Therapeutic Window for Acute Stroke Therapy (P50)

加州大学圣地亚哥分校（UCSD）卒中中心的急性卒中转化研究专业项目（SPOTRIAS）目前利用4 Cores的资源进行3项相关的临床试验，旨在满足SPOTRIAS增加溶栓治疗患者数量的总体目标。在5年的续期期间，我们建议通过6项新的临床试验来推进这一议程：(1)血管内降温治疗脑卒中-咖啡因（ICTuS-C），该研究建立在正在进行的ICTuS-L的低温研究轨道上，从论证血管内降温联合溶栓的可行性和安全性，发展到与Houston SPOTRIAS合作评估血管内诱导低温和咖啡因治疗3小时内急性缺血性脑卒中患者的安全性、可行性和早期疗效；(2)经颅超声在急性卒中中的应用，在正在进行的超声成像研究的基础上，研究超声联合rt-PA和/或超声造影剂微泡在图像引导下经颅溶栓中的诊断潜力；(3)卒中团队远程评估使用数字观测相机-优化医生在卒中中的使用（卒中DOC OPUS），该研究建立在正在进行的视听远程医疗研究轨道上，通过确定我们开创性的中心-辐条模式是否可以在其他社区复制，以及下一代，优化后的技术将在互联网技术接入有限的地区增加STRokE DOC系统的使用；(4)卒中前向血流反搏（Counterpulsation to Upgrade Forward Flow in Stroke，简称：CUFFS），对急性缺血性卒中患者在症状出现后0-48小时内进行无创体外反搏（ECP）的耐受性、可行性和安全性进行新的试点评估；(5) tPA联合经颅低能量激光治疗急性脑卒中恢复的安全性（StELLAR）， NeuroThera激光系统与rt-PA的首次联合研究；(6)预测和治疗脑出血生长的斑点征象（STOP IT），一项急性脑出血的研究，目的是确定CT血管造影预测血肿生长的敏感性和特异性，检验CT血管造影指导止血治疗的可行性。总的来说，我们关于续期的SPOTRIAS提案旨在进一步整合和综合UCSD卒中中心在进行转化研究方面的巨大优势，最终使我们的地理实践范围内和世界范围内的卒中患者受益，因为我们在2小时内治疗了更多的患者，并探索了安全有效地治疗其他不符合3小时rt-PA窗口的患者的新方法。包括通过改进患者选择和分层以及附加治疗与潜在的增强溶栓。

The Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) at the University of California San Diego (UCSD) Stroke Center currently applies the resources of 4 Cores to conduct 3 interrelated clinical trials designed to meet the overarching SPOTRIAS goal of increasing the number of thrombolytic-treated patients. Over the course of the 5-year renewal period, we propose to move this agenda forward with 6 new clinical trials: (1) Intravascular Cooling in the Treatment of Stroke-Caffeinol (ICTuS-C), which builds on the ongoing hypothermia research track of ICTuS-L, evolving from demonstration of the feasibility and safety of intravascular cooling in combination with thrombolysis to collaborative assessment, with Houston SPOTRIAS, of the safety, feasibility, and early efficacy of the endovascular induction of hypothermia and caffeinol in acute ischemic stroke patients presenting within the 3-hour window; (2) Transcranial Ultrasound in Acute Stroke, which builds on the ongoing ultrasound imaging research track to study the potential of diagnostic ultrasound in combination with rt-PA and/or ultrasound contrast agent microbubbles on image-guided transcranial thrombolysis; (3) Stroke Team Remote Evaluation Using a Digital Observation Camera - Optimizing Practitioners' Use in Stroke (STRokE DOC OPUS), which builds on the ongoing audio-visual telemedicine research track to explore the utility of remote telemedicine consultations for acute stroke by determining whether our pioneering hub-and-spoke model can be replicated in other communities and whether next-generation, optimized technology will increase use of the STRokE DOC system in areas with limited access to Internet-based technology; (4) Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS), a new pilot assessment of the tolerability, feasibility, and safety of noninvasive external counterpulsation (ECP) in acute ischemic stroke patients within 0-48 hours of symptom onset; (5) Safety of tPA plus Transcranial Emission of Low-Energy Lasers for Acute Stroke Recovery (StELLAR), the first combination study of the NeuroThera Laser System with rt-PA; and (6) Spot Sign for Predicting and Treating ICH Growth (STOP IT), a study of acute intracerebral hemorrhages to determine the sensitivity and specificity of CT angiography for the prediction of hematoma growth and to test the feasibility of CT angiography for the guidance of hemostatic therapy. Altogether, our SPOTRIAS proposal for the renewal period aims to integrate and synthesize further the considerable strengths of the UCSD Stroke Center in conducting translational research that ultimately benefits stroke victims within our geographical practice range and worldwide as we treat more patients under 2 hours and explore new ways to safely and effectively treat other, guideline-ineligible patients outside the 3-hour rt-PA window, including through improved patient selection and stratification and additional treatments combined with and potentially augmenting thrombolysis.