Botnar René M, Perez Alexandra S, Witte Sonia, Wiethoff Andrea J, Laredo James, Hamilton James, Quist William, Parsons Edward C, Vaidya Anand, Kolodziej Andrew, Barrett John A, Graham Philip B, Weisskoff Robert M, Manning Warren J, Johnstone Michael T
Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, USA.
Circulation. 2004 Apr 27;109(16):2023-9. doi: 10.1161/01.CIR.0000127034.50006.C0. Epub 2004 Apr 5.
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.
Fifteen male New Zealand White rabbits (weight, approximately 3.5 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.
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.
斑块破裂伴随后续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机制。因此，直接血栓可视化可能对诊断和治疗指导都有益处。我们试图在斑块破裂和血栓形成的实验动物模型中，测试使用磁共振成像（MRI）结合一种新型的纤维蛋白结合钆标记肽EP - 1873对急性和亚急性血栓进行直接成像的可行性。
15只雄性新西兰白兔（体重约3.5千克）在主动脉内皮损伤后喂食高胆固醇饮食以形成动脉粥样硬化。然后使用罗素蝰蛇毒（RVV）和组胺诱导斑块破裂。随后，在注射RVV前、注射RVV后以及注射EP - 1873后对肾下腹主动脉进行MRI检查。对MRI提示含有血栓的区域进行组织学检查。9只兔子（60%）发生了斑块破裂和血栓形成，其中25个血栓在注射EP - 1873后在MRI上表现为“热点”，肉眼可见。组织学相关性证实了所有25个血栓（100%），而在主动脉的其他区域未发现血栓。其余6只未发生斑块破裂的兔子（对照组），在MR图像和组织学检查中均未观察到血栓。
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的可行性。潜在的临床应用包括急性冠状动脉综合征和中风中的血栓检测。
