Development of Novel and Entirely Non-Invasive High Spatial and High Temporal Resolution Cerebrovascular Monitoring/Imaging Systems

控制流向哺乳动物大脑的血流量是由脑血管与生俱来的能力来调节的，这种能力被称为大脑自动调节，允许在一定范围的全身动脉压范围内相对恒定地流动。衰老过程和性别都会影响自我调节，血液和营养物质输送到大脑的障碍会导致持续的继发性损伤。这种二次损伤的形式要么是血液流动不足，导致脑组织饥饿，最终导致新的中风，要么是血流过多，导致肿胀和出血。然而，先前关于年龄和性别对脑自动调节的生物学影响的文献有限。造成现有知识差距的一个很大因素是，我们有限的能力持续评估人类的脑血管功能，并快速和同时在多个地区表征其地区差异。到目前为止，对人类和其他哺乳动物大脑自我调节的初步尝试依赖于断断续续的血液流动快照，使用先进的神经成像，或者通过使用生物医学工程信号处理从有创/非侵入性脑监测设备获得的数据进行非常集中的评估。这些前期工作的主要局限性导致了目前的知识差距，既是高级神经成像研究的间歇性，也是缺乏使用当前床边连续技术监测多个大脑区域的能力。我的项目重点是开发人类的新成像技术，允许在多个大脑区域同时连续快速评估大脑自动调节。我工作的短期目标将利用先进的多通道近红外光谱(NIRS)技术，结合完全无创的连续动脉血压(ABP)监测，得出人类整个大脑的大脑自动调节图，每个点都有高采样率。这项新技术将在健康人群中使用，以优化这项技术，并表征在年龄和性别范围内持续评估脑血管功能的地区差异。这些进展将有助于弥合目前的知识差距。从长远来看，我的计划将继续开发更复杂的新成像平台，这些平台是非侵入性的、可穿戴的、移动的，具有高时间/空间分辨率，用于全面表征哺乳动物的大脑生理。我的计划未来的这些方面将是将这些连续的新型生理学平台与连续的代谢和电生理数据流整合在一起，以实现更全面的脑生理测量平台，适用于大型动物和人类。该计划将负责在生物医学工程、大数据和信号分析等NSE领域每5年培训3-4名HQP。

Control of blood flow to the mammalian brain is regulated by the innate ability of the cerebral blood vessels, termed cerebral autoregulation, allowing for relatively constant flow over a range of systemic arterial pressures. Both the aging process and sex influence autoregulation, with impaired delivery of blood flow and nutrients to the brain causing ongoing secondary damage. This secondary damage takes the form of either deficient blood flow, leading to starvation of brain tissue and eventual new strokes, or as excessive blood flow, leading to swelling and hemorrhage. However, prior literature on the biological influence of aging and sex on cerebral autoregulation is limited. A large contributing factor to the existing knowledge gap, lies in our limited ability to continuously assess cerebral blood vessel function in humans, and characterize its regional differences rapidly and in multiple areas simultaneously. To date, preliminary attempts to characterize cerebral autoregulation in humans and other mammals have relied on intermittent "snap shots" of blood flow, using advanced neuroimaging, or through very focal assessments using biomedical engineering signal processing of data obtained from invasive/noninvasive cerebral monitoring devices. The overarching limitation of these preliminary works, leading to the current knowledge gap, is both the intermittent nature of advanced neuroimaging studies, and the lack of ability to monitor multiple brain regions with current bedside continuous techniques. My program focuses on the development of novel imaging techniques in humans, allowing for continuous rapid assessment of cerebral autoregulation simultaneously in multiple brain areas. The short term aims of my work will employ advanced multichannel near infrared spectroscopy (NIRS) technology, married with entirely noninvasive continuous arterial blood pressure (ABP) monitoring, to derive cerebral autoregulation maps of the entire brain in humans, with high sampling rates at each point. This novel technique will be employed in healthy human populations to allow for both optimization of this technology and the characterization of regional differences in continuously assessed cerebral vessel function across the spectrum of age and sex. Such advances will facilitate bridging the current knowledge gap. Long-term, my program will continue to develop more complex new imaging platforms that are non-invasive, wearable, mobile, with high temporal/spatial resolution, for the comprehensive characterization of mammalian cerebral physiology. Such future aspects of my program will be integration of these continuous novel physiology platforms, with continuous metabolic and electrophysiologic data streams for more comprehensive cerebral physiologic measurement platforms, applied in both large animals and humans. This program will be responsible for training ~3-4 HQP per 5-year DG cycle in the NSE fields of biomedical engineering, big data and signals analysis.