Advancing simultaneous fMRI-multiphoton imaging technique to study brain function and connectivity across different scales at ultrahigh field

推进同步功能磁共振成像多光子成像技术，研究超高场下不同尺度的大脑功能和连接性

• 批准号: 10268184
• 负责人: Wei Chen
• 金额: $ 54.75万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10268184
• 关键词: Ablation; Address; Affect; Anesthesia procedures; Animal Model; Animals; Astrocytes; Blood Vessels; Brain; Brain Diseases; Cells; Complex; Conscious; Correlation Studies; Data; Disease; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Goals; Health; Human; Image; Imaging Techniques; Imaging technology; Implanted Electrodes; Individual; Institution; Interneurons; Knowledge; Lasers; Lead; Light; Magnetic Resonance Imaging; Maps; Measurement; Measures; Metabolic; Methods; Microscopic; Modality; Multimodal Imaging; Mus; Nerve; Nervous system structure; Neurons; Neurosciences; Neurosciences Research; Outcome; Population; Positioning Attribute; Process; Records; Research; Resolution; Rest; Role; Signal Transduction; Specificity; System; Techniques; Technology; Time; Work; awake; base; blood oxygen level dependent; brain research; design; hemodynamics; human imaging; imaging system; inhibitory neuron; innovation; insight; magnetic field; microscopic imaging; multi-photon; multimodality; multiphoton imaging; neural circuit; neural network; neuroimaging; neurophysiology; neurotransmission; neurovascular; new technology; next generation; novel; optical imaging; pre-clinical; relating to nervous system; response; spatiotemporal; success; tool; two photon microscopy; Ablation; Address; Affect; Anesthesia procedures; Animal Model; Animals; Astrocytes; Blood Vessels; Brain; Brain Diseases; Cells; Complex; Conscious; Correlation Studies; Data; Disease; Functional Magnetic Resonance Imaging; Functional disorder; Generations; Goals; Health; Human; Image; Imaging Techniques; Imaging technology; Implanted Electrodes; Individual; Institution; Interneurons; Knowledge; Lasers; Lead; Light; Magnetic Resonance Imaging; Maps; Measurement; Measures; Metabolic; Methods; Microscopic; Modality; Multimodal Imaging; Mus; Nerve; Nervous system structure; Neurons; Neurosciences; Neurosciences Research; Outcome; Population; Positioning Attribute; Process; Records; Research; Resolution; Rest; Role; Signal Transduction; Specificity; System; Techniques; Technology; Time; Work; awake; base; blood oxygen level dependent; brain research; design; hemodynamics; human imaging; imaging system; inhibitory neuron; innovation; insight; magnetic field; microscopic imaging; multi-photon; multimodality; multiphoton imaging; neural circuit; neural network; neuroimaging; neurophysiology; neurotransmission; neurovascular; new technology; next generation; novel; optical imaging; pre-clinical; relating to nervous system; response; spatiotemporal; success; tool; two photon microscopy

PROJECT SUMMARY Understanding the neural circuitry and signaling in health or diseased brain requires new tools that can image neuronal activity and functional connectivity with superior spatiotemporal precision across various scales from individual and population of neural cells and microvessel at microscopic scale, neural circuits and cortical layers/columns, and functional connectivity at mesoscopic (or laminar) scale to neural networks at macroscopic scale and the nervous system level. Functional magnetic resonance imaging (fMRI) based on the blood- oxygenation-level-dependent (BOLD) contrast has gained a prominent position in neuroscience, and it is the only neuroimaging modality that can noninvasively map human neuronal activity and dynamic change to the level of neural computational units, and image functional connectivity and resting-state networks (RSNs) covering the entire brain. However, the fMRI BOLD signal is determined by a complex interplay between vascular and metabolic changes, thus, indirectly reflecting neuronal activity. The inference of underlying neuronal activity on the fMRI BOLD signal can be affected by many unknown factors at microscopic and mesoscopic scales. Although great efforts have been made to study the correlation between fMRI signals and neuronal activity, the neurophysiology origin of the BOLD signal and its specificity in mapping neuronal activity and functional connectivity at cortical lamina level remains elusive. To tackle technical challenges and address critical neuroimaging and neuroscience questions, we have formed an interdisciplinary team with experts in the ultrahigh-field (UHF) fMRI and multi-photon microscopy imaging research fields from two research institutions to develop the world first MRI fully compatible volumetric two-photon microscopy imaging (VTPMI) system, which works in one of the highest field animal MRI scanners at 16.4T Tesla. This novel VTPMI-fMRI multimodal neuroimaging system will make it possible to simultaneously measure key neurophysiological information related to activities and dynamics of excitatory/inhibitory neurons, astrocytes, different sized vessels, and ultrahigh-resolution fMRI data, thus enables delineation of cell- and layer- specific neuronal activity in the living brain. The VTPMI-fMRI technology developed in this project will be employed to study the neuro-vascular correlation and the specificity of resting-state fMRI BOLD signals for mapping the layer-specific functional connectivity in anesthetized and awake brains, with particular emphasis on investigating the roles of inhibitory interneurons. The findings and knowledge from this project will be transformative and beneficial for understanding and interpreting the human fMRI BOLD signals at the fine scale of fundamental computational units.

项目摘要 了解健康或患病大脑中的神经回路和信号传导需要新工具来形象 神经元活性和功能连通性与从各种尺度上的优质时空精度 神经细胞的个体和人群和微血管的微观尺度，神经回路和皮质 层/柱和介质（或层流）尺度上的功能连通性到宏观的神经网络 尺度和神经系统水平。基于血液的功能磁共振成像（fMRI） 氧合级依赖性（粗体）对比已在神经科学中获得了突出的地位，这是 只有神经影像模态才能非侵入性地绘制人类神经元活性和动态变化为 神经计算单元以及图像功能连接和静止状态网络（RSN）的级别 覆盖整个大脑。但是，fMRI粗体信号由血管之间的复杂相互作用确定 因此，代谢变化间接地反映了神经元活性。基础神经元活性的推断 在fMRI上，在微观和介观尺度上，许多未知因素可能会影响许多未知因素。 尽管已经做出了巨大的努力来研究fMRI信号与神经元活动之间的相关性，但 粗体信号的神经生理学起源及其在映射神经元活动和功能的特异性 皮质薄片水平的连通性仍然难以捉摸。 为了应对技术挑战并解决关键的神经影像学和神经科学问题，我们有 与超高场（UHF）fMRI和多光子显微镜的专家组成了一个跨学科团队 来自两个研究机构的成像研究领域开发世界第一MRI完全兼容的体积 两光子显微镜成像（VTPMI）系统，在最高的野外动物MRI扫描仪之一中起作用 在16.4t特斯拉。这个新颖的VTPMI-FMRI多模式神经影像系统将使同时成为可能 测量与兴奋性/抑制性神经元的活动和动态有关的关键神经生理信息， 星形胶质细胞，不同大小的容器和超高分辨率fMRI数据，因此可以描绘细胞和层 - 活大脑中的特定神经元活性。该项目开发的VTPMI-FMRI技术将是 用于研究神经血管相关性和静止状态fMRI大胆信号的特异性 在麻醉和清醒的大脑中绘制特定层特异性功能连接性，特别强调 研究抑制性中间神经元的作用。这个项目的发现和知识将是 具有变革性和有益的有益于理解和解释人类fMRI大胆信号 基本计算单元。