Development of fast penumbral imaging in acute ischemic stroke

项目总结/摘要 影像学是指导卒中患者管理的重要工具。最近的DAWN和DEFUSE-3试验 提供了明确的证据，证明成像对于指导晚期血管内治疗（EVT）至关重要，强调 需要从基于发病时间的治疗过渡到基于组织的治疗。然而，据估计， 大多数在6-24小时内出现NIH卒中量表（NIHSS）评分超过6分的卒中患者（约70%） DAWN和/或DEFUSE-3合格（Desai et al. J NeurointervSurg. 2018; 10：1033-37）。2018年美国 心脏协会中风早期管理指南指出，“...... 侧支血流状态纳入某些候选人的临床决策，以确定机械通气的资格 血栓切除术”组织代谢MRI是侧支血流状态的替代生物标志物， 满足这一临床需求。我们将开发快速pH和扩散峰度成像（DKI），并评估其价值 用于指导实验性中风模型的再灌注治疗。 在上一个资助周期中，我们在开发新的中风MRI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开发的pH特异性成像 转移（MR-APT）MRI（Guo等人，Neuroimage 2016;242-9）。使用细丝状大脑中动脉闭塞 大鼠，我们改进了灌注/弥散加权成像（PWI/DWI）病变的代谢不匹配， 半暗带和良性少血（Wang et al. Neuroimage 2019;610-7）。我们的急性中风患者研究显示 急性DKI病变体积的相关系数高于表观弥散 1个月随访T2图像的ADC图（Yin et al. Radiology 2018：651-7）。这呼应了 NINDS研究人员最近的一项研究报告说：“早期、完全性 血管重建，现在更常见的EVT，是惊人的不同，从我们的历史认识。 (Hsia例如，中风2019;50：2086-92）我们假设，新的快速MRI技术改善了组织时钟有助于 描绘缺血组织，预测永久性卒中的组织结局，并指导再灌注治疗。是 迫切需要在存在常见中风合并症的情况下和实验性中风患者中测试精细的组织时钟。 在开始未来的前瞻性临床试验之前。简而言之，我们将开发稳健的快速pH和DKI冲程 成像（目标1），建立MCAO大鼠中精细MRI的时空演变（目标2），并测试 组织时钟引导的老年和糖尿病常见卒中合并症大鼠再灌注（目的3）。的 该项目的成功将为未来的临床试验奠定基础，以测试先进的成像引导中风 在诊所治疗。

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.