Fluid mechanics of cerebral aneurysms and effects of intracranial stents on cerebral aneurysm flow

This thesis focuses on intracranial aneurysms and particularly on the effect of blood flow in the three major phases that characterize an aneurysm: initiation, growth and rupture. As it stands today, blood flow is the major driver of this disease. The understanding of the complex relationships between aneurysm hemodynamics and aneurysm wall at the level of the endothelial cells helps to model the impact of flow on aneurysm wall during the aneurysm life cycle. Blood pressure is a parameter that impacts with magnitudes of about one thousand fold larger than shear and is widely accepted to be the driver for aneurysm expansion and rupture. Its pulsatility provides also a stimulus for the formation of collagen fibers. However, the main sensors of the wall tissue that are sensitive to flow energy are located at the endothelial level, where shear translates into hormones and into biological signals that are given to the vessel wall. The analysis of shear is therefore crucial to give some insight into the potential biological behavior of the aneurysm wall and may allow for having a sight into the aneurysm evolution potential and rupture risk. Shear can be deduced from the detailed investigation of aneurysm flow. Flow patterns and magnitudes correlate well with aneurysm rupture risk and are consequently useful for risk assessment. The prediction of flow stream lines and the quantification of flow magnitude are of interest to understand the potential evolution of the vessel to an aneurysm. As to treat the disease and to remediate and improve the local aneurysm flow, correction of blood flow may induce reverse remodeling of the diseased wall, intending at healing and normalizing the wall structure. Currently, in current clinical practice, the use of endovascular flow diverters has already shown to be of interest. However, the effort to provide scientifically valid explanations and to understand the principles used by such an approach remains. This objective in mind and in the present clinical neurovascular research context, computer modeling has become increasingly interesting to visualize and integrate the multiple factors that are each responsible for parts of the complexity to understand intracranial aneurysm disease. Indeed, computer modeling and validation efforts lead to a better understanding and control of the difficulty to capture steps of evolution or of reverse remodeling. By extension, computer modeling can also include the calculation of flow effects on perforating arteries caged by flow diverters or the initial phase of aneurysm clotting. The first part of the thesis describes the clinical problem of intracranial aneurysms and details methodologies developed to assess aneurysm hemodynamics. A vast review of the literature is presented. References to numerous publications and context of the thesis in regard to current state of research are presented. A part from computer modeling, in vitro setups allow reproducing the physiological conditions and enable to test novel endovascular devices. The second chapter describes the in vitro stent test bed developed for flow assessment in intracranial aneurysms. Flow changes in two aneurysm models and the influence of flow diverters' porosity are investigated. In the third chapter, we present an initiative called the "1st Virtual Intracranial Stenting Challenge (VISC)". The VISC objectives were first to assess state-of-the-art numerical approaches to the simulation of blood flow in one stented cerebral aneurysm, second to illustrate the ability of a given stent design at reducing blood flow patterns in a patient-specific geometry and finally, to evaluate the numerical approaches on a standardized benchmark. The fourth chapter presents the influence of segmentation on geometrical parameters and on hemodynamics in cerebral aneurysms. As the reconstruction of aneurysms is based on gray-level threshold selection, such operation which usually performed by a trained radiology technician is consequently a man-dependant operation. The problem resulting in this case is that several aneurysm geometries may point to the same original aneurysm dataset. In the fifth chapter, the effects of one flow diverter are simulated using CFD based on a porous medium approach in two patient-specific intracranial aneurysm geometries. The advantage of simulating the flow diverter as a porous medium consists in reducing the number of elements and therefore the computational power. Simulation results are then compared with the real stent simulation. The described work achieved in this thesis put in evidence the need to further investigate the relationship between local aneurysm hemodynamics alteration and the aneurysm wall biological response. In vitro investigations including human cells would allow to further understand this complex mechanism. The objectives described at the beginning of the work are reached: a method allowing the quantification the aneurysm hemodynamics and their relation with aneurysm rupture risk. The quantification of the expected effects of a given endovascular device prior to the clinical intervention has also been made possible.