## 3 Symptomatic and Asymptomatic Carotid Plaques: From Pathophysiology to Diagnostic Issues
### Stenosis and Vulnerability  
Carotid artery stenosis (CAS) is usually associated with plaque progression and accounts for 10-20% of ischemic strokes due to atheorthrombotic diseases. Moreover, the risk of the first ischemic stroke, as well as the risk of its recurrence, is proportional to the degree of stenosis [53; 54]. Several non-invasive imaging techniques are used to stratify the risk of atherosclerotic plaques and assess the narrowing of the lumen diameter: magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), and ultrasound imaging (US) [55]. These techniques can help the physician stratify the stenosis into three categories: (i) mild (\(<\)50%), (ii) moderate (50-69%), and (iii) severe (70-99%). However, although the degree of stenosis has historically been considered a key element in atherosclerotic cardiovascular disease risk determination and establishing the need for surgical treatment in both symptomatic and asymptomatic carotid stenosis, it is not sufficient per se for stratifying the risk of a future stroke, as observed in both the NASCET [56] and ECST [57] trials. In fact, authors observed that more than 40% of strokes during follow-up occurred in patients with CAS \(<\) 50%, and more than 80% of patients with CAS \(>\) 50% did not suffer a stroke event during the five years of follow-up. [PERSON] et al. [58] reported that more than 20% of carotid arteries with mild stenosis (\(<\)50% stenosis) and about 8-9% of carotid arteries with normal lumen size are found to have features of vulnerability. Additionally, the American Society of Neuroradiology and the European Society of Cardiology (ESC) propose the risk of carotid-vulnerable plaque rupture should also be attributed to plaque compositions rather than only to plaque size [59; 60]. However, the difficulties in the \"vulnerability\" definition and the methodical issues regarding its detectability and quantification are still subjects of debate. The term _vulnerability_ is used to refer to plaques that are susceptible to complications and can, thus, be prone to the occurrence of thrombotic phenomena or rapid progression [61]. Additionally, it has been proposed to indirectly identify vulnerability through the evidence of some elements, such as intraplaque hemorrhages, lipid-reach necrotic cores, and microembolization in cerebral arteries, resorting to second-level diagnostic tests, such as MRI sequences using standardized protocols and transcranial Doppler [62; 63; 64; 65]. MRI has the value of providing detailed morphological information about the artery wall, luminal area, and plaque composition, although it has the disadvantage of having a long scan time and is not suitable for every patient (such as patients with metal devices). One of the best-validated techniques to identify plaque with a risk of embolization is transcranial Doppler. A prospective single-center study of 319 patients showed that the absence of transcranial microembol detection in asymptomatic stenosis identifies low-risk patients that will not benefit from endarterectomy or stenting [66]. Another prospective multi-center international study conducted on 467 patients demonstrated that the detection of asymptomatic embolization on transcranial Doppler can be used to identify high-risk patients with asymptomatic carotid stenosis [67]. Routine computed tomography angiography (CTA) can provide a qualitative, semi-quantitative, and quantitative evaluation of the vulnerability of atherosclerotic plaque and has been used for the characterization of carotid artery tissue. On the other hand, daily routine quantification of vascular diseases in carotid vessels is currently restricted to manually measured criteria, such as those described by NASCET and ECTS [68]; CTA showed very good results in detecting ulcerations [69; 70], identifying rupture of the fibrous cap [71], the evaluation of inflammation, and the extent of neovascularization, with the degree of postcontrast plaque enhancement [72].