Visiting Researcher: Andrew J. Narracott Department of Medical Physics, University of Sheffield, UK Visiting Research Fellow at RIKEN 1st October 2002 - 31st March 2003 Summary of research: Development of a model for the investigation of blood clotting in cerebral aneurysms following coiling One of the methods of treatment of intracranial aneurysms involves packing of the aneurysm with small Guglielmi Detachable Coils (GDC). This process aims to prevent flow within the aneurysm by filling the aneurysm with coils and thrombus [1]. The presence of the coil is thought to initiate clotting within the aneurysm, although the exact mechanisms behind this are unknown. Flow stasis caused by the presence of the coil geometry [2]-[4], thrombogenicity of the coil itself [5],[6] and the effects of electrothrombosis during coil deployment [7] are all thought to play some part in the progression of clot formation. A residence time based clotting model, previously validated experimentally for a simple geometry, was applied to the CFD analysis of an idealized aneurysm geometry. Coil geometry was included in an idealized form to allow the interaction of the blood with the coil to be modeled. A novel approach was employed using a combination of fluid residence time and concentration of 'clottable' fluid to model the change in viscosity of the fluid during the clotting process. The residence time was seen to increase local to the coil geometry, which caused re-circulation of the fluid. Initially the variation in residence time throughout the aneurysm was minimal as the flow has yet to become established. The residence time increased steadily with time and then approached a maximum value when the analysis time exceeded the time for fluid to be convected from the inlet to the site of the coil. The concentration of “clottable” fluid was seen to increase in value close to the coil where the source of clotting fluid was located. However, this increase is seen to saturate as the change in concentration becomes small with increase in analysis time. However, the viscosity of the fluid does not saturate as the concentration reaches its maximum value. This is due to the continuing increase in residence time between the cylinders of the coil. Eventually the viscosity also tends to a maximum value as the residence time becomes stable due to convective transport. Although long residence times were observed at the proximal side of the aneurysm the low values of concentration in these areas ensured that fluid viscosity remained low. It should be noted that the absolute values of viscosity in this analysis were much larger than those reported by Tippe et al [8]. In order to produce results in agreement with experimental blood clotting it would be necessary to modify the scaling factors of the model. The relationship between residence time, activated fluid concentration and fluid viscosity is likely to be more complex than the linear form used in these analyses. Experimental comparison will be necessary to provide appropriate data for model coefficients. However, this model has produced results which contain the features expected to occur in the clotting of cerebral aneurysms. It should be noted that no areas of high viscosity were observed in the parent vessel, which would have been inevitable with the use of a residence time-only model. The exact mechanisms for growth and rupture of aneurysms remain uncertain. Modifications to the pressure and flow within the aneurysm by the insertion of GDC coils are thought to be significant in reducing rebleeding [9]. However, the genesis of thrombus formation within the aneurysm is uncertain, although evidence that thrombus generation is initiated by the coil itself has been presented [1]-[3],[5],[7]. The model developed during the current study allows clotting to be modelled taking into account both the residence time of the fluid and the concentration of the fluid available for clotting. This is a novel approach which allows distinction between areas where clotting is unlikely to occur such as the parent vessel and areas prone to thrombus formation such as the surface of the coil. In order for such a model to be used as a predictive tool it is necessary to apply it to realistic aneurysm geometries. High quality fluid dynamics meshes of in vivo aneurysms have been obtained recently by other authors [10] and it is intended that similar methods will be applied to patient data to develop the clotting model further. This work was supported by a travel grant from the Royal Society of Engineering and research fellowship funding from the RIKEN institute. [1] Dovey, Z., Misra, M., Thornton, J., Charbel, F.T., Debrun, G.M., Ausman, J.I. "Guglielmi detachable coiling for intracranial aneurysms." Archives of Neurology 58 : 559-564 ; 2001. [2] Groden, C., Hagel, C., Delling, G., Zeumer, H. "Histological findings in ruptured aneurysms treated with GDCs: Six examples at varying times after treatment." American Journal of Neuroradiology 24 : 579-584 ; 2003. [3] Workman, M.J., Cloft, H.J., Tong, F.C., Dion, J.E., Jensen, M.E., Marx, W.F., Kallmes, D.F. "Thrombus formation at the neck of cerebral aneurysms during treatment with Guglielmi detachable coils." American Journal of Neuroradiology 23 : 1568-1576 ; 2002. [4] Piotin, M., Mandai, S., Murphy, K.J., Sugiu, K., Gailloud, P., Martin, J-B., Rufenacht, D.A. "Dense packing of cerebral aneurysms: An in vitro study with detachable platinum coils." 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