Microscopic imaging of neuro-capillary coupling in brain cortex

大脑皮层神经毛细血管耦合的显微成像

• 批准号: 8713992
• 负责人: Jonghwan Lee
• 金额: $ 9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8713992
• 关键词: Algorithms; Alzheimer' s Disease; Animals; Area; Biological; Biomedical Engineering; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain Diseases; Brain Mapping; Caliber; Cancer Biology; Cardiac; Cells; Cerebral cortex; Characteristics; Clinical Research; Coupling; Data; Data Analyses; Energy Supply; Exhibits; Functional disorder; Goals; Human; Image; Imagery; Imaging technology; In Vitro; Knowledge; Lead; Learning; Life; Measures; Mediating; Mentors; Microscopic; Morphologic artifacts; Motion; Neurons; Neurosciences; Ophthalmology; Optical Coherence Tomography; Optics; Organelles; Pericytes; Phase; Physics; Regulation; Research; Research Project Grants; Resolution; Rodent; Role; Signal Transduction; Somatosensory Cortex; Speed; Stroke; Structure; Techniques; Technology; Testing; Therapeutic; Tissues; Validation; Variant; Work; arteriole; base; capillary; career; career development; experience; hemodynamics; improved; in vivo; in vivo imaging; light scattering; neuroimaging; neuronal cell body; novel; programs; public health relevance; research study; respiratory; response; skills; somatosensory; spatiotemporal

DESCRIPTION (provided by applicant): Optical coherence tomography (OCT) enables um-resolution and high-speed imaging of tissue structure, facilitating a number of basic and clinical studies in ophthalmology, cancer biology, and neuroscience. Through the proposed K99/R00 program, the candidate will develop novel OCT-based technologies for um-resolution imaging of tissue dynamics, especially in the brain cortex of a living animal. In detail, the candidate will develop three technologies for imaging various vascular and cellular dynamics occurring in the rodent cerebral cortex: in vivo imaging of the motion of neuronal intracellular organelles with single-cell resolution (Specific Aim 1a), simultaneous imaging of blood flow speed over hundreds of capillaries with single-capillary and 1-s resolution (Specific Aim 1b), and imaging of fast optical signals of neuronal activity with single-cell and ms resolution (Specific Aim 2). Thes technologies will be generally useful for a range of neuroscience and pathophysiology studies that benefit from direct visualization of those tissue dynamics with high spatiotemporal resolution. The proposed K99/R00 program will focus on using the technologies to propose and demonstrate the concept of neuro-capillary coupling. This concept will challenge the current paradigm, neurovascular coupling, for understanding the brain's energy supply regulation and for interpreting hemodynamics-based human brain mapping data. Recently, blood flow regulation at the capillary level has been suggested in vitro as mediated by pericytes, but not demonstrated in vivo. Further, cortical capillary flow dynamics is also suggested to relate with pathophysiology. Therefore, the proposed concept will improve our understanding of blood flow regulation and thus offer new opportunities for developing therapeutic approaches to a range of disorders of the brain including stroke and Alzheimer's disease. In detail, using the technologies developed in Specific Aims 1 and 2, the candidate will test three hypotheses for demonstrating and characterizing neuro-capillary coupling in vivo (Specific Aim 3): (H1) Capillaries regulate blood flow in response to neuronal activation in the somatosensory cortex, directly proving the capillary control of flow; (H2) Neuro-capillary coupling leads to an early capillary network flow homogenization, identifying the role of the capillary flow regulation; and (H3) Neuro-capillary coupling exhibits a microscopic spatial correlation between excited neurons and responding capillaries, revealing the characteristics of neuro-capillary coupling. The proposed research project will enable the candidate to gain further research experience and scientific knowledge in the field of biomedical optics and neuroimaging. Along with the research project, the proposed career development programs including course work and seminars will assist him in achieving his career goal: to establish an independent research program in a biomedical engineering or applied physics department.

描述（由申请人提供）：光学相干断层扫描（OCT）可实现组织结构的UM分辨率和高速成像，从而促进了眼科，癌症生物学和神经科学方面的许多基本和临床研究。通过拟议的K99/R00计划，候选人将开发基于OCT的新技术，用于组织动力学的UM分辨率成像，尤其是在活动物的脑皮质中。 In detail, the candidate will develop three technologies for imaging various vascular and cellular dynamics occurring in the rodent cerebral cortex: in vivo imaging of the motion of neuronal intracellular organelles with single-cell resolution (Specific Aim 1a), simultaneous imaging of blood flow speed over hundreds of capillaries with single-capillary and 1-s resolution (Specific Aim 1b), and imaging of fast optical signals of具有单细胞和MS分辨率的神经元活性（特定目标2）。这些技术通常将对一系列神经科学和病理生理学研究有用，这些神经科学和病理生理研究受益于以高时空分辨率的直接可视化那些组织动力学。 拟议的K99/R00计划将重点介绍使用技术提出和演示神经毛细血管耦合的概念。这个概念将挑战当前的范式，神经血管耦合，以理解大脑的能量供应调节和解释基于血液动力学的人脑映射数据。最近，已在体外介导的体外表明毛细血管水平的血流调节，但在体内不显示。此外，还建议皮质毛细血管流动动力学与病理生理有关。因此，拟议的概念将提高我们对血液流量调节的理解，从而为开发治疗方法提供新的机会，以解决包括中风和阿尔茨海默氏病在内的一系列大脑疾病。详细介绍地，使用特定目标1和2中开发的技术，候选人将测试三个假设，以证明和表征体内神经毛细血管耦合（特定目的3）：（H1）毛细血管调节血液流动，以响应于体感皮质中的神经元激活，直接证明了流动毛细管控制的流动性毛细血管控制； （H2）神经毛细血管耦合导致早期的毛细血管网络流均匀化，从而识别毛细血管流量调节的作用； （H3）神经毛细血管耦合表现出激发神经元与反应毛细血管之间的微观空间相关性，从而揭示了神经毛细血管耦合的特征。 拟议的研究项目将使候选人能够在生物医学光学和神经影像学领域获得进一步的研究经验和科学知识。与研究项目一起，拟议的职业发展计划在内，包括课程工作和研讨会将有助于他实现自己的职业目标：在生物医学工程或应用物理系中建立独立的研究计划。