Informatics Algorithms for Neural Circuitry Ultrastructure

描述(由申请人提供)：本提案的总体目标是创建用于分析神经电路超微结构的信息学算法。确定大脑回路中的详细连接是神经科学中一个基本的尚未解决的问题。了解这一回路将使大脑科学家能够证实或驳斥现有的模型，开发新的模型，并更接近了解大脑是如何工作的。对早产儿的临床成像发现，灰质和白质的正常发育障碍是导致长期不良神经发育结局频繁发生的主要危险因素。对神经元、轴突和突触的成熟度和连通性进行成像和分析的技术的发展，将为研究导致不良预后的损伤机制提供重要的新见解，并有助于寻找成功的干预措施。 电子显微镜成像的最新进展现在提供了以前所未有的分辨率成像大脑超微结构的能力，并具有极大的兴趣。最近的工作是继续将体素的分辨率提高到更小的尺寸，获得更多的体素，同时实现对更大区域的自动捕获。然而，图像采集方面的这些进步还没有与能够使神经电路分析成为可能的算法和实现的进步相匹配。最近的综述指出，发展适当的信息学工具是在理解大脑连通性方面取得新成功的主要要求。 这项建议的具体目的是通过以下方式促进对神经超微结构的分析和解释：1)从2D图像创建3D体积的神经超微结构，2。)从2D相机瓷砖创建神经超微结构的大型2D图像，以及3.)神经超微结构的分割与检测。为了实现这些特定的目标，研究包括开发、实现和评估新的信息学算法，这些算法是专门为满足神经超微结构的高分辨率大数据采集电子显微镜的要求而设计的。

DESCRIPTION (provided by applicant): The overall objective of this proposal is the creation of informatics algorithms for analysis of neural circuitry ultrastructure. Determining the detailed connections in brain circuits is a fundamental unsolved problem in neuroscience. Understanding this circuitry will enable brain scientists to confirm or refute existing models, develop new ones, and come closer to an understanding of how the brain works. Clinical imaging of prematurely born infants has identified disruptions of the normal development of gray matter and white matter as the major risk factors associated with the frequent occurrence of long term adverse neurodevelopmental outcomes. The development of technology for imaging and analyzing the maturation and connectivity of neurons, axons and synapses will provide critical new insight into the mechanisms of injury that cause poor outcomes, and facilitate the search for successful interventions. Recent advances in electron microscopy imaging now provide the capability to image the ultrastructure of the brain at unprecedented resolution with extremely large volumes of interest. Recent work is continuing to increase the resolution of voxels to smaller sizes, acquiring even more voxels, while enabling automated capture of larger regions. However, these advances in image acquisition have not yet been matched by advances in algorithms and implementations that will be capable of enabling the analysis of neural circuitry. Recent reviews have identified the development of appropriate informatics tools as the primary requirement for new success in understanding the connectivity of the brain. The specific aims of this proposal are to facilitate the analysis and interpretation of neural ultrastructure by: 1.) Create 3D Volumes of Neural Ultrastructure from 2D Images, 2.) Create Large 2D Images of Neural Ultrastructure from 2D Camera Tiles, and 3.) Segmentation and Detection of Neural Ultrastructure. The research to achieve each of these specific aims involves the development, implementation and evaluation of novel informatics algorithms especially designed to meet the requirements of high resolution large data acquisition electron microscopy of neural ultrastructure.