Abstract 126: Are Carotid Plaques With Intraplaque Hemorrhage Different in Plaque Size, Distribution and Shear Stress?

Introduction: Intraplaque hemorrhage (IPH) is associated with risk at ischemic stroke. In addition, plaques that contain IPH show accelerated plaque growth, which might affect the local shear stress (SS) distribution over the plaque. Blood flow induced SS is known to be involved in the development and destabilization of atherosclerotic plaques. It is unknown whether the SS distribution over plaques with IPH differs from plaques without IPH and whether SS is involved in plaque progression/destabilization of plaques with IPH. We compared the plaque size, distribution and SS over plaques with and without IPH in symptomatic patients. Methods: 38 patients with a recent (<3 months) TIA or minor stroke of the PARISK (Plaque At Risk) study and with carotid artery stenosis 2 mm were selected for analysis. To calculate local SS, the lumen contours were used in FIDAP, a CFD software package. The mean and maximum shear stress at the plaque was normalized to the average shear stress in the common carotid artery (NSSmean, NSSmax). The NSSmean and NSSmax were compared for plaques with and without IPH. Results: In 75 carotid arteries plaque was observed (99%). The 29 plaques (39%) that contained IPH were longer (17±5 vs 11±6 mm, p<0.05) and located more proximal in the carotid bulb than plaques without IPH. Symptomatic vessels contained more often IPH (76%) than plaques from asymptomatic arteries (23%). Plaques that contained IPH in symptomatic arteries were not different in length (17±4 mm) compared to plaques with IPH in asymptomatic arteries (16±5 mm). In 18 symptomatic vessels the SS could be calculated. The NSSmean did not differ for plaques with or without IPH (0.98±0.35 vs 0.75±0.40), whereas the NSSmax for plaques with IPH was 2x higher than for plaques without IPH (1.32 ±0.35 vs 3.06±1.45, p<0.05). Conclusion: Carotid plaques that contain IPH are longer, located more proximal in the carotid bulb and exposed to higher SS than plaques without IPH. IPH determines the plaque length, which was not influenced by the presence or absence of symptoms. Since IPH is associated with stroke risk, the higher SS and larger plaque size potentially contribute to this increased stroke risk.

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Abstract 3482: Increased Matrix Metalloproteinase-9 Expression is Correlated with Carotid Intraplaque hemorrhage in a Swine Model

Stroke ◽

10.1161/str.43.suppl_1.a3482 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Zhong-Song Shi ◽

Xiao-Bing Jiang ◽

Jin-Shan Wang ◽

Wei-Si Yuan ◽

Dong-Hong Liu

Keyword(s):

Carotid Artery ◽

Matrix Metalloproteinase ◽

Vulnerable Plaque ◽

Carotid Plaque ◽

Carotid Atherosclerosis ◽

Intraplaque Hemorrhage ◽

Swine Model ◽

Carotid Plaques ◽

Rete Mirabile ◽

Atherosclerotic Changes

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.

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Abstract WP122: Asymptomatic Moderate Carotid Artery Stenosis With Intraplaque Hemorrhage ∼ Progression of Degree of Stenosis and New Ischemic Stroke

Stroke ◽

10.1161/str.47.suppl_1.wp122 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Kiyofumi Yamada ◽

Masanori Kawasaki ◽

Shinichi Yoshimura ◽

Shigehiro Nakahara ◽

Yoshikazu Sato

Keyword(s):

