Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA,
Transl Stroke Res. 2012 Mar;3(1):16-21. doi: 10.1007/s12975-011-0113-1. Epub 2011 Nov 15.
The ischemic penumbra is the target of acute stroke therapy. It can be approximated on diffusion/perfusion MRI as the ischemic region with abnormal perfusion and normal diffusion imaging. Using arterial spin labeling perfusion MRI and diffusion MRI, our group has studied the evolution of the diffusion/perfusion mismatch in rat stroke models. Additionally, we have evaluated the effects of high-flow oxygen on the natural history of penumbral evolution, demonstrating that high-flow oxygen "freezes" the evolution of the mismatch and allows for later beneficial use of intravenous tissue plasminogen activator (tPA). Two neuroprotective drugs, Granulocyte colony stimulating factor and a PSD95 inhibitor both impeded the evolution of the mismatch into infarcted tissue in vivo and by histological analysis. Employing a novel technique of clot imaging, our group was able to demonstrate that the combination of tPA plus Annexin-2 was superior to tPA alone in dissolving an embolus and also in reducing the extent of hypoperfused brain tissue of perfusion imaging. The use of these advanced MRI techniques in animal experiments will help to advance clinical imaging of the ischemic penumbra and hopefully contribute to the extension of the therapeutic time window in stroke patients.
缺血半暗带是急性卒中治疗的靶点。它可以通过磁共振弥散/灌注成像来近似模拟，即表现为灌注异常而弥散成像正常的缺血区域。我们的团队使用动脉自旋标记灌注磁共振成像和弥散磁共振成像研究了大鼠卒中模型中弥散/灌注不匹配的演变。此外，我们还评估了高流量氧对缺血半暗带演变自然史的影响，结果表明高流量氧“冻结”了不匹配的演变，从而允许更晚时间使用静脉注射组织型纤溶酶原激活剂（tPA）。两种神经保护药物，粒细胞集落刺激因子和 PSD95 抑制剂，都能阻止不匹配向梗死组织的体内演变，并通过组织学分析得到证实。我们的团队采用一种新的血栓成像技术，证明 tPA 联合 Annexin-2 比单独使用 tPA 更能溶解栓子，还能减少灌注成像中低灌注脑组织的范围。在动物实验中使用这些先进的 MRI 技术将有助于推进缺血半暗带的临床成像，并有望延长卒中患者的治疗时间窗。
