Relationship Between Wall Shear Stress and Atherosclerotic Plaque Composition in Stenotic Coronary Arteries

Atherosclerosis is a pathological condition of arteries characterized by inflammation and infiltration of cholesterol particles in the arterial wall, forming the atherosclerotic plaques. These plaques are formed by lipids, inflammatory cells, smooth muscle cells and fibrotic connective tissue and growth during people lifetime leading to the arterial lumen occlusion and lastly to severe complications, such as myocardial infarction for coronary arteries, which can lead to death. For these reasons coronary artery disease (CAD) results as the leading cause of death in most developed countries. Therefore, there is a need to develop technologies that enable early diagnosis of the disease so that timely intervention can take place. The correct and prompt diagnosis of atherosclerosis is of paramount importance. The evaluation of the severity might be based on anatomical or functional parameters. The anatomical evaluation is based on medical imaging, such as quantitative coronary angiography allowing only the quantification of percentage area stenosis. A more advanced imaging technique for the diagnosis of atherosclerotic plaques in coronary arteries is optical coherence tomography (OCT), which allow the characterization of the plaque composition with a high spatial resolution. On the other hand, the severity of coronary stenosis can be assessed with functionally measurements, based on pressure measurements. The flow impairment caused by stenosis is measured by fractional flow reserve (FFR), while recently the pressure pullback gradient (PPG) index was introduced to measure the focality of the disease. Finally, in recent years, computational fluid dynamics (CFD) analysis techniques have been used to solve the Navier-Stokes equations and compute the of wall shear stress (WSS) which may impact on the progression of atherosclerotic plaques. This thesis aims to evaluate the association between WSS-based descriptors and: 1) morphological characteristic of the atherosclerotic plaque; 2) the functional plaques phenotype, i.e., the focality or diffuseness of the disease. To achieve this goal, the hemodynamic of 29 pathological coronary arteries presenting severe stenosis was characterized. Three-dimensional models of the coronary arteries were then reconstructed from two angiographic projections and then CFD simulations were performed with two different approaches: the clinical CFD, using a prototype software with time compatible with clinical practice and the expert CFD, performed with a standard approach and presenting a higher accuracy and used to verify the clinical CFD simulations results. The hemodynamic was described in terms of time averaged WSS (TAWSS) accounting for WSS magnitude, and topological shear variation index (TSVI), accounting for the variability of WSS contraction and expansion action. Finally, the association of WSS-based descriptors with PPG index and plaque morphological characteristics was investigated. Statistically significant differences were observed between patients with high and low PPG index for both TAWSS (p<0.001) and TSVI (p<0.001), confirmed by a significant direct association emerged from regression models. Regarding plaque morphology, TAWSS resulted associated with macrophage infiltration (p=0.0184), while TSVI resulted associated with plaque rupture (p=0.0241). From the present analysis is possible to conclude that a association exist between WSS features and both plaque functional phenotype and plaque morphology.