Integrated Multiphase Blood Flow Modeling and Experiments Towards Predicting Microvascular Growth

集成多相血流建模和实验来预测微血管生长

• 批准号: 2309559
• 负责人: Peter Balogh
• 金额: $ 40万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2309559&HistoricalAwards=false
• 关键词: Integrated; Multiphase; Blood; Flow; Modeling

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.

该奖项旨在促进目前对新血管如何在体内生长的理解。这种生长是许多健康和疾病过程的核心，从胚胎发育和自然变化以及随着身体衰老的修复，到糖尿病，心脏病和癌症中的肿瘤生长。尽管重要性，目前很少有人知道的三维生物物理机制驱动新血管生长在真实的环境。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的血管网络的高分辨率成像相结合。将进行分析，以阐明这种生长行为的流体动力学和生物物理学特征，在一个新的细节水平，使预测模型。该项目将为研究界提供新的数据驱动的模型和研究，整合跨学科的概念，并提供参与当地社区的机会，并促进各级学生的指导和教育。新血管的生长脱离现有血管，或血管生成，发生在微循环中，血管直径与组成血液的单个红细胞大小相似。虽然已知流体动力学和剪切应力驱动血管功能，但目前对血管生成血液动力学的理解是基于降阶方法，其忽略了血流的基本三维细胞尺度细节。血管生成血管网络和新血管芽具有独特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。由于这些考虑，壁面剪应力模式在很大程度上是未知的，沿着其他组织侧因素和耦合的相互作用预计会影响血管生成行为。该项目的目标包括通过高保真红细胞分辨流体模拟发现出现在真实的血管生成血管网络中的剪切应力模式，阐明新血管萌芽中的流体力学和与生长模式的连接，并开发一种新的三维动态多物理学萌芽模型，该模型将多孔介质组织运输与微血管血液动力学耦合，以使血管通过组织生长。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，或使早期识别胚胎发育过程中的问题。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。