Symptomatic Plaques Research Articles

Differentiation of symptomatic and asymptomatic carotid intraplaque hemorrhage using 3D high-resolution diffusion-weighted stack of stars imaging.

Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high-resolution diffusion-weighted (DW) imaging can provide quantitative diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW-stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW-SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two-group comparison Wilcoxon-Mann-Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH-positive versus IPH-negative; and IPH-positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW-SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ±0.18 vs. 0.98 ±0.16 x 10-3 mm2 /s, p<0.001). ADC was also significantly lower in IPH-positive versus IPH-negative plaque (0.68 ±0.13 vs. 1.04 ±0.11 x 10-3 mm2 /s, p<0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH-positive plaque (0.57 ±0.09 vs. 0.75 ±0.11 x 10-3 mm2 /s, p<0.001). Our results provide strong evidence that ADC measurements from 3D DW-SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.

Characteristics of symptomatic plaque on high-resolution magnetic resonance imaging and its relationship with the occurrence and recurrence of ischemic stroke.

Atherosclerosis is the most common cause of ischemia stroke. Computed tomographic angiography (CTA) and digital subtraction angiography (DSA) are used to evaluate the degree of lumen stenosis. However, these examinations are invasive and can only reveal mild to moderate stenosis. High-resolution magnetic resonance imaging (HRMRI) seems a more intuitive way to show the pathological changes of vascular wall. Hence, we conducted a systematic retrospective study to determine the characteristics of symptomatic plaques in patients with intracranial atherosclerosis on HRMRI and their association with the occurrence and recurrence of ischemic stroke events. The PubMed database was searched for relevant studies reported from January 31, 2010, to October 31, 2020. We selected 14 clinical outcome studies. We found that plaque enhancement and positive remodeling on HRMRI indicate symptomatic plaques. Besides, intraplaque hemorrhage and positive remodeling index are closely related to the occurrence of stroke. However, it is still controversial whether the initial enhancement of plaque and the occurrence and recurrence of stroke are related. There is also no significant correlation between vascular stenosis and symptomatic plaque or the occurrence and recurrence of ischemic stroke. High-resolution magnetic resonance imaging can be used as an assessment tool to predict the risk of stroke onset and recurrence in patients with atherosclerosis, but further research is also needed.

Normalized intraplaque hemorrhage signal on MP-RAGE as a marker for acute ischemic neurological events.

This study sought to validate whether the signal intensity ratio (SIR) of carotid intraplaque hemorrhage (IPH) was associated with acute ischemic neurologic events. A retrospective review was completed of consecutive patients that underwent neck magnetic resonance angiography using magnetization prepared-rapid gradient echo (MP-RAGE) and T1-CUBE sequences between 2017 and 2020. Patients with magnetic resonance evidence of IPH were included. SIRs were measured by comparing the maximum IPH signal with the mean intramuscular signal from the adjacent sternocleidomastoid. Patients were stratified into ischemic or non-ischemic groups based on the presence of acute ipsilateral ischemic events (stroke, retinal artery occlusion). Logistic regression analysis was performed to determine if increasing IPH SIR was associated with an increased risk of ipsilateral ischemic events. Of 85 included patients (85 arteries), 66 were male (77.6%). Mean age was 71.0 (SD ± 11.1). There were 70 arteries with IPH that were ipsilateral to an ischemic event, and 15 that belonged to patients without an ischemic event. No association was found between increasing IPH SIR seen on MP-RAGE (odds ratio (OR): 0.82; 95% confidence interval (CI): 0.58-1.4; P = 0.43) or T1-CUBE sequences (OR: 0.85; 95% CI: 0.53-1.5; P = 0.56). There was no association between the SIR of IPH and acute ischemia on either MP-RAGE or T1-CUBE sequences. Further investigation is required prior to widespread acceptance of SIR as a predictive imaging marker of symptomatic carotid plaque.

