Experimental and computational investigation of mechanical function as influenced by shape and material properties in native and surgically modified heart valves

拟议研究计划的目标： 目前结构工程模型的预测还不够可信，无法纳入心脏瓣膜修复的患者特定手术计划。因此，在主动脉瓣和二尖瓣泄漏的情况下，其中天然缺陷瓣膜的功能恢复（修复）通常比用假体置换更理想，心脏外科医生必须独自掌握几何形状和材料性质的复杂相互作用以固定瓣膜。拟议的研究计划旨在解决心脏瓣膜手术修复的结构工程模型的相关性和可靠性方面的不足。具体目标是：1）获取新的实验数据，以建立更准确的工程模型，2）开发新的计算机模拟验证方法，以及3）扩展现有的工程模拟工具，以处理高度手术相关的病例。由此产生的模拟最终旨在提供可在临床试验中进一步评估的可操作信息（本提案中不包括符合逻辑的下一步）。 科学方法概述： 科学方法将包括一系列相互关联的项目，包括组织和器官水平的实验、计算建模以及实验和建模之间的综合。具体而言，将收集关于人类瓣膜组织的新实验数据，用于精确的工程建模;将开发和验证正常和患病心脏瓣膜的物理模型，用于实验室外科手术的受控测试;将根据组织和器官水平的实验数据彻底验证有限元模拟;并将开发新的指标来评估计算模拟和临床成像之间心脏瓣膜动态功能的差异，以合理化和简化模型验证过程。 工作的新奇性和预期意义： 拟议的计划将在心脏瓣膜修复手术的工程模拟方面开辟新天地。它将直接提高基础科学和工程知识，并以具体和可量化的方式将有用的，相关的工程工具带到床边，同时为至少八名HQP提供高级培训。除了工程模型和方法方面的预期进展外，拟议的计划尤其重要，因为由于加拿大和其他地方人口老龄化，瓣膜病患者的数量不断增加。总的来说，这个加拿大计划将加强申请人的小组在国际舞台上作为心血管生物医学工程研究的领导者的地位。

Objectives of the proposed research program: The current predictions from structural engineering models are not yet trustworthy enough to be factored into the patient-specific surgical planning of heart valve repairs. As a result, in cases of aortic and mitral valve leakage, where restoration of functionality in the native defective valve (repair) is generally more desirable than the replacement with a prosthesis, cardiac surgeons must single-handedly master the complex interplay of geometry and material properties to fix the valve. The proposed research program aims to address the deficit in relevance and reliability of structural engineering models for the surgical repair of heart valves. The specific objectives are: 1) the acquisition of new experimental data to establish more accurate engineering models, 2) the development of new validation methods for computer simulations, and 3) the expansion of existing engineering simulation tools to handle cases of high surgical relevance. The resulting simulations are ultimately meant to provide actionable information that can be further evaluated in clinical trials (a logical next step not included in this proposal). Summary of scientific approach: The scientific approach will consist in a series of mostly interconnected projects mixing experiments at the tissue and organ levels, computional modeling, and synthesis between experiments and modeling. Specifically, new experimental data will be collected on human valvular tissues for accurate engineering modeling; physical models of normal and diseased heart valves will be developed and validated for the controlled testing of surgical procedures in the lab; finite element simulations will be thoroughly validated against experimental data at the tissue and organ levels; and new metrics will be developed to evaluate the discrepancies in the dynamic function of heart valves between computational simulations and clinical imaging, to rationalize and ease the process of model validation. Novelty and anticipated significance of the work: The proposed program will break new ground regarding engineering simulations for heart valve repair surgeries. It will directly improve basic science and engineering knowledge, as well as bring useful, relevant, engineering tools closer to the bedside in concrete and quantifiable ways, while providing advanced training to at least eight HQP. In addition to the anticipated progress regarding engineering models and methods, the proposed program is especially relevant because the number of patients with valvular disease keeps growing due to the aging of the population in Canada and elsewhere. Overall, this Canadian program will reinforce the position of the applicant's group on the international scene as a leader in cardiovascular biomedical engineering research.