Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.
Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green.
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动脉粥样硬化的靶向近红外荧光成像：吲哚菁绿色的临床和冠状动脉内评价。
DOI：
10.1016/j.jcmg.2016.01.034
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发表时间：
2016-09
影响因子：
14
通讯作者：
Jaffer, Farouc A.
中科院分区：
文献类型：
--
作者：
Verjans, Johan W.;Osborn, Eric A.;Ughi, Giovanni J.;Press, Marcella A. Calfon;Hamidi, Ehsan;Antoniadis, Antonios P.;Papafaklis, Michail I.;Conrad, Mark F.;Libby, Peter;Stone, Peter H.;Cambria, Richard P.;Tearney, Guillermo J.;Jaffer, Farouc A.
关键词：
使用血管内 NIRF 光学相干断层扫描 (OCT) 成像确定吲哚菁绿 (ICG) 增强近红外荧光 (NIRF) 成像是否可以阐明人颈动脉粥样硬化和活体猪冠状动脉粥样硬化斑块的高风险组织学斑块特征。需要新的可翻译成像方法来识别动脉粥样硬化的高风险生物学特征。 ICG 是 FDA 批准的 NIRF 显像剂，在实验上针对内皮通透性增强区域的斑块巨噬细胞和脂质，但尚不清楚 ICG 是否可以针对患者的动脉粥样硬化。 BRIGHT-CEA 试验 (NCT01873716) 招募了 8 名患者。 5 名患者在临床指示颈动脉内膜切除术前 99±25 分钟静脉注射 ICG。三名注射生理盐水的动脉内膜切除术患者作为对照。切除的斑块通过血管内 NIRF-OCT、反射成像、显微镜和组织病理学进行分析。接下来，在 ICG 静脉注射后，体内冠状动脉内 NIRF-OCT 和血管内超声 (IVUS) 对糖尿病、胆固醇喂养的猪的三个带有粥样斑块的冠状动脉进行成像。 ICG 耐受性良好；注射后 30 天未发生不良临床事件。包括血管内 NIRF-OCT 在内的多模态 NIRF 成像显示，ICG 在所有动脉内膜切除术标本中积累。注射盐水的对照患者的斑块表现出最小的 NIRF 信号。在猪实验中，冠状动脉内 NIRF-OCT 识别了体内所有 IVUS 识别斑块中的 ICG 摄取。在详细的显微镜评估中，ICG 定位于表现出内皮完整性受损的斑块区域，包括破坏的纤维帽，以及新血管形成区域内。在人类内皮异常斑块区域内，ICG 在空间上与斑块巨噬细胞和脂质区域相关，尤其是斑块内出血。这项研究表明，ICG 靶向表现出内皮异常的人类斑块，并为其在临床和实验性动脉粥样硬化中的靶向机制提供了新的见解。 ICG 的冠状动脉内 NIRF-OCT 可能提供一种新颖的、可临床转化的方法来对冠状动脉粥样硬化的病理生物学方面进行成像。人颈动脉斑块试验中的吲哚菁绿荧光摄取 [BRIGHT-CEA] NCT01873716 我们使用可翻译技术研究了吲哚菁绿 (ICG)（一种 FDA 批准的近红外荧光 (NIRF) 成像剂）靶向和照亮人颈动脉粥样硬化斑块和活体猪冠状动脉粥样硬化斑块和冠状动脉粥样硬化斑块的能力。 血管内 NIRF 光学相干断层扫描 (OCT)。对人类斑块的组织病理学评估表明，ICG 照亮了受损的斑块内皮屏障功能，并且在这些区域下方，定位于巨噬细胞、脂质和斑块内出血区域。冠状动脉内NIRF-OCT进一步检测猪冠状动脉粥样硬化斑块中的ICG。这些结果表明，临床可翻译系统和导管可以实现 ICG NIR 荧光成像，并且 ICG NIRF 信号表明晚期人类斑块中内皮完整性受损。
To determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is an FDA-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability, but it is unknown whether ICG can target atheroma in patients. Eight patients were enrolled in the BRIGHT-CEA trial (NCT01873716). Five patients were injected intravenously with ICG 99±25 minutes before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as controls. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound (IVUS) imaged three atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. ICG was well-tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all IVUS-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related localized to zones of plaque macrophages and lipid, and notably, intraplaque hemorrhage. This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities, and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically-translatable approach to image pathobiological aspects of coronary atherosclerosis. The Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque Trial [BRIGHT-CEA] NCT01873716 We investigated the ability of indocyanine green (ICG), an FDA-approved near-infrared fluorescence (NIRF) imaging agent, to target and illuminate human carotid atherosclerotic plaques and coronary atheroma of living swine, using translatable intravascular NIRF-optical coherence tomography (OCT). Histopathological assessment of human plaques revealed that ICG illuminated impaired plaque endothelial barrier function, and beneath these areas, localized in regions of macrophages, lipid, and intraplaque hemorrhage. Intracoronary NIRF-OCT further detected ICG in swine coronary atheroma. These results demonstrate that a clinically translatable system and catheter can achieve ICG NIR fluorescence imaging, and that the ICG NIRF signal indicates impaired endothelial integrity in advanced human plaques.
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影响因子：
24
作者：
Jaffer, Farouc A.;Calfon, Marcella A.;Rosenthal, Amir;Mallas, Georgios;Razansky, R. Nika;Mauskapf, Adam;Weissleder, Ralph;Libby, Peter;Ntziachristos, Vasilis
通讯作者：
Ntziachristos, Vasilis
影响因子：
14
作者：
Hara, Tetsuya;Bhayana, Brijesh;Thompson, Brian;Kessinger, Chase W.;Khatri, Ashok;McCarthy, Jason R.;Weissleder, Ralph;Lin, Charles P.;Tearney, Guillermo J.;Jaffer, Farouc A.
通讯作者：
Jaffer, Farouc A.
DOI：
10.1161/01.atv.4.3.283
发表时间：
1984-01-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
RAMIREZ, CA;COLTON, CK;LEES, RS
通讯作者：
LEES, RS
影响因子：
5.3
作者：
ADAMS, CWM;MORGAN, RS;BAYLISS, OB
通讯作者：
BAYLISS, OB
影响因子：
2.1
作者：
Ughi, Giovanni J.;Verjans, Johan;Fard, Ali M.;Wang, Hao;Osborn, Eric;Hara, Tetsuya;Mauskapf, Adam;Jaffer, Farouc A.;Tearney, Guillermo J.
通讯作者：
Tearney, Guillermo J.