Late-Phase Contrast-Enhanced Ultrasound Reflects Biological Features of Instability in Human Carotid Atherosclerosis
Late-Phase Contrast-Enhanced Ultrasound Reflects Biological Features of Instability in Human Carotid Atherosclerosis
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DOI：
10.1161/strokeaha.111.631200
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发表时间：
2011-12-01
期刊：
影响因子：
8.3
通讯作者：
Davies, Alun H.
中科院分区：
文献类型：
--
作者：
Shalhoub, Joseph;Monaco, Claudia;Davies, Alun H.
背景和目的：发展用于动脉粥样硬化危险分层的平移功能成像模式以预测卒中。我们的研究小组已经开发了晚期超声造影（LP-CEUS）来量化颈动脉粥样硬化内的微泡造影剂滞留，并显示它可以将无症状斑块与近期脑血管事件的斑块分开。我们假设，微泡保留在斑块炎症的区域，目的是检查是否LP-CEUS信号反映斑块biology. Methods受试者等待颈动脉内膜切除术（n = 31）进行轴向LP-CEUS和病变内膜段对称划分的长轴。对一半标本进行CD 68（巨噬细胞）和CD 31（血管生成）的定量免疫组织化学分析。半个标本进行动脉粥样硬化细胞培养，24小时收集上清液进行34种分析物的多分析物分析。结果：标准化斑块晚期强度>= 0与< 0的受试者的免疫阳性面积百分比显著较高（CD 68平均值11.8对6.68，P = 0.004; CD 31平均值9.45对4.82，P = 0.025）。当LP-CEUS>= 0时，多分析物分析显示IL-6、基质金属蛋白酶-1和基质金属蛋白酶-3显著升高。结论LP-CEUS反映了炎症和血管生成的生物学特征，是斑块破裂的关键特征。进一步研究LP-CEUS作为颈动脉粥样硬化危险分层的组织特异性炎症标志物是必要的。（中风。2011; 42：3634-3636）。
Background and Purpose-Development of translational functional imaging modalities for atherosclerosis risk stratification is sought for stroke prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP-CEUS) to quantify microbubble contrast retention within carotid atherosclerosis and shown it to separate asymptomatic plaques from those responsible for recent cerebrovascular events. We hypothesized that microbubbles are retained in areas of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque biology.Methods-Subjects awaiting carotid endarterectomy (n = 31) underwent axial LP-CEUS and diseased intimal segments were symmetrically divided in the long axis. Half-specimens underwent quantitative immunohistochemical analysis for CD68 (macrophages) and CD31 (angiogenesis). Half-specimens were processed for atheroma cell culture and supernatant collected at 24 hours for multianalyte profiling for 34 analytes.Results-Percentage area immunopositivity was significantly higher in subjects in which normalized plaque late-phase intensity was >= 0 versus < 0 (CD68 mean 11.8 versus 6.68, P = 0.004; CD31 mean 9.45 versus 4.82, P = 0.025). Interleukin-6, matrix metalloproteinase-1, and matrix metalloproteinase-3 were significantly higher by multianalyte profiling when LP-CEUS was >= 0.Conclusions-LP-CEUS reflects biological features of inflammation and angiogenesis, key features predisposing to plaque rupture. Further investigation of LP-CEUS as a tissue-specific marker of inflammation for risk stratification of carotid atherosclerosis is warranted. (Stroke. 2011; 42: 3634-3636.)