Quantifying Collateral Perfusion in Cerebrovascular Disease

描述（由申请人提供）：动机侧支血流在急性缺血性卒中期间起着核心作用，并且良好侧支的存在与治疗和未治疗的临床和放射学结局指标的改善有关。尽管如此，目前评估侧支循环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术（DSA）。如果可以使用基于断层摄影的非侵入性成像方式来可视化侧支，这将是巨大的益处，以便早期治疗决策可以结合这一关键信息。目的和方法本次新申报的总体目标是使用动脉自旋标记（ASL）（一种结合灌注和血管造影的非造影MRI技术）识别和量化通过侧支途径输送的脑血流量（CBF）。DSA和氙气CT（xeCT）将分别作为侧支循环和CBF的金标准。我们的目的是显示DSA和定性和定量ASL方法之间的等效性，优化显示60例烟雾病患者的侧支循环。这些患者构成了本研究的理想人群，因为他们往往年轻且健康，但通常具有广泛的侧支循环。我们还旨在证明对慢血流敏感的ASL CBF测量值，如长标记后延迟假连续ASL和速度选择性ASL，与侧支供血区域中基于xeCT的CBF相关性优于标准ASL和基于灌注重量艾德成像（PWI）的CBF。最后，我们将从烟雾病患者中获得的知识应用于更大和更相关的急性缺血性卒中临床人群。我们将在急性卒中后24小时内和3-5天内对60例患者进行ASL、弥散加权成像（DWI）和团注PWI，以使用受试者-操作者特征（ROC）方法确定ASL侧支CBF成像识别梗死风险组织的能力。意义我们相信这些目标的成功实现有望通过验证一种基于MRI的非侵入性方法来评估侧支循环的存在及其提供的CBF量，从而显著改善急性卒中护理。我们的研究将导致更好地了解严重脑血管疾病患者的ASL CBF测量，并大大提高MRI在急性缺血性卒中中的诊断能力。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主要取决于侧支血流网络通过绕过近端凝块的迂回路线向缺血组织供血的能力。破裂侧支循环可提高溶栓治疗的疗效，降低颅内出血的危险性.尽管侧支循环在急性卒中中具有核心重要性，但对其了解甚少，主要是因为评估需要有创成像检查，即脑血管造影。该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3 T临床MRI扫描仪的更广泛引入开始将该技术纳入主流，作为评价脑血管疾病的有价值和强大的临床成像工具。为了充分描述侧支血流和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，主要发生在年轻人中，他们足够稳定，可以在非急性环境中接受MRI检查，并定期接受脑血管造影术，为可能的颅外-颅内分流术做准备。他们构成了研究广泛侧支血流的理想人群，而没有围绕急性卒中患者的时间限制。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。该项目的成功完成将导致更好地了解严重脑血管疾病患者的ASL CBF测量，并大大提高MRI在急性缺血性卒中中的诊断能力。

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.