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

Ogata, Atsushi; Kawashima, Masatou; Wakamiya, Tomihiro; Nishihara, Masashi; Masuoka, Jun; Nakahara, Yukiko; Ebashi, Ryo; Inoue, Keiji; Takase, Yukinori; Irié, Hiroyuki; Abé, Tatsuya

doi:10.3171/2016.4.jns16349

Cited by 9 publications

(9 citation statements)

References 22 publications

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“…Moreover, expression of CD34 in the intraplaque neovessels was not significantly different between the two groups. Additionally, a significantly higher rate of IPH in plaques with high-intensity on TOF-MRA was seen in the present study, and this finding was similar to a previous study's finding [11]. The arterial pericytes may play a role in vascular remodeling, calcification, and intraplaque neovascularization in advanced and complicated atherosclerotic lesions [12].…”

Section: Discussionsupporting

confidence: 92%

“…IPH has been reported as the principal factor for progression to unstable plaque and can be confirmed on magnetic resonance imaging (MRI) of human carotid plaques [10]. Additionally, an association between high-intensity carotid plaque on time-of-flight (TOF) magnetic resonance angiography (MRA) and IPH has been reported [11]. The present study aims to elucidate the associations between the pericytes in intraplaque neovessels and the MRA findings.…”

Section: Introductionmentioning

confidence: 82%

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Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings

Ogata

Wakamiya

Nishihara

et al. 2020

IJMS

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(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. The aim of the present study is to examine the relationship between the pericytes in intraplaque neovessels and MRA findings. (2) Methods: A total of 46 patients with 49 carotid artery stenoses who underwent carotid endarterectomy at our hospitals were enrolled. The patients with carotid plaques that were histopathologically evaluated were retrospectively analyzed. Intraplaque hemorrhage was evaluated using glycophorin A staining, and intraplaque neovessels were evaluated using CD34 (Cluster of differentiation) stain as an endothelial cell marker or NG2 (Neuron-glial antigen 2) and CD146 stains as pericyte markers. Additionally, the relationships between the TOF-MRA findings and the carotid plaque pathologies were evaluated. (3) Results: Of the 49 stenoses, 28 had high-intensity signals (TOF-HIS group) and 21 had iso-intensity signals (TOF-IIS group) on TOF-MRA. The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 82%

Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings

Ogata

Wakamiya

Nishihara

et al. 2020

IJMS

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“…Many previous reports have noted that vessel density and vessel number are important factors associated with IPH. 10,17,19,23 The results of our study demonstrated that microvessel luminal enlargement is also a pivotal characteristic of IPH.…”

Section: Enlarged Microvessel Formation In Vulnerable Plaquessupporting

confidence: 57%

“…Some pathology studies suggested that the expression of hypoxiainducible factor-1 alpha (HIF-1a) and vascular endothelial growth factor (VEGF) is associated with IPH in carotid stenosis. 9,17 However, the detailed pathological mechanisms through which microvessels and IPH develop remain obscure.…”

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confidence: 99%

Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis

Kashiwazaki¹,

Koh²,

Uchino³

et al. 2019

Journal of Neurosurgery

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OBJECTIVEThe relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed.METHODSThis study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1α)–, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)–positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels.RESULTSPlaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2–, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1α–positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum luminal diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1α–positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous).CONCLUSIONSThe present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.

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“…Recent studies have reported evidence of plaque hypoxia [10], and an inverse association of levels of hypoxia-inducible factor 1-alpha with the degree of plaque instability, suggesting that hypoxia within plaque may increase its vulnerability [11]. Based on these findings, the change in the size of intra-plaque vessels may be associated with restoration of plaque rupture/erosion by resolution of hypoxia.…”

Section: Discussionmentioning

confidence: 89%

Intra-Plaque Vessels on Contrast-Enhanced Ultrasound Sonography Predict Carotid Plaque Histology

et al. 2018

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Background and Purpose: Although the echogenicity of carotid plaques on carotid enhanced ultrasound (CEUS) was reported to correlate with the historological density of intra-plaque neovessels, it is unclear whether the intra-plaque vessel size is associated with carotid plaque vulnerability. We evaluated the relationship of size of intra-plaque vessels on CEUS with carotid plaque histology. Methods: We prospectively registered patients with carotid stenosis who were hospitalized to receive carotid endarterectomy between 2012 and 2016. CEUS was performed by ultrasound specialists using a 7-MHz linear transducer (GE LOGIQ7; GE Healthcare, Milwaukee, WN, USA). Sonazoid® was used for conducting CEUS. The sizes of microbubbles inside the plaques were scored at 0, 1, 3, and 5 min after the injection of contrast agent, and were categorized according to our defined vascular score (Vas-S; 0: the effect of contrast was not recognized; 1: the microbubbles were visible, but so blurred and vague that their shape could not be recognized; 2: dot or string-like microbubbles with movement, localized in part or the whole site of the plaque). At histological examination, we simplified the modified American Heart Association classification and defined as an atherosclerotic category (Ath-cat; 1: unruptured plaque; 2: ruptured plaque; 3: healed plaque). We then assessed the correlation of Vas-S with Ath-cat, which describes the process of rupture and restoration of carotid plaques. Results: A total of 97 patients were included in this study. A higher Ath-cat was significantly associated with higher Vas-S at any time. Spearman signed-rank test indicated that Vas-S at 1 min was most strongly correlated with Ath-cat (ρ = 0.43, p = 0.001). Receiver operating curve analysis indicated that a Vas-S of 0 at 1 min was significantly associated with an unruptured plaque (area under curve [AUC] 0.72, p = 0.006), while a Vas-S of 2 at 1 min was significantly associated with a healed plaque (AUC 0.72, p = 0.001). Conclusion: Vas-S values of 0 and 2 at 1 min indicated unruptured and healed plaques respectively. Thus, a Vas-S of 1 at 1 min is an indicator of a ruptured plaque. The intra-plaque vessel size on CEUS was significantly associated with carotid plaque histology, and may predict the process of plaque rupture and restoration.

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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

Cited by 9 publications

References 22 publications

Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings

Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings

Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis

Intra-Plaque Vessels on Contrast-Enhanced Ultrasound Sonography Predict Carotid Plaque Histology

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