Echolucent Plaques Research Articles

Plaque Echolucency and the Risk of Ischaemic Stroke in Patients with Asymptomatic Carotid Stenosis Within the First Asymptomatic Carotid Surgery Trial (ACST-1)

On ultrasound, potentially "high risk" carotid plaques may appear echolucent. In this study, whether a confident classification of echolucent plaque was a predictor of future ipsilateral ischaemic stroke in asymptomatic patients randomized to medical therapy in the Asymptomatic Carotid Surgery Trial-1 (ACST-1) was assessed. We performed a post-hoc analysis of 814 ACST-1 patients randomized to medical therapy alone with baseline plaque assessment classified as definitely echolucent (> 25% soft plaque) or nonecholucent (< 25% soft plaque). Kaplan-Meier survival curves were used to compare cumulative rates of ipsilateral ischaemic stroke in both groups. In the first 5 years after randomization, a significantly higher risk of ipsilateral stroke was observed in patients with definitely echolucent plaques (8.0%; 95% confidence interval [CI] 6.4-9.6) when compared with patients with definitely nonecholucent plaques (3.1%; 95% CI 2.1-4.1; p=.009). After adjustments for other risk factors, plaque echolucency was associated with a 2.5-times increased risk of ipsilateral ischaemic stroke (hazard ratio 2.52; 95% CI 1.20-5.25; p=.014). Use of lipid-lowering therapy was low in both groups during the first 5 years after randomization but rose sharply during years 5-10 of follow-up, and was significantly more likely to be prescribed for patients with echolucent plaques (p=.001). The risk of ipsilateral ischaemic stroke at 10 years was similar for both groups of patients (p=.233). Although the numbers of events in this study was low, definite plaque echolucency (> 25% soft plaque) was associated with a higher 5-year ipsilateral stroke risk in ACST-1 and may therefore help to identify patients at increased risk of stroke for whom carotid intervention may be particularly beneficial.

Plaque Echolucency May Play a Critical Role in Predicting Cerebral Embolization in Patients Undergoing Carotid Angioplasty and Stenting

Introduction Despite ongoing studies, the relationship of plaque echomorphology with increased risk of stroke in patients undergoing carotid angioplasty and stenting (CAS) remains elusive. The aim of this study is to examine whether carotid plaque echolucency is associated with greater plaque instability as determined by the quantification of captured embolic debris in CAS patients. Methods A total of 41 consecutive CAS patients with high-grade carotid stenosis were prospectively evaluated. B-mode images for 21 patients were available for analysis. Plaque echolucency was determined by grayscale median (GSM), a computer-assisted measure of echogenicity. Images were standardized with a GSM value of 0–5 for the vessel lumen and 185–195 for the adventitia. Echolucent (EL) plaques were defined by GSM &lt; 25, and echogenic (EG) plaques were defined by GSM ≥ 25. Protective filters were visualized by stereomicroscopy along three perpendicular axes and quantified through video imaging software. Because of heterogeneity in particle shape, individual particle sizes were determined by greatest length. Results Mean GSM was 45.5, and 10% plaques were echolucent. Particulate debris was detected in all filters. Plaques with lower GSM were associated with a greater number of particles (EL: 33.5 ± 10.6 particles, EG: 14.0 ± 10.3 particles; p = 0.02). Echolucent plaques also demonstrated particles of greater size: maximum size (EL: 3490 ± 1954 μm, EG: 1026 ± 1186 μm; p = 0.015) and number of particles &gt;1000 μm (EL: 3.5 ± 2.1 particles, EG: 0.7 ± 1.4 particles; p = 0.019). Conclusions Echolucent carotid plaques, as determined by GSM, may cause increased embolization of greater-sized embolic debris during CAS. Our study confirms previous findings that suggest that a GSM cut-off point of 25 may be linked with the release of more embolic debris. Therefore, increased plaque echolucency may place patients at greater risk for perioperative embolic events, making patients with such lesion characteristics more likely to experience postprocedural neurologic complications.

Cytochrome P450 Genetic Variants and Their Metabolite Levels Associated with Plaque Stability in Patients with Ischemic Stroke.

