ARTREAT project: computer, experimental and clinical analysis of three-dimensional plaque formation and progression in arteries

In this study we investigated our three-dimensional computer model of plaque formation and development which we tested on experimental results obtained from rabbits and clinical study on human carotid and coronary arteries. Firstly, a model of plaque formation in the rabbit animal LDL transport model within simple experimental design is simulated numerically using animal data and histological recordings. Then some human patient data from carotid and coronary artery were used. The 3D blood flow is described by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow, and is modeled by a convection-diffusion equation. The LDL transports in lumen of the vessel and through the vessel tissue (which has a mass consumption term) are coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using three additional reaction-diffusion partial differential equations. A full threedimensional model was created. It includes blood flow and LDL concentration, as well as plaque formation and progression. From patient human carotid artery data we matched plaque volume progression using two and three time points for baseline, three and twelve months follow up. Also a group of patients with coronary artery disease (CAD) and intermediate lesions was evaluated by Computed Tomography Angiography (CTA), together with an innovative approach to simulate the WSS-related low density lipoprotein (LDL) transport across the endothelium and to identify LDL accumulation sites. The novelty of this work lies in the systematic verification of prediction of plaque progression by repeated CTA, six months after the baseline evaluation, and by patient-specific determinations of boundary conditions, including coronary vasodilating capability, known to affect local flow conditions. Our results for plaque localization correspond to low shear stress zone and we fitted parameters from our model using nonlinear least square method. Understanding and prediction of the evolution of atherosclerotic plaques either into vulnerable or stable plaques are major tasks for the medical community.

Atherosclerosis is a progressive disease characterized by inflammation, monocyte-macrophage migration, and lipid accumulation in the vascular wall. Atherosclerosis is initially characterized by endothelial dysfunction, which favors lipid and cell elements crossing inside blood vessel wall.