Multimodality carotid plaque tissue characterization and classification in the artificial intelligence paradigm: a narrative review for stroke application.

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in the United States of America and globally. Carotid arterial plaque, a cause and also a marker of such CVD, can be detected by various non-invasive imaging modalities such as magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound (US). Characterization and classification of carotid plaque-type in these imaging modalities, especially into symptomatic and asymptomatic plaque, helps in the planning of carotid endarterectomy or stenting. It can be challenging to characterize plaque components due to (I) partial volume effect in magnetic resonance imaging (MRI) or (II) varying Hausdorff values in plaque regions in CT, and (III) attenuation of echoes reflected by the plaque during US causing acoustic shadowing. Artificial intelligence (AI) methods have become an indispensable part of healthcare and their applications to the non-invasive imaging technologies such as MRI, CT, and the US. In this narrative review, three main types of AI models (machine learning, deep learning, and transfer learning) are analyzed when applied to MRI, CT, and the US. A link between carotid plaque characteristics and the risk of coronary artery disease is presented. With regard to characterization, we review tools and techniques that use AI models to distinguish carotid plaque types based on signal processing and feature strengths. We conclude that AI-based solutions offer an accurate and robust path for tissue characterization and classification for carotid artery plaque imaging in all three imaging modalities. Due to cost, user-friendliness, and clinical effectiveness, AI in the US has dominated the most.

Lipid Core Burden Index Assessed by Near-Infrared Spectroscopy of Symptomatic Carotid Plaques: Association with Magnetic Resonance T1-Weighted Imaging

Introduction: Vulnerable plaques are a strong predictor of cerebrovascular ischemic events, and high lipid core plaques (LCPs) are associated with an increased risk of embolic infarcts during carotid artery stenting (CAS). Recent developments in magnetic resonance (MR) plaque imaging have enabled noninvasive assessment of carotid plaque vulnerability, and the lipid component and intraplaque hemorrhage (IPH) are visible as high signal intensity areas on T1-weighted MR images. Recently, catheter-based near-infrared spectroscopy (NIRS) has been shown to accurately distinguish LCPs without IPH. This study aimed to determine whether the results of assessment of high LCPs by catheter-based NIRS correlate with the results of MR plaque imaging. Methods: We recruited 82 consecutive symptomatic carotid artery stenosis patients who were treated with CAS under NIRS and MR plaque assessment. Maximum lipid core burden index (max-LCBI) at minimal luminal areas (MLA), defined as max-LCBI_MLA, and max-LCBI for any 4-mm segment in a target lesion, defined as max-LCBI_AREA, were assessed by NIRS. Correlations were investigated between max-LCBI and MR T1-weighted plaque signal intensity ratio (T1W-SIR) and MR time-of-flight signal intensity ratio (TOF-SIR) in the same regions as assessed by NIRS. Results: Both T1W-SIR_MLA and T1W-SIR_AREA were significantly lower in the high LCP group (max-LCBI >504, p < 0.001 for both), while TOF-SIR_MLA and TOF-SIR_AREA were significantly higher in the high LCP group (p < 0.001 and p = 0.004, respectively). A significant linear correlation was present between max-LCBI_MLA and both TIW-SIR_MLA and TOF-SIR_MLA (r = −0.610 and 0.452, respectively, p < 0.0001 for both). Furthermore, logistic regression analysis revealed that T1W-SIR_MLA and TOF-SIR_MLA were significantly associated with a high LCP assessed by NIRS (OR, 44.19 and 0.43; 95% CI: 6.55–298.19 and 0.19–0.96; p < 0.001 and = 0.039, respectively). Conclusions: A high LCP assessed by NIRS correlates with the signal intensity ratio of MR imaging in symptomatic patients with unstable carotid plaques.

