Imaging of high-risk carotid artery plaques: current status and future directions

2014 ◽  
Vol 36 (1) ◽  
pp. E1 ◽  
Author(s):  
J. Kevin DeMarco ◽  
John Huston

In this paper, the authors review the definition of high-risk plaque as developed by experienced researchers in atherosclerosis, including pathologists, clinicians, molecular biologists, and imaging scientists. Current concepts of vulnerable plaque are based on histological studies of coronary and carotid artery plaque as well as natural history studies and include the presence of a lipid-rich necrotic core with an overlying thin fibrous cap, plaque inflammation, fissured plaque, and intraplaque hemorrhage. The extension of these histologically identified high-risk carotid plaque features to human in vivo MRI is reviewed as well. The authors also assess the ability of in vivo MRI to depict these vulnerable carotid plaque features. Next, the ability of these MRI-demonstrated high-risk carotid plaque features to predict the risk of ipsilateral carotid thromboembolic events is reviewed and compared with the risk assessment provided by simple carotid artery stenosis measurements. Lastly, future directions of high-risk carotid plaque MRI are discussed, including the potential for increased clinical availability and more automated analysis of carotid plaque MRI. The ultimate goal of high-risk plaque imaging is to design and run future multicenter trials using carotid plaque MRI to guide individual patient selection and decisions about optimal atherosclerotic treatment strategies.

2015 ◽  
Vol 39 (3-4) ◽  
pp. 151-161 ◽  
Author(s):  
Ajay Gupta ◽  
Hediyeh Baradaran ◽  
Edward E. Mtui ◽  
Hooman Kamel ◽  
Ankur Pandya ◽  
...  

Background: Carotid plaque MRI has been a useful method to characterize vulnerable atherosclerotic plaque elements. Recent investigations have suggested that source images from CT angiography (CTA) and MR angiography (MRA) can identify the simple high-risk features of symptom-producing carotid artery plaque. We studied the correlation and relative diagnostic accuracies of CTA and MRA source images in detecting symptomatic carotid artery plaque. Methods: Subjects were eligible if they had carotid stenosis between 50 and 99% and had MRA and CTA exams performed within 10 days of one another. We measured the soft (non-calcified) plaque and hard (calcified) plaque thickness on CTA axial source images and intraplaque high-intensity signal (IHIS) on 3D-time-of-flight MRA source images in subjects. We assessed whether a correlation existed between increasing CTA soft plaque thicknesses and the presence of MRA IHIS using the Student's t-test. We calculated the differences in sensitivity and specificity measures of CTA and MRA source-imaging data with the occurrence of recent ipsilateral stroke or transient ischemic attack (TIA) as the reference standard. We also performed logistic regression analyses to evaluate the predictive strength of plaque showing both IHIS and increased CTA soft plaque thickness in predicting symptomatic disease status. Results: Of 1994 screened patients, 48 arteries met the final inclusion criteria with MRA and CTA performed within 10 days of one another. The mean and median time between CTA and MRA exams were 2.0 days and 1 day, respectively. A total of 34 of 48 stenotic vessels (70.8%) were responsible for giving rise to ipsilateral stroke or TIA. CTA mean soft plaque thickness was significantly greater (4.47 vs. 2.30 mm, p < 0.0001) in patients with MRA-defined IHIS, while CTA hard plaque thickness was significantly greater (2.09 vs. 1.16 mm, p = 0.0134) in patients without MRA evidence of IHIS. CTA soft plaque thickness measurements were more sensitive than MRA IHIS (91.2 vs. 67.6%, p = 0.011) in detecting symptomatic plaque, while differences in specificity were not significantly different (p = 0.1573). In the subset of patients with both IHIS on MRA and plaque thickness >2.4 mm on CTA, the odds ratio of detecting symptomatic plaque, corrected for stenosis severity, was 45.3 (p < 0.0005). Conclusions: Unprocessed source images from CTA and MRA, which are routinely evaluated for clinical studies demonstrate the highly correlated presence of IHIS and increasing soft plaque thickness. In particular, plaque that shows high-risk features on both MRA and CTA are very strongly associated with symptom-producing carotid plaque. With further validation, such techniques are promising practical methods of extracting risk information from routine neck angiographic imaging.


Stroke ◽  
2021 ◽  
Author(s):  
Luca Saba ◽  
Valentina Nardi ◽  
Riccardo Cau ◽  
Ajay Gupta ◽  
Hooman Kamel ◽  
...  

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


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Kiriyama ◽  
H Kaneko ◽  
H Itoh ◽  
Y Yoshida ◽  
K Nakanishi ◽  
...  