Ischemic Stroke ◽

Carotid Artery ◽

Carotid Stenosis ◽

Carotid Artery Stenosis ◽

Carotid Plaque ◽

Intraplaque Hemorrhage ◽

Progression Rate ◽

Negative Group ◽

Positive Group ◽

Carotid Plaques

Background: Carotid artery stenosis is one of the major causes of ischemic stroke. Carotid intraplaque hemorrhage (IPH) plays a critical role in the progression of carotid atherosclerotic disease. Previous studies showed that IPH was associated with high intensity signal (HIS) on maximum intensity projection (MIP) images from routine three dimensional magnetic resonance imaging (3D-TOF MRA). The aim of this study was to evaluate the relationships among HIS, new ipsilateral ischemic stroke and a progression rate in carotid plaques with moderate stenosis. Materials and Methods: We included 45 carotid plaques with moderate stenosis (50% to 69%) in 45 patients who could be followed more than 12 months. Carotid IPH was defined as the presence of HIS in carotid plaque on MIP image from routine 3DTOF MRA using the criteria previously we published. We analyzed the relation between the presence of HIS in the plaques and new ischemic strokes and annual progression rate of carotid stenosis. Results: HIS in carotid plaque was present in 21 (47%) carotid arteries. Over a follow-up period of 24 ± 9 months, six ischemic strokes occurred ipsilateral to the index carotid artery. New ipsilateral ischemic stroke occurred more frequently in HIS positive group (6 of 21, 29%) than HIS negative group (0 of 24, 0%) (p=0.017). Annual progression rate of carotid stenosis is significantly higher in HIS positive group (+3.35%/year) than HIS negative group (-0.02%/year) (p= 0.0026). In multivariate regression analysis, HIS positive was an independent predictor for annual progression rate of carotid stenosis (p=0.003). Conclusions: HIS in carotid plaques on 3DTOF-MRA MIP images are associated with new ischemic stroke and higher annual progression rate of stenosis. Evaluation of HIS in asymptomatic moderate carotid stenosis can potentially provide risk stratification of new ipsilateral ischemic strokes.

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Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging

Stroke ◽

10.1161/strokeaha.121.035692 ◽

2021 ◽

Author(s):

Luca Saba ◽

Valentina Nardi ◽

Riccardo Cau ◽

Ajay Gupta ◽

Hooman Kamel ◽

...

Keyword(s):

Carotid Artery ◽

Carotid Plaque ◽

Intraplaque Hemorrhage ◽

Calcium Deposition ◽

Carotid Artery Plaque ◽

Carotid Plaques ◽

Novel Technologies ◽

Carotid Artery Calcification ◽

Wide Range

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.

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Carotid artery stenosis with a high-intensity signal plaque on time-of-flight magnetic resonance angiography and association with evidence of intraplaque hypoxia

Journal of Neurosurgery ◽

10.3171/2016.4.jns16349 ◽

2016 ◽

Vol 126 (6) ◽

pp. 1873-1878 ◽

Cited By ~ 2

Author(s):

Atsushi Ogata ◽

Masatou Kawashima ◽

Tomihiro Wakamiya ◽

Masashi Nishihara ◽

Jun Masuoka ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Angiography ◽

Carotid Artery ◽

High Intensity ◽

Time Of Flight ◽

University Hospital ◽

Intraplaque Hemorrhage ◽

Carotid Plaques ◽

Tof Mra ◽

The Relationship

OBJECTIVEHypoxia induces angiogenesis and plays a major role in the progression of carotid plaques. During carotid intervention, plaques with high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) often cause ischemic stroke and embolic complications. However, the role of intraplaque hypoxia before carotid endarterectomy (CEA) and carotid artery stenting is not presently understood. In this study the authors aimed to investigate the relationship between intraplaque hypoxia and MRA findings.METHODSNineteen consecutive patients with 20 carotid artery stenoses who underwent CEA at Saga University Hospital between August 2008 and December 2014 were enrolled in the study. The expressions of hypoxia-inducible transcription factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemical analysis. In addition, the relationship between the findings on TOF MRA and pathology for the carotid plaques was analyzed.RESULTSHigh-intensity plaques on TOF MRA showed higher expression levels of HIF-1α (p = 0.015) and VEGF (p = 0.007) compared with isointensity plaques. The rate of intraplaque hemorrhage (IPH) on TOF MRA was also significantly higher in the high-intensity plaques than in the isointensity plaques (p = 0.024). Finally, the mean number of neovessels was significantly higher in those without plaque hemorrhage than in those with plaque hemorrhage (p = 0.010).CONCLUSIONSPlaques with high-intensity signals on TOF MRA were associated with IPH and evidence of intraplaque hypoxia. This fact may represent an opportunity to establish novel therapeutic agents targeting intraplaque hypoxia.

