Imaging the molecular constituents of the brain vasculature and lymphatic connectome

对脑脉管系统和淋巴连接组的分子成分进行成像

• 批准号: 10834499
• 负责人: David Kleinfeld
• 金额: $ 10万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10834499
• 关键词: Ablation; Atlases; Biological; Blood Vessels; Blood flow; Bone Tissue; Brain; Cerebrovascular Circulation; Cerebrovascular system; Circulation; Complex; Deterioration; Excision; Goals; Image; Imaging technology; Immune response; Label; Lymphatic; Lymphatic System; Meningeal; Meningeal lymphatic system; Meninges; Modeling; Molecular; Mus; Optical Methods; Organ; Pilot Projects; Preparation; Resolution; Sampling; Specificity; Structure; System; Tissues; Waste Products; Work; brain tissue; cell type; connectome; cranium; lymphatic vessel; molecular imaging; soft tissue; three dimensional structure

PIs: David Kleinfeld and Zhuhao Wu Project Summary Imaging the molecular constituents of the brain vasculature and lymphatic connectome The intricate connectivity of the brain vasculature that extends into the skull and the meningeal lymphatic vessels are vital in the systematic cerebral blood flow circulation, immunological responses, and waste product removal. However, our understanding of these complex networks remains limited, largely because of the challenges in imaging the complete three-dimensional structure of these structure at high resolution in heterogeneous biological tissues. Recent technical advances on two fronts, one in molecular characterization and labeling, and the other in tissue clearing, led to the discovery of skull-meninge vascular connections. However, wavefront distortion through imperfectly cleared skull and brain tissue severely deteriorate the resolution of imaging at depth. Here we propose to advance sample preparation and imaging technologies that are compatible with labeling and that mitigate the loss in resolution. Our optical methods involve non-linear imaging as well as the use of femtosecond ablation with temporal focussing of bone and soft tissue. This will enable us to obtain diffraction-limited resolution images at the skull/meningeal/brain transition zone. This pilot project will establish a pipeline to image and reconstruct the entire vasculature system and lymphatic system at cellular resolution in the mouse brain. This is a prelude to the long-term goal of imaging and reconstructing similar atlases for all organs in the body.

PI：大卫克莱菲尔德和吴祝豪 项目摘要 脑血管和淋巴连接体的分子组成成像 延伸到颅骨和脑膜淋巴管的脑血管系统的复杂连接 在系统性脑血流循环、免疫反应和废物清除中至关重要。 然而，我们对这些复杂网络的理解仍然有限，主要是因为 以高分辨率在不均匀介质中对这些结构的完整三维结构成像 生物组织 两个方面的最新技术进展，一个是分子表征和标记，另一个是组织 清理，导致发现头骨脑膜血管连接。然而，波前畸变通过 不完全清除的颅骨和脑组织严重恶化了深度成像的分辨率。这里我们 建议推进与标签兼容的样品制备和成像技术， 减少分辨率的损失。我们的光学方法包括非线性成像以及使用飞秒 骨和软组织的暂时聚焦的消融。这将使我们能够获得衍射极限分辨率 颅骨/脑膜/大脑过渡区的图像。 该试点项目将建立一个管道，以成像和重建整个脉管系统和淋巴系统。 系统在小鼠大脑中的细胞分辨率。这是一个前奏的长期目标的成像和 重建身体所有器官的相似图谱。