Multi-Physics Modeling and Meshless Methods for Atherosclerotic Plaque Progression

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Cardiovascular disease (CVD) is the leading cause of death in the developed world and is expected to become the leading cause of death worldwide by 2020. In the US alone, 36% of 45 year olds and 80% of those 75 and older have CVD (American Heart Association Statistics 2005). Atherosclerotic plaques may rupture without warning and cause acute cardiovascular syndromes such as heart attack and stroke. Many victims of the disease who are apparently healthy die suddenly without prior symptoms. Non-invasive screening and diagnostic methods are urgently needed to identify the victims early and avoid those tragic events. The objective of this project is to combine computational modeling, magnetic resonance imaging (MRI) and pathological analysis to simulate plaque progression and quantify critical blood flow and plaque stress/strain conditions under which plaque rupture is likely to occur. MRI and pathological analysis will be used to quantify human carotid plaque morphology and progression and to assess plaque vulnerability. For the first time, multi-year MRI patient-tracking data will be obtained to quantify human atherosclerotic plaque progression. MRI-based three-dimensional (3D) computational models with multi-component plaque structure and fluid-structure interactions (FSI) will be developed and solved by numerical methods based on the meshless local Petrov-Galerkin (MLPG) method to obtain critical flow and plaque stress/strain conditions, to identify suitable plaque rupture risk indicators for more accurate plaque assessment, and to simulate plaque progression for early prediction and diagnosis of related cardiovascular diseases.The computational model, MLPG method, and a better understanding of plaque progression and rupture will be considerable contributions to computational mathematics, biological sciences, bioengineering, especially in the cardiovascular research area with realistic potential clinical applications. The combination of computational fluid dynamics, solid mechanics, MRI multi-spectral plaque analysis and patient tracking, in vitro plaque modeling, and histopathological analysis can create a realistic integrative model for plaque progression and rupture. The models and methods will be applicable to problems in biological and material sciences involving multi-physics, growth, and moving geometries. This integrative computational model can be adapted to other less costly non-invasive modalities such as ultrasound to facilitate a wider use. This collaborative project will establish a research-teaching infrastructure that facilitates multi-disciplinary research-teaching activities for all related areas. Multi-disciplinary courses will be developed and offered to graduate and undergraduate students. Participation of underrepresented groups (African Americans, women, people with disabilities, and other minority groups) will be strongly encouraged. The multi-disciplinary oriented graduates will have skills and knowledge in applied and computational mathematics, bioengineering, and general biological applications. Research progress will be posted on the web with frequent updates, presented at professional meetings, and published in professional journals. Success of this project will lead to a better and quantitative understanding of plaque progression and rupture and considerable improvement in accuracy, reliability and applicability of computational modeling in real life biological applications. Improved diagnosis of all stages of carotid atherosclerosis will expand options for early treatment and result in a reduction of cerebrovascular events and healthcare costs, and improve quality of life.