Quantifying Collateral Perfusion in Cerebrovascular Disease

描述（由申请人提供）：动机侧支血流量在急性缺血性卒中中起着核心作用，良好的侧支的存在与治疗前后临床和放射学结果的改善有关。尽管如此，目前评估侧支是否充足的唯一方法是侵入性且昂贵的数字减影脑血管造影（DSA）。如果能够利用断层扫描、非侵入性成像的方式对侧枝进行可视化，那么早期的治疗决策就可以纳入这一关键信息，这将是巨大的好处。目的和方法本次新提交的总体目标是使用动脉自旋标记（ASL）识别和量化通过侧支途径输送的脑血流量（CBF）， ASL是一种结合灌注和血管造影方面的非对比MRI技术。DSA和氙气CT （xeCT）将分别作为抵押品和CBF的黄金标准。我们的目标是在60例烟雾病患者中显示DSA与定性和定量ASL方法之间的等效性。这些患者构成了本研究的理想人群，因为他们往往年轻，健康，但通常有广泛的侧支循环。我们还旨在证明对慢流敏感的ASL CBF测量，如长标签后延迟伪连续ASL和速度选择性ASL，与侧支提供区域的基于xect的CBF的相关性优于标准ASL和基于灌注加权成像（PWI）的CBF。最后，我们将把从烟雾病患者身上获得的知识应用到更大、更相关的急性缺血性卒中临床人群中。我们将对60例急性卒中后<24小时和3-5天的患者进行ASL、弥散加权成像（DWI）和灌注PWI检查，以确定ASL侧支CBF成像识别梗死危险组织的能力，采用接受者-操作者特征（ROC）方法。我们相信，通过验证一种基于非侵入性mri的方法来评估抵押品的存在和它们提供的CBF量，成功实现这些目标有望显著改善急性卒中的护理。我们的研究将有助于更好地了解严重脑血管疾病患者的ASL CBF测量，并大大增强MRI在急性缺血性脑卒中中的诊断能力。公共卫生相关性：在大血管闭塞后的最初几个小时，卒中的最终严重程度在很大程度上取决于侧支血流网络通过绕过近端血栓的迂回路线向缺血组织供血的能力。侧支血流可改善溶栓治疗的反应，降低颅内出血的风险。尽管侧枝在急性中风中具有核心重要性，但人们对其了解甚少，主要是因为评估需要进行侵入性影像学检查，即脑血管造影。本提案评估了一种称为动脉自旋标记（ASL）的非对比MRI灌注技术是否可以获得有关侧支血流的重要信息。ASL图像融合了血管造影（依赖于动脉到达时间）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3T临床MRI扫描仪的更广泛引入开始使这项技术成为主流，作为脑血管疾病评估的有价值和强大的临床成像工具。为了充分表征侧支血流与ASL之间的关系，我们将首先研究烟雾病患者。这是一种主要发生在年轻人的慢性血管病变，他们的病情足够稳定，可以在非急性情况下接受MRI检查，并常规接受脑血管造影，为可能的颅外-颅内旁路手术做准备。他们构成了一个理想的人群来研究广泛的侧支血流，而没有围绕急性中风患者的时间限制。然后，我们将从这些研究中获取信息，并将最佳的ASL方法应用于急性卒中患者。对于两组患者，我们将使用金标准，稳定的氙增强CT验证ASL脑血流量测量。本课题的成功完成将有助于更好地了解重症脑血管病患者的ASL CBF测量，并大大提高MRI在急性缺血性脑卒中中的诊断能力。

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.