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

哺乳动物大脑的血流量是由大脑血管的先天能力来控制的，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力下相对恒定的血流量。衰老过程和性别都会影响自我调节，血液和营养物质向大脑的输送受损会导致持续的继发性损伤。这种二次损伤要么表现为血流量不足，导致脑组织饥饿，最终导致新的中风，要么表现为血流量过多，导致肿胀和出血。然而，关于年龄和性别对大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重要因素是，我们持续评估人类脑血管功能的能力有限，无法同时在多个领域快速表征其区域差异。迄今为止，对人类和其他哺乳动物大脑自动调节特征的初步尝试依赖于间歇性的血流“快照”，使用先进的神经成像技术，或者通过生物医学工程信号处理对从侵入性/非侵入性大脑监测设备获得的数据进行非常集中的评估。这些初步工作的总体限制，导致了目前的知识差距，是高级神经影像学研究的间歇性，以及缺乏用当前床边连续技术监测多个大脑区域的能力。我的项目专注于开发新的人类成像技术，允许在多个大脑区域同时对大脑自动调节进行连续快速评估。我工作的短期目标将采用先进的多通道近红外光谱（NIRS）技术，与完全无创的连续动脉血压（ABP）监测相结合，以每个点的高采样率获得人类整个大脑的大脑自动调节图。这项新技术将在健康人群中使用，以优化该技术，并在连续评估的脑血管功能中描述跨年龄和性别的区域差异。这些进步将有助于弥合目前的知识差距。从长远来看，我的项目将继续开发更复杂的新型成像平台，这些平台是非侵入性的，可穿戴的，可移动的，具有高时间/空间分辨率，用于哺乳动物大脑生理学的综合表征。我的项目未来的这些方面将是整合这些连续的新颖生理平台，与连续的代谢和电生理数据流，用于更全面的脑生理测量平台，应用于大型动物和人类。该项目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DG周期培养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.