Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza

描述（由申请人提供）：低温治疗急性卒中合并溶栓成像评估（HASTIER）是一项重点辅助成像研究，用于血管内冷却治疗卒中2 （ICTuS 2）试验，这是一项正在进行的nih资助的项目，旨在研究低温联合溶栓的安全性和有效性。HASTIER的目的是解决既定的临床前问题，即低温损害静脉（IV）组织型纤溶酶原激活剂（tPA）标准溶栓治疗急性缺血性脑卒中患者的再通和再灌注。我们的假设是，低温并不影响溶栓后的再通（动脉打开）或再灌注（恢复下游血流）。这项前瞻性、辅助研究对120例ICTuS 2患者进行了2年以上的大脑中动脉卒中，使用了一种创新的多模态CT/MRI成像方法来无缝评估这些不同的血运重建方面。再通（Specific Aim 1中从基线到36小时的CTA/MRA）和再灌注（从基线到36小时的CT/MR灌注和再灌注的成像相关因素，如特异性Aim 2中出血和梗死生长）的相对影响在本研究中提出的情况下可能无法预测或解释。低温和溶栓均可改善脑卒中预后，但对低温期间溶栓受损的担忧可能会阻碍进一步的转化。HASTIER使用经验丰富的核心实验室和专业知识，从里程碑式卒中成像试验，以测试低温溶栓对建立血运重建的基准。具体目标1和2中的HASTIER结果将提供不同的，但补充的数据，对未来发展联合低温和静脉tPA溶栓至关重要。无论ICTuS 2结果如何，再通和再灌注的HASTIER成像结果可能非常有价值，可以确定驱动神经系统预后的机制，并推进除低温溶栓之外的其他血运重建研究。这项针对具体科学目标的短期重点研究的专业知识和基础设施将增加NIH对ICTuS 2的投资，扩大对人类急性中风和低温影响的血供重建的了解。

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. PUBLIC HEALTH RELEVANCE: Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revascularization (HASTIER) is an 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. Understanding the beneficial effects and potential concerns of this combination treatment to open arteries and restore blood flow in stroke, the leading cause of adult disability in the US, is a key priority for improving pulic health. Imaging evaluation of revascularization will advance development of this combined approach and prominently impact other stroke treatments.