Cytochrome P450s (CYP450) enzymes regulate inflammation and atherosclerosis and can affect carotid plaque stability in patients with ischemic stroke (IS). This study aimed to investigate the association of CYP450 genetic variants with CYP plasma metabolite levels and plaque stability in patients with IS. Eleven single nucleotide polymorphisms (SNPs) of CYP genes and their plasma metabolite [20-hydroxyeicosatetraenoic acid (HETE), total epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs)] levels were measured in 396 patients with IS who underwent high-resolution B-mode ultrasound carotid plaque detection and were stratified into the following groups: non-carotid plaque and carotid plaque groups. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP). Among the 396 patients with IS, 294 cases (74%) had plaques. The frequency of rs17110453CC, rs751141 GG, and rs9333025 GG genotypes was significantly higher in patients with plaque than those without plaque. The CC, GG, GG, and GG genotypes of rs17110453, rs776746, rs751141, and rs9333025 polymorphisms were independently associated with ELP (OR, 2.62 [1.34-5.26]; OR, 1.89 [1.16-3.58]; OR, 3.12 [1.27-7.13]; and OR, 2.06 [1.34-6.33], respectively). These polymorphisms were also associated with CYP plasma metabolite levels. Patients with ELP have also shown significantly higher levels of 20-HETE and DiHETEs, but lower levels of EETs. Our data demonstrates that CYP450 SNPs are associated with plasma CYP450 metabolite levels and echolucent plaques, indicating that these SNPs may be potential markers for plaque instability.

Definite Plaque Echolucency is Associated with a Higher Risk of Ipsilateral Ischaemic Stroke during Early Follow up in the Asymptomatic Carotid Surgery Trial-1 (ACST-1)

Definite Plaque Echolucency is Associated with a Higher Risk of Ipsilateral Ischaemic Stroke during Early Follow up in the Asymptomatic Carotid Surgery Trial-1 (ACST-1)

Ultrasound Characteristics of Symptomatic Carotid Plaques: A Systematic Review and Meta-Analysis

Background: Ultrasound is the most commonly used imaging modality for assessing carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based on the sonographic characteristics of carotid plaques. Materials and Methods: We performed a comprehensive search for studies reporting imaging findings of symptomatic and asymptomatic carotid plaques on ultrasound using MEDLINE and EMBASE. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke or transient ischemic attack. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous echogenicity, echolucency, neovascularization, surface irregularity, ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. p < 0.05 was considered statistically significant. We explored the impact of publication bias by constructing funnel plots and testing their symmetry. We conducted the meta-analysis using Comprehensive Meta-analysis version 2.2, Englewood, N.J., USA. Results: A total of 1,013 articles were screened and 23 studies with 6,706 carotid plaques were included. Ultrasound plaque characteristics with a higher prevalence in individuals with symptomatic compared to asymptomatic carotid artery stenosis included plaque neovascularity (OR = 19.68, 95% CI = 3.14-123.16), complex plaque (OR = 5.12, 95% CI = 3.42-7.67), plaque ulceration (OR = 3.58, 95% CI = 1.66-7.71), plaque echolucency (OR = 3.99, 95% CI = 3.06-5.19) and intraplaque motion (OR = 1.57, 95% CI = 1.02-2.41). Variables not associated with symptom status included heterogenous echotexture (OR = 2.68, 95% CI = 0.56-12.80) and surface irregularity without ulceration (OR = 2.38, 95% CI = 0.70-8.11). No evidence of publication bias was observed based on Eggers test (p value of 0.05 for complex plaque and 0.53 for plaque echolucency). The remaining plaque features had insufficient data to assess for publication bias. Conclusions: Our meta-analysis and systematic review of the literature demonstrated that plaques with complex features, particularly those with echolucency, neovascularization, ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound may provide stroke risk information beyond measurement of luminal stenosis. Thus, sonographic evaluation of carotid artery stenosis should focus on the detection of these plaque characteristics in addition to quantifying the degree of stenosis.

