Relationship between Carotid Artery Remodeling and Plaque Vulnerability with T1-Weighted Magnetic Resonance Imaging

doi:10.1016/j.jstrokecerebrovasdis.2013.12.010

Journal of Stroke and Cerebrovascular Diseases

Volume 23, Issue 6, July 2014, Pages 1462-1470

https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.010 Get rights and content

Background

The aim of this study was to validate the relationship between carotid artery remodeling defined as the carotid remodeling index (CRI) and plaque vulnerability by comparing the degree of outward remodeling calculated using 3-dimensional inversion recovery-based T1-weighted imaging (magnetization-prepared rapid acquisition gradient echo [MPRAGE]) with the symptomatology and histology of plaques extracted during carotid endarterectomy.

Methods

Sixty-one patients with 50% stenosis or more (North American Symptomatic Carotid Endarterectomy Trial criteria) were included. The average rate of stenosis was 79.8%. The CRI was determined by measuring the external cross-sectional vessel area (CSVA) at the maximum stenosis of the internal carotid artery (ICA) and dividing it by the external CSVA at the distal ICA (unaffected by atherosclerosis) using MPRAGE imaging.

Results

The CRI was significantly higher in symptomatic patients compared with asymptomatic patients (1.98 ± .26 versus 1.68 ± .24, P < .0001). A higher CRI positively correlated with the necrotic core area (r = .57, P < .0001) and negatively correlated with the fibrous cap thickness (r = −.33, P = .01). It was also significantly associated with severe intraplaque hemorrhage (P < .0001) and the prevalence of cap inflammation with macrophage (P = .03) and lymphocyte (P = .01) infiltration.

Conclusions

The larger outward remodeling of the carotid artery on MPRAGE imaging had symptomatic carotid plaques and histologically vulnerable plaques. This study indicates that MPRAGE imaging is useful for the assessment of carotid artery remodeling.

Section snippets

Study Population

Between May 2006 and September 2008, 70 patients with significant carotid stenosis (≥50%) who underwent CEA were selected. Nine patients were excluded after the histologic examination because their plaques were damaged during CEA and could not be histologically evaluated. Finally, 61 patients were included in this study: 36 patients had symptomatic carotid stenosis (32 men with a mean age of 70.5 ± 8.7 years and degree of stenosis of 80.3 ± 11.3%) and 25 patients had asymptomatic carotid

Patient Characteristics

The characteristics of the study population are listed in Table 1. The symptomatic and asymptomatic groups had similar demographic features and no significant differences in the frequency of conventional risk factors for carotid artery disease. With regard to their plaque characteristics, symptomatic patients had a higher number of mobile plaques (33.3% versus 8.0%, P = .03). No significant difference in the existence of ulceration and echolucency by ultrasound imaging and the SIR of carotid

Discussion

In this study, we showed that larger outward remodeling of the carotid artery was significantly associated with symptomatic carotid plaques and markers of histologic carotid plaque vulnerability such as higher NC proportion, IPH score, prevalence of fresh IPH, mural thrombus, and inflammatory cells. This is the first report to examine the relationship between histologic markers related to the carotid plaque vulnerability and carotid artery remodeling, suggesting that CRI is a useful marker of

Conclusions

This study clearly demonstrates the relationship between carotid artery remodeling and plaque vulnerability based on symptomatology and histology in significant carotid stenosis (≥50%) using MPRAGE. This study indicates that MPRAGE imaging is useful for the assessment of carotid artery remodeling. To evaluate the outward remodeling of carotid artery using MPRAGE imaging is predictive of the risk of ipsilateral ischemic events in the future.

Acknowledgment

The authors thank Mayumi Oka and Yoshifumi Higashino for collecting the patient data.