Contemporary Results of Carotid Artery Stenting Using Low-Profile Dual-Metal Layer Nitinol Micromesh Stents in Relation to Single-Layer Carotid Stents

Purpose: To evaluate patients characteristics, procedural details, perioperative outcomes, and midterm results of carotid artery stenting (CAS) performed with the Roadsaver/Casper stent (Terumo Corp, Tokyo, Japan) as compared to concurrent patients treated with other commercially available carotid stents. Materials and Methods: This is a single-center, retrospective, nonrandomized study including 200 consecutive patients who underwent a total of 205 elective CAS procedures due to severe internal carotid artery stenosis between April 2015 and December 2018. Procedural data and outcomes for patients treated with the Roadsaver/Casper stent implantation (100 procedures, in 97 patients) vs first-generation carotid stents implantations (90 procedures, in 88 patients) were compared. Fifteen patients were treated with CGuard carotid stent (InspireMD, Tel Aviv, Israel), and outcomes were reported separately. Primary endpoints were the occurrence of major adverse cerebrovascular events (MACE), including death, ipsilateral stroke, and transitory ischemic attack (TIA). Secondary endpoints were the rate of intrastent stenosis, the need for reintervention, and the occurrence of adverse cardiovascular events, including myocardial infarction, arrhythmias, and need for inotropic support. Results: No difference in demographics and preoperative risk factors were observed between patients treated with and without the Roadsaver/Casper stent. The mean procedure time was shorter in the Roadsaver/Casper group (40.7±16.9 vs 49.4±27.3 minutes; p=0.008), while radial percutaneous access was more frequent (24% vs 5%; p<0.001). The rate of stroke/TIA/death at 30 days was 3% in the Roadsaver group vs 1% in the first-generation stent group (p=0.623). The primary patencyrate was 100% and 93.4% at 1- and 3-year of follow-up in the Roadsaver/Casper groupand 99% and 94.3% in the other stent group, respectively (p=0.95). Conclusions: In this real-world cohort of patients undergoing CAS, the Roadsaver/Casper stent was used to treat more symptomatic and vulnerable carotid plaques as compared to other carotid stents. Nevertheless, patients treated with this low-profile dual-layer micromesh stent showed low events rates at both 30 days and follow-up, similar to that observed for other stents.

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression.

XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors. Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured. Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (P=0.010, r=−0.30) and directly with circulating uric acid levels (P<0.001, r=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P<0.001). XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.

Comparing Symptomatic and Asymptomatic Carotid Artery Atherosclerosis in Patients With Bilateral Carotid Vulnerable Plaques Using Magnetic Resonance Imaging.

We compared plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid vulnerable plaques using magnetic resonance imaging (MRI). Participants (n = 67; mean age: 65.8 ± 7.7 years, 61 males) with bilateral carotid vulnerable plaques were included. Vulnerable plaques were characterized by intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), or fibrous cap rupture (FCR) on MRI. Symptomatic vulnerable plaques showed greater plaque burden, LRNC volume (median: 221.4 vs 134.8 mm3, P = .003), IPH volume (median: 32.2 vs 22.5 mm3, P = .030), maximum percentage (Max%) LRNC (median: 51.3% vs 41.8%, P = .002), Max%IPH (median: 13.4% vs 9.5%, P = .022), cumulative slices of LRNC (median: 10 vs 8, P = .005), and more juxtaluminal IPH and/or thrombus (29.9% vs 6.0%, P = .001) and FCR (37.3% vs 16.4%, P = .007) than asymptomatic ones. After adjusting for plaque burden, differences in juxtaluminal IPH and/or thrombus (odds ratio [OR]: 5.49, 95% CI: 1.61-18.75, P = .007) and FCR (OR: 2.90, 95% CI: 1.16-7.24, P = .022) between bilateral sides remained statistically significant. For patients with bilateral carotid vulnerable plaques, symptomatic plaques had greater burden, more juxtaluminal IPH and/or thrombus, and FCR compared with asymptomatic ones. The differences in juxtaluminal IPH and/or thrombus and FCR between bilateral sides were independent of plaque burden.

