As a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge. Here, we propose an approach that integrates dynamic intravital imaging with computer geometric modeling and computational flow and transport modeling to develop a unified in silico framework to quantify the dynamic clot-flow interactions. We outline the development of the methodology referred to as Intravital Integrated In Silico Modeling or IVISim, and then demonstrate the method on a sample set of simulations comprising clot formation following laser injury in two mouse cremaster arteriole injury model data: one wild-type mouse case, and one diYF knockout mouse case. Simulation predictions are verified against experimental observations of transport of caged fluorescent Albumin (cAlb) in both models. Through these simulations, we illustrate how the IVISim methodology can provide insights into hemostatic processes, the role of flow and clot-flow interactions, and enable further investigations comparing and contrasting different biological model scenarios and parameter variations.

当血管损伤后血凝块形成、生长、变形和栓塞时，局部凝块-流动相互作用导致高度动态的流动环境。局部流动影响与凝血相关的生化物质的运输，并确定作用在凝块上的力，进而导致凝块变形和栓塞。尽管发挥了这一核心作用，但对凝块附近的动态凝块流动相互作用和流动环境进行定量表征仍然是一个重大挑战。在这里，我们提出了一种将动态活体成像与计算机几何建模以及计算流和传输建模相结合的方法，以开发统一的计算机框架来量化动态血块流相互作用。我们概述了被称为“活体集成硅片建模”或“IVISim”的方法的发展，然后在一组模拟样本上演示了该方法，其中包括两个小鼠提睾小动脉损伤模型数据中激光损伤后的凝块形成：一个野生型小鼠病例，以及一个 diYF 敲除鼠标盒。模拟预测根据两个模型中笼状荧光白蛋白 (cAlb) 运输的实验观察进行了验证。通过这些模拟，我们说明了IVISim方法如何深入了解止血过程、血流和血凝块-血流相互作用的作用，并能够通过比较和对比不同的生物模型场景和参数变化进行进一步的研究。