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Plasma ApoB/AI: An effective indicator for intracranial vascular positive remodeling
2022, Journal of the Neurological Sciences
Citation Excerpt :
This phenomenon is recognized as positive remodeling. Although the positive remodeling alleviates vessel stenosis to some extent, a substantial number of studies [2–4] demonstrated that positive remodeling was associated with plaque instability and increased risk of ischemic events. However, the mechanism and influenced factors for arterial positive remodeling have not been fully understood.
Both vascular positive remodeling and apolipoprotein B/apolipoprotein AI (apoB/AI) are important risk factors for ischemic stroke. However, it is unclear whether apoB/AI level plays a role in vascular positive remodeling. This study aimed to investigate the association between apoB/AI and intracranial vascular positive remodeling.
Symptomatic patients with intracranial artery 30–99% stenosis were recruited and underwent high-resolution magnetic resonance (MR) imaging. The levels of apolipoprotein B (apoB), apolipoprotein AI (apoAI) and apoB/AI were tested. Intracranial vascular remodeling index (RI) defined as the wall area ratio between maximal luminal narrowing and reference site was evaluated on MR images. Positive remodeling was defined as RI ≥1.05. The association between apoB/AI level and positive remodeling was respectively determined in anterior and posterior circulation.
Of 65 recruited patients (mean age: 58.5 ± 10.6 years; 36 males), 25 (38.5%) had positive remodeling, of which 24 (36.9%) were in the posterior circulation group. Patients with positive remodeling had significantly higher apoB (1.0 ± 0.3 g/L vs. 0.8 ± 0.3 g/L, P = 0.003) and apoB/AI (1.0 ± 0.3 vs. 0.8 ± 0.2, P = 0.008) than those without. Univariate logistic regression showed that apoB/AI (OR: 2.302, 95%CI: 1.229–4.321, P = 0.009) was significantly associated with positive remodeling. After adjusted for confounders, the association of apoB/AI (OR: 2.935, 95%CI: 1.061–8.123, P = 0.038) with positive remodeling remained significant. ApoB/AI (OR: 76.110, 95%CI: 1.169–4953.287, P = 0.042) was significantly associated with positive remodeling in posterior circulation but not in anterior circulation.
ApoB/AI is a potential indicator for intracranial vulnerable atherosclerosis characterized by positive remodeling, especially in posterior circulation.
Colchicine reduces atherosclerotic plaque vulnerability in rabbits
2021, Atherosclerosis Plus
Citation Excerpt :
The observed phenotype change of vSMCs (higher SM2 marker expression with colchicine treatment vs. placebo) therefore also suggests favorable effects of colchicine on the atherosclerotic process. Outward vascular remodelling, although limiting luminal narrowing, is considered a sign of plaque vulnerability and was reported being associated with poor clinical outcomes [23–26]. This remodelling mainly occurs because of the growing plaque, and the extent of enlargement is positively correlated to plaque inflammation [27,28].
The anti-inflammatory agent colchicine is gaining interest as a treatment for coronary artery disease. However, the effects of colchicine in atherosclerotic animal models are mostly unknown. This study aimed to evaluate colchicine in a rabbit model of atherosclerosis.
Twenty-two rabbits were fed a 0.5% cholesterol-enriched diet for 10 weeks and then randomized to receive either oral saline (n=11) or colchicine (350 μg/kg/day; n=11) for 6 weeks, with 0.2% cholesterol-diet during the treatment period. We performed intravascular ultrasound imaging (at start and end of treatment) and histology analyses of the descending thoracic aorta. Leucocyte activation was assessed in vitro on blood samples obtained during treatment.
Colchicine prevented positive aortic vascular remodelling (p=0.029 vs placebo). This effect was even more marked at high plasma cholesterol level (third quartile of plasma cholesterol, p=0.020). At high cholesterol level, both atherosclerotic plaque and media areas on histomorphology were reduced by colchicine compared to placebo (p=0.031 and p=0.039, respectively). Plaque fibrosis and macrophage area were reduced by colchicine (Masson's trichrome stain: p=0.038; RAM-11: p=0.026). The plaque vulnerability index, assessed by histology, was reduced by colchicine (p=0.040). Elastin/type I collagen ratio in media was significantly higher with colchicine compared to placebo (p=0.013). At a high level of plasma cholesterol, in vitro LPS challenge revealed a decrease in monocyte activation following treatment with colchicine (p<0.001) and no change in the placebo group (p=0.353).
Colchicine decreases plaque vulnerability with reductions in plaque inflammation, medial fibrosis, outward vascular remodelling and ex vivo monocyte activation.
Assessment of mechanical indicators of carotid plaque vulnerability: Geometrical curvature metric, plaque stresses and damage in tissue fibres
2020, Journal of the Mechanical Behavior of Biomedical Materials
Citation Excerpt :
In addition, clinical assessment for a surgical intervention to treat symptomatic carotid stenosis, namely a carotid stent or carotid endarterectomy, is still predominantly based on percentage of lumen area stenosed (Khedr et al., 2016; Moore et al., 2016; Yadav et al., 2004) even though stenosis has not been found to correlate with the likelihood of plaque rupture (Golledge et al., 2000). In fact, positive, outward remodelling has been identified to result in more unstable plaques than occlusive negative remodelling (Fukuda et al., 2014; Miura et al., 2011). Whilst plaque morphology and heterogeneity can have an influence on rupture risk, the geometry itself may be a key predictor of plaque vulnerability along with stresses in the vessel (Akyildiz et al., 2016; Li et al., 2008).
Stroke is a major cause of death worldwide. The rupture of atherosclerotic carotid plaques is the leading single cause of stroke. Currently there is no accepted clinical measure to quantitatively assess the risk of carotid plaque rupture. Structural analyses of vulnerable plaques, using finite element (FE) analysis, have retrospectively found that regions of high stress tend to be the site of plaque rupture. The current study proposes a new clinical measure, based on plaque geometry, to assess the risk of carotid plaque rupture. This measure, named the weighted curvature difference, is based on the curvature of both the lumen and intima-media boundary, and the local plaque thickness. A series of idealized and realistic, 2-D and 3-D geometries are used to systematically assess this novel geometrical metric. The areas predicted to be at high risk of rupture using this geometrical metric are compared with areas of high stress, obtained from both isotropic and anisotropic material models. These results are also compared with areas in diseased carotid arteries that are predicted to have high damage accumulation in collagen fibres using a continuum damage model. Results show the new geometrical metric consistently predicts the locations of high stress in all of the vessel geometries examined. The drawbacks of using lumen curvature only as a risk measure are highlighted; particularly in the case of outward remodelled vessels. Weighted curvature difference shows great potential to be used as a metric to efficiently distinguish the rupture prone areas in a diseased vessels in a way that is independent of material properties.