Cigarette Smoking and Carotid Plaque Echodensity in the Northern Manhattan Study

Background: We sought to determine the association between cigarette smoking and carotid plaque ultrasound morphology in a multiethnic cohort. Methods: We analyzed 1,743 stroke-free participants (mean age 65.5 ± 8.9 years; 60% women; 18% white, 63% Hispanic, 19% black; 14% current and 38% former smokers, 48% never smoked) from the Northern Manhattan Study using an ultrasound index of plaque echodensity, the Gray-Scale Median (GSM). Echolucent plaque (low GSM) represents soft plaque and echodense (high GSM) more calcified plaque. The mean GSM weighted by plaque area for each plaque was calculated for those with multiple plaques. Quintiles of GSM were compared to no plaque. Multinomial logistic regression models were used to assess associations of cigarette smoking with GSM, adjusting for demographics and vascular risk factors. Results: Among subjects with carotid plaque (58%), the mean GSM scores for quintiles 1-5 were 48, 72, 90, 105, and 128, respectively. Current smokers had over a two fold increased risk of having GSM in quintile 1 (odds ratio (OR) = 2.17; 95% confidence interval (CI), 1.34-3.52), quintile 2 (OR = 2.33; 95% CI, 1.42-3.83), quintile 4 (OR = 2.05; 95% CI, 1.19-3.51), and quintile 5 (OR = 2.13; 95% CI, 1.27-3.56) but not in quintile 3 (OR = 1.18; 95% CI, 0.67-2.10) as compared to never smokers in fully adjusted models. Former smokers had increased risk in quintile 2 (OR = 1.46; 95% CI, 1.00-2.12), quintile 3 (OR = 1.56; 95% CI, 1.09-2.24), quintile 4 (OR = 1.66; 95% CI, 1.13-2.42), and quintile 5 (OR = 1.73; 95% CI, 1.19-2.51), but not in quintile 1 (OR = 1.05; 95% CI, 0.72-1.55). Conclusions: A nonlinear, V-shaped-like relationship between current cigarette smoking and plaque echodensity was observed. Former smokers were at the highest risk for plaques in high GSM quintiles. Thus, current smokers were more likely to have either soft or calcified plaques and former smokers were at greater risk of having only echodense plaques when compared to those who have never smoked. Further research is needed to determine if plaque morphology mediates an association between smoking and clinical vascular events.

Carotid plaque calcification predicts future cardiovascular events in type 2 diabetes.

The presence of carotid plaques is associated with future cardiovascular events, with local plaque composition being an independent outcome predictor. We examined the association between ultrasonographically determined carotid plaque calcification and incident major adverse cardiovascular events (MACE) and death in type 2 diabetes (T2D). We enrolled 581 patients with T2D who underwent routine carotid ultrasonography. Plaques were classified as echolucent (lipid rich), heterogenous, and echogenic (calcific). We collected demographic, anthropometric, and clinical data at baseline and followed the patients for up to 9 years. Plaques were detected in 81.8% of the patients (echolucent in 16.4%, heterogenous in 43.2%, and echogenic in 22.2%). During follow-up (4.3 ± 0.1 years), 58 deaths (27 cardiovascular) and 236 fatal and nonfatal MACE occurred. In univariate analyses, presence versus absence of any carotid plaque was associated with incident MACE, and the hazard ratio (95% CI) progressively increased from echolucent (1.97 [0.93-3.44]), to heterogeneous (3.10 [2.09-4.23]), to echogenic (3.71 [2.09-5.59]) plaques. Compared with echolucent plaques, echogenic plaques were associated with incident MACE independently from confounders. This association was attenuated after adjusting for the degree of stenosis, but in patients with stenosis ≤30%, echogenic plaque type still predicted total and atherosclerotic MACE, even after further adjusting for mean intima-media thickness. In T2D, carotid plaque calcification predicts MACE, especially in patients with a low degree of stenosis. The biology of atherosclerotic calcification in diabetes needs to be further elucidated to understand the basis of this association.

Bone mineral density and carotid atherosclerosis in systemic lupus erythematosus: a controlled cross-sectional study

