Quantifying Collateral Perfusion in Cerebrovascular Disease

描述(由申请人提供)：动力侧支血流在急性缺血性中风中起着核心作用，良好侧支的存在与临床和放射结果的改善有关，无论是否进行治疗。尽管如此，目前评估侧支充分性的唯一方法是有创且昂贵的数字减影脑血管造影术(DSA)。如果侧支可以使用基于断层扫描的非侵入性成像方式进行可视化，那么这将是巨大的好处，这样早期的治疗决策就可以纳入这一关键信息。目的和方法这份新提交的报告的总体目标是使用动脉自旋标记(ASL)识别和量化通过侧支路径传递的脑血流量(CBF)，ASL是一种结合了灌注和血管成像方面的非对比MRI技术。数字减影血管造影(DSA)和氙气CT(XeCT)将分别作为抵押和CBF的黄金标准。我们的目标是显示DSA和定性和定量ASL方法之间的等价性，这些方法优化了对60名烟雾病患者的侧支可视化。这些患者是这项研究的理想人群，因为他们往往很年轻，在其他方面也很健康，但通常有广泛的侧支循环。我们还旨在证明，对慢血流敏感的ASL CBF测量，如标记后长延迟伪连续性ASL和速度选择性ASL，在侧支供应的区域与基于xeCT的CBF的相关性好于标准ASL和基于灌注加权成像(PWI)的CBF。最后，我们将把从Moyamoya患者那里获得的知识应用到更大、更相关的急性缺血性中风的临床人群中。我们将获得急性卒中后24小时和3-5天的60名患者的ASL、弥散加权成像(DWI)和团注PWI，以确定ASL侧支CBF成像的能力，利用受试者-操作员特征(ROC)方法识别有梗死风险的组织。意义我们相信，成功实现这些目标有望通过验证一种基于MRI的非侵入性方法来评估侧支的存在和它们提供的CBF的数量，从而显著改善急性中风的护理。我们的研究将有助于更好地了解重症脑血管病患者的ASL CBF测量，并极大地提高MRI对急性缺血性卒中的重要诊断能力。公共卫生相关性：在大血管闭塞后的早期，卒中的最终严重程度在很大程度上取决于侧支循环网络通过绕过近端血栓的迂回路线向缺血组织供应血液的能力。侧支循环可提高溶栓治疗的疗效，降低颅内出血的风险。尽管侧支在急性中风中非常重要，但人们对它们知之甚少，这主要是因为评估需要进行侵入性成像测试，即脑血管造影术。这项建议评估了一种称为动脉自旋标记(ASL)的非对比MRI灌注技术是否能提供有关侧支循环的重要信息。ASL图像融合了血管造影术(取决于动脉到达时间)和灌注(以绝对生理单位量化CBF的能力)的特征。最近的技术进步和更广泛的3T临床MRI扫描仪的引入开始使这项技术成为主流，成为评估脑血管疾病的一种有价值和强大的临床成像工具。为了充分了解侧支循环与ASL之间的关系，我们将首先研究烟雾病患者。这是一种慢性血管病变，主要发生在年轻人身上，他们足够稳定，可以在非急性情况下接受MRI检查，并且经常接受脑血管造影术，为可能的颅外到颅内搭桥术做准备。他们构成了一个理想的人群，可以研究广泛的侧支循环，而不会像急性中风患者那样受到时间限制。然后，我们将从这些研究中获取信息，并将最好的ASL方法应用于急性中风患者。对于这两组患者，我们将使用黄金标准、稳定的氙气增强CT来验证ASL脑血流测量。该项目的成功完成将使人们更好地了解严重脑血管疾病患者的ASL CBF测量，并极大地增强MRI在急性缺血性中风中已经具有的重要诊断能力。

DESCRIPTION (provided by applicant): MOTIVATION Collateral blood flow plays a central role during acute ischemic stroke, and the presence of good collaterals has been linked to improved clinical and radiological outcome measures both with and without treatment. Despite this, the only method to assess adequacy of collaterals currently is invasive and expensive, digital subtraction cerebral angiography (DSA). It would be of tremendous benefit if collaterals could be visualized using a tomographic, non-invasive imaging based modality, so that early treatment decisions could incorporate this critical piece of information. AIMS AND METHODS The overall goal of this new submission is to identify and quantify cerebral blood flow (CBF) delivered via collateral routes using arterial spin labeling (ASL), a non-contrast MRI technique that combines aspects of perfusion and angiography. DSA and xenon CT (xeCT) will act as gold standards for collaterals and CBF, respectively. We aim to show equivalence between DSA and both qualitative and quantitative ASL methods optimized to visualize collaterals in 60 patients with Moyamoya disease. These patients make up an ideal population for this study, as they tend to be young and otherwise healthy, but typically have extensive collateral circulation. We also aim to demonstrate that ASL CBF measurements sensitive to slow flow, such as long post-label delay pseudocon- tinuous ASL and velocity-selective ASL, correlate with xeCT-based CBF in regions supplied by collaterals better than standard ASL and perfusion-weight- ed imaging (PWI)-based CBF. Finally, we will apply the knowledge gained from Moyamoya patients to the much larger and more relevant clinical population of acute ischemic stroke. We will obtain ASL, diffusion-weighted imaging (DWI), and bolus PWI in 60 patients both <24 hours and 3-5 days following acute stroke to determine the ability of ASL collateral CBF imaging to identify tissue at-risk of infarction, using receiver-operator characteristic (ROC) methods. SIGNIFICANCE We believe successful attainment of these aims promises to markedly improve acute stroke care by validating a non-invasive MRI-based method to assess both the presence of collaterals and the amount of CBF they deliver. Our study will lead to better understanding of ASL CBF measurements in patients with severe cerebrovascular disease and greatly enhance the already significant diagnostic power of MRI in acute ischemic stroke. PUBLIC HEALTH RELEVANCE: In the early hours following large vessel occlusion, the ultimate severity of the stroke is largely determined by the ability of collateral flow networks to supply blood to ischemic tissue via circuitous routes that bypass the proximal clot. Ro- bust collateral flow can improve response to thrombolytic therapy and decrease the risk of intracranial hemorrhage. Despite their central importance, collaterals during acute stroke are poorly understood, largely because assessment has required an invasive imaging test, cerebral angiography. This proposal assesses whether a noncontrast MRI perfusion technique, called arterial spin labeling (ASL), can yield important information about collateral flow. ASL images blend features of angiography (dependence on arterial arrival times) and perfusion (the ability to quantify CBF in absolute physiologic units). Recent technical advances and the more widespread introduction of 3T clinical MRI scanners are beginning to bring this technique into the mainstream, as a valuable and robust clinical imaging tool for the evaluation of cerebrovascular disease. To fully characterize the relationship between collateral flow and ASL, we will first study patients with Moyamoya disease. This is a chronic vasculopathy primarily of young people, who are stable enough to undergo MRI in a non-acute setting and who routinely receive cerebral angiography in preparation for possible extracranial-to-intracranial bypass. They make up an ideal population to study extensive collateral flow without the time constraints that surround acute stroke patients. We will then take the information from these studies, and apply the best ASL methods to acute stroke patients. For both groups of patients, we will validate the ASL cerebral blood flow measurements using a gold-standard, stable xenon-enhanced CT. Successful completion of this project will lead to better understanding of ASL CBF measurements in patients with severe cerebrovascular disease and greatly enhance the already significant diagnostic power of MRI in acute ischemic stroke.