Atherosclerotic Carotid Artery Research Articles

Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability.

Metabolism is increasingly recognized as a key regulator of the function and phenotype of the primary cellular constituents of the atherosclerotic vascular wall, including endothelial cells, smooth muscle cells, and inflammatory cells. However, a comprehensive analysis of metabolic changes associated with the transition of plaque from a stable to a hemorrhaged phenotype is lacking. In this study, we integrated two large mRNA expression and protein abundance datasets (BIKE, n = 126; MaasHPS, n = 43) from human atherosclerotic carotid artery plaque to reconstruct a genome-scale metabolic network (GEM). Next, the GEM findings were linked to metabolomics data from MaasHPS, providing a comprehensive overview of metabolic changes in human plaque. Our study identified significant changes in lipid, cholesterol, and inositol metabolism, along with altered lysosomal lytic activity and increased inflammatory activity, in unstable plaques with intraplaque hemorrhage (IPH+) compared to non-hemorrhaged (IPH-) plaques. Moreover, topological analysis of this network model revealed that the conversion of glutamine to glutamate and their flux between the cytoplasm and mitochondria were notably compromised in hemorrhaged plaques, with a significant reduction in overall glutamate levels in IPH+ plaques. Additionally, reduced glutamate availability was associated with an increased presence of macrophages and a pro-inflammatory phenotype in IPH+ plaques, suggesting an inflammation-prone microenvironment. This study is the first to establish a robust and comprehensive GEM for atherosclerotic plaque, providing a valuable resource for understanding plaque metabolism. The utility of this GEM was illustrated by its ability to reliably predict dysregulation in the cholesterol hydroxylation, inositol metabolism, and the glutamine/glutamate pathway in rupture-prone hemorrhaged plaques, a finding that may pave the way to new diagnostic or therapeutic measures.

Atherosclerotic carotid artery disease Radiomics: A systematic review with meta-analysis and radiomic quality score assessment

BackgroundStroke, a leading global cause of mortality and neurological disability, is often associated with atherosclerotic carotid artery disease. Distinguishing between symptomatic and asymptomatic carotid artery disease is crucial for appropriate treatment decisions. Radiomics, a quantitative image analysis technique, and ML have emerged as promising tools in medical imaging, including neuroradiology. This systematic review and meta-analysis aimed to evaluate the methodological quality of studies employing radiomics for atherosclerotic carotid artery disease analysis and ML algorithms for culprit plaque identification using CT or MRI. Materials and methodsPubmed, WoS and Scopus databases were searched for relevant studies published from January 2005 to May 2023. RQS assessed methodological quality of studies included in the review. QUADAS-2 assessed the risk of bias. A meta-analysis and three meta regressions were conducted on study performance based on model type, imaging modality and segmentation method. ResultsRQS assessed methodological quality, revealing an overall low score and consistent findings with other radiology domains. QUADAS-2 indicated an overall low risk, except for a single study with high bias. The meta-analysis demonstrated that radiomics-based ML models for predicting culprit plaques had a satisfactory performance, with an AUC of 0.85, surpassing clinical models. However, combining radiomics with clinical features yielded the highest AUC of 0.89. Meta-regression analyses confirmed these findings. MRI-based models slightly outperformed CT-based ones, but the difference was not significant. ConclusionIn conclusion, radiomics and ML hold promise for assessing carotid plaque vulnerability, aiding in early cerebrovascular event prediction. Combining radiomics with clinical data enhances predictive performance.

Identification of microRNA biomarkers simultaneously expressed in circulating extracellular vesicles and atherosclerotic plaques.