IntroductionAs osteoporosis is reported to be associated with atherosclerosis in the general population we examined the relationship between bone mass and carotid measurements in patients with systemic lupus erythematosus (SLE) and controls, and possible links between them in SLE.MethodsIn a cross-sectional study, 111 SLE-patient were compared with 111 age- and sex-matched controls, mean age 48.7(12.9) years, 89% were women, of which 51% postmenopausal. Carotid intima media thickness (cIMT), carotid plaque occurrence and echogenicity were determined by B-mode ultrasound and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA).ResultsBMD and cIMT were inversely associated both in patients and controls. Patients, but not controls, with carotid plaque had higher cIMT at low BMD than at normal BMD, p = 0.010. Logistic regression indicated more than doubled odds ratio (OR) of carotid plaque in patients, particularly in post-menopausal women, than in controls in relation to all BMD measurements. For low BMD at hip, significant increased OR for echolucent plaque was shown for patients compared with controls.In patients, significant impact of age, body mass index, smoking, systolic blood pressure, blood lipids, diabetes mellitus, impaired renal function, low levels of complement C3 and C4, history of nephritis, SLE-damage index and ever use of antimalarial was found for association between BMD and higher cIMT and carotid plaque. In multivariate regression, low C4 was independent contributor to association between total BMD and upper cIMT tertile, accounted for OR (95% confidence interval) of 3.2 (1.03-10.01), and also for association with bilateral carotid plaque, OR of 4.8 (1.03-22.66). The contribution of low C4 for the association between BMD and carotid atherosclerosis was enhanced within the second and third tertiles of total BMD.ConclusionThis study is the first to demonstrate inverse association between BMD and carotid measurements in both SLE-patients and controls. Our results suggest that SLE-patients may suffer higher burden of (sub)clinical atherosclerotic disease, especially presence of both echolucent and echogenic plaque, than controls with the same bone mineral status. Low complement C4 seems to play an important role in earlier development of carotid atherosclerosis already within (sub)normal ranges of total BMD in patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0595-4) contains supplementary material, which is available to authorized users.

Abstract T P141: Current Cigarette Smoking Is Associated With Echodensity of Carotid Plaque in the Northern Manhattan Study

Introduction: Many pathological mechanisms associated with smoking have been described, but studies on cigarette smoking in relation to carotid plaque morphology are lacking. Given that certain plaque compositions are more prone to cause cerebrovascular events, we sought to determine the association of carotid plaque density and cigarette smoking in an urban multi-ethnic cohort. Methods: This cross-sectional study analyzed 1743 stroke-free participants from the population-based Northern Manhattan Study using an ultrasonographic index of plaque echodensity, the Grey Scale Median (GSM). Echolucent plaque (low GSM) is more soft and fibrous, while echodense (high GSM) is more calcified. For individuals with multiple plaques, the mean GSM weighted by plaque area for each plaque was calculated. Quintiles of GSM were calculated among those with plaque and compared to those with no plaque as the reference. We used multinomial logistic regression models to assess the associations of current cigarette smoking with GSM, adjusting for demographics and vascular risk factors. Results: The mean age was 65.5±8.9 years, 60% were women, 18% white, 63% Hispanic, 19% black, 14% current smokers, 38% former smokers, and 48% never smokers. Carotid plaque was present in 58% of subjects. Current smokers were at a two-fold increased risk of being in GSM quintiles 1, 2, 4, and 5 as compared to never smokers (Table). Conclusions: A U-shaped relationship between current cigarette smoking and plaque echodensity is observed. Smoking is associated with both echodense calcified plaque as well as with echolucent, soft plaque that are more prone to rupture. Research is needed to determine if these vulnerable plaque phenotypes may mediate an association between cigarette smoking and clinical vascular events.

Abstract 212: Factors Associated with Symptom Development in Asymptomatic Carotid Artery Stenosis: Multimodal Carotid and Perfusion Imaging Study

Background: The predictors of symptom development in asymptomatic carotid stenosis are still unclear. We sought to identify factors associated with symptom development in asymptomatic carotid stenosis using multimodal imaging technique. Methods: We retrospectively collected patients who had carotid artery revascularization procedures (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) from April 2007 to May 2013. Patients who had event of cerebral ischemic stroke during 6 months before CEA or CAS were categorized as a symptomatic carotid stenosis. Results from carotid Duplex sonography, CT angiography, brain MRI and MRA, perfusion-weighted MRI (PWI), and demographic profiles were compared. Multivariate logistic regression analysis was performed to identify factors associated with symptom carotid stenosis. Results: A total of 684 patients (asymptomatic 58%, symptomatic 42%) with carotid stenosis more than 50% were included. The presence of ischemic heart diseases, peripheral artery occlusive disease and use of statin were higher in the asymptomatic carotid stenosis. On Duplex scan, ulceration, echolucent plaque, and heterogeneous components of plaque were more frequent in symptomatic carotid stenosis. Angiographic data showed the length of plaque was longer in symptomatic carotid stenosis. Presence of deep white matter hyperintensity, FLAIR vessel sign and GRE vessel sign were more frequently observed in symptomatic carotid stenosis. Patients with symptomatic carotid stenosis had increased cerebral blood flow, cerebral blood volume (CBV), and delayed time to peak when compared to the asymptomatic stenosis. Multivariate analysis revealed length of plaque (&gt;20mm), deep white matter hyperintensity and increased CBV were associated with symptomatic carotid stenosis (Odd ratio [OR]=2.339, 95% confidence interval [CI] 1.312-4.169, P=0.004; OR=2.315, 95% CI 1.160-4.619, P=0.017; OR=2.242, 95% CI 1.127-4.463, P=0.021, respectively). Conclusion: Plaque burden, deep white matter hyperintensity, and increased CBV were independent predictors of symptom development in carotid stenosis. Multimodal imaging may be useful to identify high risk patients of ischemic stroke among asymptomatic carotid stenosis.

