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Objectives: Cryptogenic stroke represents a type of ischemic stroke with an unknown origin, presenting a significant challenge in both stroke management and prevention. According to the Trial of Org 10,172 in Acute Stroke Treatment criteria, a stroke is categorized as being caused by large artery atherosclerosis only when there is >50% luminal narrowing of the ipsilateral internal carotid artery. However, nonstenosing carotid artery plaques can be an underlying cause of ischemic stroke. Indeed, emerging evidence documents that some features of plaque vulnerability may act as an independent risk factor, regardless of the degree of stenosis, in precipitating cerebrovascular events. This review, drawing from an array of imaging-based studies, explores the predictive values of carotid imaging modalities in the detection of nonstenosing carotid plaque (<50%), that could be the cause of a cerebrovascular event when some features of vulnerability are present., Methods: Google Scholar, Scopus, and PubMed were searched for articles on cryptogenic stroke and those reporting the association between cryptogenic stroke and imaging features of carotid plaque vulnerability., Results: Despite extensive diagnostic evaluations, the etiology of a considerable proportion of strokes remains undetermined, contributing to the recurrence rate and persistent morbidity in affected individuals. Advances in imaging modalities, such as magnetic resonance imaging, computed tomography scans, and ultrasound examination, facilitate more accurate detection of nonstenosing carotid artery plaque and allow better stratification of stroke risk, leading to a more tailored treatment strategy., Conclusions: Early detection of nonstenosing carotid plaque with features of vulnerability through carotid imaging techniques impacts the clinical management of cryptogenic stroke, resulting in refined stroke subtype classification and improved patient management. Additional research is required to validate these findings and recommend the integration of these state-of-the-art imaging methodologies into standard diagnostic protocols to improve stroke management and prevention., Competing Interests: Disclosures None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features., Objectives: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score., Methods: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports., Results: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories., Conclusions: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists., Competing Interests: Funding Support and Author Disclosures The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government. The identification of specific products or scientific instrumentation does not constitute endorsement or implied endorsement on the part of the author, Department of Defense, or any component agency. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Stroke represents a major cause of morbidity and mortality worldwide with carotid atherosclerosis responsible for a large proportion of ischemic strokes. Given the high burden of the disease , early diagnosis and optimal secondary prevention are essential elements in clinical practice. For a long time, the degree of stenosis had been considered the parameter to judge the severity of carotid atherosclerosis. Over the last 30 years, literature has shifted attention from stenosis to structural characteristics of atherosclerotic lesion, eventually leading to the "vulnerable plaque" model. These "vulnerable plaques" frequently demonstrate high-risk imaging features that can be assessed by various non-invasive imaging modalities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed., Subjects and Methods: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques., Results: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture., Conclusions: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events.

This study aimed to evaluate the differences of brain connectivity between healthy subjects (HS) and patients with extracranial internal carotid artery (eICA) stenosis before and after carotid endarterectomy (CEA). An exploratory prospective study was designed. The study population consisted of a patient group (PG) of 20 patients with eICA stenosis eligible for CEA, and a control group (CG) of 20 HS, matched for age and sex. The subjects of the PG group underwent Magnetic Resonance Imaging (MRI) for resting-state functional connectivity MRI (rs-fc MRI) analysis within one week from the CEA (pre-CEA) and 12 months following CEA (post-CEA). The CG underwent a single MRI with the same protocol utilized for the PG. Three region-of-interest to region-of-interest (ROI-to-ROI) rs-fc MRI analyses were conducted: analysis 1 to compare pre-CEA PG and CG; analysis 2 to compare pre-CEA PG and post-CEA PG; analysis 3 to compare post-CEA PG and CG. The Functional Network Connectivity multivariate parametric technique was used for statistical analysis, adopting a p-uncorrected (p-unc) < 0.05 as connection threshold, and a cluster level False Discovery Rate corrected p (p-FDR) < 0.05 as cluster threshold. The clusters were defined by using a data-driven hierarchical clustering procedure. Analysis 1 revealed two clusters of reduced interhemispheric connectivity of pre-CEA PG when compared to CG. Analysis 2 and 3 showed no statistically significant differences. Our exploratory analysis suggests that patients with eICA stenosis have reduced interhemispheric connectivity when compared to a matched control group, and this difference was not evident anymore following endarterectomy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: CT is considered the standard reference both for quantification and characterization of carotid artery calcifications. Our aim was to investigate the relationship among different types of calcium configurations detected with CT within the plaque with a novel classification and to investigate the prevalence of cerebrovascular events., Materials and Methods: Seven hundred ninety patients (men = 332; mean age, 69.7 [SD, 13] years; 508 symptomatic for cerebrovascular symptoms and 282 asymptomatic) who underwent computed tomography of the carotid arteries were retrospectively included in this institutional review board-approved study. The plaque was classified into 6 types according to the different types of calcium configurations as the following: type 1, complete absence of calcification within the plaque; type 2, intimal or superficial calcifications; type 3, deep or bulky calcifications; type 4, adventitial calcifications with internal soft plaque of <2 mm thickness; type 5, mixed patterns with intimal and bulky calcifications; and type 6, positive rim sign., Results: The highest prevalence of cerebrovascular events was observed for type 6, for which 89 of the 99 cases were symptomatic. Type 6 plaque had the highest degree of correlation with TIA, stroke, symptoms, and ipsilateral infarct for both sides with a higher prevalence in younger patients. The frequency of symptoms observed by configuration type significantly differed between right and left plaques, with symptoms observed more frequently in type 6 calcification on the right side (50/53; 94%) than on the left side (39/46; 85%, P  < .001)., Conclusions: We propose a novel carotid artery plaque configuration classification that is associated with the prevalence of cerebrovascular events. If confirmed in longitudinal analysis, this classification could be used to stratify the risk of occurrence of ischemic events., (© 2022 by American Journal of Neuroradiology.)

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

Objective: Atherosclerosis is one of the leading causes of disability and mortality worldwide. Inflammation, including monocytes, T and B cells, plays a key role in its pathogenesis. Our purpose was to evaluate plasma cells' presence in a large series of carotid artery plaques and the clinical association., Patients and Methods: Forty-eight consecutive patients treated with carotid endarterectomy were retrospectively analyzed to assess plasma cells' presence inside the plaque. A semiquantitative grading score was applied, ranging from absence, scattered, clusters of 5-10, and sheets of >10 plasma cells. Plasma cell's location, as intraplaque, subendothelial or peri-adventitial, was also defined., Results: In 75% of plaques analyzed, plasma cells were detected: scattered in 63.9%, in clusters in 22.2%, and in sheets in 13.9% of cases. In all cases, plasma cells were observed only inside the plaque. In 13.9% and in 11.1% of cases, plasma cells showed, respectively, a concomitant subendothelial or peri-adventitial distribution. In 5.6% of plaques, there was a simultaneous distribution in subendothelial, peri-adventitial layer, and intraplaque. Association between the presence of symptoms and plasma cells infiltrate was found., Conclusions: Our results suggest that plasma cells could be a key parameter linked to plaque instability. Some types of configurations are significantly associated with the occurrence of cerebrovascular symptoms.