Quantitative analysis of estrogen and sleep deprivation-induced blood and lymphatic vascular remodeling in the brain system

雌激素和睡眠剥夺引起的大脑系统血液和淋巴血管重塑的定量分析

• 批准号: 10404487
• 负责人: Olga V Glinskii
• 金额: $ 53.13万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10404487
• 关键词: Acute; Algorithmic Analysis; Algorithms; Alzheimer' s Disease; Anatomy; Aneurysm; Animals; Arteriovenous fistula; Blood; Blood Circulation; Blood Vessels; Blood capillaries; Brain; Brain Mapping; Cardiovascular system; Cephalic; Cerebrospinal Fluid; Cerebrovascular Disorders; Chronic; Chronic Insomnia; Communication; Complex; Computer software; Cystic Lymphangioma; Development; Disease; Dura Mater; Dural Arteriovenous Fistulas; Effectiveness; Elements; Estrogens; Evaluation; Female; Functional disorder; Geometry; Gonadal Steroid Hormones; Health; Hematoma; Heterogeneity; Hybrids; Image; Image Analysis; Imaging Techniques; Impaired cognition; Impairment; Individual; Knowledge; Lead; Life; Link; Lymphatic; Lymphatic System; Machine Learning; Magnetic Resonance Imaging; Maps; Measurement; Meningeal; Metabolism; Methods; Microscopy; Migraine; Modeling; Molecular; Morphology; Mosaicism; Multiple Sclerosis; Mus; Nerve; Neuraxis; Neuroglia; Neurologic; Neurons; Optical Coherence Tomography; Parietal; Pathogenesis; Pathologic; Pathway interactions; Physiological; Positioning Attribute; Resolution; Route; Sex Differences; Shapes; Site; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Software Tools; Stroke; Structure; Subdural Hematoma; Subdural Hygroma; System; Techniques; Testing; Therapeutic; Therapeutic Intervention; Thinness; Tissues; Translations; Treatment Effectiveness; Vascular Diseases; Vascular remodeling; Vascular resistance; Venous; associated symptom; base; body system; cerebral microvasculature; cerebrovascular; clinically relevant; confocal imaging; deep learning; deprivation; detection limit; diagnostic tool; disability; effectiveness evaluation; geometric structure; in vivo; lymphatic circulation; lymphatic vasculature; lymphatic vessel; machine learning algorithm; male; microleakage; nervous system disorder; neuronal circuitry; noninvasive diagnosis; novel; response; sex; sleep pattern; solute; stem; submicron; translational progress; wasting

Abstract Numerous small vessels making up the central nervous system blood and lymphatic vascular networks are heterogeneous and region-specific dynamic structures, whose segments, position, shape and function can change in response to physiological and pathophysiological conditions. To date it has not been possible to integrate blood and lymphatic vascular elements and their microenvironment to achieve a holistic quantitative characterization of the combined brain and meningeal tissue-scale vascular networks, its structure and function in normal and disease states. This application proposes to develop microscopy- based high-throughput image analysis techniques for automated extraction of blood and lymphatic vascular networks enabling quantitative morphodynamic characterization of cerebrovascular microenvironment changes in two intracranial compartments – the brain and dura mater. The study will focus on new algorithms for precise region-specific microvessel registration, mosaicing, segmentation, fusion and colocalization for constructing large tissue scale spatially aligned dual blood/lymphatic vascular network structural maps in the animals of both sexes, as well as characterization of heterogeneities of microvascular networks, including blood and lymphatic vasculature, under estrogen and sleep deprivation (the conditions relevant to multiple cerebrovascular disorders) compared to physiological settings. In other words, advanced microscopy-based techniques will be used to image blood and lymphatic vessels at sub-micron resolution in dura mater and the brain, and then cutting-edge deep machine learning imaging analysis methods will be employed to segment and quantify these vessels, their geometry, vessel wall structure, functionality, and interrelationship. Detailed structural analysis of microvascular networks is essential for accurate evaluation of the distribution of physical forces, substrate delivery and tissue clearance of waste, as well as sex differences and consequences of intracranial networks remodeling under physiological and pathological conditions. This will create knowledge enabling a better understanding of the pathogenesis of vascular impairments under estrogen and sleep deprivation, identify common molecular mechanisms and the efficacy and effectiveness of different therapeutic treatments. Without the ability to construct total structural and functional blood/lymphatic vascular network maps from studies limited to individual tissue component parts, it is little wonder that translation from the molecular and cellular levels to the whole organ and system levels is deficient and hinders translational progress towards a comprehensive understanding of the pathophysiology associated with a range of neurological disorders.

摘要 构成中枢神经系统血液和淋巴管网络的许多小血管， 异质和区域特定的动态结构，其片段，位置，形状和功能， 对生理和病理生理条件的反应变化。迄今为止， 整合血液和淋巴管成分及其微环境以实现整体 定量表征的组合脑和脑膜组织规模的血管网络，其 正常和疾病状态下的结构和功能。这项申请提出发展显微镜- 基于高通量图像分析技术的血液和淋巴管自动提取 脑血管微环境的定量形态动力学表征网络 两个颅内隔室--大脑和硬脑膜--的变化。该研究将集中在新的 用于精确区域特异性微血管配准、镶嵌、分割、融合和 共定位构建大组织规模空间对齐的双重血液/淋巴血管网络 两种性别动物的结构图，以及微血管异质性的表征 网络，包括血液和淋巴管系统，在雌激素和睡眠剥夺（条件 与多种脑血管疾病相关）。换句话说， 先进的显微镜技术将被用于亚微米的血管和淋巴管成像 硬脑膜和大脑的分辨率，然后进行尖端的深度机器学习成像分析 将采用方法来分割和量化这些血管、它们的几何形状、血管壁结构 功能和相互关系。微血管网络的详细结构分析对于 准确评估物理力的分布、基质输送和废物的组织清除， 以及生理和生理条件下颅内网络重塑的性别差异和后果， 病理条件。这将创造知识，使人们能够更好地了解发病机制， 雌激素和睡眠剥夺下的血管损伤，确定共同的分子机制， 不同治疗方法的功效和效果。如果没有能力构建 仅限于单个组织研究的结构和功能性血液/淋巴管网络图 从分子和细胞水平到整个器官的翻译， 和系统水平是不足的，阻碍了全面理解的转化进展， 与一系列神经系统疾病相关的病理生理学。