Abstract T P180: Ultrasound Characteristics of Symptomatic Carotid Plaques: A Systematic Review and Meta-analysis

Background and Purpose: Ultrasound is the most commonly used imaging modality for assessment of carotid artery stenosis. A number of studies have demonstrated that surface irregularities, heterogeneous echotexture and hypoechoic plaques are risk factors for acute ischemic stroke. We performed a systematic review and meta-analysis of the literature to better define the risk of stroke based off of the sonographic characteristics of carotid plaques. Materials and Methods: We performed a comprehensive literature search evaluating the association of carotid plaque characteristics on ultrasound with ischemic outcomes. We included both case-control and cohort studies examining the relationship between complex plaque and acute ischemic stroke. Complex plaque was defined as plaque that had any of the following characteristics: heterogeneous plaque echogenicity, hypoechoic plaque, plaque neovascularization, plaque surface irregularity, plaque ulceration, and intraplaque motion. Meta-analyses using the random-effects model were performed for complex plaque and each of the individual complex plaque characteristics. Results: A total of 1013 articles were screened and 30 studies with 11528 patients (3054 symptomatic and 8474 asymptomatic) were included. The odds ratios for the association between complex plaque and ischemic symptoms was 5.18 (95%CI=4.63-5.79). Heterogeneous echotexture (OR=11.72, 95%CI=9.82-13.98), intraplaque motion (OR=1.57, 95%CI=1.02-2.41), plaque echolucency (OR=3.23, 95%CI=2.72-3.84), plaque neovascularity (OR=5.66, 95%CI=3.15-10.16) and plaque ulceration (OR=2.65, 95%CI=1.89-3.73) were all associated with ischemic symptoms. Surface irregularity without frank ulceration was not associated with ischemic symptoms (OR=1.35, 95%CI=0.98-1.86). Conclusions: Complex plaque, heterogeneous plaque echogenicity, hypoechoic plaque, plaque neovascularization, plaque ulceration and intraplaque motion are associated with ischemic symptoms. Assessment of carotid plaque on ultrasound provides stroke risk information beyond measurement of luminal stenosis.

Age-Related Effects of Smoking on Coronary Artery Disease Assessed by Gray Scale and Virtual Histology Intravascular Ultrasound

Although smoking is a risk factor for coronary atherosclerosis, the age-related impact on lesion morphology has not been studied. The aim of this study was to assess the age-related impact of smoking on the extent of atherosclerosis and arterial remodeling. In Providing Regional Observations to Study Predictors of Events in the Coronary Tree, 687 patients with acute coronary syndrome underwent 3-vessel gray scale and virtual histology intravascular ultrasound imaging of 3,185 nonculprit lesions. In 207 patients ≤65 years, current (smoking within 1 month) and former (no smoking for >1 month) smokers showed significantly smaller normalized volumes of external elastic membrane (EEM), lumen, and P + M (plaque + media) compared with nonsmokers. At the minimal lumen area site, current and former smokers had significantly smaller EEM, lumen, and P + M areas than nonsmokers. Conversely, in 480 patients >65 years, current smokers had greater normalized P + M volumes than nonsmokers with no difference in normalized EEM or lumen volumes. Finally, in patients >65 years (but not in patients ≤65 years), current smokers showed more plaque ruptures (4.7% vs 1.8%, p = 0.05) and echolucent plaques (8.3% vs 3.9%, p = 0.05) compared with nonsmokers. On multivariable analysis, a history of smoking (combining current and former smoking) predicted smaller normalized EEM volumes compared with nonsmokers ≤65 years. In conclusion, in patients ≤65 years, but not in patients >65 years, smoking had a vascular constrictive effect that contributed to severe luminal stenosis. Conversely, smokers >65 years had more plaque with greater plaque instability.

