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Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%-20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Atherosclerotic plaques prone to rupture may cause acute myocardial infarction (MI) but can also heal without causing an event. Certain common histopathological features, including inflammation, a thin fibrous cap, positive remodelling, a large necrotic core, microcalcification, and plaque haemorrhage are commonly found in plaques causing an acute event. Recent advances in imaging techniques have made it possible to detect not only luminal stenosis and overall coronary atherosclerosis burden but also to identify such adverse plaque characteristics. However, the predictive value of identifying individual adverse atherosclerotic plaques for future events has remained poor. In this Position Paper, the relationship between vulnerable plaque imaging and MI is addressed, mainly for non-invasive assessments but also for invasive imaging of adverse plaques in patients undergoing invasive coronary angiography. Dynamic changes in atherosclerotic plaque development and composition may indicate that an adverse plaque phenotype should be considered at the patient level rather than for individual plaques. Imaging of adverse plaque burden throughout the coronary vascular tree, in combination with biomarkers and biomechanical parameters, therefore holds promise for identifying subjects at increased risk of MI and for guiding medical and invasive treatment., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Purpose: To investigate the natural history of carotid atherosclerosis in patients who experienced a TIA or ischemic stroke., Patients and Methods: Ninety-two TIA/stroke patients (57 men, mean age 67.7 ± 9.8 years) with ipsilateral <70% carotid stenosis underwent multisequence MRI of the plaque ipsilateral to the symptomatic side at baseline and after one year. For each plaque, several parameters were assessed at both time points., Results: Carotid lumen, wall and total vessel ( = carotid lumen and wall) volume did not significantly change. Forty-four patients had a plaque with a lipid-rich necrotic core (LRNC) at baseline, of which 34 also had a LRNC after one year. In three patients a LRNC appeared after one year. Thirty patients had a plaque with a thin and/or ruptured fibrous cap (FC) at both time points. In seven patients, FC status changed from thin and/or ruptured into thick and intact. In three patients, FC status changed from thick and intact into thin and/or ruptured. Twenty patients had intraplaque hemorrhage (IPH) at both time points. In four patients, IPH disappeared, whereas in three patients, new IPH appeared at follow-up., Conclusion: In TIA/stroke patients, carotid plaque morphology does not significantly change over a one-year period. IPH and FC status change in a minority of patients.

Background: Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD., Methodology: Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4 ± 10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1 ± 4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared., Principal Findings: Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05)., Conclusions: In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis., Trial Registration: ClinicalTrials.gov NCT00456950.

Background and Purpose: The objectives of this study were to assess plaque characteristics in symptomatic patients with mild and moderate carotid stenosis and to explore associations with cardiovascular risk factors and statin use., Methods: One hundred patients with transient ischemic attack or stroke with ipsilateral mild and moderate carotid stenosis underwent MR plaque imaging., Results: Patients with moderate stenosis had plaques with a higher prevalence of intraplaque hemorrhage (48.7% versus 19.7%, P=0.002) and a thin and/or ruptured fibrous cap (61.5% versus 36.1%, P=0.013), and larger lipid-rich necrotic core percentage (12.3% versus 6.8%, P=0.042) and smaller fibrous tissue percentage (82.7% versus 88.4%, P=0.024). Increasing age was positively associated with intraplaque hemorrhage (OR [per year]=1.08; 95% CI, 1.02 to 1.14; P=0.011). Statin use was negatively associated with intraplaque hemorrhage (OR=0.30; 95% CI, 0.10 to 0.93; P=0.038), a thin and/or ruptured fibrous cap (OR=0.34; 95% CI, 0.13 to 0.89; P=0.028), and with lipid-rich necrotic core percentage (B=-7.91; 95% CI, -13.60 to -2.22; P=0.007). Statin use was positively associated with fibrous tissue percentage (B=7.77; 95% CI, 2.40 to 13.14; P=0.005)., Conclusions: We found that symptomatic patients with moderate stenosis have a higher prevalence of complicated plaques than patients with mild stenosis. Exploratory analysis showed that increasing age was positively associated with intraplaque hemorrhage, whereas statin use was negatively associated with complicated plaque features.

