CAREER: Hybrid Experimental-Computational Modeling Framework for Transformative Research and Multidisciplinary Education in Cardiovascular Biomechanics

心血管疾病或心脏病是美国的主要死因。 有许多类型的心脏病，但它们都以某种方式影响心脏的机械性能-导致心脏难以充分泵送血液到自身和/或身体其他部位。 许多设备正在开发，以解决心脏病的机械影响，但证明他们可以安全有效地工作之前，他们被植入患者可能是一个挑战。 此外，心血管外科医生希望能够根据特定患者的解剖结构和疾病影响确定最佳植入物。 高质量的工程模型为应对这些挑战提供了潜在的解决方案。 然而，目前可用的心血管疾病建模技术存在显著差距。尽管计算和实验室模拟模型取得了重大进展，但在统一框架中利用这些进展的能力仍然遥不可及。该项目将有助于开拓新一代心血管生物力学模型，能够桥接计算和实验方法。研究目标是实现和验证一个完整的混合框架，将实验（模拟）力学与计算生理学相结合。这个新的框架将有选择地利用优势，同时绕过所使用的单个建模方法的限制。这一进展将改变当前的医疗器械开发和治疗计划方法，有助于减少必要的动物和人体试验量，改善临床决策支持，降低开发成本，并加快医疗产品向患者的供应。基于这项研究的教育目标包括通过研究生院跨越K-12的相关课程的管道，在各个层面提供增强，特别强调增加少数民族学生的包容性。这些教育增强将丰富STEM教育，培养下一代多学科工程师，以解决美国老龄化人口最紧迫的医疗需求（心血管健康），建立一个可持续的管道，在生物医学STEM教育中继续培训年轻人。该项目将联合收割机结合现实，计算生理学模型与流体动力学模拟，将捕获心脏的自动调节反应，并允许在混合系统内集成实际的医疗设备。 通过开发一个结合计算和体外建模的硬件在环系统，称为生理学建模耦合实验（PMCE），该项目将从整体上推进心血管建模。 第一个目标是开发强大的耦合方法接口的计算和实验领域，包括：多个实验计算接口;不连续的流量和压力波形;和模拟，包括顺应性元素。 第二个目标是开发一个通用的计算生理学模型，考虑自动调节，因此将产生现实的血液动力学，可以与患者的特征，如身体大小，体重指数，年龄，健身，和代谢状态。 第三个目标是使用描述各种植入物（包括左心室辅助装置、经导管主动脉瓣置换术和Fontan心肺辅助系统）的真实的血液动力学的临床数据来验证混合模型。 综合教育活动将从K-12级别的公共宣传过渡，包括在南卡罗来纳州格林维尔艺术节上的STEAM展览，通过专注于过渡到大学，本科研究和过渡到研究生院的计划。所有的教育活动都有既定的目标，PI将评估这些活动的有效性，以便在适当的情况下进行修改。该奖项反映了NSF的法定使命，并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，被认为值得支持。

Cardiovascular disease, or heart disease, is the leading cause of death in the United States. There are many types of heart disease, but all of them affect the mechanical performance of the heart in some way -- resulting in a heart that struggles to adequately pump blood to itself and/or the rest of the body. Many devices are being developed to address the mechanical affects of heart disease, but proving that they can work safely and effectively before they are implanted in patients can be a challenge. In addition, cardiovascular surgeons would like to be able to identify the best implant for a particular patient based on his or her anatomy and disease-effects. High-quality engineering models offer a potential solution for addressing these challenges. However, there are significant gaps in the currently available technology for modeling of cardiovascular disease. Despite significant advances in computational and laboratory simulation models, the ability to take advantage of these advances in a unified framework is still beyond reach. This project will help pioneer a new generation of cardiovascular biomechanics models capable of bridging computational and experimental approaches. The research objective is to implement and validate a complete, hybrid framework that integrates experimental (simulation) mechanics with computational physiology. This new framework will selectively harness the strengths while bypassing the limitations of the individual modeling approaches used. This advance will transform current medical device development and treatment planning methods, serving to reduce the amount of animal and human testing necessary, improve clinical decision support, reduce development costs, and expedite the availability of medical products to patients. The educational objectives based on this research include a pipeline of related programs spanning K-12 through graduate school, providing enhancements at every level, with a particular emphasis on increasing the inclusion of minority students. These educational enhancements will enrich STEM education and train the next generation of multidisciplinary engineers to tackle the most pressing medical needs of the aging US population (cardiovascular health), establishing a sustainable pipeline for continued training of young minds in biomedical STEM education.This project will combine a realistic, computational physiology model with fluid dynamic simulations that will capture the autoregulation response of the heart and allow the integration of actual medical devices within the hybrid system. By developing a hardware-in-the-loop system that combines computational and in vitro modeling, called a Physiology Modeling Coupled Experiment (PMCE), the project will advance cardiovascular modeling as a whole. The first aim is to develop robust coupling methods to interface the computational and experimental domains, including: multiple experimental-computational interfaces; discontinuous flow and pressure waveforms; and simulations that include compliant elements. The second aim is to develop a generalized computational physiology model that accounts for autoregulation, and will therefore produce realistic hemodynamics that can be related to patient characteristics such as body size, body mass index, age, fitness, and metabolic state. The third aim will be to validate the hybrid model using clinical data that describes real world hemodynamics with various implants, including left ventricular assist devices, transcatheter aortic valve replacement, and Fontan cardiopulmonary assist systems. The integrated educational activities will transition from public outreach at the K-12 level, including STEAM exhibits at the Artisphere Festival in Greenville, SC, through programs focused on transitioning to college, to undergraduate research, and transitioning to graduate school. All educational activities have established objectives, and the PI will assess the effectiveness of these activities so that changes can be made if appropriate.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.