Developing a Computational Model to Predict Clot Transport

这项由该奖项支持的研究将开发一种新的工具，以更好地了解生物医学植入物可能发生的潜在危险并发症。在美国，每年有数千名患者成功地植入了心脏瓣膜、支架、导管和血泵等与血液接触的装置。虽然在提高它们的安全性和有效性方面已经取得了巨大的进步，但这些装置中血栓的形成仍然是一个主要问题。当设备中形成血栓时，它可能会阻止设备正常工作，或者从设备中脱离并导致中风等并发症。这项工作将开发一种计算工具来模拟这些设备中的血液流动和生化如何相互作用，从而导致凝血。该工具将利用美国国家科学基金会提供的最先进的超级计算资源。由于最近在批准新的生物医学设备时促进使用这种计算机模拟的努力，这项工作有可能影响人类健康。具体地说，这里开发的模型可以用来提供新设备的安全性和有效性的额外证据，降低开发成本，并缩短上市时间。这项研究结合了几个学科，包括生物化学、物理和高性能计算，将有助于扩大代表不足的群体的参与。各种与血液接触的心血管设备已被证明可以改善心血管疾病患者的预后，但血栓栓塞症仍然是主要的危险因素。这些装置的性质使得血栓栓塞症的体外研究变得复杂和昂贵，在理解装置和身体之间复杂的相互作用方面留下了空白。这项研究的目标是开发一种电子计算机方法来模拟血栓栓塞症，将血液与合成材料之间的生化表面相互作用、凝血级联的动力学以及血液凝块的粘弹性特性纳入流体动力学解算器。重要的模型过程将得到实验验证，包括促凝血剂血浆蛋白的浓度曲线、血栓的机械性能以及发生栓塞的流体动力学条件。为了解决许多模拟过程中的巨大不确定性和现象学问题，将使用蒙特卡洛实验来评估模型预测的可信度。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。

The research supported by this award will develop a new tool to better understand potentially dangerous complications that can occur with biomedical implants. Blood-contacting devices such as a heart valves, stents, catheters, and blood pumps are successfully implanted into thousands of patients every year in the United States. While huge strides have been made in improving their safety and effectiveness, the formation of blood clots in these devices remains a leading problem. When a clot forms in a device, it can prevent it from working properly, or break away from the device and result in complications such as stroke. This work will develop a computational tool to simulate how blood flow and biochemistry in these devices interact to result in clotting. This tool will take advantage of state-of-the-art supercomputing resources made available by the National Science Foundation. Thanks to recent efforts to promote the use of such computer simulations in approval of new biomedical devices, there is potential for this work to impact human health. Specifically, the model developed here may be used to offer additional evidence of safety and effectiveness of new devices, reduce development costs, and shorten time to market. This research combines several disciplines, including biochemistry, physics, and high-performance computing, and will help broaden the participation of underrepresented groups.Various blood-contacting cardiovascular devices have been shown to improve outcomes in patients with cardiovascular disease, but thromboembolism remains as a leading risk factor. The nature of these devices makes in-vitro investigation of thromboembolism complicated and costly, leaving gaps in the understanding of the complex interactions between the device and the body. The goal of this research is to develop an in-silico method to model thromboembolism, incorporating biochemical surface interactions between blood and synthetic materials, the kinetics of the coagulation cascade, and the viscoelastic properties of blood clots into a fluid-dynamics solver. Important model processes will be experimentally validated, including concentration curves of pro-coagulant plasma proteins, clot mechanical properties, and fluid-dynamic conditions where embolization occurs. To address the large uncertainties and phenomenology in many of the simulated processes, Monte-Carlo experiments will be used to evaluate the credibility of the models’ predictions.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.