Abstract Background Cigarette smoking is closely associated with the development of cardiovascular diseases (CVD), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines recommend smoking bans.On the other hand, the relationship between cigarette smoking and subclinical atherosclerosis has not been fully studied. Carotid intima-media thickness (cIMT) is commonly used as a subclinical atherosclerosis marker, and a carotid plaque feature is also known to be an important predictor of cardiovascular diseases. Purpose We sought to clarify the association between cigarette smoking and subclinical atherosclerosis by evaluating carotid plaque including cIMT and carotid plaque features in general population. Methods and results Among 1,209 participants with no prior coronary artery disease who received a medical check-up with cardiovascular examination at our institution, 450 participants (37.2%) were smokers (including both past and current smokers). We defined carotid plaque as cIMT ≥1.1 mm and high-risk plaque as carotid plaque with hypoechoic dominant and/or plaque ulceration. The value of cIMT and the rate of carotid plaque were not different between smokers and never smokers (Figure A & B). However, the rate of carotid high-risk plaque was significantly higher in participants with smokers than those with never smokers (29.7%, vs 23.5%, p=0.011) (Figure C). Even after adjustment with covariates including age, gender and traditional cardiovascular risk factors, cigarette smoking was independently associated with high-risk plaque formation (odds ratio 1.384, 95% CI 1.020–1.877; p=0.037). According to the subgroup analysis classified by age, cigarette smoking was associated with not only the development of high-risk plaque but also the increased value of cIMT in the subgroup over 60 years old, whereas only the rate of high-risk plaque was higher in smokers than never smokers in the subgroup under 60 years old. Carotid plaque and smoking Conclusion The development of high-risk carotid artery plaque may precede thickening of cIMT in cigarette smokers, suggesting that the novel insight for the pathological mechanism underlying cardiovascular events and cigarette smoking.


2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Zhong-Song Shi ◽  
Xiao-Bing Jiang ◽  
Jin-Shan Wang ◽  
Wei-Si Yuan ◽  
Dong-Hong Liu

Purpose: The limited number of large animal carotid atherosclerotic models restricts the preclinical evaluation of endovascular therapies. Carotid intraplaque hemorrhage may be associated with a higher risk of ischemic stroke in patients with carotid disease. In this study, we assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with vulnerable atherosclerotic carotid plaque and intraplaque hemorrhage in a Swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for MMP-9 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. Atherosclerotic changes were classified by AHA/Stary stage (type I to VI). The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of MMP-9 expression in the plaque with the vulnerable plaque and intraplaque hemorrhage was further analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 segments had vulnerable plaque (Stary IV to VI). Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal ( P <0.0001). Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for MMP-9 tended to be greater in the vulnerable plaque than in the stable plaque (8.69 ± 0.73% vs. 7.04 ± 0.94%, p=0.35). Areas positive for MMP-9 were significantly greater in the plaque with intraplaque hemorrhage than in the plaque without intraplaque hemorrhage (11.84 ± 1.22% vs. 6.63 ± 0.59%, p<0.001). On multivariate analysis, positive expression of MMP-9 was an independent predictor of intraplaque hemorrhage (p=0.007). Conclusion: Vulnerable carotid plaques with distal embolism were created in a Swine model of carotid atherosclerosis. Increased expression of MMP-9 may be associated with vulnerable carotid plaques, especially having the feature of intraplaque hemorrhage.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Claudio A Bravo ◽  
Jee-Young Moon ◽  
Jean Claude Uwamungu ◽  
Robert Kaplan ◽  
Kathryn Anastos ◽  
...  

