction and is currently the main parameter used in deciding between carotid intervention (endarterectomy or stent placement) and pharmacologic intervention. Plaque morphology is considered an additional, independent predictor of cerebral infarction: plaques containing a necrotic lipid core covered by a thin fibrous cap (known as unstable or vulnerable plaque) are prone to rupture,1,2 releasing thromboembolic particles to the brain. Therefore, noninvasive, in vivo assessment of plaque components in the carotid artery would be useful in therapy determination. Carotid stenosis of a severity that warrants surgical or endovascular treatment is found in 10 to 20% of all patients with transient ischemic attack (TIA) or ischemic stroke. Atrial fibrillation occurs in 5% to 10% of these patients and small vessel disease in 25%. In the remaining patients, moderate carotid atherosclerosis with low-grade stenosis is probably an important causative prognostic factor, but this has not been systematically studied. Indeed, prediction of recurrent stroke lacks precision, probably because we lack simple, reliable, and valid indicators of moderate carotid atherosclerosis. 3,4 Noninvasive analysis of plaque morphology could fill this gap. Until recently, angiography and ultrasound were the most common methods of analyzing atherosclerotic disease. Angiography provides information on the degree of stenosis but only limited information on the morphology of the atherosclerotic plaque. Ultrasound is able to visualize the plaque and to demonstrate the presence of calcifications. Based on echogenicity and texture (homogeneity), additional, noncalcified plaque structures can be discerned, but these structures bear no clear relationship with known plaque components. In addition, interobserver variability in the ultrasonic assessment of plaque components is high. 5 These factors make angiography and ultrasound less appropriate for standard diagnostic assessment of plaque morphology. Two existing noninvasive imaging modalities—magnetic resonance imaging (MRI) and computed tomography (CT)— are able to detect atherosclerotic disease and to image different plaque components. Because of its superior contrast resolution, MRI has the potential to provide more detailed information on the morphology of the atherosclerotic plaque