Imaging of the Vulnerable Carotid Plaque: Biological Targeting of Inflammation in Atherosclerosis using Iron Oxide Particles and MRI
Imaging of the Vulnerable Carotid Plaque: Biological Targeting of Inflammation in Atherosclerosis using Iron Oxide Particles and MRI
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DOI：
10.1016/j.ejvs.2014.01.017
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发表时间：
2014-05-01
影响因子：
5.7
通讯作者：
Gibbs, R. G. J.
中科院分区：
文献类型：
--
作者：
Chan, J. M. S.;Monaco, C.;Gibbs, R. G. J.
目的：识别高危无症状颈动脉斑块患者仍然是预防卒中的一个难以捉摸但必不可少的步骤。炎症是斑块不稳定和动脉粥样硬化病变倾向导致临床后遗症的关键过程。目前没有临床成像技术可用于评估与斑块相关的炎症程度。本研究旨在使用抗体结合的超顺磁性氧化铁（SPIO）颗粒作为MRI探针来可视化和表征动脉粥样硬化，以评估人类动脉粥样硬化斑块中的炎症。从20名连续的患者中收集动脉粥样硬化斑块（n = 10例来自有症状的患者，n = 10例无症状患者）接受颈动脉内膜切除术（CEA）治疗颅外高度颈内动脉（伊卡）狭窄（>70%管腔狭窄）。应用抗VCAM-1抗体和抗E-选择素抗体标记的SPIO，通过离体磁共振成像（MRI）对人动脉粥样硬化斑块上的炎症标志物进行检测和表征，并进行确证性免疫组织化学染色。症状性斑块与无症状性斑块可通过炎症程度区分，MR对比效果与斑块炎症程度显著相关（r = 0.64，p <0.001）。无症状斑块人群在炎症方面表现出异质性。双靶点SPIO诱导的MR信号不仅与内皮激活密切相关，（即VCAM-1和E-选择素的内皮表达），但也反映了斑块病变内的巨噬细胞负荷，为动脉粥样硬化中炎症活动的定量MRI提供了潜在的成像工具。这些功能性分子MRI探针构成了一种新的成像工具，在分子水平上离体表征动脉粥样硬化。进一步的发展和转化到临床竞技场将有助于更准确的危险分层在颈动脉疾病的未来。(C)2014年欧洲血管外科学会。由爱思唯尔有限公司出版。保留所有权利。
Objectives: Identification of those patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and the propensity of atherosclerotic lesions to cause clinical sequelae. There is currently no clinical imaging technique available to assess the degree of inflammation associated with plaques. This study aims at visualizing and characterizing atherosclerosis using antibody-conjugated superparamagnetic iron oxide (SPIO) particles as an MRI probe to assess inflammation in human atherosclerotic plaques.Methods: Atherosclerotic plaque's were collected from 20 consecutive patients (n = 10 from symptomatic patients, n = 10 from asymptomatic patients) undergoing carotid endarterectomy (CEA) for extracranial high-grade internal carotid artery (ICA) stenosis (>70% luminal narrowing). Inflammatory markers on human atherosclerotic plaques were detected and characterized by ex vivo magnetic resonance imaging (MRI) using anti-VCAM-1 antibody and anti-E-selectin antibody-conjugated SPIO with confirmatory innmunohistochemistry.Results: Inflammation associated with human ex vivo atherosclerotic plaques could be imaged using dual antibody-conjugated SPIO by MRI. Symptomatic plaques could be distinguished from asymptomatic ones by the degree of inflammation, and the MR contrast effect was significantly correlated with the degree of plaque inflammation (r = .64, p < .001). The asymptomatic plaque population exhibited heterogeneity in terms of inflammation. The dual-targeted SPIO-induced MR signal not only tracked closely with endothelial activation (i.e. endothelial expression of VCAM-1 and E-selectin), but also reflected the macrophage burden within plaque lesions, offering a potential imaging tool for quantitative MRI of inflammatory activity in atherosclerosis.Conclusions: These functional molecular MRI probes constitute a novel imaging tool for ex vivo characterization of atherosclerosis at a molecular level. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid artery disease in the future. (C) 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.