Atherosclerosis is a widespread disorder of the cardiovascular system. The early detection of plaques by circulating biomarkers is highly clinically relevant to prevent the occurrence of major complications such as stroke or heart attacks. It is known that extracellular vesicles (EVs) are important in intercellular communication in atherosclerotic disorders and carry many components of their cells of origin, including microRNAs (miRNAs). In this study, we test the assumption that miRNAs present in material acquired from plaques in patients undergoing surgery for atherosclerotic carotid artery stenosis are also expressed in circulating EVs obtained from the identical patients. This would allow the adoption of a liquid biopsy approach for the detection of plaques. We studied 22 surgical patients with atherosclerotic carotid arterial stenosis and 28 healthy controls. EVs were isolated from serum by precipitation. miRNA expression profiles of serum-derived EVs were obtained by small RNA sequencing and in plaque material simultaneously acquired from patients. A comparative analysis was performed to identify circulating atherosclerosis-associated miRNAs that are also detectable in plaques. Seven miRNAs were found to be differentially regulated in patient serum compared with the serum of healthy controls. Of these, miR-193b-5p, miR-193a-5p, and miR-125a-3p were significantly upregulated in patients compared with that in healthy controls and present in both, circulating EVs and plaque material. An overrepresentation analysis of experimentally validated mRNA targets revealed an increased regulation of inflammation and vascular growth factors, key players in atherosclerosis and plaque formation. Our findings suggest that circulating EVs reflect plaque development in patients with symptomatic carotid artery stenosis, which can serve as biomarker candidates for detecting the presence of atherosclerotic plaques.

In-stent restenosis estimation following carotid artery stenting: The robust predictive value of atherogenic index of plasma and other non-traditional lipid profiles.

Atherosclerotic carotid artery stenosis is a significant contributor to ischemic strokes, and carotid artery stenting (CAS) has emerged as a pivotal treatment option. However, in-stent restenosis (ISR) remains a concern, impacting the long-term patency of CAS. This study aimed to investigate the predictive value of non-traditional lipid profiles, including the atherogenic index of plasma (AIP), in ISR development. This retrospective single-center study involved patients presenting at a tertiary healthcare facility with severe carotid artery disease between 2016 and 2020 who subsequently underwent CAS. A total of 719 patients were included in the study. The study cohort was divided into ISR and non-ISR groups based on restenosis presence, confirmed by angiography following ultrasonographic follow-up assessments. Non-traditional lipid indices, such as AIP, atherogenic index (AI), and lipoprotein combined index (LCI), were evaluated along with traditional risk factors. During a 24-month follow-up, ISR occurred in 4.03% of patients. To determine the predictors of restenosis, three different models were constructed in multivariate analysis for non-traditional lipid indices. Multivariate analysis revealed AIP as a robust independent predictor of ISR (OR: 4.83 (CI 95 % 3.05-6.63, p < .001). Notably, AIP demonstrated superior predictive accuracy compared to AI and LCI, with a higher Area Under the Curve (AUC) of 0.971. Non-traditional lipid profiles, especially AIP, were found to be associated with an increased risk of ISR and may serve as predictors of ISR in patients undergoing CAS.

An evolution in carotid care: Contemporary TCAR data and optimization techniques

ObjectiveCarotid endarterectomy (CEA) is the gold standard for revascularization of atherosclerotic extra-cranial carotid artery lesions. The introduction of transfemoral carotid artery stenting (TFCAS) led to multiple randomized controlled trials to compare the safety and efficacy of an endovascular approach against traditional CEA in the management of carotid artery stenosis. The operative management of carotid artery stenosis continues to evolve, with the more recent introduction of TransCarotid artery revascularization (TCAR) and a novel flow-reversal neuroprotection system. This manuscript reviews a brief history regarding carotid artery revascularization, as well as the indications, technical considerations, and clinical outcomes of the TCAR procedure. Technical considerationsThe preoperative, intraoperative, and postoperative medical and technical considerations are explored. Topics of discussion will include the indications and contraindications for TCAR, anatomic requirements, instructions for use (IFU) and off-label utility, optimal pharmacologic regimen with carotid stent placement, standard deployment and suggestions for hostile anatomy, as well as recommended postoperative management and surveillance imaging. DiscussionThe Society for Vascular Surgery (SVS) has published a consensus statement on the pathways available to obtain clinical competency and maintain technical proficiency with TCAR. Meta-analyses reviewing the contemporary technical success and clinical outcomes of TCAR have demonstrated high rates of procedural success and low rates of stroke, myocardial infarction, and death. Studies have further illustrated comparable one-year rates of peri‑procedural stroke between TCAR and CEA, for asymptomatic and symptomatic carotid lesions, with both outperforming TFCAS. ConclusionManagement of extra-cranial carotid artery stenosis utilizing TCAR with the ENROUTE flow-reversal neuroprotection system has been widely adopted, yielding clinical outcomes and stroke prevention similar to traditional CEA and superior to TFCAS.

