Computational and Statistical Framework to Model Tissue Shape and Mechanics

项目摘要 组织的形态学和机械特征是理解组织的基本特征的基础。 人体的发育、稳态和病理学。在上一次融资期间，我们 开发了统计形状建模（SSM）方法，并将其应用于结构性髋关节疾病的研究。 我们还开发了初始框架，将SSM与有限元（FE）分析相结合，以实现研究 形状和力学的结合。如果纳入临床实践，SSM和FE分析可以识别 可能导致损伤、重塑或修复的解剖结构特征。SSM和FE所需的几何结构 模型通常通过分割体积成像数据来生成。这一步可能会非常缓慢， 容易出错且成本过高，这阻碍了这些计算技术的临床应用。我们 创建了一个深度机器学习算法“DeepSSM”，该算法使用卷积神经网络来 直接从未分割的图像建立对应关系模型。在目标1中，我们将DepSSM应用于 通过描述解剖学差异提高对结构性髋关节疾病临床认识 有症状和无症状的个体;这些形态学比较将识别解剖特征 最能说明疾病，从而指导诊断的改进。计算技术的进步 简化了生成患者特定FE模型的过程，从而实现了临床重点研究。然而，在这方面， 没有框架来共同地可视化、比较和解释（即，后处理）结果 FE模型。目前，受试者间比较需要过度简化，例如对结果取平均值 主观定义的区域。在目标2中，我们将开发新的后处理方法来集体可视化， 解释和统计分析多个受试者和研究组的FE结果。我们将绘制FE结果 涉及使用对应模型表示统计上有意义的分布的合成解剖结构。 将应用统计参数标测以通过统计测试保留解剖细节。我们将 使用我们发布的髋关节力学有限元模型作为测试系统。最后，体积图像提供了 以熟悉的格式提供给医生的丰富信息。然而，没有工具可以解释 模型数据与来自体积图像的临床发现。在目标3中，我们将开发评估 通过综合分析从成像中收集的形状、力学和临床结果之间的关系 统计测试和利用标准本体的半自动医学图像注释工具。 髋关节的定量CT和MRI图像，估计骨密度和软骨超微结构， 将分别作为测试数据集进行评价。为了产生广泛的影响，我们将把我们的方法传播给 社区作为开源软件，将调用现有开源软件提供的核心功能， 拥有庞大用户群的软件（FEBio、ShapeWorks）。

PROJECT SUMMARY The morphologic and mechanical characteristics of a tissue are fundamental to understanding the development, homeostasis, and pathology of the human body. During the previous period of funding, we developed statistical shape modeling (SSM) methods and applied these to the study of structural hip disease. We also developed the initial framework to integrate SSM with finite element (FE) analysis to enable the study of shape and mechanics together. If incorporated into clinical practice, SSM and FE analysis could identify features of the anatomy likely responsible for injury, remodeling, or repair. Geometry needed for SSM and FE models is typically generated by segmentation of volumetric imaging data. This step can be painstakingly slow, error prone, and cost prohibitive, which hampers clinical application of these computational techniques. We have created a deep machine learning algorithm ‘DeepSSM’ that uses a convolutional neural network to establish the correspondence model directly from unsegmented images. In Aim 1 we will apply DepSSM to improve clinical understanding of structural hip disease by characterizing differences in anatomy between symptomatic and asymptomatic individuals; these morphometric comparisons will identify anatomic features most telling of disease, thereby guiding improvements in diagnosis. Computational advancements have simplified the process to generate patient-specific FE models, enabling clinically focused research. However, there is no framework to collectively visualize, compare, and interpret (i.e., post-process) results from multiple FE models. Currently, inter-subject comparisons require oversimplifications such as averaging results over subjectively defined regions. In Aim 2 we will develop new post-processing methods to collectively visualize, interpret and statistically analyze FE results across multiple subjects and study groups. We will map FE results to synthetic anatomies representing statistically meaningful distributions using the correspondence model. Statistical parametric mapping will be applied to preserve anatomic detail through statistical testing. We will use our published FE models of hip joint mechanics as the test system. Finally, volumetric images provide a wealth of information that is delivered to physicians in a familiar format. Yet, tools are not available to interpret model data with clinical findings from volumetric images. In Aim 3, we will develop methods that evaluate relationships between shape, mechanics, and clinical findings gleaned from imaging through integrated statistical tests and semi-automatic medical image annotation tools that utilize standard ontologies. Quantitative CT and MRI images of the hip, which estimate bone density and cartilage ultrastructure, respectively, will be evaluated as test datasets. To impart broad impact, we will disseminate our methods to the community as open source software that will call core functionality provided by existing, open source software that has a large user base (FEBio, ShapeWorks).