Atherosclerotic plaques prone to rupture may cause acute myocardial infarction (MI) but can also heal without causing an event. Certain common histopathological features, including inflammation, a thin fibrous cap, positive remodelling, a large necrotic core, microcalcification, and plaque haemorrhage are commonly found in plaques causing an acute event. Recent advances in imaging techniques have made it possible to detect not only luminal stenosis and overall coronary atherosclerosis burden but also to identify such adverse plaque characteristics. However, the predictive value of identifying individual adverse atherosclerotic plaques for future events has remained poor. In this Position Paper, the relationship between vulnerable plaque imaging and MI is addressed, mainly for non-invasive assessments but also for invasive imaging of adverse plaques in patients undergoing invasive coronary angiography. Dynamic changes in atherosclerotic plaque development and composition may indicate that an adverse plaque phenotype should be considered at the patient level rather than for individual plaques. Imaging of adverse plaque burden throughout the coronary vascular tree, in combination with biomarkers and biomechanical parameters, therefore holds promise for identifying subjects at increased risk of MI and for guiding medical and invasive treatment. [ABSTRACT FROM AUTHOR]

Background: Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. Methods: A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCEMRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. Results: The 75th percentile adventitial (OR 1.97, 95% CI 1.18-3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. Conclusions: This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events. [ABSTRACT FROM AUTHOR]

Purpose: To assess parameter agreement of volume transfer coefficient (Ktrans ) between two vascular regions and to study the correlation with microvessel density on histology. The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter Ktrans is frequently used to study atherosclerotic plaque microvasculature. Ktrans has been reported using different descriptive statistics (mean, median, 75th percentile) either for the whole vessel wall or the adventitia in previous studies.Materials and Methods: DCE-MRI parameter agreement was analyzed in 110 symptomatic patients with ≥2 mm carotid plaque that underwent a 3T carotid DCE-MRI examination. Ktrans was estimated in the entire vessel wall and adventitia. Twenty-three patients underwent carotid endarterectomy and were used for comparison with histological quantification of microvessel density of the plaque using CD31 immunohistochemistry. DCE-MRI parameters in the vessel wall regions were compared using Pearson's correlation coefficient, Bland-Altman analysis, and a two-sided paired samples t-test. Correlation of the DCE-MRI parameters with histology was studied using the Pearson's correlation coefficient.Results: Median adventitial Ktrans was 5% higher (P = 0.003) than entire vessel wall Ktrans , with no differences for other descriptive statistics. Vessel wall and adventitial Ktrans showed similar moderately strong correlations with plaque microvessel density on histology (Pearson's ρ: 0.59-0.65 [P < 0.003] and 0.52-0.64 [P < 0.011], respectively).Conclusion: The similar moderately strong correlations for vessel wall and adventitial Ktrans with microvessel density on histology suggested that both regions reflected plaque microvessel density. Care should to be taken when comparing absolute values between studies. Future studies incorporating thresholds for risk stratification need to agree upon standardization of DCE-MRI parameters.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1053-1059. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of a heart rate (HR) lowering agent (Ivabradine) on features of atherosclerotic plaque vulnerability with magnetic resonance imaging (MRI), ultrasound imaging, and histology. Approach and results: Atherosclerosis was induced in the abdominal aorta of 19 rabbits. Nine rabbits were treated with Ivabradine (17 mg/kg/day) during the entire study period. At week 14, imaging was performed. Plaque size was quantified on contrast-enhanced T1-weighted MR images. Microvascular flow, density, and permeability was studied with dynamic contrast-enhanced MRI. Plaque biomechanics was studied by measuring the aortic distension with ultrasound. After, animals were sacrificed and histology was performed. HR was reduced by 16% (p = 0.026) in Ivabradine-treated animals. No differences in absolute and relative vessel wall beat-to-beat distension were found, but due to the reduction in HR, the frequency of the biomechanical load on the plaque was reduced. Plaque size (MR and histology) was similar between groups. Although microvessel density (histology) was similar between groups, AUC and Ktrans, indicative for plaque microvasculature flow, density, and permeability, were decreased by 24% (p = 0.029) and 32% (p = 0.037), respectively. Macrophage content (relative RAM11 positive area) was reduced by 44% (p<0.001) on histology in Ivabradine-treated animals. Conclusions: HR lowering treatment with Ivabradine in an atherosclerotic rabbit model is associated with a reduction in vulnerable plaque features. The current study suggests that HR reduction may be beneficial for inducing or maintaining a more stable plaque phenotype. [ABSTRACT FROM AUTHOR]