Microplastics in three types of human arteries detected by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS)

Microplastics are ubiquitous in the environment. Human body can be exposed to microplastics through inhalation and ingestion and some microplastics can enter the blood and accumulate in various tissues and organs throughout the body. Animal experiments have suggested that microplastics may promote atherosclerosis. However, data on microplastics in human arteries and clinical evidence supporting a link between microplastics and atherosclerosis are currently lacking. Pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was used in this study to detect microplastics in three types of human arteries: coronary and carotid arteries with atherosclerotic plaques, as well as the aorta without plaques. Microplastics were detected in all 17 arterial samples, with an average concentration of 118.66 ± 53.87 μg/g tissue. Four types of microplastics were identified: polyethylene terephthalate (PET, 73.70%), polyamide-66 (PA-66, 15.54%), polyvinyl chloride (PVC, 9.69%), and polyethylene (PE, 1.07%). Most importantly, the concentration of microplastics in arteries containing atherosclerotic plaques, both coronary arteries (156.50 ± 42.14 vs. 76.26 ± 14.86 μg/g tissue, P = 0.039), and carotid arteries (133.37 ± 60.52 vs. 76.26 ± 14.86 μg/g tissue, P = 0.015), was significantly higher than that in aortas which did not contain atherosclerotic plaques, suggesting that microplastics might be associated with atherosclerosis in humans. This study provides valuable data for further hazard assessments of microplastics on human cardiovascular health.

Cilostazol-based dual antiplatelet treatment in ischemic stroke or transient ischemic attack patients with asymptomatic carotid artery disease: a propensity score matching analysis.

The optimal treatment for asymptomatic atherosclerotic carotid artery disease remains controversial. Data on the efficacy of antiplatelet agents and stroke outcomes are limited. This study aimed to examine the efficacy and safety of cilostazol-based dual antiplatelet therapy in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery disease. This retrospective cohort study was conducted in a tertiary-care setting and included baseline characteristics and clinical outcomes of participants. The study included patients who had experienced first-ever ischemic stroke or transient ischemic attack and asymptomatic atherosclerotic carotid artery stenosis, with a minimum follow-up period of 1 year. Asymptomatic carotid artery stenosis refers to stenosis in patients without neurological symptoms referable to the carotid arteries. Propensity scores were estimated using a logistic regression model based on participants' baseline characteristics. The efficacy outcome was the composite outcome of recurrent ischemic events and vascular-related death in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery stenosis. The safety outcome was the occurrence of hemorrhagic complications such as intracranial hemorrhages or extracranial hemorrhages. The effectiveness of dual therapy compared to monotherapy was evaluated at various time points following the initiation of antiplatelet treatment. This study included 516 patients with a 1-year follow-up period. At 1 year, composite events occurred in 10 (6.3%) patients in the dual antiplatelet group compared with 12 (7.6%) in the single antiplatelet group (HR, 0.74; 95% CI, 0.61-0.90; p = 0.024). Extracranial hemorrhage occurred in 12 (7.6%) patients in the dual antiplatelet group compared with nine (5.7%) in the single antiplatelet group (HR, 1.35; 95% CI, 1.13-1.48; p = 0.017). No intracranial hemorrhages were observed in this cohort. Patients with asymptomatic carotid artery stenosis who received cilostazol-based dual antiplatelet therapy had a lower risk of composite events but a higher risk of minor extracranial hemorrhage than those who received a single antiplatelet agent.

Another cause of treatable dementia: rapid cognitive improvement after carotid endarterectomy. Illustrative case.