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Carotid Plaques From Symptomatic Patients With Mild Stenosis Is Associated With Intraplaque Hemorrhage

Hypertension ◽

10.1161/hypertensionaha.121.18128 ◽

2021 ◽

Author(s):

Valentina Nardi ◽

John Benson ◽

Melanie C. Bois ◽

Luca Saba ◽

Anthony S. Larson ◽

...

Keyword(s):

Carotid Artery ◽

Carotid Artery Stenosis ◽

Continuous Variable ◽

Interquartile Range ◽

Artery Stenosis ◽

Intraplaque Hemorrhage ◽

Plaque Vulnerability ◽

Carotid Plaques ◽

Mild Stenosis ◽

Cerebrovascular Events

Carotid plaque vulnerability features beyond the degree of stenosis may play a key role in the pathogenesis and recurrence of ischemic cerebrovascular events. This study sought to compare intraplaque hemorrhage (IPH) as a marker of plaque vulnerability in symptomatic patients with mild (<50%), moderate (50%–69%), and severe (≥70%) carotid artery stenosis. We included patients who experienced ischemic cerebrovascular events with no other identifiable sources and underwent carotid endarterectomy for mild (n=32), moderate (n=47), and severe (n=58) carotid artery stenosis. The degree of stenosis and imaging hallmarks were assessed by computed tomography angiography or magnetic resonance angiography. Plaque specimens were stained with hematoxylin and eosin and Movat pentachrome staining. Carotid plaques of patients with mild stenosis had a higher extent of IPH (%) on tissue analysis compared with patients with moderate (mild, 15.7% [interquartile range, 7.8%–26.7%]; moderate, 3.9% [0.0%–9.2%]; P <0.001) and severe carotid artery stenosis (mild, 15.7% [interquartile range, 7.8%–26.7%]; severe, 2.5% [interquartile range, 0.0%–11.2%]; P <0.001). When considering the degree of carotid artery stenosis as a continuous variable, a lower lumen narrowing was associated with higher extent of IPH ( P <0.001; R, −0.329). Our major finding is the association of IPH with mild carotid artery stenosis based on histological analysis. The current study may suggest that IPH potentially plays a role in the mechanism of stroke in patients with nonobstructive carotid stenosis.

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Association between Intraplaque Hemorrhage and Vascular Remodeling in Carotid Arteries: The Plaque at RISK (PARISK) Study

Cerebrovascular Diseases ◽

10.1159/000511935 ◽

2020 ◽

pp. 1-6

Author(s):

Kristine Dilba ◽

Anouk C. van Dijk ◽

Geneviève A.J.C. Crombag ◽

Anton F.W. van der Steen ◽

Mat J. Daemen ◽

...

Keyword(s):

At Risk ◽

Carotid Artery ◽

Cross Section ◽

Carotid Artery Stenosis ◽

Vascular Remodeling ◽

Artery Stenosis ◽

Intraplaque Hemorrhage ◽

Plaque Size ◽

Symptomatic Carotid ◽

Wall Area

Introduction: Vascular remodeling is a compensatory enlargement of the vessel wall in response to atherosclerotic plaque growth. We aimed to investigate the association between intraplaque hemorrhage (IPH), vascular remodeling, and luminal dimensions in recently symptomatic patients with mild to moderate carotid artery stenosis in which the differences in plaque size were taken into account. Materials and Methods: We assessed vessel dimensions on MRI of the symptomatic carotid artery in 164 patients from the Plaque At RISK study. This study included patients with recent ischemic neurological event and ipsilateral carotid artery stenosis <70%. The cross section with the largest wall area (WA) in the internal carotid artery (ICA) was selected for analysis. On this cross section, the following parameters were determined: WA, total vessel area (TVA), and lumen area (LA). Vascular remodeling was quantified as the remodeling ratio (RR) and was calculated as TVA at this position divided by the TVA in an unaffected distal portion of the ipsilateral ICA. Adjustment for WA was performed to correct for plaque size. Results: Plaques with IPH had a larger WA (0.56 vs. 0.46 cm2; p < 0.001), a smaller LA (0.17 vs. 0.22 cm2; p = 0.03), and a higher RR (2.0 vs. 1.9; p = 0.03) than plaques without IPH. After adjustment for WA, plaques containing IPH had a smaller LA (B = −0.052, p = 0.01) than plaques without IPH, but the RR was not different. Conclusion: After correcting for plaque size, plaques containing IPH had a smaller LA than plaques without IPH. However, RR was not different.

