Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza

描述（由申请人提供）：低温治疗急性卒中伴溶栓血管重建成像评价（HASTIER）是一项针对血管内冷却治疗卒中2（ICTuS 2）试验的辅助成像研究，该试验是一项正在进行的NIH资助的关于低温联合溶栓的安全性和有效性的项目。HASTIER的目的是解决已确立的临床前问题，即低温会损害静脉（IV）组织纤溶酶原激活剂（tPA）标准溶栓治疗对人类急性缺血性卒中的再通和再灌注。我们的假设是，低温不会损害再通（动脉开放）或再灌注（恢复下游流量）与溶栓。这项对120例ICTuS 2级大脑中动脉卒中受试者进行的2年以上前瞻性辅助研究使用了创新的成像方法，即多模式CT/MRI，以无缝评价血运重建的这些不同方面。如果没有本研究中提出的成像，可能无法预测或解释再通（特定目标1中从基线到36小时的CTA/MRA）和再灌注（特定目标2中从基线到36小时的CT/MR灌注和再灌注的成像相关性，如出血和梗死生长）的相对影响。低温和溶栓各自提供了改善卒中结局的潜在益处，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具有里程碑意义的卒中成像试验的专业知识，根据既定的血运重建基准测试低温溶栓。特定目标1和2中的HASTIER结局将为未来联合低温和IV tPA溶栓的开发提供独特但互补的数据。无论ICTuS 2结果如何，HASTIER再通和再灌注成像结果都可能非常有价值，可以识别驱动神经系统结局的机制，并推动其他血运重建研究超越低温溶栓。这项针对具体科学目标的短期集中研究的专业知识和基础设施将加强NIH对ICTuS 2的投资，扩大对人类急性中风血运重建和低温影响的了解。 公共卫生相关性：低温治疗急性卒中伴溶栓血管重建成像评价（HASTIER）是一项辅助成像研究，用于血管内冷却治疗卒中2（ICTuS 2）试验，该试验是一项正在进行的NIH资助的关于低温联合溶栓的安全性和有效性的项目。了解这种联合治疗的有益效果和潜在问题，以打开动脉并恢复中风的血流，这是美国成人残疾的主要原因，是改善公众健康的关键优先事项。血运重建的影像学评价将促进这种联合方法的发展，并显著影响其他卒中治疗。

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.