Revascularization techniques in cervical internal carotid artery (ICA) stenosis are indicated to prevent the onset or recurrence of ischemic events in the setting of atherosclerotic carotid artery disease. Recent reports, case series, and comparative studies have suggested that revascularization techniques may also improve cognitive outcome in both symptomatic and asymptomatic patients, thus raising the question of whether another surgically treatable dementia has presented itself. A 70-year-old right-handed female with a history of hypertension, diabetes, and bilateral silent cerebral infarcts was evaluated for progressive cognitive impairment over a 1-year period, which was associated with a severe left cervical ICA stenosis. Carotid endarterectomy (CEA) was indicated as a revascularization technique, and the patient showed significant neurocognitive improvement as early as one month postoperatively, consistent with blood flow restoration to the left hemisphere on control imaging. This case serves as a reminder that CEA may improve the cognitive outcome of patients previously impaired by uncomplicated severe cervical ICA atherosclerotic disease, which can be another cause of treatable dementia. Further prospective studies may help to assess this potential benefit.

Evaluation of Turbulence Index and Flow Pattern for Atherosclerotic Carotid Stenosis: A High-Frame-Rate Vector Flow Imaging Study

ObjectiveThe emerging high-frame rate vector flow imaging (H-FRV Flow) provides a new way of hemodynamic evaluation for complex blood flow. This study aimed to explore quantitatively the characteristics of complex flow with turbulence (Tur) index and analyze flow pattern in atherosclerotic internal carotid artery stenosis (ICAS) using H-FRV Flow. MethodsThis study prospectively included 60 patients with ICAS. Tur values in different segments of stenosis and cardiac phases were compared. Meanwhile Spearman correlation analysis was performed between clinical plaque characteristics with turbulence grading by ln (Tur). Three complex flow patterns were qualitatively drawn on vector flow mode, and the detection rate of flow patterns in different stenosis groups and ulceration groups were compared. ResultsHighly disordered blood flow was observed in the stenosis (Tur (%) (M, QR) =12.5, 21.5) and distal segment (15.4, 27.2), particularly during systole (21.0, 30.7/ 33.3, 38.7, P<0.05). Spearman correlation analysis showed that stenosis rate was correlated with turbulence grading in the stenosis (ρ=0.65, P<0.05) and distal segment (ρ=0.79, P<0.05), and ulcer formation was correlated with turbulence grading in the stenosis segment (ρ=0.58, P<0.05). The overall detection rate of three flow patterns was higher respectively in the severe stenosis group (22/22) versus mild to moderate stenosis group (21/38) (P<0.001) and the ulcer group (21/23) versus non-ulcer group (23/37) (P<0.001). ConclusionH-FRV Flow was helpful for assess the severity and characteristics of flow turbulence. Lumen geometric factors could affect the flow turbulence and blood flow patterns around the plaque. This would provide important hemodynamic information for the detection of high-risk plaque.

3-D Contrast-Enhanced Fusion Ultrasound for Accurate Volume Assessment of Vessel Lumen and Plaque in Carotid Artery Disease as Compared With Computed Tomography Angiography

ObjectiveThree-dimensional contrast-enhanced fusion ultrasound (3D-CEFUS) of atherosclerotic carotid arteries provides spatial visualisation of the vessel lumen, creating a lumenography. As in 3D computed tomography angiography (3D-CTA), 3D-CEFUS outlines the contrast-filled lumen. Plaque and vessel contours are distinguished in 3D-CEFUS, allowing plaque volume quantification as a valid estimate of carotid plaque burden. 3D-CEFUS is unproven in inter-modality studies, vindicating the assessment of 3D-CEFUS applicability and comparing 3D-CEFUS and 3D-CTA lumenography as a proof-of-concept study. MethodsUsing an ultrasound system with magnetic tracking, a linear array transducer, and SonoVue contrast agent generated 3D-CEFUS acquisitions by spatial stitching of serial 2D images. From 3D-CEFUS and 3D-CTA imaging, the atherosclerotic carotid arteries were reconstructed with lumenography in an offline software programme for lumen and plaque volume quantification. Bland-Altman analysis was used for inter-image-modality agreement. ResultsThe study included 39 carotid arteries. Mean lumen and plaque volume in 3D-CEFUS were 0.63 cm3 (SD 0.26) and 0.62 cm3 (SD 0.26), respectively. Lumen volume differences between 3D-CEFUS and 3D-CTA were non-significant, with mean difference of 0.01 cm3 (SD 0.02, p = .26) and limits of agreement range (LoA-range) of ±0.11 cm3. Mean plaque volume difference was -0.12 cm3 (SD 0.19, p = .006) with LoA-range of ±0.39 cm3. ConclusionStrong agreement in lumenography between 3D-CEFUS and 3D-CTA was found. The inter-image-modality difference in plaque volumes was substantial due to challenging vessel wall definition in 3D-CTA. 3D-CEFUS is viable in quantifying carotid plaque volume burden and can potentially monitor plaque development over time.

