ABSTRACT Atherosclerosis is the leading cause of morbidity and mortality in Western countries, in large part due to plaque rupture. Vulnerable plaques are the most likely to rupture, being the major cause of acute myocardial infarction and sudden cardiac death. Neovascularization of the arterial walls by adventitial vasa vasorum appears to participate in the progression of atherosclerosis and atherosclerotic plaque neovascularization was shown to be one of the strongest predictors of future cardiovascular events. No techniques are currently available for the quantitative assessment of vulnerable plaque, which remains an unmet need. Microbubbles are extremely powerful contrast agents for ultrasonic imaging of the vasculature and Contrast Enhanced IntraVascular UltraSound (CE-IVUS) seems to be one of the most promising imaging modalities for the detection of atherosclerosis and vulnerable plaque. However, although this technique allows the detection of the vasa vasorum, CE-IVUS currently does not provide a quantitative characterization of its micro-architecture. The specificity of CE- IVUS needs to be improved. A quantitative assessment of the vasa vasorum network in vivo would strongly predict cardiovascular events yet no such techniques currently exist. We propose using ultrasound multiple scattering to characterize the microstructural properties of neovascular networks. By using ultrasound multiple scattering to characterize the architecture of the neovascularization, we will add a new dimension to CE-IVUS. With the technique we propose to develop here, CE-IVUS will not only be used for the detection of plaque related neo-angiogenesis, but also for its quantitative characterization. This will dramatically increase the specificity of CE-IVUS for the assessment of plaque vulnerability. Ultimately, it will enable the ultrasonic assessment of the vasa vasorum to become a widely used clinical tool for screening, diagnosis and monitoring of plaque vulnerability.

The rupture of atherosclerotic plaques is the major cause of acute myocardial infarction and sudden cardiac death. Atherosclerotic plaque neovascularization was shown to be a strong predictors of future cardiovascular events. We propose developing methods based on ultrasound multiple scattering to characterize the microstructural properties of neovascular networks, in order to improve the prediction of plaque rupture, which remains an unmet need.