The effect of shear stress on ISR in patients has not been investigated in BVS systems in detail before. One recent study, concluded that low shear stress is associated with increased neointimal thickness, but this study did not include the 3D nature of the artery. The only 3D human dataset containing detailed reconstructions of stent struts reported in literature deals with very small patient population (n=6), and did not investigate correlations between shear stress and progression of the disease.
InSilc Fluid Dynamics Module will focus on two different levels, using two different approaches.
The first level concerns a full characterization of the macroscopic flow phenomena in the area where the drug-eluting BVS is implanted. For the macroscopic approach, blood will be treated as a continuum, and the velocity and shear stress patterns in the drug-eluting BVS will be computed. The use of patient specific boundary conditions is essential to determine these hemodynamic parameters reliably, therefore new tools will be developed to include how uncertainties in the measurements propagate into the obtained solution. Furthermore, we will combine reduced order models of the distal vascular bed with the functional data obtained in the animal study and the proof of concept clinical study to characterize the state of the microcirculatory system. We will be able to generate patient specific velocity and shear stress patterns in high detail , with the corresponding reliability interval. We will focus on the distribution of low shear stress levels, and the size of the recirculation zones, both of which have been implied in ISR.
The second level that will be addressed deals with flow patterns on a microscopic scale, and blood cannot be treated as a continuum on this scale. By adopting this approach, multiscale models will be applied to describe the process of ISR . In these models, blood components and the vessel wall are included on a cellular level, and endothelial denudation, thrombus formation, SMC migration and the impact of the several laminae on the process of ISR will be studied. Applying this multiscale approach will allow us to couple patient specific data on blood and vessel wall composition and the local hemodynamic environment to improve our understanding of ISR. InSilc will go beyond the state of the art in the examination of the fluids dynamic effects after drug-eluting BVS deployment. InSilc will be able to generate comprehensive data in a sizeable patient population to study the macroscopic effect of shear stress for the first time. In addition, the inclusion of a multiscale approach will provide more insights into the underlying processes. The combination of high-resolution imaging over time and the biomarkers collected from the patients will allow us to validate the predictive nature of the multiscale models. Moreover, the degradation process of the drug-eluting BVS struts will be studied in combination with the environments they are degrading in.