From histology and imaging data to models for in-stent restenosis

The implantation of stents has been used to treat coronary artery stenosis for several decades. Although stenting is successful in restoring the vessel lumen and is a minimally invasive approach, the long-term outcomes are often compromised by in-stent restenosis (ISR). Animal models have provided insights into the pathophysiology of ISR and are widely used to evaluate candidate drug inhibitors of ISR. Such biological models allow the response of the vessel to stent implantation to be studied without the variation of lesion characteristics encountered in patient studies.This paper describes the development of complementary in silico models employed to improve the understanding of the biological response to stenting using a porcine model of restenosis. This includes experimental quantification using microCT imaging and histology and the use of this data to establish numerical models of restenosis. Comparison of in silico results with histology is used to examine the relationship between spatial localization of fluid and solid mechanics stimuli immediately post-stenting. Multi-scale simulation methods are employed to study the evolution of neointimal growth over time and the variation in the extent of neointimal hyperplasia within the stented region. Interpretation of model results through direct comparison with the biological response contributes to more detailed understanding of the pathophysiology of ISR, and suggests the focus for follow-up studies.In conclusion we outline the challenges which remain to both complete our understanding of the mechanisms responsible for restenosis and translate these models to applications in stent design and treatment planning at both population-based and patient-specific levels

3D reconstruction of stented porcine coronaries for cfd and mass transfer analyses of in-stent restenosis

Almost 10% coronary artery stenting procedures using bare metal stents are associated with in-stent restenosis, that is, a severe hyperplastic intimal tissue response within the stented region. This results in an obstruction to flow and a return of clinical symptoms. The present study investigates the hypothesis that a greater neointimal growth response is associated with regions of the vessel wall that are subject to low (<0.5 Pa) wall shear stress (WSS) following stent deployment. Such regions may be associated with arterial wall hypoxia. The 3D geometry of a stented porcine coronary artery was used to inform a computational fluid dynamics (CFD) model of coronary flow. This type of model has the potential to predict flow patterns with greater accuracy than a model based on idealised stent geometry alone, providing predictive capabilities for clinical application. Current results support the role of low WSS in the formation of in-stent restenosis through direct comparison of case-specific CFD results with the corresponding histological sections. The methodology shows promise for the elucidation of the role of arterial wall hypoxia