Improvement in the contrast-to-noise ratio and quantitative measurement of T1 and T2* values for carotid atherosclerotic plaque using multi-echo phase-sensitive inversion recovery.

Quantitative magnetic resonance imaging is required to accurately evaluate carotid plaque vulnerability. We prospectively evaluated the potential for fast quantitative black-blood carotid vessel wall imaging using a three-dimensional (3D) multi-echo phase-sensitive inversion recovery (mPSIR) sequence. Forty-nine patients with carotid atherosclerotic plaques were examined. Two-dimensional (2D) turbo spin-echo (TSE), 3D volumetric isotropic turbo spin-echo, and 3D mPSIR imaging were performed. The contrast-to-noise ratios (CNRs) between the carotid plaque and adjacent muscle were compared for the three imaging methods. The T1 and T2* values of the carotid plaques were measured using 3D mPSIR images. These values were compared with those of symptomatic and asymptomatic plaques. For carotid plaques with a signal intensity ratio ≥ 1.55, between the carotid plaque and adjacent muscle in 2D TSE images, the CNR of the mPSIR images was significantly higher than that of the other sequences. T1 values for symptomatic and asymptomatic plaques were 544.0 ± 258.0 and 569.1 ± 301.7, respectively. T2* values for symptomatic and asymptomatic plaques were 34.0 ± 33.0 and 21.8 ± 20.3ms, respectively. There were no significant differences in the T1 and T2* values between the symptomatic and asymptomatic plaques. 3D mPSIR improves the CNR of T1-weighted images for carotid plaques and the adjacent muscle while simultaneously providing the T1 and T2* values of the carotid plaque. This improved CNR may be useful for assessing the vulnerability of carotid plaques.

Shear-Wave Elastography Enables Identification of Unstable Carotid Plaque

Shear-wave elastography (SWE) is a novel ultrasound technique for quantifying tissue elasticity. The aim of this study was to identify differences in atherosclerotic plaque elasticity measured using SWE among individuals with symptomatic, asymptomatic progressive and asymptomatic stable carotid plaques. Consecutive patients from the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the Carotid Bifurcation Plaque Study were screened for this research. Neurosonography examination of carotid arteries was performed to identify plaque stenosis of ≥50% using B-mode ultrasound and SWE imaging to measure the mean, maximal and minimal elasticity. The set consisted of 97 participants—74 with asymptomatic stable stenosis, 12 with asymptomatic progressive stenosis and 11 with symptomatic stenosis. The mean elasticity in the asymptomatic stable plaque group was significantly higher than in the asymptomatic progressive (52.2 vs. 30.4 kPa; p < 0.001) and symptomatic (52.2 vs. 36.4 kPa; p = 0.033) plaque groups. No significant differences were found between asymptomatic progressive and symptomatic (p > 0.1) plaque groups. Asymptomatic stable, asymptomatic progressive and symptomatic plaques did not differ in echogenicity, calcifications, homogeneity, occurrence of ulcerated surface, or intra-plaque hemorrhage (p > 0.05 in all cases). SWE was a helpful modality for differentiating between stable and unstable atherosclerotic plaques in carotid arteries.

Carotid Intraplaque Hemorrhage and Stenosis: At What Stage of Plaque Progression Does Intraplaque Hemorrhage Occur, and When is It Most Likely to Be Associated with Symptoms?