Introduction: Cardiovascular disease is a major contributor to morbidity and mortality among women living with HIV (WLWH). We previously found HIV infection to be associated with carotid artery plaque, a marker of subclinical atherosclerosis. Plaque morphology and composition may predict plaque rupture and cardiovascular disease events. We characterized the association of HIV-related factors with carotid plaque echomorphology in the WIHS. Methods: Using B-mode ultrasound, we characterized plaque (focal intima-media thickness >1.5 mm) at 6 locations in the right carotid artery in 1,722 participants (1,230 HIV+, 492 HIV-) of the WIHS, a cohort study of women with or at risk for HIV at 6 US sites. Plaque echomorphologic features included relative echogenicity (>50% of plaque is echolucent vs >50% of plaque is echogenic) and surface morphology (smooth vs irregular, i.e., height variations along contour of plaque). We used multinomial logistic regression to assess the odds of each feature vs no plaque comparing HIV+ and HIV- women, adjusting for demographic (e.g., age, race/ethnicity, socioeconomic status), behavioral (e.g., drug/alcohol use, smoking, HCV infection, smoking), cardiometabolic (e.g., systolic blood pressure, BMI, lipids, diabetes) and HIV-related risk factors (e.g., antiretroviral therapy use, current CD4+ T-cell count, AIDS). We further stratified WLWH by CD4+ count (<200, 200-499, 500+ cells/uL) and HIV-1 RNA suppression. Results: Among 1,722 women (median age 40, IQR 33-46, 59% black, 29% Hispanic, 71% HIV+), 160 (9%) had at least one carotid plaque (128 HIV+, 32 HIV-). In unadjusted analyses, WLWH had more echolucent plaque (5.3% vs 2.6%, p=0.02) and plaques with smooth surface (2.7% vs 0.6%, p=0.005) than HIV-negative women. After covariate adjustment, HIV serostatus remained significantly associated with smooth plaque (odds ratio [OR] 3.45, 95% CI 1.12-10.62) but not with echolucent plaque (OR 1.60, 95% CI 0.84-3.05). Stratified by HIV viremia, WLWH with unsuppressed HIV viremia had significantly more smooth plaque (OR 3.34, 95% CI 1.26-8.87) than HIV- women, whereas suppressed WLWH did not (OR 1.79, 95% CI 0.55-5.83). In a dose-response manner, lower CD4+ count among WLWH was associated with smooth plaque (e.g., OR for <200 cells/uL compared with HIV-negative women 7.43, 95% CI 1.46-37.87), and this association was of greater magnitude than that with irregular plaque (OR 2.46, 95% CI 1.14-5.32). Low CD4+ count was also associated with both echolucent (OR 3.36 for <200 cells/uL vs HIV-negative, 95% CI 1.29-8.77) and echogenic plaque (OR 2.65, 95% CI 1.18-5.96). Conclusions: Unsuppressed viremia and low CD4+ count, which are markers of suboptimal HIV care, were associated with certain echomorphologic features of carotid plaque. Further work should assess whether these features differentially lead to cardiovascular morbidity and mortality in WLWH.


Stroke ◽  
2020 ◽  
Vol 51 (2) ◽  
pp. 504-510 ◽  
Author(s):  
Hooman Kamel ◽  
Babak B. Navi ◽  
Alexander E. Merkler ◽  
Hediyeh Baradaran ◽  
Iván Díaz ◽  
...  

Background and Purpose— Carotid artery plaque with <50% luminal stenosis may be an underappreciated stroke mechanism. We assessed how many stroke causes might be reclassified after accounting for nonstenosing plaques with high-risk features. Methods— We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis. Results— Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2–6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4–3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1–2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4–3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7–3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis. Conclusions— High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.


Author(s):  
Marialaura Simonetto ◽  
Sushrut Dharmadhikari ◽  
Ari Bennett ◽  
Nelly Campo ◽  
Negar Asdaghi ◽  
...  

2021 ◽  
Author(s):  
Yu Wang ◽  
Runhua Zhang ◽  
Yong Jiang ◽  
Miaoxin Yu ◽  
Huiyu Qiao ◽  
...  

Abstract BackgroundTo investigate the association between hemoglobin A1c (HbA1c) and intraplaque hemorrhage (IPH) in carotid atherosclerotic plaque detected by high-resolution magnetic resonance imaging (HR-MRI) in a community-based population. MethodsIn this cross-sectional, community-based study, a total of 598 participants were recruited from May 2015 to September 2019. All participants underwent carotid artery HR-MRI. Data on demographics, medical history, and physical examinations were obtained through face-to-face interview, and fasting blood sample were collected. HbA1c was determined using high-performance liquid chromatographic analysis. Presence or absence of carotid plaque IPH was determined by HR-MRI. Multiple stepwise logistic regression analysis was performed to investigate the association between HbA1c levels and carotid plaque IPH. ResultsOf the 598 participants, 317 (53.0%) had atherosclerotic plaques, and 25 (4.2%) had IPH in carotid arteries. HbA1c was associated with the presence of IPH (OR, 1.94; 95% CI, 1.38-2.73) in the univariate analysis, and the association remained significant after adjustment for age, sex, traditional vascular factors, high-sensitivity C-reactive protein, and other potential confounders (OR, 1.70; 95% CI, 1.14-2.52).ConclusionsThis study showed that high HbA1c was associated with carotid plaque IPH detected by HR-MRI, which suggests that individuals with high HbA1c may have a higher risk of developing vulnerable carotid plaques.


Author(s):  
William Hicks ◽  
Cylaina Bird ◽  
Kalil Abdullah

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study gliomagenesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.


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