Carotid Plaque Inflammation Assessed with 18F-FDG PET/CT is Higher in Symptomatic Compared with Asymptomatic Patients

Carotid artery plaque inflammation is thought to be an important marker of plaque vulnerability and increased stroke risk. The main aim of this study was to assess the level of agreement between 2-deoxy-2-[(18)F] fluoro-D-glucose (18F-FDG) uptake on PET (positron emission tomography) scan in carotid plaques, with cerebrovascular symptoms, carotid plaque ultrasound echogenicity and histological assessments of plaque inflammation. Thirty-six patients with ≥70% carotid stenosis scheduled for carotid endarterectomy underwent a Colour Duplex ultrasound, (18)F-FDG PET/CT and blood tests less than 24 h prior to surgery. Plaques were defined as symptomatic when associated with ipsilateral cerebral ischemic symptoms within 30 days prior to inclusion. Plaques were assessed histologically following endarterectomy. The level of agreement between (18)F-FDG uptake (mean SUVmax and SUVmax ), and target-to-background ratio, symptoms, plaque echolucency, and histological evidence of inflammation was assessed. The amount of (18)F-FDG uptake in plaques and the amount of inflammation on histological assessment were significantly correlated (r = 0·521, P = 0·003). (18)F-FDG uptake was significantly higher in symptomatic plaques with median SUVmax 1·75 (1·26-2·04) in symptomatic, and 1·43 (1·15-2·28) in asymptomatic patients (P = 0·03). (18)F-FDG uptake was also positively correlated with echolucency on Doppler ultrasound (P = 0·03). (18)F-FDG uptake on PET/CT correlated with histological assessments of inflammation and was higher in patients with symptomatic compared with asymptomatic carotid artery plaques. These results support the use of (18)F-FDG PET/CT in the detection inflammation in carotid atherosclerosis, which may be of help in the detection of vulnerable plaques.

Echolucent Carotid Plaque is Associated with Future Renal Dysfunction in Patients with Stable Coronary Artery Disease.

Functional and structural abnormalities of the peripheral arteries are associated with renal dysfunction, independent of the presence of renal artery stenosis. This study investigated whether echolucent carotid plaque is associated with a future decline in the renal function in patients with coronary artery disease (CAD). Ultrasound assessments of carotid plaque echolucency with integrated backscatter (IBS) analyses were performed in 327 patients with stable CAD and carotid plaque who exhibited a normal renal function (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2)) at baseline. A lower IBS value reflects the presence of echolucent and lipid-rich unstable plaque. All patients were followed up for 36 months or until the occurrence of renal dysfunction, defined as an eGFR of ＜45 mL/min/1.73 m(2). During the follow-up period, 39 patients developed renal dysfunction. A multivariate logistic regression analysis showed that the presence of carotid plaque with a low IBS value was significantly associated with progression to renal dysfunction (odds ratios 0.48; 95% CI 0.30-0.78, p= 0.003). In addition, carotid plaque with a low IBS value had a significant incremental effect on the predictive value of known risk factors for renal dysfunction in analyses using c-statistics (AUC of the baseline risk model with and without IBS: 0.83 vs. 0.79, respectively, p=0.04), net reclassification improvement (index=0.549, p=0.001) and integrated discrimination improvement (index=0.068, p=0.002). Echolucency of the carotid arteries is associated with future renal dysfunction in patients with stable CAD, indicating that the mechanisms related to plaque instability may be involved in the onset of renal dysfunction.

Fully Automated Carotid Plaque Segmentation in Combined Contrast-Enhanced and B-Mode Ultrasound

Carotid plaque segmentation in B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) is crucial to the assessment of plaque morphology and composition, which are linked to plaque vulnerability. Segmentation in BMUS is challenging because of noise, artifacts and echo-lucent plaques. CEUS allows better delineation of the lumen but contains artifacts and lacks tissue information. We describe a method that exploits the combined information from simultaneously acquired BMUS and CEUS images. Our method consists of non-rigid motion estimation, vessel detection, lumen–intima segmentation and media–adventitia segmentation. The evaluation was performed in training (n = 20 carotids) and test (n = 28) data sets by comparison with manually obtained ground truth. The average root-mean-square errors in the training and test data sets were comparable for media–adventitia (411 ± 224 and 393 ± 239 μm) and for lumen–intima (362 ± 192 and 388 ± 200 μm), and were comparable to inter-observer variability. To the best of our knowledge, this is the first method to perform fully automatic carotid plaque segmentation using combined BMUS and CEUS.

