Image-Based Modeling of Ca2+ Signaling in Ventricular Myocytes

基于图像的心室肌细胞 Ca2 信号传导建模

基本信息

批准号：
7940176
负责人：
Zeyun Yu
金额：
$ 36.42万
依托单位：
UNIVERSITY OF WISCONSIN MILWAUKEE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-21 至 2013-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7940176
关键词：
Academic Research Enhancement Awards Algorithms Anatomic Models Apoptosis Architecture Binding Biological Calcium Calcium Signaling Cardiac Cardiac Myocytes Cell physiology Cells Cellular Structures Cessation of life Communities Computers Country Coupling Data Disease Doctor of Philosophy Electrons Elements Encapsulated Environment Event Fertilization Generations Goals Heart Atrium Heart Diseases Heart failure Human Image Imagery Membrane Methods Microscopic Modeling Monte Carlo Method Muscle Cells Myocardial Contraction Organelles Play Prevalence Principal Investigator Process Proteins Recovery Research Role Sarcoplasmic Reticulum Signal Transduction Specific qualifier value Surface Techniques Testing Three-Dimensional Imaging To specify United States United States National Institutes of Health Variant Ventricular base bioimaging fundamental research graphical user interface image processing interest mathematical model membrane model models and simulation public health relevance response simulation tool user-friendly

项目摘要

DESCRIPTION (provided by applicant): Calcium has been one of the most versatile biological messengers in a cell, playing critical roles in regulating the cell's functions. In particular, the transient change of calcium concentration in cardiac muscle cells (myocytes) forms the basis of cell-wide contraction that eventually results in the whole heart contraction. Studying calcium signaling in cardiac myocytes is thus a fundamental research topic in understanding the excitation-contraction (E-C) coupling in the cells and ultimately revealing the microscopic mechanism of heart disease. The main goal of the present proposal is to utilize three-dimensional (3D) electron microscopic (EM) images and mathematical simulation techniques to explore image-based modeling of calcium signaling in ventricular myocytes to achieve a realistic understanding of the microscopic environment of heart disease. The specific aims of the proposed studies are: (A) Constructing realistic geometric models from advanced 3D EM imaging data. Efficient computational approaches of image processing, analysis and geometric modeling will be developed and implemented to extract the sub-cellular structures of interest and to construct high-fidelity, high-quality surface and volumetric meshes that will be used in the subsequent mathematical simulation. (B) Characterizing calcium signaling using both stochastic and deterministic methods. We shall explore how unitary calcium release events (i.e. calcium sparks) are formed within/around a single CRU using the Monte Carlo method. Anatomical models extracted from 3D EM images will be used to specify the simulation domains. In addition, finite element (deterministic) methods will be employed to investigate the calcium signaling (waves) across CRUs, where the simulation domains will be specified with realistic geometric models extracted from advanced 3D EM images. Both normal and diseased ventricular myocytes will be investigated. (C) Developing a graphical user interface (GUI) to streamline anatomical modeling and visualization of biomedical images. A user-friendly GUI will be created to encapsulate all the computational modules for image processing, feature extraction, and mesh generation. This toolkit is made to streamline multiple computational processes from 2D/3D images to 3D anatomical models and will be made available to the biomedical community. PUBLIC HEALTH RELEVANCE: Heart failure has been one of the leading causes of human deaths in many countries including the United States. The prevalence of this disease is largely due to our lack of accurate understanding of excitation-contraction (E-C) coupling in cardiomyocytes. Computer and mathematical modeling of calcium signaling has been an important way to achieve this goal. The proposed study will enable us to model calcium signaling using the structural information extracted from the 3D imaging data, which would provide a more realistic and accurate understanding of the mechanism of heart disease.

描述（由申请人提供）：钙是细胞中最通用的生物信使之一，在调节细胞功能中发挥着关键作用。特别是，心肌细胞（肌细胞）中钙浓度的瞬时变化形成了细胞范围收缩的基础，最终导致整个心脏收缩。因此，研究心肌细胞中的钙信号传导是了解细胞中兴奋-收缩（E-C）耦合并最终揭示心脏病微观机制的基础研究课题。本提案的主要目标是利用三维（3D）电子显微镜（EM）图像和数学模拟技术来探索心室肌细胞中钙信号传导的基于图像的建模，以实现对心脏病微观环境的真实理解。拟议研究的具体目标是： (A) 从先进的 3D EM 成像数据构建真实的几何模型。将开发和实施图像处理、分析和几何建模的有效计算方法，以提取感兴趣的亚细胞结构，并构建将在后续数学模拟中使用的高保真、高质量表面和体积网格。 (B) 使用随机和确定性方法表征钙信号传导。我们将探索如何使用蒙特卡罗方法在单个 CRU 内/周围形成单一钙释放事件（即钙火花）。从 3D EM 图像中提取的解剖模型将用于指定模拟域。此外，将采用有限元（确定性）方法来研究跨 CRU 的钙信号（波），其中将使用从高级 3D EM 图像提取的真实几何模型来指定模拟域。将研究正常和患病的心室肌细胞。 (C) 开发图形用户界面 (GUI) 以简化生物医学图像的解剖建模和可视化。将创建一个用户友好的 GUI 来封装用于图像处理、特征提取和网格生成的所有计算模块。该工具包旨在简化从 2D/3D 图像到 3D 解剖模型的多个计算过程，并将提供给生物医学界。公共卫生相关性：心力衰竭一直是包括美国在内的许多国家人类死亡的主要原因之一。这种疾病的流行很大程度上是由于我们对心肌细胞的兴奋-收缩（E-C）耦合缺乏准确的理解。钙信号传导的计算机和数学建模是实现这一目标的重要途径。拟议的研究将使我们能够利用从 3D 成像数据中提取的结构信息对钙信号传导进行建模，这将提供对心脏病机制的更现实和准确的理解。