Quantitative PET/MRI of brain oxygenation in cerebrovascular disease

中风是导致死亡和残疾的主要原因，仅在美国每年就造成340亿美元的社会负担。虽然新的血管内治疗已经显示出改善中风预后和恢复的希望，但由于缺乏无创生物标志物来识别适合这些治疗的患者，它们一直受到阻碍。特别是，脑氧合成像是卒中社区长期公认但未满足的需求，我们建议使用磁共振成像（MRI）来满足这一需求。本项目开发一种临床可行的工具集，通过磁共振成像无创成像脑组织氧合。我们的具体目标是：(1)开发新的MRI技术，定量BOLD和血管指纹，利用新的脉冲序列来量化脑组织中的氧提取分数（OEF）水平；(2)验证MR OEF成像与同时[15O]正电子发射断层扫描（PET）参考图像在脑血管疾病患者中的应用；(3)应用MRI OEF方法研究脑卒中高危颈动脉狭窄患者的氧合状态。这项工作的创新之处在于开发了一种新的成像技术来定量评估脑组织中的OEF。使用混合PET/MRI系统来验证新的OEF成像方法，同时使用[15O] PET进行测量也是非常新颖的。建议的结果是一种有效的MRI成像OEF的工具，以及颈动脉狭窄患者OEF的定量MRI观察及其与患者症状和灌注状态的关系。这项工作的意义在于一个临床可行的MRI方案来成像可转移到任何临床部位的组织OEF。这个可重复且强大的工具将使脑卒中成像社区能够更好地对患者进行新治疗，并实施多中心试验来评估血管内干预措施，以降低这些人群的脑卒中风险。

Stroke is a leading cause of death and disability and creates a societal burden of $34 billion each year in the United States alone. While new endovascular treatments have shown promise to improve stroke outcomes and recovery, they have been hampered by the lack of noninvasive biomarkers to identify patients who are good candidates for these therapies. In particular, imaging of brain oxygenation is a long-recognized but unmet need in the stroke community, and we propose to use magnetic resonance imaging (MRI) to address this need. This project develops a clinically feasible toolset to noninvasively image brain tissue oxygenation by magnetic resonance imaging. Our specific aims are (1) to develop new MRI techniques, quantitative BOLD and vascular fingerprinting, that utilize a novel pulse sequence to quantify oxygen extraction fraction (OEF) levels in cerebral tissues; (2) to validate MR OEF imaging with simultaneous [15O] positron emission tomography (PET) reference images in patients with cerebrovascular disease; and (3) to apply MRI OEF methods to study oxygenation status in patients with carotid artery stenosis who are at high risk of stroke. The innovation of this work lies in the development of a novel imaging technique to assess quantitative OEF in brain tissues. The use of a hybrid PET/MRI system to validate the new OEF imaging methods with simultaneous measurements by [15O] PET is also highly novel. The outcome of proposal is a validated MRI tool to image OEF, and quantitative MRI observations of OEF in patients with carotid artery stenosis, and its relationship to patient symptoms and perfusion status. The significance of this work is a clinically feasible MRI protocol to image tissue OEF that is transferrable to any clinical site. The reproducible and robust tool will allow the stroke imaging community to better stratify patients for new treatments, and implement multi-center trials to evaluate endovascular interventions to reduce stroke risk in these populations.