AUTOMATED 3D TRACING AND ANALYSIS OF NEUROANATOMY

长期目标是开发计算机软件来执行 对神经元的快速和全自动跟踪。这将消除 当前的枯燥、缓慢、成本、不准确和主观性 手动/半自动追踪法。它将实现新的功能， 例如对大批量样本进行快速定量研究， 对响应于刺激的结构变化进行自动量化， 定量连通性分析，几何尺寸精确测量 体积、长度和弯曲度等功能以及自动化分析 树枝状刺之类的结构。我们之前的工作展示了 选择性染色大鼠海马神经元启动追踪的成功 来自3D共焦图像堆栈。该方法基于3D分割 和骨架提取，然后检测分支和 终止点与图论拓扑的计算 神经元的表示。 这项拟议的研究将把目前的方法扩展到其他显微镜。 医疗模式，包括必要的附加功能，如自动SOMA检测 和图像蒙太奇，并建立执行例程的可行性， 对大批量复杂数据集进行无监督、稳健的处理 涉及各种形态不同的神经元，来自视觉 皮层，以及海马区的CA1和CA3区。 拟议的商业应用：最直接的，尽管有限的， 市场是在对单个神经元的自动跟踪(约100 站点)。对于多个神经元和电路的多个蒙太奇区域， 近期潜在地点包括世界各地的每一所研究型医学院 (2000-5000个站点)。该产品，经过5到10年的时间，将成长为 临床病理学和眼科在示踪中的应用 微血管系统。虽然不是立竿见影的市场，但还有另一个 2000到5000个(或更多)这些未来的临床站点。

The long-term objective is the development of computer software to perform rapid and fully automated tracing of neurons. This will eliminate the tedium, slowness, cost, inaccuracy and subjectivity of current manual/semiautomatic tracing methods. It will enable new capabilities, such as rapid quantitative studies over large batches of specimens, automated quantitation of structural changes in response to stimuli, quantitative connectivity analysis, accurate measurement of geometric features such as volumes, lengths and tortuosities, and automated analysis of structures such as dendritic spines. Our earlier work demonstrated successful tracing of selectively-stained rat hippocampal neurons starting from a 3D confocal image stack. The method was based on 3D segmentation and skeleton extraction, followed by the detection of branching and terminating points, and computation of a graph-theoretic topological representation of the neuron. The proposed research will extend the present method to other microscopy modalities, incorporate needed additions such as automatic soma detection and image montaging, and establish the feasibility of performing routine, unsupervised, and robust processing of large batches of complex data sets involving a variety of morphologically diverse neurons from the visual cortex, and CA1 and CA3 regions of the hippocampus. PROPOSED COMMERCIAL APPLICATION: The most immediate, albeit limited, market is in the automated tracing of individual neurons (about 100 sites). For multiple montaged fields of multiple neurons and circuits, immediate potential sites include every research Medical School worldwide (2000-5000 sites). The product, over 5 to 10 years, will grow into clinical pathology and ophthalmology applications in tracing microvasculature. Although not an immediate market, there are another 2000 to 5000 (or more) of these future clinical sites.