Intracranial aneurysm (IA) can cause a lethal subarachnoid hemorrhage after rupture. Thereby, the correct understanding of the pathogenesis of the disease is essential to develop a novel therapeutic strategy to prevent progression. The accumulating evidence from simulation of hemodynamics targeting human cases has implied the role of hemodynamic force in IAs. In another point of view, experimental evidence mainly from animal studies has clarified the crucial role of macrophage-mediated long lasting-inflammation in the pathogenesis. However, how hemodynamic stress triggers such molecular events in arterial walls to develop IAs remains unclear. Recent experimental studies have revealed some of the potential machineries regulating hemodynamic stress-triggered IA formation. High walls shear stress activates endothelial cells and induces expression of MCP-1 at the earliest stage of IA formation. At adventitia, mechanical stretch induces MCP-1 expression in fibroblasts as well. MCP-1-mediated infiltration of macrophages into intracranial arterial walls thus occurs. In infiltrating macrophages, EP2 functions to exacerbate inflammation through formation of positive feedback loop, synergistic action with TNF-α and auto-amplification loop among macrophages. Given the nature of IAs as a vascular disease, further studies focused on hemodynamic force-mediated molecular events regulating the pathogenesis are necessary to understand the whole picture of the disease.
Computational fluid dynamics (CFD) is considered to be a promising tool for haemodynamic analysis of the intracranial aneurysm. However, aneurysm CFD is still not regarded as fully reliable mainly because the computational result is influenced by too many factors such as the luminal geometry of the model, spatiotemporal resolutions and boundary conditions. Among the influential factors, this paper focuses on outflow boundary conditions used when the computational domain has multiple outlets. Four outflow strategies found in published articles are reviewed: 1) prescription of constant or zero pressure, 2) flow splitting based on the power law, 3) traction-free and zero velocity-gradient conditions and 4) coupling of CFD with a reduced-order model. None of them has proved definitely superior or inferior to others. For accurate quantification of the haemodynamic state in the aneurysm, it is crucial to incorporate the physiologically correct flow splitting ratio in CFD analysis by means of accurate specification of pressure or flow rate at the outlets. A coupling of CFD and a 0-d model (a subtype of the reduced-order model) appears to be the most promising although further study is necessary to achieve accurate estimation of model parameters.
A cerebral aneurysm is a vascular condition characterized by local ballooning of an artery in the brain. Although aneurysm formation and growth are thought to be the result of destruction of the blood vessel wall, the details of the etiology are unclear. We review the formation and growth of cerebral aneurysms as follows. In the first part, we summarize the history of theories on the pathogenesis of cerebral aneurysm in chronological order from epidemiological and pathological viewpoints and based on data obtained from animal models of experimentally induced cerebral aneurysms, with a focus on the involvement of hemodynamic stress on the arterial wall. In the second part, we review computational fluid dynamics (CFD) studies on the initiation of cerebral aneurysms with a brief overview of the history of CFD in hemodynamics analysis. Of the hypotheses presented, strong emphasis is placed on that of high wall shear stress and a high wall shear stress gradient. Other leading hypotheses involving hemodynamics-related parameters are also reviewed. In the third part, we review CFD studies on the growth of cerebral aneurysms, in which hemodynamic parameters were compared between growing and stable aneurysms, to highlight the hemodynamic characteristics associated with their growth.
Researchers have aimed to identify unruptured intracranial aneurysms at a higher risk of rupture during follow-up for a long time. Computational fluid dynamics has been used widely to identify a hemodynamic discriminator between ruptured and unruptured aneurysms. However, this method has yet to reach a consensus between groups, which may be due, in part, to the significant degrees of freedom in hemodynamic indexes and computational workflows. The present review aims to characterize the degree of association between ruptured aneurysms and hemodynamic indexes, as well as the degree of variability between groups. A PubMed search identified 588 relevant studies. Thirteen met our criteria, yielding a total of 3,692 aneurysms. The definition of hemodynamic indexes were first carefully assessed and then classified accordingly. The variability of hemodynamic indexes between groups displayed a significant index-dependent nature. Normalizing hemodynamic indexes was an effective measure of reducing variability. Hemodynamic indexes were evaluated for associability and quantifiability. Overall, in an attempt to advance the diagnostic performance of hemodynamic indexes, these results shed light on the poor ability to interpret hemodynamic states pathologically. Future studies should incorporate the pathological significance of hemodynamic states into the design of hemodynamic indexes.
Various coil modeling techniques have been applied for computational fluid dynamics (CFD) analysis to predict recanalization after aneurysm coil embolization. Investigation on the technical difficulties and the effects on CFD analysis results when using the four main coil modeling methods (solid model, porous model, Dynamic Path Planning, finite element method (FEM) structural analysis) revealed that the expertise required for the analysis as well as the time needed for the analysis increased the more the results were realistic. In addition, by applying the four coil modeling methods to cases that actually underwent coil embolization surgery, hemodynamic factors such as blood flow velocity or mass flow rate were reported to have an effect on the occurrence of recanalization. It was also reported that the consideration of hemodynamic factors is useful for predicting recanalization. Although various validations are required, CFD analysis may be a useful tool for predicting recanalization of aneurysms after coil embolization in the future.