Development of diagnostic and predictive computational mechanics methods for cardiovascular system

心血管系统的主要功能是运输、控制和维持全身的血液流动。异常的血流动力学极大地改变了这种平静的画面，导致疾病的发生和发展。心血管疾病是全球死亡的主要原因。在加拿大，每四个死亡中就有一个死于心血管疾病。血流定量对准确、早期诊断有很大帮助，但对许多心血管疾病仍缺乏适当的诊断方法。此外，由于大多数干预措施旨在恢复健康状况，因此预测特定干预措施后的血液动力学和生物力学的能力对挽救生命具有重大影响。尽管医学成像取得了显著进步，但预测方法仍然很少。******本提案的主要目标是开发计算力学框架，用于诊断和预测最基本的挑战条件：复杂心室-瓣膜相互作用（CVVI）。CVVI代表多种瓣膜和心室病变彼此之间有机械相互作用的情况，其中与每种病理相关的物理现象放大了其他病理对心血管系统的影响。经导管瓣膜置换术（Transcatheter valve replacement， TVR）是治疗严重瓣膜病变的一种微创治疗方法。研究表明，许多患者在TVR后经历了显著的改善，但在许多其他患者中，CVVI恶化或改变为其他形式的CVVI。由于CVVI的病理本质上是流体动力学性质，它们最好用力学来量化。事实上，即使是新兴的治疗创新，如TVR，本身也是机械的。然而，迄今为止，很少有人使用基本力学来诊断这些病理和预测对干预措施的反应。心脏位于复杂的血管网络中，其负荷对心脏功能施加边界条件。有效的诊断和预测取决于心脏负荷的量化（整体效应）和CVVI和TVR的血流动力学（局部效应）。******本提案解决了深刻的科学和工程挑战，以发展以下创新的计算力学诊断和预测方法：******(1)计算力学和基于成像的诊断方法：*** (a)局部：利用拉格朗日相干结构（LCS）对CVVI和TVR中的涡旋动力学、流体输运和混合进行无创量化；*** (b)全局：无创量化全局血流动力学，根据心脏负荷诊断CVVI中存在的病理。******(2)一种多尺度预测计算力学框架，将干预前局部血流动力学与整体循环心血管系统动态耦合，以预测tvr后局部和整体血流动力学。

The main functions of the cardiovascular system are to transport, control and maintain blood flow in the entire body. Abnormal hemodynamics greatly alters this tranquil picture, leading to initiation and progression of disease. Cardiovascular disease is the leading cause of death globally. In Canada, one in every four deaths is from cardiovascular disease. Flow quantification can be greatly useful for accurate and early diagnosis but we still lack proper diagnostic methods for many cardiovascular diseases. Furthermore, as most interventions intend to recover the healthy condition, the ability to predict hemodynamics and biomechanics following a particular intervention can have significant impacts on saving lives. Despite remarkable advances in medical imaging, predictive methods remain rare.******The main objective of this proposal is developing computational-mechanics frameworks for diagnosis and prediction for the most fundamentally challenging condition: complex ventricular-valvular interactions (CVVI). CVVI represent conditions in which multiple valvular and ventricular pathologies have mechanical interactions with one another wherein physical phenomena associated with each pathology amplify effects of others on the cardiovascular system. Transcatheter valve replacement (TVR) is a minimally invasive and growing alternative intervention in patients with severe valvular pathologies. It was shown that many patients experience a significant improvement after TVR but in many others CVVI worsens or changes to other forms of CVVI. As pathologies in CVVI are essentially of fluid-dynamic nature, they are best quantified using mechanics. Indeed, even the emerging innovations in therapeutics such as TVR are themselves mechanical. Yet, few to date have used basic mechanics for diagnosis of these pathologies and for prediction of response to interventions. The heart resides in a sophisticated vascular network whose loads impose boundary conditions on the heart function. Effective diagnosis and prediction hinge on quantifications of the heart workload (global effect) and of hemodynamics of CVVI and TVR (local effect).******This proposal tackles profound scientific and engineering challenges to develop the following innovative computational-mechanics methods for diagnosis and prediction:******(1) Computational-mechanics and imaging-based diagnostic methods: *** (a) Local: to noninvasively quantify vortex dynamics, fluid transport, and mixing in CVVI and TVR using Lagrangian coherent structures (LCS); *** (b) Global: to noninvasively quantify global hemodynamics to diagnose pathologies present in CVVI in terms of heart workload.******(2) A multiscale predictive computational-mechanics framework that dynamically couples the local hemodynamics with the global circulatory cardiovascular system in pre-intervention condition to predict local and global hemodynamics post-TVR.