The relationship between carotid intraplaque hemorrhage and luminal stenosis severity is not well-established. We sought to determine whether intraplaque hemorrhage is related to carotid stenosis and at what degree of stenosis intraplaque hemorrhage most likely contributes to ischemic symptoms. Consecutive patients who underwent MR carotid plaque imaging with MPRAGE sequences to identify intraplaque hemorrhage were retrospectively reviewed. Degrees of stenoses were categorized as minimal (<30%), moderate (30%-69%), and severe (>70%). Arteries were categorized into 2 groups: symptomatic (ipsilateral to a cerebral ischemic event) and asymptomatic (from a patient without an ischemic event). Multiple regression analyses were used to determine independent associations between the degree of stenosis and intraplaque hemorrhage and the presence of intraplaque hemorrhage with symptoms among categories of stenosis. We included 449 patients with 449 carotid arteries: Two hundred twenty-five (50.1%) were symptomatic, and 224 (49.9%) were asymptomatic. An increasing degree of stenosis was independently associated with the presence of intraplaque hemorrhage (OR = 1.02; 95% confidence interval, 1.01-1.03). Intraplaque hemorrhage was independently associated with ischemic events in arteries with <30% stenosis (OR = 5.68; 95% CI, 1.49-21.69). No such association was observed in arteries with >30% stenosis. Of symptomatic arteries with minimal stenosis, 8.7% had intraplaque hemorrhage versus 1.7% of asymptomatic arteries (P = .02). No differences in intraplaque hemorrhage prevalence were found between symptomatic and asymptomatic groups with moderate (P = .18) and severe stenoses (P = .99). The presence of intraplaque hemorrhage on high-resolution plaque imaging is likely most useful in identifying symptomatic plaques in cases of minimal stenosis.

Mass Spectrometry Imaging as a Tool to Investigate Region Specific Lipid Alterations in Symptomatic Human Carotid Atherosclerotic Plaques.

Atherosclerosis is characterized by fatty plaques in large and medium sized arteries. Their rupture can causes thrombi, occlusions of downstream vessels and adverse clinical events. The investigation of atherosclerotic plaques is made difficult by their highly heterogeneous nature. Here we propose a spatially resolved approach based on matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to investigate lipids in specific regions of atherosclerotic plaques. The method was applied to a small dataset including symptomatic and asymptomatic human carotid atherosclerosis plaques. Tissue sections of symptomatic and asymptomatic human carotid atherosclerotic plaques were analyzed by MALDI mass spectrometry imaging (MALDI MSI) of lipids, and adjacent sections analyzed by histology and immunofluorescence. These multimodal datasets were used to compare the lipid profiles of specific histopathological regions within the plaque. The lipid profiles of macrophage-rich regions and intimal vascular smooth muscle cells exhibited the largest changes associated with plaque outcome. Macrophage-rich regions from symptomatic lesions were found to be enriched in sphingomyelins, and intimal vascular smooth muscle cells of symptomatic plaques were enriched in cholesterol and cholesteryl esters. The proposed method enabled the MALDI MSI analysis of specific regions of the atherosclerotic lesion, confirming MALDI MSI as a promising tool for the investigation of histologically heterogeneous atherosclerotic plaques.

Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability.

[Figure: see text].

Abstract P771: Monocyte-Chemoattractant Protein-1 Levels in Human Carotid Atherosclerosis Associate With Hallmarks of Plaque Vulnerability

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Methods: We measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy from the Athero-Express Biobank. We explored associations of plaque MCP-1 levels with histopathological features of plaque vulnerability, clinical plaque instability (symptomatic vs. asymptomatic plaque), molecular markers of plaque inflammation and remodeling, and with incident vascular events up to three years after plaque removal. Results: MCP-1 plaque levels were associated with individual histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage), as well as with a cumulative vulnerability index (range 0-5, beta: 0.42, 95%CI: 0.30-0.53, p=5.4x10 -13 ) independently of age, sex, and conventional vascular risk factors. Furthermore, MCP-1 levels were higher among patients with symptomatic, as compared to asymptomatic plaques (p=0.0001) and were associated with the levels of pro-inflammatory cytokines involved in leukocyte adhesion, as well as with matrix metalloproteinase activity in the plaque. In the follow-up analyses, MCP-1 levels were associated with a higher risk of peri-procedural events (up to 30 days after surgery). Conclusions: Our findings highlight a role of MCP-1 in human plaque vulnerability, the leading mechanism underlying vascular events like stroke and myocardial infarction. As such, they suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

