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

标准功能磁共振成像校准对皮质层不同微血管血流和氧合反应的影响

• 批准号: 10654249
• 负责人: Ikbal Sencan-Egilmez
• 金额: $ 24.87万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654249
• 关键词: Affect; Age; Aging; Anesthesia procedures; Animal Model; Area; BRAIN initiative; Biophysics; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain Pathology; Breathing; Caffeine; Caliber; Calibration; Carbon Dioxide; Catheters; Cerebrovascular Circulation; Cerebrum; Chronic; Clinical; Complex; Computer Models; Coupled; Data; Development; Environment; Faculty; Functional Magnetic Resonance Imaging; Gases; General Hospitals; Goals; Health; Human; Hypercapnia; Hyperoxia; Image; Imaging Device; Injections; Intake; Intraventricular; Ipsilateral; Link; Maps; Massachusetts; Measurement; Mentors; Metabolism; Methodology; Methods; Modeling; Morphology; Mus; Nature; Neurons; Neurosciences; Noise; Optics; Oxygen; Partial Pressure; Pathologic; Pharmacologic Substance; Positioning Attribute; Procedures; Radiology Specialty; Research; Research Design; Research Methodology; Resolution; Rest; Shoulder; Signal Transduction; Technology; Time; Tissues; Training; Vibrissae; Visual; Work; aging brain; arterial spin labeling; arteriole; awake; base; biomedical imaging; biophysical model; blood oxygen level dependent; career development; experimental study; healthy aging; hemodynamics; imaging modality; improved; insight; interdisciplinary collaboration; medical schools; metabolic rate; microscopic imaging; middle age; neuroimaging; neurovascular coupling; next generation; novel; response; tenure track; tool; training opportunity; two-photon; venule

This proposed project focuses 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.

该提议的项目着重于量化皮质氧代谢和神经血管耦合中的空间和暂时多样性，并通过整合新的技术和概念方法来告知下一代血液氧依赖性（BOLD）功能磁共振成像（FMRI）测量的生物物理模型。该应用的广泛和长期目标是（1）在空间（毛细血管下到全大脑）和临时（µs至数月）领域的多个尺度上对大脑的理解，（2）以发现跨皮层组织，功能区域以及对模型的高度响应的皮质层跨性别层的血液动力响应的多样性，并构成量的量，并构成量子的量，并构成型号的量子，并构成了模型，并构成了模型，并构成了型号，并构成了模型的范围。健康的清醒老鼠。意识到这些目标将有助于通过实现大脑倡议的目标，以理解大脑在行动中，发现多样性，绘制多样性，绘制/联系跨空间和临时量表的活动以及了解fMRI信号的生物物理基础，从而有助于改善人类健康。拟议项目的具体目的可以总结为：（1）对大脑血流（CBF），氧气（PO2）的局部压力（PO2）和大脑代谢速率（CMRO2）（CMRO2）（CMRO2），（2）的多样性，以量化CMRO2和CBFF的多样性，以更快，更深，更深，更深，更深，更纵向测量的测量。健康老鼠的层和微脉管系统类型，以及（3），以量化标准的fMRI校准（例如高碳酸酯，高氧和咖啡因）对静止和功能激活期间CMRO2和CBF的影响。该项目中将使用的研究设计和方法将包括（1）对绝对氧气浓度的更快，更深的慢性成像，以评估皮质PO2，CMRO2和血液流动在脑部激活过程中的皮质PO2和血流变化之间的关系，以及（2）（2）氧气，血液流动和定量的氧化量和变性的态度，以实现的态度和较实际的响应量，并量身定期，代表性地依赖于型号的态度，以实现的态度依赖型号，以实用的态度依赖型号，以实现的态度和型号的态度，以实现的态度依赖性量度良好，而有效性地构成了效果良好的效果。用于大胆fMRI成像中通常使用的校准程序。 Sencan博士（哈佛医学院马萨诸塞州综合医院和放射学系的Athinoula A. Martinos生物医学成像中心）的研究环境配备了执行该项目所需的最先进的技术，并且具有在神经科学，职业发展，跨学科协作中培训的机会。她拥有一支由潜水员和强大专业知识的导师，合作者和顾问团队，他们致力于支持Sencan博士的研究以及她的职业发展。所有这些因素将促进拟议项目的成功执行，Sencan博士在神经影像学领域的培训以及她向独立的终身教师职位的过渡。