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

项目摘要/摘要：这一拟议项目的重点是量化 皮质氧代谢和神经血管偶联，并告知下一代生物物理模型 血氧水平依赖(BOLD)功能磁共振成像(FMRI)测量的结果 通过整合新的技术和概念方法。这方面的广泛和长期目标 应用是(1)在空间(从毛细血管下到整体)的多尺度上沟通对大脑活动的理解。 脑)和时间(从S到月)域，(2)有助于发现血流动力学响应的多样性 跨皮质组织层、功能区和微血管分支，以及(3)支持建模 BOLD信号对健康老化清醒小鼠大脑皮质血流动力学反应的量化作用。 实现这些目标将有助于共同努力通过以下方式改善人类健康 实现大脑计划的目标，即在行动中了解大脑，发现多样性， 跨空间和时间尺度的映射/链接活动，并了解功能磁共振成像的生物物理基础 信号。拟议项目的具体目标可以概括为：(1)更快、更深、更快地发展， 脑血流量(CBF)、氧分压(PO2)和脑血流量的纵向测量 氧代谢率(CMRO2)，(2)量化CMRO2和CBF对功能反应的多样性 健康老龄化中不同皮质功能区、皮质层和微血管类型的激活 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。 静息和功能激活时对CMRO2和CBF的影响。研究的设计和方法将是 该项目将包括(1)开发更快和更深的绝对氧气慢性成像 用浓度评估大脑激活过程中皮质PO2、CMRO2与血流变化的关系 跨皮质区域和层，以及(2)真实的氧合、血流量和 健康衰老小鼠和小鼠微血管功能激活的代谢反应 对BOLD功能磁共振成像中常用的校准程序的响应。研究环境 Sencan博士(马萨诸塞州总医院阿蒂努拉·A·马蒂诺斯生物医学成像中心 和哈佛医学院放射学系)配备了所需的最先进的技术 执行拟议的项目，并有丰富的神经科学培训机会，职业发展， 和跨学科协作。她有一个由导师、合作者和顾问组成的团队，他们拥有不同的 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。所有这些都是 这些因素将有助于成功执行拟议的项目，完成Sencan博士在 神经成像，以及她过渡到一个独立的终身教职员工职位。

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.