Identification of pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis based on comprehensive bioinformatics analysis and machine learning.

Bioinformatics methods were applied to investigate the pivotal genes and regulatory networks associated with atherosclerotic carotid artery stenosis (ACAS) and provide new insights for the treatment of this disease. The study utilized five ACAS datasets (GSE100927, GSE11782, GESE28829, GSE41571, and GSE43292) downloaded from the NCBI GEO database. The first four datasets were combined as the training set (n = 99), while GSE43292 (n = 64) was used as the validation set. Difference analysis and functional enrichment analysis were then performed on the training set. The pathogenic targets of ACAS were screened by protein-protein interaction networks and MCODE analyses, combined with three machine learning algorithms. The results were next verified by analysis of inter-group differences and ROC curve analysis. Next, immune-related function and immune cell correlation analyses were performed, and plaques of human ACAS were applied to verify the results via immunohistochemistry (IH) and immunofluorescence (IF). Finally, the competing endogenous RNAs (ceRNA) and transcription factors (TFs) regulatory networks of the characterized genes were constructed. A total of 177 differentially expressed genes were identified, including 67 genes downregulated and 110 genes upregulated. Gene set enrichment analysis revealed that five pathways were active in the experimental group, including xenograft rejection, autoimmune thyroid disease, graft-versus-host disease, leishmaniasis infection, and lysosomes. Four key genes were identified, with C3AR1 being upregulated and FBLN5, PPP1R12A, and TPM1 being downregulated. The analysis of inter-group differences demonstrated that the four characterized genes were differentially expressed in both the control and experimental groups. The ROC analysis showed that they had high AUC values in both the training and validation sets. Therefore, a predictive ACAS patient nomogram model based on the screened genes was established. Correlation analysis revealed a positive correlation between C3AR1 expression and neutrophils, which was further validated in IH and IF. One or multiple lncRNAs may compete with the characterized genes for binding miRNAs. Additionally, each characterized gene interacts with multiple TFs. Four pivotal genes were screened, and relevant ceRNA and TFs were predicted. These molecules may exert a crucial role in ACAS and serve as potential biomarkers and therapeutic targets.

European Carotid Surgical Trial-based diameter measurement using B-mode ultrasound imaging to quantify low-grade carotid artery stenosis: the QUAMUS study

BackgroundIdentification of carotid atherosclerotic lesions with no hemodynamic effect on Doppler ultrasound examination is a common situation. Although the use of B-mode ultrasound examination has been recommended to assess this type of lesion, there is no validated examination procedure to date for quantifying low-grade carotid stenosis. MethodsWe conducted a single-center prospective study (QUAntification Morphologique en UltraSonographie [QUAMUS] study) to assess the reproducibility of B-mode ultrasound quantification of low-grade internal carotid artery stenosis using the European Carotid Surgical Trial (ECST) measurement method. We included consecutive patients with <50% North American Symptomatic Carotid Endarterectomy Trial carotid stenosis identified by the University of Washington duplex criteria (ie, maximum systolic velocity of <125 cm/second at a Doppler angle of 50°-60°). The examination was carried out and interpreted independently, blindly, and successively by two operators according to a precise methodology based on the measurement of cross-sectional diameter in B-mode and calculation of the stenosis percentage according to the ECST method. The primary objective was to assess the measurement concordance of the stenosis percentage for a difference not exceeding 10% between the two operators. The secondary objective was to assess concordance in relation to examination quality. ResultsAmong the 86 patients included, 159 atherosclerotic carotid arteries were eligible and 157 could be explored (feasibility of 98.74%). The conditions were considered as good by the two operators in 69.43% of cases and poor in 2.55%. The concordance of the stenosis percentage measurement for a maximum difference of 10% between the two operators was 89.17% (95% confidence interval, 83.23-93.56) with a Lin concordance correlation coefficient of 0.87 (95% confidence interval, 0.82-0.90). Under examination conditions estimated as good, average, and poor, the concordance was 95.37%, 78.95%, and 60.00%, respectively. ConclusionsOur study shows that ECST-based B-mode ultrasound measurement of low-grade carotid stenosis is reliable and can be performed in routine practice in most patients with a measurement variation of <10% using a simple standardized examination procedure.

