Toward the detection of intraplaque hemorrhage in carotid artery lesions using photoacoustic imaging

Abstract Background Intimal calcification typically develops in advanced atherosclerosis, and microcalcification may promote plaque progression and instability. Conversely, intraplaque hemorrhage and erythrocyte extravasation may stimulate osteoblastic differentiation and intralesional calcium phosphate deposition. The presence of erythrocytes and their main cellular components (membranes, hemoglobin, and iron) and colocalization with calcification has never been systematically studied. Methods and Results We examined three types of diseased vascular tissue specimens, namely, degenerative aortic valve stenosis (n = 46), atherosclerotic carotid artery plaques (n = 9), and abdominal aortic aneurysms (n = 14). Biomaterial was obtained from symptomatic patients undergoing elective aortic valve replacement, carotid artery endatherectomy, or aortic aneurysm repair, respectively. Serial sections were stained using Masson–Goldner trichrome, Alizarin red S, and Perl's iron stain to visualize erythrocytes, extracelluar matrix and osteoid, calcium phosphate deposition, or the presence of iron and hemosiderin, respectively. Immunohistochemistry was employed to detect erythrocyte membranes (CD235a), hemoglobin or the hemoglobin scavenger receptor (CD163), endothelial cells (CD31), myofibroblasts (SMA), mesenchymal cells (osteopontin), or osteoblasts (periostin). Our analyses revealed a varying degree of intraplaque hemorrhage and that the majority of extravasated erythrocytes were lysed. Osteoid and calcifications also were frequently present, and erythrocyte membranes were significantly more prevalent in areas with calcification. Areas with extravasated erythrocytes frequently contained CD163-positive cells, although calcification also occurred in areas without CD163 immunosignals. Conclusion Our findings underline the presence of extravasated erythrocytes and their membranes in different types of vascular lesions, and their association with areas of calcification suggests an active role of erythrocytes in vascular disease processes.

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Associations between carotid intraplaque hemorrhage and new ipsilateral ischemic lesions after carotid artery stenting: a quantitative study with conventional multi-contrast MRI

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-018-01521-5 ◽

2019 ◽

Vol 35 (6) ◽

pp. 1047-1054 ◽

Cited By ~ 3

Author(s):

Aihua Ji ◽

Peng Lv ◽

Yuanyuan Dai ◽

Xueqin Bai ◽

Xiao Tang ◽

...

Keyword(s):

Carotid Artery ◽

Quantitative Study ◽

Carotid Artery Stenting ◽

Intraplaque Hemorrhage

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E-177 Cardiovascular risk factors are associated with carotid artery intraplaque hemorrhage

10.1136/neurintsurg-2020-snis.209 ◽

2020 ◽

Author(s):

A Larson ◽

J Benson ◽

G Lanzino ◽

W Brinjikji

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Carotid Artery ◽

Cardiovascular Risk Factors ◽

Intraplaque Hemorrhage

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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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