Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza

描述(申请人提供)：急性卒中的低温与溶栓成像评估(HASTER)是对血管内冷却治疗中风2(ICTUS 2)试验的重点辅助成像研究，该试验是由美国国立卫生研究院资助的一个正在进行的关于低温与溶栓相结合的安全性和有效性的项目。HASTER的目标是用静脉(IV)组织纤溶酶原激活剂(TPA)对人类急性缺血性中风进行标准的溶栓治疗，以解决公认的临床前担忧，即低温损害再通和再灌注。我们的假设是，低温不会损害溶栓治疗的再通(动脉开放)或再灌注(恢复下游血流)。这项针对超过2年的大脑中动脉中风患者的前瞻性辅助研究使用了一种创新的成像方法，结合多模式CT/MRI来无缝评估血管重建的这些不同方面。再通(CTA/MRA从基线到特定靶点36小时)和再通(CT/MR灌注从基线到36小时，以及再灌注的成像相关性，如出血和梗死在特定靶点2的增长)的相对影响可能无法预测或破译本研究中提出的成像。低温和溶栓治疗都对改善卒中预后有潜在的益处，然而，对低温期间溶栓功能受损的担忧可能会阻碍进一步的翻译。Hastier使用经验丰富的核心实验室和里程碑式的中风成像试验中的专业知识，根据既定的血管重建基准测试低温溶栓。在特定目标1和2中更快的结果将提供不同的、但补充的数据，这对于未来联合低温和静脉tPA溶栓治疗的发展是必不可少的。无论Ictus 2的结果如何，更快的血管再通和再灌注成像结果可能是非常有价值的，确定驱动神经结果的机制，并推动超越低温溶栓的其他血管再通研究。这项针对具体科学目标的简短、重点研究的专业知识和基础设施将增加NIH对Ictus 2的投资，扩大关于人类急性中风的血管重建和低温影响的知识。

DESCRIPTION (provided by applicant): Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revascularization (HASTIER) is a focused ancillary imaging study to the Intravascular Cooling in the Treatment of Stroke 2 (ICTuS 2) trial, an ongoing, NIH-funded project on the safety and efficacy of hypothermia combined with thrombolysis. The objective of HASTIER is to address established preclinical concerns that hypothermia impairs recanalization and reperfusion with standard thrombolytic treatment with intravenous (IV) tissue plasminogen activator (tPA) for acute ischemic stroke in humans. Our hypothesis is that hypothermia does not impair either recanalization (opening of the artery) or reperfusion (restoration of downstream flow) with thrombolysis. This prospective, ancillary study of 120 ICTuS 2 subjects with middle cerebral artery stroke over 2 years uses an innovative imaging approach with multimodal CT/MRI to seamlessly evaluate these distinct aspects of revascularization. The relative impact of recanalization (CTA/MRA from baseline to 36 hours in Specific Aim 1) and reperfusion (CT/MR perfusion from baseline to 36 hours and imaging correlates of reperfusion such as hemorrhage and infarct growth in Specific Aim 2) may be impossible to predict or decipher without imaging as proposed in this study. Hypothermia and thrombolysis each offer potential benefit to improve stroke outcome, yet the concern regarding impaired thrombolysis during hypothermia may impede further translation. HASTIER uses an experienced core lab and expertise from landmark stroke imaging trials to test hypothermic thrombolysis against established revascularization benchmarks. HASTIER outcomes in Specific Aims 1 and 2 will provide distinct, yet complementary data essential to future development of combined hypothermia and thrombolysis with IV tPA. HASTIER imaging outcomes for recanalization and reperfusion may be extremely valuable irrespective of ICTuS 2 results, identifying the mechanisms that drive neurological outcomes and advancing other studies of revascularization beyond hypothermic thrombolysis. The expertise and infrastructure for this short, focused study of concrete scientific objectives will enhance the NIH investment in ICTuS 2, expanding knowledge on revascularization for acute stroke in humans and the impact of hypothermia.