Atherosclerosis Neovascularization and Imaging

Abstract

Neovascularization in atherosclerotic plaques is particularly prominent in complicated lesions, and has been recently identified as a marker of plaque vulnerability. This observation has led to a growing interest in the development of imaging techniques with the ability to visualize and quantify the extent of plaque neovascularization. Such feature may play an important role in identifying those lesions more prone to destabilization and rupture, and in the guidance and monitoring of therapeutic interventions. Several modalities have emerged as potential candidates for imaging neovessels in atherosclerotic lesions. They include magnetic resonance imaging, x-ray computed tomography, positron emission tomography, single photon emission computed tomography, ultrasound, or near-infrared optical imaging. These techniques differ in their achievable spatial and temporal resolution, availability, cost, reproducibility, degree of intrusiveness, capability to image atherosclerotic plaques in various vascular territories and ability to discern different plaque components, specifically the presence of neovessels. Molecular imaging, a rapidly evolving multidisciplinary field devoted to the visualization of specific physiopathologic processes at the cellular or molecular level, appears particularly well suited for this purpose because of its ability to target and visualize individual molecules specific to neoangiogenesis. In this manuscript we will review current evidence on the potential application of the various modalities, with a particular emphasis in molecular imaging.

Detection of Carotid Adventitial Vasa Vasorum and Plaque Vascularization With Ultrasound Cadence Contrast Pulse Sequencing Technique and Echo-Contrast Agent

“…11 For these reasons, plaque remodeling has been the target of medical therapies, such as statins, aiming at the possibility of transforming an unstable plaque into a more stable plaque, reducing the cerebrovascular risk. 12 In our patients, studied with ultrasound contrast pulse sequencing and SonoVue, we observed that UCA penetrates easily in the fibrous and fatty tissue and, according to our histological findings and to recent observations, 4,13 it is related to the plaque vascularization. The constant observation of a little vessel under ulcerations may further support the hypothesis that intraplaque hemorrhage may be related to the rupture of newly formed intraplaque microvessels, a triggering factor for further embolic processes.…”

Imaging of Carotid Plaque Angiogenesis

“…As a matter of fact, an enhanced assessment of the arterial lumen and plaque morphology and an improved resolution of carotid intima-media thickness can be obtained [21, 22]. Consistent data also report that the direct visualization of adventitial vasa vasorum and plaque neovascularization is now possible with this simple, low cost, minimally invasive and in vivo technique[22,23,24,25,26]. …”

“…Carotid ultrasound, with ultrasound contrast agents (UCAs), is an emerging valuable tool to obtain more accurate data on carotid atherosclerosis, providing an enhanced assessment of the arterial lumen and plaque morphology and an improved resolution of carotid intima-media thickness [21]. Furthermore, recent observations have demonstrated that contrast carotid ultrasound may also identify adventitial vasa vasorum and plaque neovascularization [22,23,24,25,26], with the principal advantage of being a simple, low cost and minimally invasive technique available in vivo.…”

“…The development of software for image analysis with increased spatial resolution has led to the possibility of using UCAs not only to ameliorate imaging of small-caliber vessels, but also to identify microcirculation and to image and quantify blood perfusion in organs. For these reasons, in the past 2 years contrast carotid ultrasound has been applied both to better define plaque morphology and to detect intraplaque angiogenesis: from the first studies by Feinstein [21, 22] several authors [23,24,25,26] described the possibility of identifying carotid plaque neovascularization in vivo.…”

Molecular Imaging in Cardiovascular Diseases

“…This process, called neoangiogenesis, is primarily triggered by local hypoxic states [65]. Progredient neoangiogenesis has a direct connection to increased plaque instability.…”