IMPROVED ANALYSIS OF ELECTRON-MICROSCOPIC AUTORADIOGRAMS

改进电子显微镜自动放射图的分析

• 批准号: 3302247
• 负责人: LEWIS J THOMAS
• 金额: $ 20.18万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3302247
• 关键词: autoradiography; computer graphics /printing; computer program /software; computer simulation; electron microscopy; image processing; personal computers; radiodiagnosis; radiotracer; statistics /biometry

The broad goal of the proposed work is to implement and extend a new method for electron-microscopic autoradiographic (EMA) analysis so that it can be made widely available to biomedical investigators. The new method has been shown in simulation and real-data general use. The new method is based on the maximum-likelihood method of statistics and uses the expectation-maximization algorithm, which leads to recursive equation that was, in its original formulation, too computationally demanding to be practical for conventional computers. Recent reformulations of the algorithm render it computationally practical on small PC-class computers generally available to laboratory investigators. Specific aims are: (1) to implement the new method for small computers in a generalized form that can be accommodated by a wide range of commonly available machines, and offer it to the national community; (2) to develop an EMA simulator which uses the experimental data to produce with every analysis of sets of micrographs, a statistical measure of the reliability of the estimates produced, and which functions as a utility for establishing the experimental requirements necessary for testing biological hypotheses; (3) to determine the fundamental resolving power of the method and how it is influenced by factors affecting point-spread for different radio-isotopes; and (4) to develop an automated EM-image segmentation (structure delineation) method in order to reduce the tedium inherent in current manual methods for data acquisition. The significance of the new method is that in comparison to the cross-fire method (1) it yields estimates of tracer concentrations with much greater accuracy, (2) it is able to produce biologically meaningful results from far fewer EM images and/or at much lower levels of radioactivity, (3) it guarantees global convergence on the maximum-likelihood estimate, thereby eliminating the need for ad hoc "rim compartments." The power of the new method has been demonstrated in a study of sarcolemmal uptake of arachidonic acid by injured myocytes, which has yielded new insights into the pathogenesis of ischemic myocardial injury.

拟议工作的广泛目标是实施和扩展新的 电子 - 微观自显影（EMA）分析的方法，以便它 可以为生物医学研究人员广泛使用。 新方法 已在仿真和真实数据中显示。 新方法是 基于统计的最大样本方法，并使用 期望最大化算法，这导致递归方程 在其原始配方中，计算上的要求太高了 对于传统计算机而言实用。 最近对 算法在小型PC级计算机上渲染计算实用 通常可供实验室调查人员使用。 具体目的是：（1）在 广泛的形式，可以通过广泛的常见来容纳 可用的机器，并将其提供给国家社区； （2）发展 EMA模拟器，该模拟器使用实验数据与每个 分析显微照片集，可靠性的统计度量 产生的估计值，哪个起作用 建立测试所需的实验要求 生物学假设； （3）确定 该方法及其如何受到影响点传播因素的影响 不同的放射性异构体； （4）开发自动em图像 分割（结构描绘）方法，以减少乏味 当前的数据采集手册方法固有。 新方法的意义是与交叉火相比 方法（1）它得出示踪剂浓度的估计值更大 准确性，（2）它能够从生物学上有意义的结果 少于EM图像和/或放射性水平要少得多，（3） 保证全球融合最大样式估计，从而保证 消除了对临时“轮隔室”的需求。 新的力量 在一项研究中已经证明了方法 肌细胞受伤的肌细胞产生了新的见解 缺血性心肌损伤的发病机理。