CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP)

描述（由申请人提供）：中风是美国残疾的头号原因。为了减轻中风造成的残疾负担，需要更好的中风治疗，使更多的中风患者能够获得。血管内治疗正越来越多地被使用，并且可能满足这一需求，因为它们具有较高的再通率。然而，尚不清楚哪些患者在临床上受益。 先前的研究表明，具有小体积的不可逆缺血性损伤（梗死核心）和大体积的可逆缺血性损伤（半暗带）的中风患者最有可能从血流恢复中受益。MRI显示了识别缺血核心和半暗带的前景，但在美国急诊室中的可用性非常有限。计算机断层扫描灌注（CTP）成像是一种潜在的解决方案，因为它是广泛可用的，可以很容易地添加到非造影剂头部CT，已经常规获得评估中风患者在急诊室。然而，用于处理CTP图像的方法和用于解释图像的标准仍然不成熟。因此，基于CTP图像的患者选择尚未准备好在临床试验或临床实践中实施。 CTP预测缺血性卒中再通反应项目（CRISP）的总体目标是开发一种实用工具，以识别可能从血管内治疗中获益的急性卒中患者。 该项目有两个主要部分。在第一部分（第1年），我们建议开发一个全自动系统（RAPID），用于处理CT灌注（CTP）图像，该图像将生成缺血核心和半暗带的大脑地图。我们还将根据这些CTP图定义标准，预测患者是否可能从血流恢复中受益。这些标准将基于在圣卢克医院接受治疗的95例患者的回顾性队列数据。在第二部分（第2-5年），我们的目标是证明急诊医生在全自动CTP分析程序（RAPID）的帮助下，可以准确预测接受血运重建的卒中患者对再通的反应。为了实现这一目标，我们将对100例在血管内治疗前接受CTP扫描的连续卒中患者进行前瞻性队列研究。本研究将在两个研究中心（斯坦福大学和圣卢克医院）进行。患者将在6小时内进行早期随访扫描以评估再灌注，并在第5天进行晚期随访扫描以确定最终梗死。 这项研究的成功执行将为医生提供一种简单、自动化的方法来选择可能从血流恢复中受益的患者。这种方法，由于易于获得CT技术，将是非常有价值的患者选择在多中心临床急性中风试验，并最终在常规临床实践。 公共卫生相关性：CTP预测缺血性卒中再通反应项目（CRISP）的关键目标是获得足够的初步数据，以优化设计确定性研究，评估旨在恢复血流的新卒中治疗的风险和获益。我们相信CRISP将阐明特定的CT灌注结果可以识别可能从恢复脑血流中受益的患者。这些发现最终将为目前不符合治疗条件的大量中风患者提供有效的治疗方法，并大大减少中风相关的残疾。

DESCRIPTION (provided by applicant): Stroke is the number one cause of disability in the United States. In order to reduce the burden of disability caused by stroke there is a need for better stroke treatments that are available to more stroke victims. Endovascular therapies are increasingly being used and may fill this need as they have high rates of recanalization. It is, however, not known which patients benefit clinically. Previous studies suggest that stroke patients with a small volume of irreversible ischemic injury (infarct core) and a large volume of reversible ischemic injury (penumbra) are most likely to benefit from restoration of blood flow. MRI shows promise for identification of the ischemic core and penumbra but it has very limited availability in US emergency rooms. Computed Tomography Perfusion (CTP) imaging is a potential solution as it is widely available and can easily be added to a non-contrast head CT, already routinely obtained to evaluate stroke patients in the emergency room. However, methods for processing of CTP images and criteria for interpretation of the images are still immature. Therefore, patient selection based on CTP images is not ready for implementation in clinical trials or clinical practice. The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to develop a practical tool to identify acute stroke patients who are likely to benefit from endovascular therapy. The project has two main parts. During the first part (year 1), we propose to develop a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will generate brain maps of the ischemic core and penumbra. We will also define criteria, based on these CTP maps, which predict if a patient is likely to benefit from restoration of blood flow. These criteria will be based on data from a retrospective cohort of 95 patients treated at St Luke's hospital. During the second part (years 2-5), we aim to demonstrate that physicians in the emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can accurately predict response to recanalization in stroke patients undergoing revascularization. To achieve this aim we will conduct a prospective cohort study of 100 consecutive stroke patients who will undergo a CTP scan prior to endovascular therapy. The study will be conducted at two sites (Stanford University and St Luke's Hospital). Patients will have an early follow-up scan within 6 hours to assess reperfusion and a late follow-up scan at day 5 to determine the final infarct. The successful execution of this research will provide physicians with an easy, automated method to select patients who are likely to benefit from restoration of blood flow. Such a method, thanks to easy accessibility to CT technology, would be of great value for patient selection in multi-center clinical acute stroke trials and, eventually, in routine clinical practice. PUBLIC HEALTH RELEVANCE: The key objective of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to obtain sufficient preliminary data to optimally design a definitive study to assess the risks and benefits of new stroke treatments aimed at restoration of blood flow. We believe that CRISP will clarify that specific CT perfusion findings can identify patients who are likely to benefit from restoration of blood flow to the brain. These findings will eventually lead to effective therapies for a large population of stroke patients who are currently ineligible for treatment and substantially reduce stroke-related disability.