Association of carotid atherosclerotic plaque and intima-media thickness with the monocyte to high-density lipoprotein cholesterol ratio among low-income residents of rural China: a population-based cross-sectional study

BackgroundThe monocytes to high-density lipoprotein cholesterol ratio (MHR) has been identified as a potential biomarker for cardiovascular and cerebrovascular diseases. In this population-based cross-sectional study, we explored the relationships among carotid artery disease (CAD), including the presence of carotid atherosclerotic plaque (CAP) and carotid artery intima-media thickness (CIMT), the MHR, and related parameter changes.MethodsThis cross-sectional study, Conducted from April to June 2019 in a rural area of Tianjin, involved middle-aged and elderly participants. Based on carotid ultrasound examinations, participants were divided into CAP and non-CAP groups. Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were utilized to assess MHR’s predictive value for CAP. Gender-specific analyses were also performed to examine predictive variations. The relationship between CIMT and MHR was evaluated using linear regression.ResultsOf the 2109 participants meeting the inclusion criteria, 51.6% were identified with CAP. Multivariate analysis revealed a significant association between MHR and CAP prevalence, (OR, 9.670; 95% CI, 2.359–39.631; P = 0.002), particularly in females (OR, 5.921; 95% CI, 1.823–19.231; P = 0.003), after adjusting for covariates. However, no significant correlation was found between CIMT and MHR when adjusted for other factors. The ROC analysis showed the area under the curve for MHR and CAP to be 0.569 (95% CI: 0.544–0.593; P < 0.001).ConclusionsThese findings suggested that it is crucial to enhance early screening and intervention for CAD, specifically focusing on the prevention and progression of CAP, to address the unique health challenges faced by low-income groups in rural settings. Emphasizing these preventive measures could significantly contribute to improving cardiovascular health outcomes in this vulnerable population.

Thrombus Aspirates From Patients With Acute Ischemic Stroke Are Infiltrated by Viridans Streptococci.

Acute ischemic stroke may be due to embolism from ruptured atherosclerotic carotid arteries. DNA of oral bacteria, mainly the viridans streptococci group, has been detected in thrombus aspirates of patients with ischemic stroke as well as in carotid endarterectomy samples. Because viridans streptococci are known to possess thrombogenic properties, we studied whether their presence in thrombus aspirates and in carotid artery specimens can be confirmed using bacterial immunohistochemistry. Thrombus aspirates from 61 patients with ischemic stroke (70.5% men; mean age, 66.8 years) treated with mechanical thrombectomy, as well as carotid endarterectomy samples from 20 symptomatic patients (65.0% men; mean age, 66.2 years) and 48 carotid artery samples from nonstroke autopsy cases (62.5% men; mean age, 66.4 years), were immunostained with an antibody cocktail against 3 species (Streptococcus sanguinis, Streptococcus mitis, and Streptococcus gordonii) of viridans streptococci. Of the thrombus aspirates, 84.8% were immunopositive for viridans streptococci group bacteria, as were 80.0% of the carotid endarterectomy samples, whereas immunopositivity was observed in 31.3% of the carotid artery samples from nonstroke autopsies. Most streptococci were detected inside neutrophil granulocytes, but there were also remnants of bacterial biofilm as well as free bacterial infiltrates in some samples. Oral streptococci were found in aspirated thrombi of patients with acute ischemic stroke as well as in carotid artery samples. Our results suggest that viridans streptococci group bacteria may play a role in the pathophysiology of ischemic stroke.

