Relating functional MRI to neuronal activity: accounting for effects of microarchitecture

将功能 MRI 与神经元活动联系起来：解释微结构的影响

• 批准号: 10397243
• 负责人: Anna I Blazejewska
• 金额: $ 9.98万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397243
• 关键词: Accounting; Address; Affect; Anatomy; Animals; Area; Atlases; Award; BRAIN initiative; Back; Blood; Blood Vessels; Blood flow; Brain; Brain region; Cell Nucleus; Cerebral cortex; Cerebrum; Characteristics; Consultations; Contrast Media; Data; Data Analyses; Feedback; Functional Imaging; Functional Magnetic Resonance Imaging; General Hospitals; Goals; Gold; Heme; Histologic; Histology; Human; Image; Imaging Techniques; Individual; Investigation; Iron; Knowledge; Magnetic Resonance Imaging; Maps; Masks; Massachusetts; Measurement; Measures; Mentors; Methodology; Methods; Microanatomy; Modeling; Myelin; Neocortex; Neurons; Neurosciences; Output; Pathway interactions; Phase; Physics; Property; Research; Research Personnel; Resolution; Role; Signal Transduction; Source; Specificity; Specimen; Stains; Stimulus; Structure; System; Techniques; Technology; Testing; Tissue Model; Tissues; Training; Variant; Visual Cortex; Weight; area V1; area striata; bioimaging; brain circuitry; career; cerebral blood volume; collaborative environment; computer science; density; design; experience; experimental study; extrastriate visual cortex; histological specimens; human data; imaging facilities; in vivo; in vivo imaging; indexing; luminance; medical schools; monocular; neuronal circuitry; novel; programs; regional difference; relating to nervous system; response; skills

Project Summary/Abstract The central goal of the BRAIN Initiative is to understand the structure and function of human brain circuits. Functional magnetic resonance imaging (fMRI) has great potential to achieve this goal, however fMRI is fundamentally an indirect measure of neuronal activity—it assesses brain function through the measurement of changes in blood flow and oxygenation driven by local neuronal activity, and is also influenced by regional differences in tissue anatomy including vascular density. The cerebral cortex consists of layers that are well- known to serve as inputs or outputs for the connections across brain regions, and so localizing fMRI signals to individual layers will be key to deciphering brain circuitry in humans. However, the cortical microanatomy varies dramatically across layers, introducing biases that have been demonstrated to confound our ability to detect and localize activity within layers with fMRI, and therefore to hinder the interpretation and use of laminar fMRI. Our aim is to characterize and remove these fMRI signal biases due to local differences in microanatomy, in order to address this fundamental limitation of fMRI and to more accurately relate fMRI to neuronal activity. We will achieve this goal by combining histology of human brain specimens with advanced ex vivo and in vivo imaging to develop a framework for enhancing fMRI neuronal specificity—through deriving a mapping between tissue microarchitecture and quantitative MRI, and then correcting fMRI signal bias related to tissue microstructure. The candidate is trained in physics and computer science; has experience in high-resolution structural MRI and in correlating in vivo and ex vivo MRI with histology; and seeks training in experimental neuroscience in order to become an independent researcher in this field. During the mentored phase, she will develop a model of intracortical microstructure using ex vivo data from regions of visual cortex. She will measure vascular density in vivo to map out this additional source of fMRI signal bias, then develop a model to derive predictions of cortical microstructure and fMRI responses in vivo, and validate it through an fMRI experiment using a wide range of acquisition parameters. To achieve these goals, the candidate—with guidance from the experienced mentors, the pioneers of laminar microanatomy and fMRI—will extend her knowledge, gain new skills in advanced ultra- high-field fMRI acquisition and data analysis. Building on this, in the independent phase she will apply the model to laminar fMRI experiments designed to validate the bias correction. This project will prepare the candidate for her long-term career goal of establishing a research program applying non-invasive functional imaging techniques, with aid of quantitative tissue property analyses, to study the circuitry of the human brain. The mentored phase will be carried out at the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, a highly collaborative environment with state-of-the-art imaging facilities and world-class experts available for mentoring/consultation. The K99 award will facilitate the required training and research components of this project to aid the candidate in becoming an independent researcher.

项目摘要/摘要 大脑计划的核心目标是了解人脑电路的结构和功能。 功能磁共振成像（fMRI）具有实现此目标的巨大潜力，但是fMRI是 从根本上讲，间接测量神经元活动 - 它通过测量来评估大脑功能 局部神经元活性的血流和氧合驱动的变化，也受区域的影响 组织解剖结构（包括血管密度）的差异。大脑皮层由良好的层组成 被称为跨大脑区域连接的输入或输出，因此将fMRI信号定位到 单个层将是破译人类脑电路的关键。但是，皮质微解剖学品种 在各个层之间急剧，引入了已证明的偏见，以使我们检测和检测能力混淆 通过fMRI将活动定位在层中，因此阻碍了laminar fMRI的解释和使用。我们的 目的是表征和消除由于微解剖学局部差异而导致的这些fMRI信号偏见，以便为了 解决fMRI的基本局限性以及与神经元活动更准确相关的fMRI。我们将 通过将人脑标本的组织学与先进的外体和体内成像相结合来实现这一目标 开发一个增强fMRI神经元特异性的框架 - 通过推导组织之间的映射 微结构和定量MRI，然后纠正与组织微观结构有关的fMRI信号偏置。 候选人接受了物理和计算机科学的培训；具有高分辨率结构性MRI和 在体内和离体MRI与组织学相关的过程中；并寻求实验神经科学的培训 成为该领域的独立研究人员。在修订阶段，她将开发一个模型 使用来自视觉皮层区域的离体数据的心脏内微观结构。她将测量血管密度 在体内绘制fMRI信号偏置的额外来源，然后开发一个模型来得出皮质的预测 微观结构和fMRI在体内的反应，并通过fMRI实验对其进行验证 采集参数。为了实现这些目标，候选人在经验丰富的导师的指导下， 层状微型解剖和fMRI的先驱 - 将扩大她的知识，获得高级超级技术的新技能 高场fMRI获取和数据分析。在此基础上，在独立阶段，她将应用模型 旨在验证偏置校正的层流FMINAR FMRI实验。该项目将为候选人做好准备 她的长期职业目标是建立应用非侵入功能成像的研究计划 借助定量组织性能分析，技术研究人脑的电路。这 指导阶段将在马萨诸塞州的Athinoula A. Martinos生物医学成像中心进行 哈佛医学院综合医院，一个高度协作的环境，具有最先进的成像 设施和世界一流的专家可用于心理/咨询。 K99奖将主持所需的 该项目的培训和研究组成部分，以帮助候选人成为一名独立的研究人员。