Molecular MRI of intracranial thrombus in a rat ischemic stroke model.
Molecular MRI of intracranial thrombus in a rat ischemic stroke model.
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DOI：
10.1161/strokeaha.109.575662
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发表时间：
2010-06
期刊：
影响因子：
8.3
通讯作者：
Caravan P
中科院分区：
文献类型：
--
作者：
Uppal R;Ay I;Dai G;Kim YR;Sorensen AG;Caravan P
颅内血栓是大多数缺血性卒中的主要特征，血栓的位置和大小可能与溶栓治疗的结果和反应相关。EP-2104 R是一种纤维蛋白特异性分子MR剂，先前在动物模型和最近的临床试验中显示出增强颅外血栓。这项工作的目的是确定纤维蛋白特异性分子MR探针是否可以无创地表征颅内血栓。通过用老化血栓闭塞右侧颈内动脉在成年大鼠中诱导栓塞性中风。在使用造影剂EP-2104 R（10 µ mol/kg，n = 6）或Gd-DTPA（200 µ mol/kg，对照，n = 5）之前和之后，在4.7 T下进行弥散加权成像、飞行时间血管造影和高分辨率三维T1加权MRI。通过离体元素分析测定血栓、脑和血液中的Gd水平。在所有动物中，MR血管造影显示血流不足，弥散加权成像显示与缺血一致的高信号。EP-2104 R增强MRI使所有6只动物的所有闭塞性血栓（6/6）可视化，并使血管壁增强，与血液的噪音相比具有高对比度（EP-2104 R后10.7 vs.前0.54，p <0.0001）。注射Gd-DTPA的动物无闭塞性血栓或血管壁强化（0/5）。在EP 2104后血栓中的Gd浓度是血池中的18倍。EP-2104 R增强MRI成功识别大鼠栓塞性卒中模型中的颅内血栓。
Intracranial thrombus is a principal feature in most ischemic stroke, and thrombus location and size may correlate with outcome and response to thrombolytic therapy. EP-2104R, a fibrin-specific molecular MR agent, was previously shown to enhance extracranial thrombi in animal models and recently, in clinical trials. The purpose of this work was to determine if a fibrin-specific molecular MR probe could noninvasively characterize intracranial thrombi. Embolic stroke was induced in adult rats by occlusion of the right internal carotid artery with an aged thrombus. Diffusion weighted imaging, time of flight angiography, and high resolution three dimensional T1-weighted MRI were performed at 4.7T prior to and following contrast agents EP-2104R (10 µmol/kg, n=6) or Gd-DTPA (200 µmol/kg, control, n=5). Gd levels in thrombus, brain, and blood were determined by ex vivo elemental analysis. In all animals, MR angiography revealed a flow deficit and diffusion-weighted imaging showed a hyperintensity consistent with ischemia. EP-2104R-enhanced MRI resulted in visualization of all occlusive thrombi (6/6) as well as vessel wall enhancement in all 6 animals with high contrast to noise relative to blood (10.7 post EP-2104R vs. 0.54 pre, p<0.0001). Gd-DTPA injected animals showed no occlusive thrombus or vessel wall enhancement (0/5). The concentration of Gd in the thrombus post-EP2104 was 18 times that in the blood pool. EP-2104R enhanced MRI successfully identifies intracranial thrombus in a rat embolic stroke model.