3D patient-specific modeling and structural finite element analysis of atherosclerotic carotid artery based on computed tomography angiography

The assessment of carotid plaque vulnerability is a relevant clinical information that can help prevent adverse cerebrovascular events. To this aim, in this study, we propose a patient-specific computational workflow to quantify the stress distribution in an atherosclerotic carotid artery, by means of geometric modeling and structural simulation of the plaque and vessel wall. Ten patients were involved in our study. Starting with segmentation of the lumen, calcific and lipid plaque components from computed tomography angiography images, the fibrous component and the vessel wall were semi-automatically reconstructed with an ad-hoc procedure. Finite element analyses were performed using local pressure values derived from ultrasound imaging. Simulation outputs were analyzed to assess how mechanical factors influence the stresses within the atherosclerotic wall. The developed reconstruction method was first evaluated by comparing the results obtained using the automatically generated fibrous component model and the one derived from image segmentation. The high-stress regions in the carotid artery wall around plaques suggest areas of possible rupture. In mostly lipidic and heterogeneous plaques, the highest stresses are localized at the interface between the lipidic components and the lumen, in the fibrous cap.

Abstract 13981: Computed Tomography Angiography Measures of Carotid Artery Plaque Burden in Patients With Atherosclerotic Carotid Artery Disease Stratified by Status of Chronic Kidney Disease

Introduction: Atherosclerotic carotid artery disease (ACAD) is associated with an increased risk of cerebrovascular mortality and morbidity. We have analyzed associations of computed tomography angiography (CTA) measures of carotid artery (CA) plaque burden with chronic kidney disease (CKD). Hypothesis: CTA-based measures of CA plaque burden in patients with ACAD differ across stages of CKD. Methods: A total of 63 ACAD patients (13 without CKD, 50 with CKD), who completed CTA imaging and had demographic data were included in a retrospective analysis of patients from the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC), Houston, Texas. CA plaque burden measures include the normalized wall index (NWI), wall area (WA), and lumen area (LA) at three distinct CA locations: CA bifurcation (BF), maximum total vessel cross-sectional area (MTVA) of the internal CA (ICA), and ICA peak stenosis (PS). CTA measures and patient demographics were compared across three CKD classes (no disease: n=13; CKD stages 1 and 2: n=31; and CKD stage 3 and above; n=19). Results: Baseline characteristics differed among CKD groups for the estimated glomerular filtration rate (p=&lt;0.0001) and the body mass index (p=0.046). Inter-observer variability, assessed by intraclass correlation (ICC) analysis, was excellent for CA lumen area and wall area (0.964 (confidence interval [CI]: 0.946, 0.976); 0.865 (CI: 0.804, 0.908): n=100 CTA slices, both). The mean NWI differed significantly among the CKD groups for two of the three CA locations (BF: p=0.018, MTVA: p=0.01; PS: p=0.057). Similarly, lumen area significantly differed between CKD categories (BF: p=0.045, MTVA: p=0.013; PS: p=0.017) but not the wall area. Conclusion: CTA-based measures of carotid plaque burden in ACAD patients are highly reproducible and differed across CKD groups. Imaging-based measures of CA plaque burden may be of interest in stratifying risk assessment of ACAD patients with concomitant CKD.

The Diagnostic Value of Trace Metal Concentrations in Hair in Carotid Artery Disease.

Several studies showed the role of trace elements in the increase in human susceptibility to cardiovascular diseases. Carotid artery stenosis is a leading cause of ischemic neurological events. We aimed to analyze the potential role of trace elements in hair as biomarkers of atherosclerotic carotid artery disease. Materials and Methods: Fifty-seven (n = 31 (54%) men and n = 26 (46%) women) individuals with a mean age of 67.7 ± 7.7 years who were white, European, non-Hispanic, and non-Latino were diagnosed and treated in hypertensiology/internal medicine and surgical departments over three consecutive months. Of these patients, forty were diagnosed with advanced carotid artery disease, and seventeen comprised a group of healthy controls. Inflammatory and oncological diseases were exclusion criteria. Hair samples were collected, and 14 trace elements were analyzed. Clinical and laboratory data were compared and revealed differences in the co-existence of diabetes (p = 0.036) and smoking history (p = 0.041). In the multivariable analysis, zinc, chrome, and copper revealed predictive value for the occurrence of carotid artery disease, and their combined receiver operating curve showed area under the curve of 0.935, with a sensitivity of 95% and a specificity of 82.4%. Conclusion: Our report shows the significance of trace elements analyses in patients with advanced carotid artery disease. We revealed that zinc, copper, and chrome concentrations are of particular importance in differentiating atherosclerotic disease and may serve as biomarkers of carotid atherosclerosis. Hair samples represent an easily obtained and beneficial biomatrix for the assessment of biomarkers.

