A Computational Framework for the Clinical Evaluation of the Soft Tissue Mechanics in Pregnancy

项目总结/摘要 尽管产前护理取得了进步，但美国和世界各地的早产率仍然很高。 在上升。这一事实强调了我们对早产的原因知之甚少， 新生儿死亡的主要原因。我们的最终研究目标是降低早产率， 通过提供一个有效的计算框架， 确定怀孕期间机械功能障碍的可能性。研究人员和临床医生都知道， 胎儿周围软组织的健康机械功能对于成功的 怀孕特别地，子宫、胎膜和子宫颈必须承受机械力， 保护、支持和维持发育中的婴儿的最佳生长环境。的 这些组织的应力和拉伸的大小被认为控制生理过程， 调节组织生长、重塑、收缩性和破裂，并且通常假设， 这些机械信号是正常分娩和早产的临床提示。然而，机械 这些组织在怀孕期间的应力和拉伸尚未确定，限制了 了解怀孕期间重要的机械生物学过程。为了了解是什么导致了 机械功能障碍在怀孕期间，我们将建立一个有限元（FE）模拟框架， 确定驱动子宫、宫颈和胎膜组织的解剖学和/或材料因素 重塑和变形。为了建立和验证这些计算模型，我们将纵向 测量低- 在整个怀孕期间早产的风险。我们还将进行多尺度结构-功能 对离体宫颈、子宫和胎膜组织的研究，以使我们的模型具有子宫内膜的特征 组织超微结构。然后，我们将构建一个灵活的、参数化的FE框架， 可以直接结合我们的实验测量。最后，我们将验证FE框架， 根据实验证据评估模型的预测能力，我们将 进行材料和几何参数的敏感性研究，以揭示 组织应力和拉伸。在完成我们建议的研究后，我们将有一个 怀孕的计算模型，可以识别宫颈，子宫， 胎儿膜变形，并指导适当的临床研究的发展， 早产风险高的妇女。

PROJECT SUMMARY/ABSTRACT Despite advances in prenatal care, the rate of preterm birth in the US and around the world remains on the rise. This fact underscores how little we know about the causes of preterm birth, which is a leading cause of neonatal deaths. Our ultimate research goal is to reduce the preterm birth rate and the associated emotional and societal costs by providing a validated computational framework to identify the potential for mechanical dysfunction in pregnancy. Researchers and clinicians know that the healthy mechanical function of soft tissues surrounding the fetus is crucial for a successful pregnancy. Particularly, the uterus, fetal membrane, and cervix must withstand mechanical forces to protect, support, and maintain an optimal growth environment for the developing baby. The magnitude of stress and stretch of these tissues are thought to control physiologic processes that regulate tissue growth, remodeling, contractility, and rupture, and it is generally hypothesized that these mechanical signals are clinical cues for normal labor and preterm birth. Yet, the mechanical stress and stretch of these tissues during pregnancy have not been determined, limiting the understanding of vital mechnobiology processes in pregnancy. To understand what causes the mechanical dysfunction in pregnancy, we will build a finite element (FE) simulation framework to identify the anatomical and/or material factors that drive uterine, cervical, and fetal membrane tissue remodeling and deformation. To build and validate these computational models we will longitudinally measure the anatomical features and cervical tissue properties of pregnant patients who are at low- risk for preterm birth throughout pregnancy. We will also conduct multi-scale structure-function studies on ex vivo cervical, uterine, and fetal membrane tissue to equip our model with features of the underlying tissue ultrastructure. We will then construct a flexible, parameterized FE framework that can directly incorporate our experimental measurements. Lastly, we will validate the FE framework by assessing the predictive capabilities of the model based on experimental evidence, and we will conduct a sensitivity study of material and geometric parameters to uncover the driving factors of tissue stress and stretch. Upon completion of our proposed research study, we will have a computational model of pregnancy that can identify the mechanistic cause of cervical, uterine, and fetal membrane deformation and guide the development of appropriate clinical studies that target women who are at high-risk for preterm birth.