Abstract 35: Vessel Wall Magnetic Resonance Imaging Biomarkers of Symptomatic Intracranial Atherosclerosis: A Meta-Analysis

Background: Intracranial vessel wall MR imaging (VWI) may be able to identify imaging biomarkers of symptomatic plaque. A meta-analysis was performed to evaluate the strength of association of imaging features of symptomatic plaque on VWI and downstream ischemia. Methods: PubMed, Scopus, Web of Science, EMBASE and Cochrane databases were searched up to October 2019. Studies evaluating acute/subacute cerebrovascular ischemia using VWI on 1.5 or 3 Tesla MR were included. Studies with insufficient exclusion of other stroke etiologies, insufficient or duplicated data and conference abstracts were excluded. Two independent reviewers extracted data on study design, VWI techniques, imaging endpoints, and conducted a study design risk bias assessment using the QUADAS-2 tool. Per-lesion odds ratios (OR) were calculated and pooled using a bivariate random-effects model. Subgroup analyses and evaluation of publication bias were performed. Results: Twenty-one articles met inclusion criteria (1,750 lesions; 1,542 subjects). Plaque enhancement (OR 7.4, 95% CI 3.4-16.4; Figure), positive remodeling (OR 5.6, 95% CI 2.2-14.0), surface irregularity (OR 4.5, 95% CI 1.4-8.6), and T1 hyperintensity (OR 2.1, 95% CI 1.3-3.3) were significantly associated with downstream ischemia. T2 signal intensity was not significant (p=0.59). Plaque enhancement showed stronger associations when measured in retrospectively designed studies (OR 35.3, 95% CI 7.4-141, p=0.02), by a radiologist as a rater (OR 12.6, 95% CI 5.3-29.7, p&lt;0.001), and on VWI pulse sequences with lower spatial resolution (OR 30.4, 95% CI 7.0-132.4, p=0.02). There was no publication bias (Egger’s test p=0.48). Conclusions: Plaque enhancement, positive remodeling, T1 hyperintensity and surface irregularity emerged as imaging biomarkers of symptomatic plaque. Plaque enhancement had the strongest association and remained significant accounting for sources of bias and variability in both study design and instrument.

Characterisation of symptomatic intracranial plaque without substantial stenosis using high-resolution vessel wall MRI

To characterise symptomatic intracranial plaque without substantial stenosis using three-dimensional (3D) high-resolution contrast-enhanced black-blood magnetic resonance imaging (BBMRI) and to determine plaque features associated with recent cerebrovascular events. The institutional review board approved this retrospective study. The case notes from patients with evidence of intracranial atherosclerosis in a large intracranial artery with preceding BBMRI were reviewed retrospectively. Symptomatic and asymptomatic plaques with substantial luminal stenosis (<50%) were matched by plaque location and patient age. All MRI images were de-identified and interpreted by two neuroradiologists who were blinded to the history of symptoms. Qualitative analyses including the presence of intraplaque haemorrhage (IPH), eccentricity, surface irregularity, and grade of plaque enhancement were recorded. Quantitative analyses including normal wall index and degree of contrast enhancement were calculated. Multivariate regression analysis was performed to identify the association with cerebrovascular ischaemic events. A total of 38 pairs of symptomatic and asymptomatic plaques from 74 patients were analysed. Compared to asymptomatic plaques, symptomatic plaques demonstrated higher degree of contrast enhancement (29.77±19.23 versus 18.21±12.18%, p=0.039) and presence of IPH (26% versus 8%, p=0.032). No significant differences were detected regarding eccentricity, surface irregularity, and normal wall index. Events were associated with contrast enhancement (OR, 1.212; 95% confidence interval [CI], 1.086-1.352) after controlling for age, sex, cardiovascular risk factors, and stenosis degree. IPH was not associated with events. Contrast enhancement in the intracranial plaque without substantial stenosis is associated with previous events, and may serve as the vulnerable feature, thereby stratifying stroke risk not achievable by luminal stenosis.

