CDS&E: Uncertainty Quantification and Bayesian Updating in Data-Driven Cardiovascular Modeling

心血管疾病是美国和世界面临的主要问题之一。虽然心血管血流动力学的模拟现在被用于研究基本过程，但由于几个不确定性，在为患者做出临床决策之前，缺乏对个性化模拟结果的信任。这正是这项提案的目的所在，调查这些不确定性并开发技术，以便做出知情的医疗决定。联合PIS建议将他们的计算工具作为开放源码程序进行传播。虽然众所周知，心血管模拟需要大量的假设和不确定的临床数据的同化，但这些不确定性目前被掩盖了，要求最终用户将确定性模拟预测接受为没有相关统计数据的“真理”。因此，研究人员和临床医生不禁要问，“鉴于无数的不确定性，模拟预测的可靠性如何？”以及“产出预测的统计数据如何随着不同的方法和假设而变化？”这些问题导致了研究和临床社区合理的怀疑，并成为采用的障碍。目前该领域缺乏评估不确定性的变革性技术的开发，对于安全和常规地采用模拟进行个性化医学和生物力学研究至关重要。这就是这项提案要涵盖的领域，因为它渴望开发能够导致纳入数据驱动的心血管模型的技术，以便为围绕药物治疗、装置放置、手术方法和个别患者干预措施的选择提供决策信息。该建议有两个目标：1)开发快速的自动化方法，用于参数估计和将不确定数据同化到多尺度模型中；2)开发一个有效的框架，将不确定性从临床和成像数据传播到模拟预测。建议通过将不确定性量化(UQ)框架应用于冠状动脉疾病(CAD)的多尺度模拟来演示该框架，尽管该框架将适用于广泛的其他心血管和呼吸系统疾病。模拟将在使用多级并行算法结构的高性能计算(HPC)环境中运行。最终目标是解决心血管模拟中目前尚未回答的可靠性和稳健性问题。这项工作的结果如果成功，将使人们能够接受计算模型，并建立可靠性衡量标准，以指导模型改进和数据收集。心血管模拟有可能为个别患者提供个性化的治疗方法，并表征体内的机械环境，提供从医学成像中无法轻易获得的关键生物力学数据。所提出的计算框架可以应用于生物医学计算、生物建模和使用计算流体动力学的工程应用中的一系列问题。传播将通过对SimVculate开源项目的贡献来实现，Marsden博士是该项目的PI。建议在研究生课程中引入统计学概念，并向初中生推广，使研究与教学相结合的活动。

CBET - 1508794Marsden, Alison L.Cardiovascular disease is one of the major problems facing US and the world. While simulations of cardiovascular hemodynamics are now being used to study fundamental processes, trust in personalized simulation results before making clinical decisions for a patient is absent due to several uncertainties. This is exactly what this proposal is about, investigating these uncertainties and developing techniques to allow informed medical decisions. The co-PIs propose to disseminate their computational tools as open source programs. Though it is well known that cardiovascular simulations require numerous assumptions and assimilation of uncertain clinical data, these uncertainties currently get swept under the rug, asking end-users to accept deterministic simulation predictions as "truth" with no associated statistics. As a result, researchers and clinicians are left to wonder "How reliable are simulation predictions in light of myriad uncertainties?" and "How do the statistics on output predictions change with differing methodologies and assumptions?". These questions lead to justified skepticism in the research and clinical community, and are a roadblock to adoption. Development of transformative technology to assess uncertainty, currently lacking in the field, is of paramount importance for safe and routine adoption of simulations for personalized medicine and biomechanics research. This is the area that this proposal comes to cover, as it aspires to develop techniques that can lead to the incorporation of data-driven cardiovascular models to inform decisions surrounding choices of drug therapy, device placement, surgical methods and interventions for individual patients. The proposal has two goals: 1) Develop fast automated methods for parameter estimation and assimilation of uncertain data into multiscale models, 2) Develop an efficient framework to propagate uncertainties from clinical and imaging data to simulation predictions. It is proposed to demonstrate the uncertainty quantification (UQ) framework through application to multiscale simulations of coronary artery disease (CAD), though the framework will apply to a wide range of other cardiovascular and respiratory diseases. Simulations will be run in a high performance computing (HPC) environment using a multi-level parallel algorithm structure. The ultimate goal is to address currently unanswered questions about reliability and robustness in cardiovascular simulation. Results from this work, if successful, would enable acceptance of computational models and establish reliability metrics to guide model improvement and data collection. Cardiovascular simulations have potential to personalize treatments for individual patients and to characterize the in vivo mechanical environment, providing key biomechanical data that cannot be readily obtained from medical imaging. The proposed computational framework could be applicable to a range of problems in biomedical computing, biological modeling, and engineering applications using computational fluid dynamics. Dissemination will be achieved through contributions to the SimVascular open source project, for which Dr. Marsden is the PI. Activities that integrate research and teaching by introducing statistics concepts in graduate level courses and through outreach to middle and high school students are proposed.