Microvascular Measures of Perfusion in Stroke Recanalization

描述（申请人提供）：缺血性脑卒中后脑再通是恢复脑功能的最佳手段。然而，血流的恢复往往伴随着脑损伤和组织死亡。可靠地描述血流恢复和可挽救的脑是有临床意义的。MRI成像从T2、DWI和灌注成像中对脑卒中损伤提供诊断有用的描述。然而，我们需要改进灌注方法，以便最好地绘制和区分组织状态的血流。临床假设脑再灌注是在抢救脑的时间窗口内恢复血流的过程，并且能够描述该再灌注过程的两个方面对于每天在世界范围内进行的数百次再灌注手术至关重要。这项新提交的总体目标是通过动态敏感性对比（DSC）灌注加权MRI （PWI）方法识别和改进脑血流（CBF）技术，该方法可以描述血流恢复以及微血管状态，从而与DWI进行最佳比较，形成临床有用的DWI-PWI不匹配，代表危险脑组织或可挽救的大脑。为此，我们将评估梯度回波（GRE）和自旋回波（SE）信号在多次、多回波和DSC第一遍灌注造影剂MRI技术中同时获得的灌注成像的价值。灌注图将与CBF的金标准氙CT （xeCT）值进行比较。我们的目标是显示GRE-和SE-DSC达到金标准的等效性，以便可视化120例接受再通手术的中风患者的血管和微血管状态。我们将对120例在再灌注后6-48小时出现的患者进行T1、T2、T2*、弥散加权成像（DWI）和PWI，并在30天内进行第二次随访研究，作为组织结局和临床评估的衡量指标。我们相信，通过验证对血管状态和组织微血管状态敏感的基于mri的灌注方法，成功实现这些目标有望显著改善急性卒中护理。本研究将更好地了解重症脑血管病患者的制图流程和微血管状态，并通过更好地绘制再灌注后代谢-灌注错配，极大地增强MRI在急性缺血性脑卒中中已经很重要的诊断能力。公共卫生相关性：在大血管闭塞后的最初几个小时内，中风的最终严重程度将在很大程度上取决于闭塞持续的时间以及血管打开和血流恢复到大脑的速度。然而，有一个问题是，如何描绘中风后大脑中哪些区域会通过血流恢复而恢复，哪些部分最终会死亡。该提案评估了一种从MRI获取血流数据的快速方法是否可以准确可靠地测量大脑各部分的血流，以及这种MR方法是否可以从大脑注定死亡的区域看到可恢复的大脑。在此过程中，我们将比较不同的磁共振成像方法绘制血流图与放射学中已知的标准。这些基于核磁共振成像的方法使用注射造影剂，可以给出血流图、血容量、血液的运输时间、血流到达时间和其他血管状态的测量。它们还可以描绘对所有血管敏感的血流，包括对中风区域较大的供血动脉，以及向脑组织输送氧气所必需的小毛细血管床。我们将纳入120例中风患者，这些患者在6至48小时的时间窗口内进行了再灌注手术。对于所有患者，我们将使用金标准，稳定的氙增强CT检查验证MRI脑血流量测量。这个项目的成功完成将使我们更好地了解MRI测量血流的效果，以及哪些MRI测量方法可以让我们最好地了解在再通（或再灌注）后恢复血流的大脑区域，以及哪些区域即使在恢复血流后也可能死亡。这将大大增强MRI在急性缺血性脑卒中中的诊断能力。

DESCRIPTION (provided by applicant): The recanalization of brain following ischemic stroke is the best means of recovering brain. However, restoration of flow is often accompanied by brain injury and tissue death. A reliable depiction of restoration of flow together with salvageable brain is of clinical significance. Imaging with MRI offers diagnostically useful depictions of stroke injury from T2, DWI, and perfusion imaging. However, we need improved methods of perfusion in order to best map and differentiate flow from tissue status. The clinical hypothesis that reperfusion of brain is a process of restoration of flow in the time window of salvaging brain, and being able to depict both aspects of that reperfusion process are crucial to the hundreds of reperfusion procedures done daily worldwide. The overall goal of this new submission is to identify and improve cerebral blood flow (CBF) techniques from dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI) methods that can depict both restoration of flow together with the microvascular status that would optimally compare with DWI to form a clinically useful DWI-PWI mismatch representing brain tissue-at-risk or salvageable brain. To do this, we will assess the value of mapping perfusion with a gradient- echo (GRE) and a spin-echo (SE) signal acquired together in a multi-shot, multi- echo, and DSC first-pass bolus contrast agent MRI technique. The perfusion maps will be compared with a gold-standard xenon CT (xeCT) value of CBF. We aim to show equivalence between GRE- and SE-DSC to the gold-standard in order to visualize vascular and microvascular status in 120 stroke patients having had recanalization procedures. We will obtain T1, T2, T2*, diffusion-weighted imaging (DWI), and bolus PWI in 120 patients presenting at 6-48 hours following reperfusion and obtain a second follow-up study at 30 days as a measure of tissue outcome together with clinical assessments. We believe successful attainment of these aims promises to markedly improve acute stroke care by validating a MRI-based perfusion methods sensitive to both vascular status and tissue microvascular status. This study will lead to better understanding of mapping flow and microvascular status in patients with severe cerebrovascular disease and greatly enhance the already significant diagnostic power of MRI in acute ischemic stroke by better mapping metabolic- perfusion mismatches after reperfusion. PUBLIC HEALTH RELEVANCE: In the early hours following large vessel occlusion, the ultimate severity of the stroke will be greatly determined by how long the occlusion has gone on and how soon the vessels can be opened and flow restored to the brain. One question however, is how to depict the regions of the brain suffering from the stroke that will be recovered by restoration of flow and which parts will eventually die. This proposal assesses whether a rapid means of acquiring blood flow data from MRI can accurately and reliably measure the blood flow in various parts of the brain and whether this MR method can see recoverable brain from regions of the brain destined to die. The do this, we will compare various MRI methods of mapping blood flow with known standards in radiology. These MRI-based methods use an injected contrast agent that can give maps of blood flow, blood volume, transit time of the blood, arrival times of the blood flow and other measures of vascular status. They can also depict flow that is sensitive to all vessels including the larger feeding arteries to the stroked region as well as the small capillary beds necessary for delivering oxygen to the brain tissue. We will include 120 stroke patients into this study that have had reperfusion procedures done within a time window of 6 to 48 hours. For all patients, we will validate the MRI cerebral blood flow measurements using a gold-standard, stable xenon-enhanced CT exam. Successful completion of this project will lead to better understanding of how well MRI can measure blood flow and which MRI measurement will give us the best view of brain regions that have had flow restored after recanalization (or reperfusion) and which regions are likely to die even after restoration of flow. This will greatly enhance the already significant diagnostic power of MRI in acute ischemic stroke.