Imaging of human brain oxygenation and oxygen metabolism dynamics

摘要 人类大脑需要持续的氧气输送来满足其巨大的代谢需求， 当氧气供应中断时会产生毁灭性的后果，如中风。虽然新的血管内 治疗已经显示出改善脑血管结局的希望，但由于缺乏 非侵入性生物标志物来对适合这些治疗的患者进行分层。特别是， 氧摄取分数（OEF）和脑氧代谢率（CMRO 2）的成像是一个长期的， 中风社区中公认但未满足的需求。该项目开发了新颖的、临床上可行的工具 用于非侵入性氧合成像，以研究大脑如何动态地满足其氧气需求， 确定神经系统患者的关键病理生理学。 我们的具体目标是（1）通过新的“指纹”增强基于MRI的OEF图重建 匹配”到微血管体素模拟和[15 O]-氧气PET参考的验证; 和（2）开发一种混合PET和MRI方法来快速成像CMRO 2动力学及其功能 在一个单一的休息扫描网络。 这项工作的新奇在于利用同步PET/MRI扫描仪的独特功能。 使用PET/MRI系统验证和增强临床OEF评估的仅MRI方法 同步PET扫描是非常创新的。混合测量还可以实现新的快速CMRO 2 成像方法体现了每种模式的最佳效果-快速和定量-以模拟大脑 功能连接和疾病。这项提议的成功将产生新的神经成像工具， 研究脑耗氧量，广泛适用于任何部位的MRI扫描仪。这些 这些进展将使生理成像生物标志物能够用于评价血管内治疗 降低中风风险，增强我们的基本神经科学能力， 大脑功能的血管基础。

Abstract The human brain requires continual oxygen delivery to meet its enormous metabolic demand, and suffers devastating consequences when this oxygen supply is disrupted, as in stroke. While new endovascular treatments have shown promise to improve cerebrovascular outcomes, they are hampered by the lack of noninvasive biomarkers to stratify patients who are good candidates for these therapies. In particular, imaging of oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2) is a long- recognized but unmet need in the stroke community. This project develops novel, clinically feasible tools for non-invasive oxygenation imaging, to study how the brain dynamically meets its oxygen needs and identify key pathophysiology in neurological patients. Our specific aims are (1) to enhance MRI-based reconstructions of OEF maps through novel “fingerprint matching” to microvascular voxel simulations and validation with the [15O]-oxygen gas PET reference; and (2) to develop a hybrid PET and MRI approach to rapidly image CMRO2 dynamics and its functional networks during a single resting scan. The novelty of this work lies in leveraging the unique capabilities of simultaneous PET/MRI scanners. The use of a PET/MRI system to validate and augment MRI-only methods for clinical OEF assessment with simultaneous PET scans is highly innovative. Hybrid measurements also allow for new, rapid CMRO2 imaging approaches that embody the best of each modality – fast and quantitative – to model brain functional connectivity and disease. Success of this proposal will generate novel neuroimaging tools to study brain oxygen consumption that are broadly applicable to any site with an MRI scanner. These advancements will enable use of physiological imaging biomarkers to evaluate endovascular therapies and reduce stroke risk, and enhance our fundamental neuroscience capabilities to understand the vascular underpinnings of brain function.