Arterial Spin Labeled Perfusion MRI in Acute Ischemic Stroke

描述(申请人提供)：灌注成像在急性缺血性中风(AIS)治疗中的作用是确定局部脑血流量(CBF)减少的程度和程度，并有助于识别缺血半暗带--可通过溶栓和/或血管内再通治疗挽救的低灌注区。动态磁化率对比增强(DSC)技术已成为AIS的主要MR灌注成像方法。最初的溶栓队列研究表明，灌注-弥散失配可以预测溶栓治疗的临床反应。然而，随机试验(如EPETHET、DIAS)得出的结果并不明确，表明只有在使用灌注和扩散失配作为溶栓治疗患者选择标准时才会受益。到目前为止，在AIS的治疗中识别缺血半暗带的价值仍然不是很确定。动脉自旋标记(ASL)灌注MRI是一种新兴的测量CBF的非对比剂MRI方法。通过使用伪连续ASL(PCASL)和背景抑制的3D GRASE的最新实现，我们最近证明ASL可以可靠地应用于急性卒中成像，并提供与DSC灌注MRI一致的结果来显示低灌注区。ASL还显示了通过延迟的动脉传输效应以及血管选择性ASL的使用来说明侧支供血的潜力。由于ASL简单、快速且不需要注射造影剂，因此可以进行连续灌注成像来追踪再灌注的动态，并与临床结果相关联。这项建议的主要目的是进一步开发、改进和评估ASL在AIS中的临床应用。在AIM 1中，我们将通过测量动脉通过时间(ATT)来改进ASL的灌注定量，并对ASL和DSC的灌注MRI进行系统的评估。在目标2中，我们将通过与数字减影血管造影的金标准比较，评价多延迟ASL和血管编码的pCASL在判断AIS侧支循环灌注状态中的价值。在目标3中，我们将通过与AIS患者的再灌注、出血性转化(HT)和DSC测量血脑屏障(BBB)通透性等临床结果的相关性来评价ASL系列灌注成像的临床应用价值。我们假设ASL过度灌流与再灌流、血脑屏障渗漏有关，是AIS患者高血压的预测因子。本项目利用加州大学洛杉矶分校AIS神经成像和治疗的极其丰富的临床资源。这是一个翻译项目，目标是开发和验证一种完全无创的定量MRI方法，用于AIS和其他脑血管疾病的常规临床评估。

DESCRIPTION (provided by applicant): The role of perfusion imaging in the management of acute ischemic stroke (AIS) is to establish the degree and extent of reduced regional cerebral blood flow (CBF), and to contribute to the identification of the ischemic penumbra - regions of hypoperfusion that may be salvaged by thrombolytic and/or endovascular recanalization therapies. Dynamic susceptibility contrast enhanced (DSC) techniques have been the main MR perfusion imaging method used in AIS. The initial DEFUSE cohort study suggested that perfusion-diffusion mismatch may predict clinical responses to thrombolytic therapy. Randomized trials (e.g. EPITHET, DIAS), however, have yielded ambiguous findings showing only trends to benefit when using perfusion and diffusion mismatch as a patient selection criterion for thrombolysis. To date, the value for identifying the ischemic penumbra in the management of AIS remains less than firmly established. Arterial spin labeled (ASL) perfusion MRI is an emerging non-contrast MRI method to measure CBF. With the latest implementation using pseudo- continuous ASL (pCASL) and background suppressed 3D GRASE, we recently demonstrated that ASL can be reliably applied for acute stroke imaging, and provides consistent results with DSC perfusion MRI for delineating hypoperfused brain regions. ASL also demonstrates the potential to illustrate collateral blood supply through delayed arterial transit effects as well as the use of vessel-selective ASL. Because ASL is easy, fast and does not require the injection of contrast agents, serial perfusion imaging can be performed to trace the dynamics of reperfusion and correlate with clinical outcomes. The main purpose of this proposal is to further develop, refine and evaluate the clinical utility of ASL for perfusion imaging in AIS In Aim 1, we will improve ASL perfusion quantification by including arterial transit time (ATT) measurement and perform a systematic evaluation of ASL and DSC perfusion MRI. In Aim 2, we will evaluate the utility of multi-delay ASL and vessel encoded pCASL in determining the state of collateral perfusion in AIS by comparison with the gold standard of digital subtraction angiography. In Aim 3, we will evaluate the clinical utility of serial ASL perfusion imaging by correlating with clinical outcomes such as reperfusion, hemorrhagic transformation (HT) and DSC measures of blood-brain barrier (BBB) permeability in AIS patients. We hypothesize that ASL hyperperfusion is associated with reperfusion, BBB leakage and is a predictor of HT in AIS patients. The present project capitalizes on the extremely rich clinical resources for AIS neuroimaging and treatments at UCLA. It is a translational project with the goal to develop and validate an entirely noninvasive and quantitative MRI method for routine clinical evaluation of AIS as well as other cerebrovascular disorders.