Carotid contrast ultrasound (CU) can be a useful clinical tool for diagnosing surrogate markers of atherosclerosis and identifying the presence of subclinical cardiovascular disease. Although ultrasound contrast agents are currently approved for use in enhancing echocardiograms (ECGs) only, with appropriate Institutional Review Board (IRB) approvals these contrast agents can also be used to enhance ultrasound images of the carotid arteries. The applications of this technique are important clinically because if disease is identified during the carotid exam this finding generally represents diffuse atherosclerosis.
It has been demonstrated that enhanced ultrasound images of the carotid arteries produce high-resolution, realtime images of the plaque neovascularization and the vasa vasorum—surrogate markers of atherosclerosis. Further, it has been shown that carotid CU screening improves the identification of the carotid intima-media thickening (c-IMT), a well-established surrogate marker of atherosclerosis.
Using carotid CU, for the first time, neovascular blood has been observed flowing from the adventitial vasa vasorum into the media and intima of the carotid plaque, literally 'feeding' the atherosclerotic plaque (tumor) with nutrient blood. Carotid CU images indicate that, as the vascular wall disease progresses leading to an increase in neovascularization, these new angiogenic vessels are 'leaky' and contribute to further inflammatory and atherosclerotic processes within the plaque. These events are believed to lead to plaque instability, which may trigger a plaque rupture resulting in a heart attack or stroke.
Over the years, pathologists and cardiovascular surgeons have observed that there is a clinical correlation between excessive neovascularization (adventitial vasa vasorum), plaque instability, and cardiovascular events. However, until now, there has been no realtime, direct imaging evidence linking neovascularization of the vasa vasorum to the plaque.
Previous researchers described preclinical experimental studies in which statin therapy reduced neovascularization in atherosclerosis. Similarly, a reduction in the presence of the neovascular vessels after treatment with statin therapy following carotid CU imaging has been shown in several patients. These preliminary clinical studies appear to support the earlier preclinical research.
Due to the fact that contrast ultrasound is an established imaging modality for cardiac imaging, these new contrast-enhanced, vascular applications appear to be a logical extension for the detection of preclinical atherosclerosis in patients at risk for a cardiovascular event. Ultimately, if clinicians use these newer imaging methods, an initial carotid CU could be used for the detection of atherosclerosis and indicate which patients should be considered candidates for additional preventive therapies.
Similar to atherosclerosis imaging, CU techniques may be applicable for detecting and monitoring neovascular blood supply associated with cancerous tumors, because the nourishment of atherosclerotic plaque appears to be analogous to the process by which external blood vessels nourish a tumor. In both cases, tumor neovascularization appears to play a key role in promoting growth of a disease process. These non-invasive imaging techniques using ultrasound contrast may contribute to the understanding of atherosclerosis and cancerous tumors; permitting improved diagnosis and therapy.