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.

项目概要/摘要 BRAIN Initiative 的中心目标是了解人类大脑回路的结构和功能。 功能磁共振成像 (fMRI) 在实现这一目标方面具有巨大潜力，但 fMRI 从根本上说是神经活动的间接测量——它通过测量 由局部神经活动驱动的血流和氧合变化，也受到区域的影响 组织解剖学的差异，包括血管密度，大脑皮层由良好的层组成。 已知可作为跨大脑区域连接的输入或输出，因此将功能磁共振成像信号定位到 各个层将是破译人类大脑回路的关键然而，皮质的微观解剖结构各不相同。 显着地跨越各层，引入偏差，这些偏差已被证明会混淆我们检测和识别的能力 使用功能磁共振成像将活动定位在层内，因此阻碍了层流功能磁共振成像的解释和使用。 目的是表征并消除这些由于显微解剖学局部差异而导致的 fMRI 信号偏差，以便 我们将解决功能磁共振成像的这一基本局限性，并更准确地将功能磁共振成像与神经活动联系起来。 通过将人脑标本的组织学与先进的离体和体内成像相结合来实现这一目标 开发一个增强功能磁共振成像神经特异性的框架——通过导出组织之间的映射 微结构和定量 MRI，然后纠正与组织微结构相关的 fMRI 信号偏差。 候选人接受过物理学和计算机科学方面的培训；具有高分辨率结构 MRI 和 将体内和离体 MRI 与组织学联系起来，并寻求实验神经科学方面的培训，以便 在指导阶段，她将成为该领域的独立研究员。 她将使用来自视觉皮层区域的离体数据来测量皮质内微观结构。 体内绘制出功能磁共振成像信号偏差的额外来源，然后开发一个模型来推导出皮质的预测 体内微观结构和功能磁共振成像反应，并通过使用各种材料的功能磁共振实验进行验证 为了实现这些目标，候选人在经验丰富的导师的指导下， 层状显微解剖学和功能磁共振成像的先驱 - 将扩展她的知识，获得先进的超微解剖学的新技能 在此基础上，她将在独立阶段应用该模型。 层流功能磁共振成像实验旨在验证偏差校正，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性功能成像的研究项目 技术，借助定量组织特性分析，研究人脑的电路。 指导阶段将在马萨诸塞州 Athinoula A. Martinos 生物医学成像中心进行 哈佛医学院总医院，拥有最先进成像技术的高度协作环境 K99 奖项将提供所需的设施和世界级专家的指导/咨询。 该项目的培训和研究部分旨在帮助候选人成为一名独立研究员。