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: 10553103
• 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/10553103
• 关键词: 3-Dimensional; Acceleration; Acidosis; Acute; Alteplase; Amides; Animal Model; Animals; Area; Benign; Brain hemorrhage; Brain imaging; Brain region; Cause of Death; Chemicals; Clinic; Clinical; Clinical Trials; Decision Making; Diffusion; Diffusion Magnetic Resonance Imaging; Eligibility Determination; Excision; Frequencies; Goals; Hemorrhage; Hour; Human; Image; Imaging Techniques; Incidence; Infarction; Intervention; Intravenous; Ischemia; 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; Therapeutic Intervention; Time; Tissues; Training; Translating; Translations; United States; Variant; Visualization; Work; acute stroke; 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 prediction; risk/benefit ratio; standard care; stroke patient; stroke therapy; targeted treatment; thrombolysis; time use; transmission process; 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率和死亡率的主要原因之一 中风疗法是通过使用再灌注来挽救有梗塞风险但仍然可行的组织 策略。当前的再灌注疗法受到严格的治疗时间和潜在风险的限制 大脑出血。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 治疗。出现在标准治疗时间窗口以外的患者时，可以从治疗中受益 根据多模式MRI识别；但是，可挽救的组织的精确鉴定是 必不可少的，因为必须权衡治疗的潜在有益效果，并与出血风险相比。 尽管已提出扩散/灌注MRI不匹配作为指导，以确定存在 可挽救的组织的选择，并用作溶栓的选择标记，使用此临床试验的结果 标准尚无定论，部分原因是寡血症中含有少血症的区域，该区域是阴影中的 高估了有风险的组织的大小。酰胺质子转移（APT）MRI在检测 在动物模型和人类中风患者中，这种基于酸中毒的缺血性阴茎。但是，大多数 当前使用的APT成像协议不是很实用，并且相对于 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 由于使用多个RF饱和频率，多次采集和长RF饱和脉冲引起的时间 （或脉冲火车），由于中风发作之间非常小的时间窗口，所有这些都阻碍了临床翻译 以及可能的溶栓治疗。我们的长期目标是开发一种超快的pH成像技术 常规临床用途可在各种治疗时间指导超急性中风患者的再灌注疗法 窗户，并预测急性缺血性中风后出血转化（HT）的风险。第一个 临床假设是，与动物研究相似，由于缺血性组织酸中毒而引起的pH成像阴影 如果未启动再灌注，则可以预测最大最终梗塞大小。我们的第二个临床假设是 缺血性核心中严重的组织酸中毒的存在与继发性的概率增加有关 HT。我们的假设将通过三个特定目的进行检验：1）开发和优化超快定量 pH成像方法； 2）验证这项技术并评估基于酸中毒的诊断准确性 在临床环境中的缺血性半月； 3）开发一个新颖的深度学习模型，以预测HT 急性缺血性中风后，并量化pH成像的灵敏度和特异性。期望这项工作 将APT-MRI转化为临床可行且健壮的方法。添加pH成像 对于标准的MRI方案，预计可以更好地可视化真实的缺血性阴茎，因此 改善对临床结果的预测并降低HT的发生率。