Imaging of human brain oxygenation and oxygen metabolism dynamics

摘要 人脑需要持续的氧气输送来满足其巨大的新陈代谢需求，并遭受 当这种氧气供应中断时，如中风时，会产生毁灭性的后果。而新的血管内治疗 治疗已经显示出改善脑血管结果的希望，但缺乏治疗效果受到阻碍。 非侵入性生物标记物来对那些适合接受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(CMRO2)的成像是一项长期的研究。 中风社区中公认但未得到满足的需求。该项目开发了新的、临床上可行的工具 对于无创氧合成像，研究大脑如何动态满足其氧气需求和 确定神经科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图的重建 匹配“到微血管体素模拟和验证与[150]-氧气PET参考； 和(2)发展一种PET和MRI的混合方法来快速成像CMRO2的动力学及其功能 单次静态扫描期间的网络。 这项工作的新颖性在于利用了同步PET/MRI扫描仪的独特功能。 使用PET/MRI系统验证和增强仅有MRI的临床OEF评估方法 同时进行正电子发射计算机断层扫描是一项非常创新的技术。混合测量还允许新的、快速的CMRO2 体现每种模式最好的成像方法--快速和定量--来建立大脑模型 功能连通性和疾病。这项提议的成功将产生新的神经成像工具 研究广泛适用于任何有核磁共振扫描仪的部位的脑耗氧量。这些 进展将使使用生理成像生物标志物来评估血管内治疗成为可能 降低中风风险，并增强我们的基础神经科学能力，以理解 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.