Metagenomics Analysis of Thrombus Samples Retrieved from Mechanical Thrombectomy.

PurposeThe purpose of this study was to assess the microbiota in middle cerebral artery thrombi retrieved in mechanical thrombectomy arising out of symptomatic carotid plaque within 6 hours of acute ischemic stroke. Thrombi were subjected to next-generation sequencing for a bacterial signature to determine their role in atherosclerosis.Materials and MethodsWe included 4 human middle cerebral artery thrombus samples (all patients were male). The median age for the patients was 51±13.6 years. Patients enrolled in the study from Pacific Medical University and Hospital underwent mechanical thrombectomy in the stroke window period. All patients underwent brain magnetic resonance angiography (MRA) and circle of Willis and neck vessel MRA along with the standard stroke workup to establish stroke etiology. Only patients with symptomatic carotid stenosis and tandem lesions with ipsilateral middle cerebral artery occlusion were included in the study. Thrombus samples were collected, stored at –80 degrees, and subjected to metagenomics analysis.ResultsOf the 4 patients undergoing thrombectomy for diagnosis with ischemic stroke, all thrombi recovered for bacterial DNA in qPCR were positive. More than 27 bacteria were present in the 4 thrombus samples. The majority of bacteria were Lactobacillus, Stenotrophomonas, Pseudomonas, Staphylococcus, and Finegoldia.ConclusionGenesis of symptomatic atherosclerotic carotid plaque leading to thromboembolism could be either due to direct mechanisms like acidification and local inflammation of plaque milieu with lactobacillus, biofilm dispersion leading to inflammation like with pseudomonas fluorescence, or enterococci or indirect mechanisms like Toll 2 like signaling by gut microbiota.

Advance ultrasound techniques for the assessment of plaque vulnerability in symptomatic and asymptomatic carotid stenosis: a multimodal ultrasound study.

Advanced carotid ultrasound techniques may be useful in characterizing plaque vulnerability, but comprehensive studies are still lacking. The aim of this study was to identify factors associated with vulnerable plaques using advanced ultrasound techniques. This is a prospective observational study of patients with >50% internal carotid stenosis (ICA). All patients underwent conventional ultrasound, superb microvascular imaging (SMI) and shear wave elastography (SWE) examinations. Plaque size, echogenicity, stiffness and intraplaque neovascularization (IPN) were assessed and compared between symptomatic and asymptomatic groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of SWE and SMI of the vulnerable plaques. The final analysis included 123 patients (78.9% male; mean age, 66±8 years), 65 were enrolled in the symptomatic group, and 58 were enrolled in the asymptomatic group. The mean elasticity was 78.1±25.4 kPa for asymptomatic and 51.5±18.3 kPa for symptomatic plaques. Symptomatic plaques showed higher visual IPN grades on SMI than asymptomatic plaques (P<0.001). Multivariate regression analysis showed that plaque stiffness (PS) (OR 0.95, 95% CI, 0.919-0.974) and IPN level (OR 4.17, 95% CI, 2.008-8.664) were independently associated with symptomatic plaques. The combination of the two factors had a preferable accuracy to discriminate symptomatic plaques (AUC 0.89, 95% CI, 0.827-0.944). Advanced carotid ultrasound techniques can identify plaque characteristics that are associated with ischemic events and may be potentially indicative of plaque vulnerability. These factors may ultimately be used in the clinical management of carotid stenosis.

Monosit/Yüksek Yoğunluklu Lipoprotein Kolesterol Oranı Yüksekliği Orta Düzey Karotis Arter Darlığında Semptomatik Plak Için Öngördürücü Müdür?