Purpose Atherosclerotic carotid plaques can be quantified in vivo by MRI. However, the accuracy in segmentation and quantification of components such as the thin fibrous cap (FC) and lipid-rich necrotic core (LRNC) remains unknown due to the lack of a submillimeter scale ground truth. Methods A novel approach was taken by numerically simulating in vivo carotid MRI providing a ground truth comparison. Upon evaluation of a simulated clinical protocol, MR readers segmented simulated images of cross-sectional plaque geometries derived from histological data of 12 patients. Results MR readers showed high correlation ( R) and intraclass correlation (ICC) in measuring the luminal area ( R = 0.996, ICC = 0.99), vessel wall area ( R = 0.96, ICC = 0.94) and LRNC area ( R = 0.95, ICC = 0.94). LRNC area was underestimated (mean error, −24%). Minimum FC thickness showed a mediocre correlation and intraclass correlation ( R = 0.71, ICC = 0.69). Conclusion Current clinical MRI can quantify carotid plaques but shows limitations for thin FC thickness quantification. These limitations could influence the reliability of carotid MRI for assessing plaque rupture risk associated with FC thickness. Overall, MRI simulations provide a feasible methodology for assessing segmentation and quantification accuracy, as well as for improving scan protocol design. Magn Reson Med 72:188-201, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: In addition to stenosis grading, magnetic resonance imaging (MRI) may provide valuable information about plaque ‘status’, e.g. hyperintense vulnerable carotid plaque, associated with higher morbidity and mortality. In the present study, we investigated the prevalence, clinical and radiological correlates of hyperintense carotid plaques on T1-weighted turbo-field echo (T1w-TFE) MRI in patients with ischemic symptoms. Methods: A total of 153 patients presenting with transient ischemic attack or ischemic infarct, studied with contrast-enhanced magnetic resonance angiography (CEMRA), were retrospectively examined. Stenosis grade was obtained from CEMRA images, presence or absence of hyperintense carotid plaque from T1w-TFE MRI. Stenosis grade and baseline characteristics were compared between patients with and without a hyperintense plaque. Results: Twenty-eight patients (18%) showed one or more hyperintense internal carotid (ICA) plaques. Hyperintense plaques were found in patients with <50% stenosis (6 of 158 ICAs), 50–70% stenosis (4 of 11), >70% stenosis (14 of 74) and carotid occlusion (4 of 28). Presence of hyperintense plaque was associated with older age (70 vs. 62 years; p < 0.05), higher prevalence of cardiac disease (61 vs. 28%; p < 0.01), ischemic infarct as presenting symptom (37 vs. 14%; p < 0.01), ischemic cerebral lesions on MRI (63 vs. 32%; p < 0.01), and the ICA on the patients’ symptomatic side (70 vs. 42%; p < 0.01). Conclusions: More than one third of patients with 50–70% stenosis present with a hyperintense plaque. This subgroup of patients could in the future possibly benefit from more aggressive medicinal therapy or revascularization. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and aims Plaque fissuring, a phenomenon morphologically distinct from the classical rupture of a thinned fibrous cap, has not been well characterized in carotid atherosclerosis. The aim of this study was to establish the prevalence of plaque fissures in advanced carotid plaques with an otherwise intact luminal surface, and to determine whether they might be a source of intraplaque hemorrhage (IPH). Methods We evaluated 244 surgically intact, ‘en bloc’ embedded, serially sectioned carotid endarterectomy specimens and included only those plaques with a grossly intact luminal surface. Results Among the 67 plaques with grossly intact luminal surface, cap fissure was present in 39 (58%) plaques. A total of 60 individual fissures were present, and longitudinally mean fissure length was 1.3 mm. Most fissures were found distal to the bifurcation (63%), proximal to the stenosis (88%), and in the posterior (opposite the flow divider) or lateral quadrants (80%). 36% of the fissures remained in the superficial third of the plaque. 52% extended from the lumen surface to the middle third of the plaque and 12% reached the outer third of the plaque on cross section. Fissures often occurred between two tissue planes and were connected to IPH (fresh: 63%; any type: 92%) and calcifications (43%). No correlation was found with patient characteristics such as symptom status, carotid stenosis, hypertension, diabetes, smoking and medications (statins or antiplatelet agents). Conclusions Plaque fissures are common in advanced carotid plaques with an otherwise grossly intact luminal surface and are associated with fresh intraplaque hemorrhage. As they occur on the interface between plaque components with different mechanical properties, further biomechanical studies are needed to unravel the underlying failure mechanisms. [ABSTRACT FROM AUTHOR]