Atherosclerotic plaque rupture in arteries is the primary cause of cardiovascular events such as heart infarct and stroke, which are responsible for 45% of deaths in Europe. Plaque rupture is a mechanical event, where the collagenous plaque tissue fails to withstand blood pressure loading. Identifying plaques at high risk of rupture is the key to prevent these fatal events. However, the current risk assessment strategy fails to achieve this as it lacks mechanistic insights into tissue failure. To address this unmet, urgent clinical need, I propose a paradigm shift to a biomechanistic risk assessment concept. I will achieve this with the MicroMechAthero project by revealing plaque failure mechanisms and developing a clinically applicable computational risk assessment framework. MicroMechAthero will combine ex-vivo, in-silico, and in-vivo research. Ex-vivo mechanical failure tests on post-mortem human plaque samples will involve tissue's collagen architecture imaging with recently developed polarization-sensitive optical coherence tomography and full-field, local, 3D tissue deformation measurements with the digital volume correlation technique. This frontier opto-mechanical approach will revolutionize soft tissue testing and, coupled with the virtual fields method, will provide unprecedented data for local, heterogeneous (hyper)elastic and failure properties of fibrous plaque tissue, linked to the underlying collagen network. Furthermore, a microstructure-based, in-silico tissue failure framework will be developed, using eXtended Finite Element Modeling technique, for plaque-specific risk prediction. This computational framework will be validated and tested for its clinical potential in an in-vivo patient study.
The overarching aim of this project is to develop a clinically applicable, biomechanistic rupture risk assessment strategy for atherosclerotic plaques. To achieve this aim, several distinct gaps in our knowledge
and technical/theoretical advances will be addressed through the following specific objectives:
1. Reveal local elastic and failure properties of fibrous plaque tissue with respect to the collagen network,
2. Establish a microstructure-based computational framework for fibrous plaque tissue failure,
3. Validate the new biomechanistic rupture risk assessment approach and test its feasibility for clinical use.
Overall, MicroMechAthero will provide a ground-breaking advance in our understanding of plaque rupture and develop a biomechanistic in-silico framework for patient-specific in-vivo risk analysis, leading to revolutionary changes in cardiovascular medicine.
