Inflammation and neovascularization intertwined in atherosclerosis: imaging of structural and molecular imaging targets.

Abstract

Atherosclerosis is a chronic inflammatory disease characterized by lipid-containing inflammatory lesions of large- and medium-sized arteries. It is primarily a disease of the inner layer of the arterial wall, the intima. As the disease advances, the adventitia, however, also participates in the pathogenesis of the atherosclerosis. Herrmann et al1 have proposed that the development of human atherosclerotic lesions can be considered to involve 3 distinct stages. In the first stage, early alterations in cellular function result from the interaction of environmental risk factors and genetic predisposition. The second stage is characterized by the proliferation of adventitial vasa vasorum with subsequent extension of the neovessels into the inner media and eventually into the enlarging plaque. In vulnerable plaques, vessel density increases from 2- to 4-fold in disrupted plaques, compared with several obstructive stable lesions. Chronic lesions can enter the third stage with further neovascularization, especially in the vulnerable shoulder areas of the plaques. At this stage, the intraplaque neovessels may rupture, leading to intraplaque hemorrhage. This may be because of compromised integrity of the microvascular endothelium and plaque weakening secondary to inflammation. The exacerbation of tightly intertwined plaque inflammatory activity and neovascularization results in plaque rupture, leading to arterial thrombosis with ensuing clinical syndromes. Revolution in the field of radiology in the last 3 decades has enabled imaging of inflammation and neovascularization within atherosclerotic tissue. In this article, we review advances in various clinical and preclinical imaging modalities aimed at unraveling the pathobiology of atherosclerosis. The use of ultrasound (US) for molecular imaging of the cardiovascular system is an extension of contrast echocardiographic principles already in clinical use. Nontargeted US contrast agents (UCAs) act purely as intravascular blood tracers behaving as red blood cells within the microcirculation. Targeted UCAs decorated with ligands, by affinity-based interaction, localize to a site where …