10-channel phased-array coil for carotid wall MRI at 3T.

Accurate assessment of plaque accumulation near the carotid bifurcation is important for the effective prevention and treatment of stroke. However, vessel and plaque delineation using MRI can be limited by low contrast-to-noise ratio (CNR) and long acquisition times. In this work, a 10-channel phased-array receive coil design for bilateral imaging of the carotid bifurcation using 3T MRI is proposed. The proposed 10-channel receive coil was compared to a commercial 4-channel receive coil configuration using data acquired from phantoms and healthy volunteers (N = 9). The relative performance of the coils was assessed, by comparing signal-to-noise ratio (SNR), noise correlation, g-factor noise amplification, and the CNR between vessel wall and lumen using black-blood sequences. Patient data were acquired from 12 atherosclerotic carotid artery disease patients. The 10-channel coil consistently provided substantially increased SNR in phantoms (+77 ± 27%) and improved CNR in healthy carotid arteries (+62 ± 11%), or reduced g-factor noise amplification. Patient data showed excellent delineation of atherosclerotic plaque along the length of the carotid bifurcation using the 10-channel coil. The proposed 10-channel coil design allows for improved visualization of the carotid arteries and the carotid bifurcation and increased parallel imaging acceleration factors relative to a commercial 4-channel coil design.

Local characterization of collagen architecture and mechanical failure properties of fibrous plaque tissue of atherosclerotic human carotid arteries.

Atherosclerotic plaque rupture in carotid arteries is a major cause of cerebrovascular events. Plaque rupture is the mechanical failure of the heterogeneous fibrous plaque tissue. Local characterization of the tissue's failure properties and the collagen architecture are of great importance to have insights in plaque rupture for clinical event prevention. Previous studies were limited to average rupture properties and global structural characterization, and did not provide the necessary local information. In this study, we assessed the local collagen architecture and failure properties of fibrous plaque tissue, by analyzing 30 tissue strips from 18 carotid plaques. Our study framework entailed second harmonic generation imaging for local collagen orientation and dispersion, and uniaxial tensile testing and digital image correlation for local tissue mechanics. The results showed that 87% of the imaged locations had collagen orientation close to the circumferential direction (0°) of the artery, and substantial dispersion locally. All regions combined, median [Q1:Q3] of the predominant angle measurements was -2° [-16°:16°]. The stretch ratio measurements clearly demonstrated a nonuniform stretch ratio distribution in the tissue under uniaxial loading. The rupture initiation regions had significantly higher stretch ratios (1.26 [1.15-1.40]) than the tissue average stretch ratio (1.11 [1.10-1.16]). No significant difference in collagen direction and dispersion was identified between the rupture regions and the rest of the tissue. The presented study forms an initial step towards gaining better insights into the characterization of local structural and mechanical fingerprints of fibrous plaque tissue in order to aid improved assessment of plaque rupture risk. STATEMENT OF SIGNIFICANCE: Plaque rupture risk assessment, critical to prevent cardiovascular events, requires knowledge on local failure properties and structure of collagenous plaque tissue. Our current knowledge is unfortunately limited to tissue's overall ultimate failure properties with scarce information on collagen architecture. In this study, local failure properties and collagen architecture of fibrous plaque tissue were obtained. We found predominant circumferential alignment of collagen fibers with substantial local dispersion. The tissue showed nonuniform stretch distribution under uniaxial tensile loading, with high stretches at rupture spots. This study highlights the significance of local mechanical and structural assessment for better insights into plaque rupture and the potential use of local stretches as risk marker for plaque rupture for patient-specific clinical applications.

Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs

We first identified thrombomodulin (TM) and endothelial nitric oxide (NO) synthase as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Then, recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug were immobilized on the surface of the vascular grafts. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts. Importantly, we found that the combination of TM and NO also promoted endothelialization, whereas it reduced adverse intimal hyperplasia, which is critical for the maintenance of vascular homeostasis, as confirmed in rat and pig models.