In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent

In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent
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DOI:
10.1161/01.cir.0000127034.50006.c0
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发表时间:
2004-04-27
期刊:
影响因子:
37.8
通讯作者:
Johnstone, MT
Johnstone, MT
中科院分区:
医学1区
文献类型:
--
作者:
Botnar, RM;Perez, AS;Johnstone, MT

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背景-斑块破裂及随后的血栓形成被认为是大多数急性冠状动脉综合征和中风的潜在病理生理学。因此,直接血栓可视化可能有利于诊断和治疗指导。我们试图在斑块破裂和血栓形成的实验动物模型中,使用 MRI 和新型纤维蛋白结合钆标记肽 EP-1873 来测试急性和亚急性血栓形成直接成像的可行性。 方法和结果 - 15 只雄性新西兰白兔(体重约 3.5 kg)在内皮主动脉损伤后通过喂食高胆固醇饮食而导致动脉粥样硬化。然后使用拉塞尔蝰蛇毒液 (RVV) 和组胺诱导斑块破裂。随后,在 RVV 前、RVV 后和 EP-1873 后进行肾下主动脉 MRI。对 MRI 显示含有血栓的区域进行组织学检查。 9 只兔子 (60%) 出现斑块破裂和血栓,其中 25 个血栓在注射 EP-1873 后在 MRI 上可见为“热点”。组织学相关性证实了所有 25 个血栓(100%),在主动脉的其他区域没有看到血栓。在其余 6 只没有斑块破裂的兔子(对照)中,在 MR 图像或组织学上没有观察到血栓。结论 - 我们证明了在动脉粥样硬化和急性/亚急性血栓形成的动物模型中使用新型纤维蛋白结合 MRI 造影剂进行体内“分子”MRI 检测急性和亚急性血栓形成的可行性。潜在的临床应用包括急性冠脉综合征和中风的血栓检测。
Background-Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis.Methods and Results-Fifteen male New Zealand White rabbits (weight, approximate to3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell's viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as "hot spots" after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology.Conclusions-We demonstrate the feasibility of in vivo "molecular" MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.