Plaque Characteristics of Patients with Symptomatic Mild Carotid Artery Stenosis
2018, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
It has also been reported that plaque with high signal intensity on BB-MRI(T1) is vulnerable.12,25,26 There have been reports that expansive remodeling was also correlated with vulnerable plaque.27-30 Ischemic events within 6 months were significantly higher in patients with T1 high signal intensity in the carotid artery and expansive remodeling than in patients without them.31
Carotid revascularization may be considered for severe stenosis, but its use for symptomatic mild stenosis (<50%) with vulnerable plaque or ulcer remains uncertain. The characteristics of patients with symptomatic mild stenosis who underwent revascularization are reviewed.
The subjects of this study were 18 patients with symptomatic mild stenosis (<50%) on angiography from among 175 patients who underwent revascularization in our department. The plaques were evaluated by black-blood magnetic resonance imaging (BB-MRI) and ultrasonography (US) and classified into 2 types: type 1 (n = 15), a lesion with an ulcer or mobile plaque or thrombosis on angiography or US; and type 2 (n = 3), a lesion without any of the above. Fourteen patients underwent carotid endarterectomy (CEA), and 4 patients underwent carotid artery stenting.
The stenosis on angiography was 27.2% ± 10.7 (5%-41%), and the area carotid artery stenosis rate on US was 69.8 ± 14.5% (44.5%-97%). The stenosis rate of these 2 methods was not at all correlated. In type 1 plaque that underwent CEA, 10 of 11 patients had vulnerable plaque by histopathology, and 1 patient had thrombus on the plaque by operative findings. In type 2 plaque that underwent CEA, all patients had vulnerable plaque by histopathology. During the follow-up period, none of the patients had restenosis or stroke.
The findings of US and BB-MRI in patients with symptomatic mild stenosis (<50%) on angiography are important for determining treatment. If BB-MRI or US shows the findings of vulnerable plaque in mild stenosis, surgical treatment may be considered for these patients.
Inhibition of plaque progression and promotion of plaque stability by glucagon-like peptide-1 receptor agonist: Serial in vivo findings from iMap-IVUS in Watanabe heritable hyperlipidemic rabbits
2017, Atherosclerosis
Glucagon-like peptide-1 (GLP-1) is thought to inhibit development of aortic atherosclerosis and plaque formation. However, whether GLP-1 stabilizes fully developed atherosclerotic plaque or alters the complicated plaque composition remains unclarified.
Ten Watanabe heritable hyperlipidemic (WHHL) rabbits were divided into GLP-1 receptor agonist treatment group and control group. After confirmation of atherosclerotic plaques in brachiocephalic arteries by iMap intravascular ultrasound (iMAP-IVUS), GLP-1 receptor agonist lixisenatide was administered to WHHL rabbits at 30 nmoL/kg/day for 12 weeks by osmotic pump. An equal volume of normal saline was administered in a control group. After evaluation by iMAP-IVUS at 12 weeks, brachiocephalic arteries were harvested for pathological histological analysis.
iMAP-IVUS analysis revealed larger fibrotic plaque components and smaller necrotic and calcified plaque components in the GLP-1 group than in the control group; %fibrotic area: 66.30 ± 2.06% vs. 75.14 ± 2.62%, p < 0.01, %necrotic area: 23.25 ± 1.87% vs. 16.17 ± 2.27%, p = 0.02, %calcified area: 2.15 ± 0.24% vs. 1.00 ± 0.18%, p < 0.01), indicating that GLP-1 receptor agonist might modify plaque composition and increase plaque stability. Histological analysis confirmed that GLP-1 receptor agonist treatment improved smooth muscle cell (SMC)-rich plaque with increased fibrotic content. Furthermore, plaque macrophage infiltration and calcification were significantly reduced by GLP-1 receptor agonist treatment; %SMC area: 6.93 ± 0.31% vs. 8.14 ± 0.48%, p = 0.02; %macrophage area: 9.11 ± 0.80% vs. 6.19 ± 0.85%, p < 0.01; %fibrotic area: 54.75 ± 1.63% vs. 69.60 ± 2.12%, p = 0.02; %calcified area: 3.25 ± 0.67% vs. 0.75 ± 0.15%, p = 0.02).
GLP-1 receptor agonist inhibited plaque progression and promoted plaque stabilization by inhibiting plaque growth and modifying plaque composition.
N<sup>ε</sup>-(carboxymethyl)lysine Concentration in Debris from Carotid Artery Stenting Correlates Independently with Signal Intensity on T1-Weighted Black-Blood Magnetic Resonance Images
2017, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
A comparison of MRI and histologic findings on carotid plaques obtained by carotid endarterectomy (CEA) revealed that the SI of different plaque components varied on T1WI and T2WI scans. Plaques with high SI on T1WI scans are thought to reflect complex atheromas mainly comprised of a lipid core and associated hemorrhage16 whereas high SI on T2WI scans suggests that the plaques contain a large amount of extracellular matrix.4 In our study population, significantly more patients with the higher than the lower SIR-P/M on T1WI developed new post-CAS ischemic DWI lesions.
Because magnetic resonance imaging (MRI) focuses on the morphological characteristics of carotid artery plaques, its diagnostic value with respect to plaque vulnerability is limited. We examined the correlation between N^ε-(carboxymethyl)lysine (CML), a main chemical structure of advanced glycation end-products, and the vulnerability of plaques visualized on MRI scans.
We enrolled 43 patients who had undergone carotid artery stenting (CAS) for carotid artery stenosis; all underwent MRI studies, including black-blood MRI and diffusion-weighted imaging (DWI). The signal intensity ratio (SIR) of plaques to adjacent sternocleidomastoid muscle (P/M) on T1- and T2-weighted images (T1WI, T2WI) was calculated. Protein samples were extracted from debris trapped by a filter device. The concentrations of CML and myeloperoxidase (MPO) were measured by solid-phase enzyme-linked immunosorbent assay.
The patients were classified into 2 groups based on their SIR-P/M on T1WI and T2WI scans. We observed a higher incidence of post-CAS DWI lesions in patients with a higher than a lower SIR-P/M on T1WI; the CML and MPO concentrations in their CAS debris were also higher. No such differences were seen in patients with a higher or lower SIR-P/M on T2WI scans. The concentration of CML in CAS debris correlated independently with the SIR-P/M on T1WI of the carotid plaques, and was related to the concentration of MPO in CAS debris.
Our findings suggest CML as a candidate molecular imaging probe for the identification of vulnerable plaques.

