Visualization of clot lysis in a rat embolic stroke model: application to comparative lytic efficacy.
Visualization of clot lysis in a rat embolic stroke model: application to comparative lytic efficacy.
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DOI：
10.1161/strokeaha.110.602102
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发表时间：
2011-04
期刊：
影响因子：
8.3
通讯作者：
Fisher M
中科院分区：
文献类型：
--
作者：
Walvick RP;Bråtane BT;Henninger N;Sicard KM;Bouley J;Yu Z;Lo E;Wang X;Fisher M
本研究的目的是建立一种新的MRI方法来成像大鼠栓塞性卒中模型中的血栓溶解，并比较重组Annexin-2(RA2)和组织纤溶酶原激活剂(TPA)对血栓溶解的影响。实验1：使用浓度从5μ到50μ的多种磁共振造影剂，在250μ的L血液中进行血栓显示的体外优化。实验2：利用上一次实验中开发的血栓在体内表征血栓溶解的时间过程。分别于治疗前和治疗期间进行弥散、灌注、血管成像和T1加权磁共振血栓成像检查，治疗前和治疗期间分别给予Vehicle、tPA或Ra2+tPA。取脑进行体外凝块定位。使用25μL磁控仪创建的凝块最稳定，对比度噪声比最高。在赋形剂组，T1加权成像评估的血栓长度与组织学相关(r=0.93)。治疗开始后15分钟，Ra2+tPA组的血栓长度和CBF来源的缺血损伤体积明显小于载体，而tPA组直到治疗开始后30分钟才观察到明显小于载体。在治疗开始后60分钟和90分钟，Ra2+tPA组的血栓长度显著短于tPA组，在治疗开始后90分钟，Ra2+tPA组的CBF差值显著小于tPA组。我们介绍了一种新的基于MRI的血栓成像方法，用于体内监测血栓溶解。RA2可提高tPA的裂解效率。
The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model, and to compare tissue plasminogen activator (tPA) based clot lysis with and without recombinant Annexin-2 (rA2). Experiment 1: In vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50μL in 250μL blood. Experiment 2: In vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted prior to and during treatment with vehicle (n=6), tPA (n=8) or rA2+tPA (n=8) at multiple time-points. Brains were removed for ex vivo clot localization. Clots created with 25μL Magnevist© were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r=0.93). Clot length and CBF-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes post-treatment initiation in the rA2+tPA group, while in the tPA group no significant reduction from vehicle was observed until 30 minutes post-treatment initiation. The rA2+tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes post-treatment initiation, and significantly smaller CBF deficit than the tPA group at 90 minutes post-treatment initiation. We introduce a novel MRI based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2.