Future development may be represented by the sonographic follow-up of the plaque vascularization, to evaluate the potential benefit or specific effect of medical therapy on plaque remodeling, as regression of plaque vascularization may occur [22]. It is also our experience that vascularization is detectable not only in unstable plaques with a high grade stenosis that are addressed to carotid endoarterectomy, but even in light to moderate stenosis and in asymptomatic patients [23], [27] and [28]. The observation of apparently “stable” plaques Pexidartinib in asymptomatic patients, determining internal carotid stenosis without

indications for surgery, but with evidence of intense vascularization with contrast ultrasound, may open the discussion for

further reconsidering mild, non hemodynamic carotid stenosis, in order to better evaluate stroke risk in these cases (Fig. 4). In this view, further large-scale studies are mandatory for a complete understanding of the natural history of these vascularized lesions, to eventually adopt the adequate preventive strategy. One limit of this approach of this technique regards the modality for the evaluation of the vascularization: at present, a method of a real numerical objective this website quantification of the global “plaque perfusion” is indeed not available for carotid plaques. Differently from the evaluation of the heart, in which myocardial tissue perfusion is the expression of a normal condition, and differently from small coronary plaques, in which there is a different ratio due to the size of the vessel, in carotid DOK2 atherosclerosis this pattern may interest only limited regions of the plaque and therefore quantitative analysis of the mean signal enhancement derived from the whole plaque may not be expressive of the real perfusion. The finding of a “harmful” pattern of plaque vascularization may indeed be limited to a small area of the plaque, but its identification is, in our experience, highly representative of the “plaque activity”. This was confirmed in our histologial and immunohistochemical specimen finding of a high angiogenesis with high density

of microvessels and with a strong fixation in these areas of endothelial growth factors and inflammatory markers [41]. Moreover, the semi-quantitative evaluation of ultrasound images with time intensity curves, being arbitrary selected areas, may not be considered as really representative of plaque vascularization, also because it is evaluated in bidimensional images. The identification of these patterns then requires a very careful visual and morphological observation, by sonographers trained in this field. Contrast carotid ultrasound is an emerging technique, easily available and quick to perform, that adds important clinical and research information of the “in vivo” pathophysiological status, with low costs and invasiveness.