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: Grant support: None.

: Disclosure: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this article.

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Original ArticleRelationship between Carotid Artery Remodeling and Plaque Vulnerability with T1-Weighted Magnetic Resonance Imaging

Background

Methods

Results

Conclusions

Section snippets

Study Population

Patient Characteristics

Discussion

Conclusions

Acknowledgment

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Lancet

J Vasc Surg

Atherosclerosis

Compensatory enlargement of human atherosclerotic coronary arteries

N Engl J Med

Relationship between coronary artery remodeling and plaque vulnerability

Circulation

Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study

Circulation

Three-dimensional black-blood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease

Circulation

Plaque vulnerability in internal carotid arteries with positive remodeling

Cerebrovasc Dis Extra

The impact of expansive arterial remodeling on clinical presentation in carotid artery disease: a multidetector ct angiography study

AJNR Am J Neuroradiol

Remodeling of carotid arteries detected with MR imaging: atherosclerosis risk in communities carotid MRI study

Radiology

In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques

Circulation

Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization

J Magn Reson Imaging

In vivo detection of hemorrhage in human atherosclerotic plaques with magnetic resonance imaging

J Magn Reson Imaging

Characterization of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischemia

Circulation

Assessment of human atherosclerotic carotid plaque components with multisequence MR imaging: Initial experience

Radiology

Association between signal hyperintensity on T1-weighted MR imaging of carotid plaques and ipsilateral ischemic events

AJNR Am J Neuroradiol

Assessment of necrotic core with intraplaque hemorrhage in atherosclerotic carotid artery plaque by MR imaging with 3d gradient-echo sequence in patients with high-grade stenosis. Clinical article

J Neurosurg

Original Article
Relationship between Carotid Artery Remodeling and Plaque Vulnerability with T1-Weighted Magnetic Resonance Imaging