Aim: Monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is a new and easily measurable marker positively associated with inflammation. In this study, we aimed to evaluate if there was a relationship between MHR and the risk of presence of symptomatic plaque in patients with intermediate carotid artery stenosis. Materials and Methods: A total of 179 of patients who had 50%-70% stenosis in the carotid artery were included in this retrospective cohort study. Patients were assigned into two groups based on symptomatic (n=104) and asymptomatic (n=75) group. Groups were compared in terms of MHR. Predictive role of MHR for presence of symptomatic plaque was investigated. Results: Monocyte to high-density lipoprotein cholesterol ratio was significantly higher in the symptomatic group (11.40 ± 4.24 vs 18.33 ± 9.06, p &amp;lt; 0.001). Monocyte to high-density lipoprotein cholesterol ratio &amp;gt; 13.48; had 70.19% sensitivity and 76.0% specificity for prediction of symptomatic plaque (AUC: 0.787, 95% CI: 0.720–0.840, p &amp;lt; 0.001) in patients with intermediate carotid artery stenosis. In a univariate analysis age, gender, hemoglobin, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), smoking, total cholesterol and MHR were significantly associated with presence of symptomatic carotid plaques. Monocyte to high-density lipoprotein cholesterol ratio (OR:1.330, p &amp;lt; 0.001) and hemoglobin (OR:1.441, p = 0.013) were found to be significant independent predictors of symptomatic plaques in the carotid artery in a multivariate analysis, after adjusting for other risk factors. Conclusion: MHR plays a moderate role for prediction of symptomatic plaques in the carotid artery.

Ultrasound-based internal carotid artery plaque characterization using deep learning paradigm on a supercomputer: a cardiovascular disease/stroke risk assessment system.

Visual or manual characterization and classification of atherosclerotic plaque lesions are tedious, error-prone, and time-consuming. The purpose of this study is to develop and design an automated carotid plaque characterization and classification system into binary classes, namely symptomatic and asymptomatic types via the deep learning (DL) framework implemented on a supercomputer. We hypothesize that on ultrasound images, symptomatic carotid plaques have (a) a low grayscale median because of a histologically large lipid core and relatively little collagen and calcium, and (b) a higher chaotic (heterogeneous) grayscale distribution due to the composition. The methodology consisted of building a DL model of Artificial Intelligence (called Atheromatic 2.0, AtheroPoint, CA, USA) that used a classic convolution neural network consisting of 13 layers and implemented on a supercomputer. The DL model used a cross-validation protocol for estimating the classification accuracy (ACC) and area-under-the-curve (AUC). A sample of 346 carotid ultrasound-based delineated plaques were used (196 symptomatic and 150 asymptomatic, mean age 69.9 ± 7.8years, with 39% females). This was augmented using geometric transformation yielding 2312 plaques (1191 symptomatic and 1120 asymptomatic plaques). K10 (90% training and 10% testing) cross-validation DL protocol was implemented and showed an (i) accuracy and (ii) AUC without and with augmentation of 86.17%, 0.86 (p-value < 0.0001), and 89.7%, 0.91 (p-value < 0.0001), respectively. The DL characterization system consisted of validation of the two hypotheses: (a) mean feature strength (MFS) and (b) Mandelbrot's fractal dimension (FD) for measuring chaotic behavior. We demonstrated that both MFS and FD were higher in symptomatic plaques compared to asymptomatic plaques by 64.15 ± 0.73% (p-value < 0.0001) and 6 ± 0.13% (p-value < 0.0001), respectively. The benchmarking results show that DL with augmentation (ACC: 89.7%, AUC: 0.91 (p-value < 0.0001)) is superior to previously published machine learning (ACC: 83.7%) by 6.0%. The Atheromatic runs the test patient in < 2s. Deep learning can be a useful tool for carotid ultrasound-based characterization and classification of symptomatic and asymptomatic plaques.