Development of fast penumbral imaging in acute ischemic stroke

项目摘要/摘要 影像是指导卒中患者治疗的重要工具。最近的黎明和聚变3号试验 提供了明确的证据，表明成像对指导晚期血管内治疗(EVT)至关重要，强调 需要从基于起效时间的治疗过渡到基于组织的治疗。然而，据估计， 大多数(~70%)出现6-24小时NIH卒中评分(NIHSS)超过6分的卒中患者 曙光和/或聚变-3符合条件(Desai等人《神经外科杂志》2018；10：1033-37)。2018年美国人 心脏病协会卒中早期管理指南指出，它是“…”成立公司是合理的 部分应聘者临床决策中的侧支循环状态确定是否符合机械治疗条件 血栓切除术。“组织代谢磁共振是侧支循环状态的替代生物标志物，有望 满足这一临床需求。我们将开发快速pH和弥散峰度成像(DKI)并评估其价值 用于指导实验性中风模型的再灌注治疗。 在前一个资金周期中，我们在开发新的中风磁共振技术方面取得了稳步进展。我们 基于磁化转移和弛豫归一化酰胺质子的pH比成像 Transfer(MR-APT)MRI(Guo等人《神经影像》2016；242-9)。大脑中动脉细丝栓塞法 大鼠，我们改进了灌注/扩散加权成像(PWI/DWI)病变与代谢的不匹配 半暗带和良性少血症(Wang et al.NeuroImage 2019；610-7)。我们的急性中风患者研究显示 DKI急性期病灶体积比表观弥漫性体积相关系数高 系数(ADC)图和1个月的跟踪T2图像(Yen等人放射学2018：651-7)。这呼应了 NINDS研究人员最近的一项研究报告称：“早期、完全性ADC患者的ADC演变 再血运重建，现在更常见的是EVT，与我们的历史理解有很大的不同。 (Hsia et al.，Stroke.2019；50：2086-92)我们假设新的快速核磁共振技术精炼的组织时钟有助于 描绘缺血组织，预测永久性卒中的组织结果，并指导再灌注治疗。它是 在常见的卒中并发症和实验中，迫切需要测试改进的组织时钟 在启动未来的前瞻性临床试验之前。简而言之，我们将发展出强健的快速pH和DKI中风 成像(目标1)，建立MCAO大鼠改良MRI的时空演变(目标2)，并测试 普通卒中合并年龄和糖尿病大鼠的组织时钟引导再灌注(目标3)。这个 该项目的成功将为未来测试高级成像引导中风的临床试验奠定基础 在诊所接受治疗。

PROJECT SUMMARY/ABSTRACT Imaging is an essential tool to guide stroke patient management. Recent DAWN and DEFUSE-3 trials have provided the definitive evidence that imaging is critical to guide late endovascular therapy (EVT), underscoring the need to transition from onset time-based to tissue-based treatment. However, it has been estimated that the majority of stroke patients (~70%) presenting 6-24 hrs with NIH Stroke Scale (NIHSS) over 6 are not DAWN and/or DEFUSE-3 eligible (Desai et al. J Neurointerv Surg. 2018; 10:1033-37). The 2018 American Heart Association Stroke Early Management Guidelines pointed out that it is “… reasonable to incorporate collateral flow status into clinical decision making in some candidates to determine eligibility for mechanical thrombectomy.” Tissue metabolic MRI is a surrogate biomarker of the collateral flow status that is promising to address this clinical need. We will develop fast pH and diffusion kurtosis imaging (DKI) and evaluate their value for guiding reperfusion therapy in experimental stroke models. During the previous funding cycle, we made steady progress in developing new stroke MRI techniques. We developed pH-specific imaging based on magnetization transfer and relaxation-normalized amide proton transfer (MR-APT) MRI (Guo et al. Neuroimage 2016;242-9). Using filament middle cerebral artery occlusion rats, we refined the perfusion/diffusion-weighted imaging (PWI/DWI) lesion mismatch for the metabolic penumbra and benign oligemia (Wang et al. Neuroimage 2019;610-7). Our acute stroke patient study showed that the volumes of acute DKI lesions have a higher correlation coefficient than those on the apparent diffusion coefficient (ADC) maps with 1-month follow-up T2 images (Yin et al. Radiology 2018:651-7). This echoes the recent study from NINDS investigators who reported: “ADC evolution in patients with early, complete revascularization, now more commonly seen with EVT, is strikingly different from our historical understanding.” (Hsia et al., Stroke. 2019;50:2086-92) We hypothesize that new fast MRI techniques refined tissue-clock helps delineate ischemic tissue, predict tissue outcomes in permanent stroke, and guide reperfusion treatment. It is urgent to test the refined tissue-clock, in the presence of common stroke comorbidities and in the experimental setting, before initiating future prospective clinical trials. Briefly, we will develop robust fast pH and DKI stroke imaging (Aim 1), establish the spatiotemporal evolution of the refined MRI in MCAO rats (Aim 2), and test tissue-clock-guided reperfusion in rats of common stroke comorbidities of age and diabetes (Aim 3). The success of the project will lay the groundwork for future clinical trials to test advanced imaging-guided stroke treatment in the clinic.