Plaque Echolucency May Play a Critical Role in Predicting Cerebral Embolization in Patients Undergoing Carotid Angioplasty and Stenting

Introduction Despite ongoing studies, the relationship of plaque echomorphology with increased risk of stroke in patients undergoing carotid angioplasty and stenting (CAS) remains elusive. The aim of this study is to examine whether carotid plaque echolucency is associated with greater plaque instability as determined by the quantification of captured embolic debris in CAS patients. Methods A total of 41 consecutive CAS patients with high-grade carotid stenosis were prospectively evaluated. B-mode images for 21 patients were available for analysis. Plaque echolucency was determined by grayscale median (GSM), a computer-assisted measure of echogenicity. Images were standardized with a GSM value of 0–5 for the vessel lumen and 185–195 for the adventitia. Echolucent (EL) plaques were defined by GSM &lt; 25, and echogenic (EG) plaques were defined by GSM ≥ 25. Protective filters were visualized by stereomicroscopy along three perpendicular axes and quantified through video imaging software. Because of heterogeneity in particle shape, individual particle sizes were determined by greatest length. Results Mean GSM was 45.5, and 10% plaques were echolucent. Particulate debris was detected in all filters. Plaques with lower GSM were associated with a greater number of particles (EL: 33.5 ± 10.6 particles, EG: 14.0 ± 10.3 particles; p = 0.02). Echolucent plaques also demonstrated particles of greater size: maximum size (EL: 3490 ± 1954 μm, EG: 1026 ± 1186 μm; p = 0.015) and number of particles &gt;1000 μm (EL: 3.5 ± 2.1 particles, EG: 0.7 ± 1.4 particles; p = 0.019). Conclusions Echolucent carotid plaques, as determined by GSM, may cause increased embolization of greater-sized embolic debris during CAS. Our study confirms previous findings that suggest that a GSM cut-off point of 25 may be linked with the release of more embolic debris. Therefore, increased plaque echolucency may place patients at greater risk for perioperative embolic events, making patients with such lesion characteristics more likely to experience postprocedural neurologic complications.

Echogenicity of Medium-to-Large Carotid Plaques Predicts Future Vascular Events

Background: Although the echolucent plaque in carotid stenosis is associated with future ischemic stroke, the predictive value of echogenicity in small and medium size carotid plaques on vascular events has not been thoroughly examined. Thus, we prospectively tested the hypothesis that plaque echogenicity of carotid atheroma can predict the future total cardiovascular events in patients with vascular risk factors. Methods: Ultrasound assessment of carotid intima-media complex thickness (IMT) and plaque echogenicity using integrated backscatter (IBS) analysis was performed in 596 patients aged 40 or more, with any history of vascular events or with at least 1 risk factor, who were enrolled between 2001 and 2006 in the Osaka Follow-up Study for Carotid Atherosclerosis, part 2 (OSACA2). We followed the incidence of total cardiovascular events including cerebrovascular events, coronary heart disease (CHD), and peripheral artery disease (PAD) for 6.4 years. We divided the patients into two groups according to the IBS index above (echorich plaques) and under (echolucent plaque) the median value, and calculated the hazard ratios (HR) of the echolucent group compared with the echogenic group in the risk of cardiovascular events. Results: Among 596 patients, carotid stenosis was found only in 87 patients. During the follow-up period, we observed 121 cardiovascular events including 63 cerebrovascular events, 45 CHD cases, and 13 PAD cases. The patients with incident cardiovascular events had larger plaque thickness and lower IBS index than those without incident vascular events. The relative risk of vascular events for echolucent versus echorich plaques was 1.45 (95% confidence interval [CI] 0.99-2.13, p = 0.058) after adjustment for risk factors and plaque thickness. In patients with plaque size above the median value (>2.1 mm), the relative risk of vascular events for echolucent plaques was 1.72 (95% CI 1.06-2.85, p = 0.029), but this association was not observed in patients with plaque size <2.0 mm. Conclusions: The association between echogenicity of carotid plaque and incident vascular events is dependent on the plaque size. Echolucent medium-to-large plaques, but not small plaques, are associated with the risk of future total cardiovascular events. This finding suggests that measurement of echolucency in medium-to-large carotid plaques may improve selection of patients at high risk for total vascular events.

