Microvascular Measures of Perfusion in Stroke Recanalization

描述（由申请人提供）：缺血性卒中后的脑再通是恢复脑功能的最佳方法。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具有临床意义。MRI成像提供了从T2、DWI和灌注成像中诊断中风损伤的有用提示。然而，我们需要改进的灌注方法，以便最好地映射和区分组织状态的流量。脑再灌注是在挽救脑的时间窗内恢复血流的过程的临床假设，并且能够描述该再灌注过程的两个方面对于全世界每天进行的数百次再灌注手术至关重要。本次新申报的总体目标是从动态磁敏感对比（DSC）灌注加权MRI（PWI）方法中识别和改进脑血流量（CBF）技术，该方法可以描述血流恢复以及微血管状态，与DWI进行最佳比较，以形成代表风险脑组织或可挽救脑的临床有用的DWI-PWI不匹配。为此，我们将评估在多激发、多回波和DSC首过团注造影剂MRI技术中同时采集的梯度回波（GRE）和自旋回波（SE）信号的标测灌注值。将灌注图与CBF的金标准氙CT（xeCT）值进行比较。我们的目的是证明GRE和SE-DSC与金标准之间的等效性，以可视化120例接受再通手术的卒中患者的血管和微血管状态。我们将在再灌注后6-48小时对120例患者进行T1、T2、T2*、弥散加权成像（DWI）和团注PWI，并在30天时进行第二次随访研究，作为组织结局的测量和临床评估。我们相信，这些目标的成功实现有望通过验证对血管状态和组织微血管状态敏感的基于MRI的灌注方法来显著改善急性卒中护理。这项研究将导致更好地了解映射流和微血管状态的严重脑血管疾病患者，并大大提高了MRI在急性缺血性中风的诊断能力，更好地映射后再灌注代谢-灌注不匹配。公共卫生相关性：在大血管闭塞后的最初几个小时，中风的最终严重程度将在很大程度上取决于闭塞持续了多长时间以及血管多久可以打开并恢复流向大脑。然而，一个问题是如何描述中风后大脑中哪些区域会通过恢复血流而恢复，哪些部分最终会死亡。该提案评估了从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方法是否可以从注定死亡的大脑区域看到可恢复的大脑。为此，我们将比较各种MRI方法映射血流与已知的标准在放射学。这些基于MRI的方法使用注射的造影剂，其可以给出血流、血容量、血液的通过时间、血流的到达时间和血管状态的其他测量的图。它们还可以描绘对所有血管敏感的血流，包括中风区域的较大供血动脉以及向脑组织输送氧气所需的小毛细血管床。我们将纳入120名在6至48小时的时间窗内进行再灌注手术的卒中患者。对于所有患者，我们将使用金标准验证MRI脑血流测量，该项目的成功完成将使我们更好地了解MRI如何测量血流，以及MRI测量将为我们提供在再通（或再灌注）后恢复血流的脑区域的最佳视图，以及即使在恢复血流后哪些区域可能死亡。这将极大地增强MRI在急性缺血性卒中中已经显着的诊断能力。

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.