Quantitative PET/MRI of brain oxygenation in cerebrovascular disease

中风是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显示出改善卒中结局和恢复的前景，但由于缺乏非侵入性生物标志物来识别适合这些治疗的患者，因此受到阻碍。特别是，脑氧合成像是中风社区长期认识到但未满足的需求，我们建议使用磁共振成像（MRI）来满足这一需求。 该项目开发了一种临床上可行的工具集，通过磁共振成像对脑组织氧合进行无创成像。我们的具体目标是：（1）开发新的MRI技术，定量BOLD和血管指纹，利用一种新的脉冲序列来量化脑组织中的氧提取分数（OEF）水平;（2）在脑血管疾病患者中验证MR OEF成像与同步[15 O]正电子发射断层扫描（PET）参考图像;（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评估脑组织中的定量OEF。使用混合PET/MRI系统来验证新的OEF成像方法，同时通过[15 O] PET进行测量也是非常新颖的。该提案的结果是一种经验证的MRI工具，用于对颈动脉狭窄患者的OEF进行成像和定量MRI观察，以及其与患者症状和灌注状态的关系。这项工作的意义是一个临床上可行的MRI协议，以成像组织OEF，可转移到任何临床网站。可重复和强大的工具将使卒中成像社区能够更好地对患者进行分层，以进行新的治疗，并实施多中心试验，以评估血管内介入治疗，以降低这些人群的卒中风险。

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.