B-mode ultrasound and spiral CT for the assessment of carotid atherosclerosis

Atherosclerotic plaques are thought to result from an excessive inflammatory-fibroproliferative response to numerous insults, for example, accumulation of extracellular plasma lipoproteins in the intima [1]. The plaque rupture hypotheses were based on pathologic findings in coronary plaques [2-6]. Coronary and carotid plaques are thought to have similar atherogenesis [3-5,7-11]. Carotid artery disease has therefore long been used as a surrogate model for coronary atherosclerosis, as it is much easier to investigate carotid than coronary arteries with noninvasive methods. The vulnerability of a plaque depends on the thickness of the fibrous cap, the degree of inflammation within the cap, and the size of the lipid core. The most accepted plaque rupture theory is based upon the rupture of a thin fibrous cap covering a large lipid-rich core, with a predilection to occur at the macrophage-rich shoulder regions of the plaque [3,4,8]. Accordingly, most thorough quantitative histologic studies have actually identified a positive association between atheromatous, lipid-rich material in the plaque and neurologic symptoms [12-17]. Using immunohistochemical characterizations, macrophages, T-lymphocytes, increased matrix metalloproteinase-9 activity, and fibrous cap thinning are also positively correlated with plaque rupture of carotid plaques, [18,19] microembolism [20], proximity with last cerebral ischemic event [21], and having experienced cerebral ischemic symptoms [22,23]; however, Hatsukami et al [14] did not find any correlation with presence of cerebral ischemic symptoms and quantitative pathologic constituents. Alternative to fibrous cap rupture, intraplaque hemorrhage is thought to derive from bleeding into plaques from thin-walled new vessels originating from vasa vasorum, frequently found at the plaque base [24,25] This bleeding theoretically could increase the intraplaque pressure with resultant cap rupture from the inside [26]. Paradoxically, this has to happen against a much higher luminal pressure. McCarthy et al identified more and larger neovessels in carotid plaques and fibrous caps in symptomatic plaques as compared to asymptomatic plaques [27]. Conversely, Leen et al found that most blood vessels are located at the base of plaques and are unrelated to hemorrhage in the plaque [28]. Vulnerable plaques may be triggered to rupture by intrinsic (ie, the continued accumulation of lipoproteins from plasma with or without uptake in macrophage foam cells) or extrinsic stresses (ie, changes in blood pressure). Hereby, the thrombogenic plaque interior is exposed to the lumen, which may lead to intraplaque hemorrhage, formation of superimposed thrombosis, embolism, and subsequent myocardial/neurologic symptoms. Plaque rupture depends on the balance between the reparative mechanisms, the smooth muscle cell production of collagen to strengthen the fibrous cap, and destabilizing effects of lipids and inflammation as well as the rupture triggers (eg, hypertension) [1,29]. Because numerous endothelial lesions are present in mild to moderate stenotic plaques in coronary arteries, this questions the plaque rupture theory as being the only determinant of clinical events [30].