Effects of standard fMRI calibrations on the diverse microvascular blood flow and oxygenation responses in cortical layers

项目概要/摘要：本项目的重点是量化空间和时间的多样性， 皮质氧代谢和神经血管耦合，并为下一代生物物理模型提供信息 血氧水平依赖（BOLD）功能性磁共振成像（fMRI）测量 通过整合新的技术和概念方法。这一广泛和长期的目标 应用是（1）在空间的多个尺度（毛细血管下到整个- 脑）和时间（µs至月）域，（2）有助于发现血流动力学反应的多样性 跨皮质组织层、功能区和微血管分支，以及（3）支持建模 通过量化健康老龄清醒小鼠皮质中的血流动力学反应，研究了BOLD信号的效果。 实现这些目标将有助于共同努力， 实现BRAIN Initiative的目标，了解大脑的活动，发现多样性， 在空间和时间尺度上映射/链接活动，并理解fMRI的生物物理基础 信号了该项目的具体目标可以概括为：（1）更快、更深、 脑血流量（CBF）、氧分压（pO 2）和脑血流的纵向测量 氧代谢率（CMRO 2），（2）量化CMRO 2和CBF对功能性 健康老化中不同皮质功能区、皮质层和微血管类型的激活 小鼠，以及（3）量化标准fMRI校准（例如高碳酸血症，高氧和咖啡因）的影响 在休息和功能激活期间对CMRO 2和CBF的影响。研究设计和方法 在这个项目中使用的将包括（1）开发更快和更深的绝对氧气慢性成像 浓度，以评估大脑激活期间皮质pO 2、CMRO 2和血流变化之间的关系 跨皮层区域和层，和（2）氧合，血流，和 在健康老龄小鼠和老年小鼠中， 响应于BOLD fMRI成像中常用的校准程序。研究环境 Sencan博士（Athinoula A.马萨诸塞州总医院Martinos生物医学成像中心 哈佛医学院放射科）配备了所需的最先进的技术 执行拟议的项目，并在神经科学，职业发展， 和跨学科的合作。她拥有一个由导师，合作者和顾问组成的团队， 强大的专业知识，致力于支持Sencan博士的研究和她的职业发展。所有这些 因素将促进拟议项目的成功执行，完成Sencan博士在 神经成像，以及她向独立终身教职的过渡。

Project Summary/Abstract: This proposed project focus on quantifying the spatial and temporal diversity in cortical oxygen metabolism and neurovascular coupling, and informing next generation of biophysical models of the Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) measurements by integrating new technological and conceptual approaches. Broad and long term objectives of this application are (1) to bridge understanding of brain in action at multiple scales in spatial (subcapillary to whole- brain) and temporal (µs to months) domains, (2) to contribute discovering diversity of hemodynamic responses across cortical tissue layers, functional areas, and microvascular branches, and (3) to support the modelling efforts of BOLD signal by to quantifying hemodynamic responses in cortex of healthy-aging awake mice. Realizing these objectives would contribute to the joined efforts towards improving human health through accomplishing BRAIN Initiative goals of understanding the brain in action, discovering diversity, mapping/linking activity across spatial and temporal scales, and understanding the biophysical basis of fMRI signal. The specific aims of the proposed project can be summarized as: (1) to develop faster, deeper, longitudinal measurements of the cerebral blood flow (CBF), partial pressure of oxygen (pO2), and cerebral metabolic rate of oxygen (CMRO2), (2) to quantify the diversity of CMRO2 and CBF responses to functional activation across different cortical functional areas, cortical layers, and microvasculature types in healthy-aging mouse, and (3) to quantify the effects of standard fMRI calibrations (e.g. hypercapnia, hyperoxia, and caffeine) on the CMRO2 and CBF at rest and during functional activation. The research design and methods that will be used in this project will include (1) developing faster and deeper chronic imaging of absolute oxygen concentration to assess relation between cortical pO2, CMRO2, and blood flow changes during brain activation across the cortical areas and layers, and (2) realistic measurements of the oxygenation, blood flow, and metabolism responses to functional activation at the microvascular scales in healthy-aging mice and in response to calibration procedures that are commonly used in BOLD fMRI imaging. The research environment of Dr. Sencan (the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Radiology Department in Harvard Medical School) is equipped with state-of-the-art technologies required to execute the proposed project and is rich with opportunities for training in neuroscience, career development, and interdisciplinary collaborations. She has a team of mentors, collaborators and advisors with diverse and strong expertise, who are committed to support Dr. Sencan’s research, and her career development. All these factors will facilitate the successful execution of the proposed project, the completion of Dr. Sencan’s training in neuroimaging, and her transition to an independent tenure-track faculty position.