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Surgical management of extracranial carotid artery aneurysms

VASA ◽

10.1024/0301-1526/a000528 ◽

2016 ◽

Vol 45 (3) ◽

pp. 223-228 ◽

Cited By ~ 2

Author(s):

Jan Paweł Skóra ◽

Jacek Kurcz ◽

Krzysztof Korta ◽

Przemysław Szyber ◽

Tadeusz Andrzej Dorobisz ◽

...

Keyword(s):

Carotid Artery ◽

Surgical Management ◽

Minor Stroke ◽

Stroke Rate ◽

Extracranial Carotid Artery ◽

Long Term Follow Up ◽

End To End ◽

Dacron Patch ◽

Major Stroke

Abstract. Background: We present the methods and results of the surgical management of extracranial carotid artery aneurysms (ECCA). Postoperative complications including early and late neurological events were analysed. Correlation between reconstruction techniques and morphology of ECCA was assessed in this retrospective study. Patients and methods: In total, 32 reconstructions of ECCA were performed in 31 symptomatic patients with a mean age of 59.2 (range 33 - 84) years. The causes of ECCA were divided among atherosclerosis (n = 25; 78.1 %), previous carotid endarterectomy with Dacron patch (n = 4; 12.5 %), iatrogenic injury (n = 2; 6.3 %) and infection (n = 1; 3.1 %). In 23 cases, intervention consisted of carotid bypass. Aneurysmectomy with end-to-end suture was performed in 4 cases. Aneurysmal resection with patching was done in 2 cases and aneurysmorrhaphy without patching in another 2 cases. In 1 case, ligature of the internal carotid artery (ICA) was required. Results: Technical success defined as the preservation of ICA patency was achieved in 31 cases (96.9 %). There was one perioperative death due to major stroke (3.1 %). Two cases of minor stroke occurred in the 30-day observation period (6.3 %). Three patients had a transient hypoglossal nerve palsy that subsided spontaneously (9.4 %). At a mean long-term follow-up of 68 months, there were no major or minor ipsilateral strokes or surgery-related deaths reported. In all 30 surviving patients (96.9 %), long-term clinical outcomes were free from ipsilateral neurological symptoms. Conclusions: Open surgery is a relatively safe method in the therapy of ECCA. Surgical repair of ECCAs can be associated with an acceptable major stroke rate and moderate minor stroke rate. Complication-free long-term outcomes can be achieved in as many as 96.9 % of patients. Aneurysmectomy with end-to-end anastomosis or bypass surgery can be implemented during open repair of ECCA.

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Free-Floating Thrombus in the Distal Internal Carotid Artery Causing a Stroke

International Journal of Angiology ◽

10.1055/s-0040-1720973 ◽

2020 ◽

Author(s):

Spyros Papadoulas ◽

Konstantinos Moulakakis ◽

Natasa Kouri ◽

Petros Zampakis ◽

Stavros K. Kakkos

Keyword(s):

Carotid Artery ◽

Internal Carotid Artery ◽

Medical Management ◽

Internal Carotid ◽

Treatment Strategies ◽

Rare Condition ◽

Residual Stenosis ◽

Floating Thrombus ◽

Distal Internal Carotid Artery ◽

Carotid Bulb

AbstractWe present a patient suffering from a stroke with a free-floating thrombus extending up to the distal internal carotid artery. The thrombus was totally resolved after a 2-week anticoagulation regimen without leaving behind any severe residual stenosis in the carotid bulb. The optimal treatment of this rare condition remains uncertain. We report some important treatment strategies that have been used in the literature, emphasizing the anticoagulation as the mainstay of therapy. Immediate surgical and interventional manipulations carry the risk of thrombus dislodgement and embolization and should be considered if there are recurrent symptoms despite medical management.

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