Integrated Multiphase Blood Flow Modeling and Experiments Towards Predicting Microvascular Growth

该奖项旨在促进当前对新血管如何在体内生长的理解。这种生长在健康和疾病的许多过程中都是核心的，从胚胎发育和身体衰老的自然变化和修复，到糖尿病、心脏病和癌症中的肿瘤生长。尽管这很重要，但目前人们对现实环境中驱动新血管生长的三维生物物理机制知之甚少。为了满足这一需求，该项目将在内部最先进的模拟平台内开发新的数据驱动模型，将高保真生物物理模拟与正在生长和适应的真实血管网络的高分辨率成像相结合。将进行分析，以在新的细节水平上阐明这种生长行为背后的流体动力学和生物物理特征，以实现预测模型。这个项目将为研究界提供新的数据驱动的模型和研究，这些模型和研究整合了跨学科的概念，并提供了与当地社区接触的机会，并在不同层面上培养学生的指导和教育。新血管的生长，或血管生成，发生在微循环中，其中血管直径与组成血液的单个红细胞的大小相似。虽然众所周知，流体动力学和剪应力驱动血管功能，但目前对血管生成血流动力学的理解是基于降阶方法，忽略了血液流动的基本三维细胞尺度细节。新生血管网络和新的血管萌芽具有独特的复杂的三维几何形状，红细胞通过这些几何形状流动和挤压。由于这些因素导致的壁面剪应力模式以及其他组织侧因素和耦合作用预计将影响血管生成行为，目前尚不清楚。该项目的目标包括通过高保真的红细胞分辨流体模拟发现真实血管新生血管网络中出现的剪应力模式，阐明新血管萌芽内的流体力学及其与生长模式的联系，并开发一种新的三维动态多物理萌芽模型，该模型将多孔介质组织传输与微血管血流动力学相结合，以使血管能够通过组织生长。这项工作的潜在贡献包括帮助预测肿瘤生长模式和指导新的治疗方法，或使更早地发现胚胎发育期间的问题。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This award aims to advance current understanding of how new blood vessels grow in the body. Such growth is central to many processes in health and disease, from embryonic development and natural changes and repairs as the body ages, to diabetes, heart disease, and tumor growth in cancer. Despite the importance, little is currently known about the three-dimensional biophysical mechanisms driving new vessel growth in real environments. To address this need, this project will develop new data-driven models within an in-house state-of-the-art simulation platform, integrating high-fidelity biophysical simulation with high-resolution imaging of real blood vessel networks undergoing growth and adaptation. Analyses will be performed to elucidate characteristics of the fluid dynamics and biophysics underlying this growth behavior at a new level of detail, towards enabling predictive models. This project will provide the research community with new data-driven models and studies which integrate concepts across disciplines, and provide opportunities to engage the local community, and foster mentorship and education of students at various levels.The growth of new blood vessels off existing vessels, or angiogenesis, occurs in the microcirculation where vessel diameters are similar in size to the individual red blood cells which comprise blood. While it is known that fluid dynamics and shear stresses drive vascular function, current understanding of angiogenic hemodynamics is based on reduced-order approaches which neglect essential three-dimensional cell-scale details of blood flow. Angiogenic vessel networks and new vessel sprouts have uniquely complex three-dimensional geometries through which red blood cells flow and squeeze. Wall shear stress patterns due to these considerations are largely unknown, along with other tissue-side factors and coupled interactions expected to influence angiogenic behavior. The goals of this project include discovering shear stress patterns which emerge in real angiogenic vessel networks through high-fidelity red blood cell-resolved fluid simulations, elucidating the fluid mechanics within new vessel sprouts and connections to growth patterns, and developing a new three-dimensional dynamic multiphysics sprout model which couples porous media tissue transport with microvascular hemodynamics to enable vessel growth through tissue. Potential contributions resulting from this work include helping to predict tumor growth patterns and guiding new treatment approaches, or enabling earlier identification of problems during embryonic development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.