Lumen segmentation and motion estimation in B-mode and contrast-enhanced ultrasound images of the carotid artery in patients with atherosclerotic plaque.

In standard B-mode ultrasound (BMUS), segmentation of the lumen of atherosclerotic carotid arteries and studying the lumen geometry over time are difficult owing to irregular lumen shapes, noise, artifacts, and echolucent plaques. Contrast enhanced ultrasound (CEUS) improves lumen visualization, but lumen segmentation remains challenging owing to varying intensities, CEUS-specific artifacts and lack of tissue visualization. To overcome these challenges, we propose a novel method using simultaneously acquired BMUS&CEUS image sequences. Initially, the method estimates nonrigid motion (NME) from the image sequences, using intensity-based image registration. The motion-compensated image sequence is then averaged to obtain a single "epitome" image with improved signal-to-noise ratio. The lumen is segmented from the epitome image through an intensity joint-histogram classification and a graph-based segmentation. NME was validated by comparing displacements with manual annotations in 11 carotids. The average root mean square error (RMSE) was 112±73 μm . Segmentation results were validated against manual delineations in the epitome images of two different datasets, respectively containing 11 (RMSE 191±43 μm) and 10 (RMSE 351±176 μm ) carotids. From the deformation fields, we derived arterial distensibility with values comparable to the literature. The average errors in all experiments were in the inter-observer variability range. To the best of our knowledge, this is the first study exploiting combined BMUS&CEUS images for atherosclerotic carotid lumen segmentation.

Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis.

Ultrasonographic plaque echolucency has been studied as a stroke risk marker in carotid atherosclerotic disease. We performed a systematic review and meta-analysis to summarize the association between ultrasound-determined carotid plaque echolucency and future ipsilateral stroke risk. We searched the medical literature for studies evaluating the association between carotid plaque echolucency and future stroke in asymptomatic patients. We included prospective observational studies with stroke outcome ascertainment after baseline carotid plaque echolucency assessment. We performed a meta-analysis and assessed study heterogeneity and publication bias. We also performed subgroup analyses limited to patients with stenosis ≥50%, studies in which plaque echolucency was determined via subjective visual interpretation, studies with a relatively lower risk of bias, and studies published after the year 2000. We analyzed data from 7 studies on 7557 subjects with a mean follow-up of 37.2 months. We found a significant positive relationship between predominantly echolucent (compared with predominantly echogenic) plaques and the risk of future ipsilateral stroke across all stenosis severities (0% to 99%; relative risk, 2.31; 95% confidence interval, 1.58-3.39; P<0.001) and in subjects with ≥50% stenosis (relative risk, 2.61; 95% confidence interval, 1.47-4.63; P=0.001). A statistically significant increased relative risk for future stroke was preserved in all additional subgroup analyses. No statistically significant heterogeneity or publication bias was present in any of the meta-analyses. The presence of ultrasound-determined carotid plaque echolucency provides predictive information in asymptomatic carotid artery stenosis beyond luminal stenosis. However, the magnitude of the increased risk is not sufficient on its own to iden tify patients likely to benefit from surgical revascularization.

Ultrasound Speckle Tracking Strain Estimation of in Vivo Carotid Artery Plaque with in Vitro Sonomicrometry Validation

Our objective was to validate a previously developed speckle tracking (ST) algorithm to assess strain in common carotid artery plaques. Radial and longitudinal strain was measured in common carotid artery gel phantoms with a plaque-mimicking inclusion using an in-house ST algorithm and sonomicrometry. Moreover, plaque strain by ST for seven patients (77 ± 6 y) with carotid atherosclerosis was compared with a quantitative visual assessment by two experienced physicians. In vitro, good correlation existed between ST and sonomicrometry peak strains, both radially (r = 0.96, p < 0.001) and longitudinally (r = 0.75, p < 0.01). In vivo, greater pulse pressure-adjusted radial and longitudinal strains were found in echolucent plaques than in echogenic plaques. This illustrates the feasibility of ultrasound ST strain estimation in plaques and the possibility of characterizing plaques using ST strain in vivo.