Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis

To evaluate the haemodynamic changes induced by flow diversion treatment in cerebral aneurysms, resulting in thrombosis or persisting aneurysm patency over time. Eight patients with aneurysms at the para-ophthalmic segment of the internal carotid artery were treated by flow diversion only. The clinical follow-up ranged between 6 days and 12 months. Computational fluid dynamics (CFD) analysis of pre- and post-treatment conditions was performed in all cases. True geometric models of the flow diverter were created and placed over the neck of the aneurysms by using a virtual stent-deployment technique, and the device was simulated as a true physical barrier. Pre- and post-treatment haemodynamics were compared, including mean and maximal velocities, wall-shear stress (WSS) and intra-aneurysmal flow patterns. The CFD study results were then correlated to angiographic follow-up studies. Mean intra-aneurysmal flow velocities and WSS were significantly reduced in all aneurysms. Changes in flow patterns were recorded in only one case. Seven of eight aneurysms showed complete occlusion during the follow-up. One aneurysm remaining patent after 1 year showed no change in flow patterns. One aneurysm rupturing 5 days after treatment showed also no change in flow pattern, and no change in the maximal inflow velocity. Relative flow velocity and WSS reduction in and of itself may result in aneurysm thrombosis in the majority of cases. Flow reductions under aneurysm-specific thresholds may, however, be the reason why some aneurysms remain completely or partially patent after flow diversion.

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

Luca Augsburger

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.

EPFL2008

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model - A report on the Virtual Intracranial Stenting Challenge 2007

Luca Augsburger, Philippe Reymond, Daniel Ruefenacht

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning. (C) 2008 Elsevier Ltd. All rights reserved.

2008

Biomechanical analysis of cerebral arteries

Edouard Fonck

The intent of this thesis is to study the function of elastin in cerebral arteries, its contribution into the aging process and its implication into different cerebral diseases and in particular cerebral aneurysms. As of today, little is known on the genesis, growth and rupture of cerebral aneurysm. It is widely thought that these lesions rupture when hemodynamically induced wall stress exceeds wall strength. Therefore, there is a clear need for biomechanical analysis of the aneurysmal wall, which would include precise characterization of the stress and strain field experienced in vivo. The characterization of the stress and strain field requires knowledge of geometry, loading conditions as well as precise knowledge of the elastic properties of the aneurysmal and adjacent parent vessel walls. Because elastin is relatively absent in the aneurismal wall and elastin destruction is thought to be part of the aneurysm formation process, one of the main goals of this thesis was to characterize the effects of elastin degradation on the mechanical properties of arteries while assessed with a constituent-based strain energy function developed by Zulliger et al (). The first chapter had as primary objective to assess the contribution of elastin on the biomechanical properties of the rabbit common carotid wall, by selectively destructing elastin with elastase. The second objective was to assess the interaction of elastin with the other structural elements and in particular with collagen and its fiber engagement profile. A number of earlier studies have reported that aging process affects elastin, a key component of the arterial wall integrity and functionality as shown in chapter one. Thus, the part two of this thesis focused on the effects of aging on the biomechanical properties human cerebral arteries and in particular on the contribution of elastin. Cerebral arteries from human cadavers were analyzed biomechanically and morphologically in order to quantify the structural remodeling with aging. The effects of aging on functionality of elastin were assessed via selective enzymatic degradation and structural analysis of the elastin. Furthermore, quantification of desmosine and fibrillin cross-linking were evaluated. The main conclusion is that elastin, although physically present as evidenced by histology, is not functional with minimal contribution to the elasticity of aged cerebral wall. Reduced elasticity and non-functional elastin may affect the metabolism of endothelial and medial cells with important clinical implications in relation to the development of cerebrovascular disease. In the third part of this thesis, we were concerned with methods to collect aneurysmal tissues from different clinical centers for later mechanical testing. Thus, the effect of cryopreservation on the arterial matrix was analyzed in the absence of vascular smooth muscle cells. The experiments provided evidence cryopreservation affects only marginally extracellular matrix (ECM), suggesting thus that changes observed in arterial properties after cryopreservation are likely attributed to VSM cells, either as a direct result of VSM cells damage or as indirect effects of VSM cells injury on ECM. The study results also suggested that acellular tissues (i.e., cerebral aneurysms) can be stored without damage at -80°C with cryoprotectant agents (CPA) for later mechanical testing. In the fourth part, we sought a correlation between non-invasively measured biomechanical properties of common carotid arteries and the existence of cerebral aneurysms. This was based on earlier studies, which have showed that risk for cardiovascular events may be assessed by noninvasively measured markers such as stiffness or high pulse pressure. To that end, we measured geometry and elasticity of human carotids in patients with and without cerebral aneurysms. The findings suggested that patients carrying a cerebral aneurysm, present significantly higher diameters of the common carotid arteries at diastolic pressures and, furthermore, the diameters exhibit significantly higher asymmetry, as expressed by the difference between the left and right common carotid systolic and diastolic diameters. This asymmetry in diameters (and likely in other biomechanical properties) may be exploited as clinical indicators for the existence or future development of cerebral aneurysms. Larger clinical studies are required to reconfirm our interesting, yet preliminary findings. ---------------------------------------- () Zulliger MA, Rachev A, Stergiopulos N. A constitutive formulation of arterial mechanics including vascular smooth muscle tone. Am J Physiol Heart Circ Physiol. 2004;287:H1335-1343

EPFL2008

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

Luca Augsburger

EPFL2008

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model - A report on the Virtual Intracranial Stenting Challenge 2007

Luca Augsburger, Philippe Reymond, Daniel Ruefenacht

2008

Biomechanical analysis of cerebral arteries

Edouard Fonck

EPFL2008