Ultrafast Quantitative pH MRI for Acute Ischemic Stroke Patients

用于急性缺血性中风患者的超快定量 pH MRI

• 批准号: 10328241
• 负责人: Hye Young Heo
• 金额: $ 38.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10328241
• 关键词: 3-Dimensional; Acidosis; Acute; Alteplase; Amides; Anaerobic Bacteria; Animal Model; Animals; Area; Benign; Brain; Brain hemorrhage; Brain imaging; Brain region; Cause of Death; Chemicals; Clinic; Clinical; Clinical Trials; Decision Making; Diffusion; Diffusion Magnetic Resonance Imaging; Excision; Frequencies; Goals; Hemorrhage; Human; Image; Imaging Techniques; Incidence; Infarction; Intervention; Intravenous; Ischemic Penumbra; Ischemic Stroke; Magnetic Resonance Imaging; Metabolism; Methods; Morbidity - disease rate; Outcome; Patient Selection; Patients; Perfusion; Physiologic pulse; Physiological; Population; Probability; Protocols documentation; Protons; Reperfusion Therapy; Research Proposals; Retrospective Studies; Risk; Scanning; Selection for Treatments; Sensitivity and Specificity; Signal Transduction; Speed; Stroke; Symptoms; Techniques; Testing; Therapeutic; Time; Tissues; Training; Translating; Translations; Variant; Visualization; Work; acute stroke; base; blood-brain barrier permeabilization; clinical translation; deep learning; deep learning algorithm; deep learning model; design; detection sensitivity; diagnostic accuracy; disability; endovascular thrombectomy; human imaging; imaging modality; improved; mortality; multimodality; novel; perfusion imaging; predict clinical outcome; radio frequency; risk benefit ratio; standard care; stroke patient; stroke therapy; targeted treatment; thrombolysis; time use; treatment effect

ABSTRACT Ischemic stroke is one of the leading causes of morbidity and mortality in the U.S. The goal of acute ischemic stroke therapy is to salvage tissue that is at risk of infarction, but still viable, through the use of reperfusion strategies. Current reperfusion therapies are limited by a tight time window for treatment and by the potential risk of brain hemorrhage. Using this time-based approach, only a limited number of stroke patients are eligible for treatment. Patients who present beyond the standard treatment time windows can benefit from therapy when identified based on multimodal MRI; however, precise and accurate identification of the salvageable tissue is essential, as the potential beneficial effect of treatment must be weighed against the risk of hemorrhage. Although a diffusion/perfusion MRI mismatch has been suggested as a guide with which to identify the presence of salvageable tissues and to serve as a selection marker for thrombolysis, the results of clinical trials using this criterion have been inconclusive, in part because of the inclusion of regions of oligemia in the penumbra, which overestimates the size of the tissue at risk. Amide proton transfer (APT) MRI has shown promise in detecting such an acidosis-based ischemic penumbra in animal models and in human stroke patients. However, most currently used APT imaging protocols are not very practical and not optimized with respect to the magnitude of signal changes caused by the pH effect. More quantitative APT-MRI typically would require an even longer scan time due to the use of multiple RF saturation frequencies, multiple acquisitions, and a long RF saturation pulse (or pulse train), all of which hamper clinical translation due to the very small time-window between stroke onset and possible thrombolysis treatment. Our long-term goal is to develop an ultrafast pH imaging technique for routine clinical use to guide reperfusion therapies for hyperacute stroke patients at various therapeutic time windows, as well as predict the risk of hemorrhagic transformation (HT) following acute ischemic stroke. The first clinical hypothesis is that, similar to animal studies, the pH imaging penumbra due to ischemic tissue acidosis predicts the maximum final infarction size if no reperfusion is initiated. Our second clinical hypothesis is that the presence of severe tissue acidosis in the ischemic core is associated with an increased probability of secondary HT. Our hypotheses will be tested through three specific aims: 1) to develop and optimize an ultrafast quantitative pH imaging method; 2) to validate this technique and assess the diagnostic accuracy of the acidosis-based ischemic penumbra in a clinical setting; and 3) to develop a novel deep-learning model with which to predict HT following acute ischemic stroke, and quantify the sensitivity and specificity of pH imaging. This work is expected to accelerate the translation of APT-MRI into a clinically viable and robust method. The addition of pH imaging to the standard MRI protocol is expected to enable better visualization of the true ischemic penumbra, thus improving predictions of clinical outcome and reducing the incidence of HT.

抽象的 缺血性中风是美国发病和死亡的主要原因之一。急性缺血性中风的目标 中风治疗是通过再灌注来挽救有梗塞风险但仍然可行的组织 策略。目前的再灌注疗法受到治疗时间窗口紧张和潜在风险的限制 的脑出血。使用这种基于时间的方法，只有有限数量的中风患者有资格获得 治疗。超出标准治疗时间窗的患者可以从治疗中受益： 基于多模态 MRI 进行识别；然而，精确和准确地识别可挽救的组织是 至关重要，因为必须权衡治疗的潜在有益效果与出血风险。 尽管扩散/灌注 MRI 不匹配已被建议作为识别存在的指南 的可挽救组织并作为溶栓的选择标记，使用此的临床试验结果 标准尚无定论，部分原因是半影中包含了寡血症区域，这 高估了危险组织的大小。酰胺质子转移 (APT) MRI 在检测方面显示出前景 在动物模型和人类中风患者中存在这种基于酸中毒的缺血半暗带。然而，大多数 目前使用的 APT 成像协议不是很实用，并且没有针对 APT 的大小进行优化。 pH 效应引起的信号变化。更定量的 APT-MRI 通常需要更长的扫描时间 由于使用多个射频饱和频率、多次采集和长射频饱和脉冲而缩短了时间 （或脉冲串），由于中风发作之间的时间窗口非常小，所有这些都阻碍了临床转化 以及可能的溶栓治疗。我们的长期目标是开发一种超快 pH 成像技术 常规临床用于指导超急性卒中患者在不同治疗时间的再灌注治疗 窗口，以及预测急性缺血性中风后出血性转化（HT）的风险。第一个 临床假设是，与动物研究类似，pH 成像半暗带是由于缺血性组织酸中毒引起的 如果不开始再灌注，则可以预测最终的最大梗塞面积。我们的第二个临床假设是 缺血核心区严重组织酸中毒的存在与继发性酸中毒的可能性增加有关 HT。我们的假设将通过三个具体目标进行检验：1）开发和优化超快定量 pH成像法； 2) 验证该技术并评估基于酸中毒的诊断准确性 临床环境中的缺血半暗带； 3) 开发一种新颖的深度学习模型来预测 HT 急性缺血性中风后，并量化 pH 成像的敏感性和特异性。这项工作预计 加速将 APT-MRI 转化为临床上可行且稳健的方法。添加 pH 成像 标准 MRI 协议有望能够更好地可视化真正的缺血半暗带，因此 改善临床结果的预测并降低 HT 的发生率。