Research About Computational Fluid Dynamics Combined With Pathology On Growth And Rupture Mechanism Of Intracranial Aneurysms

Part I Analysis of hemodynamic and histopathology on unruptured intracranial aneurysmsObjective:The aim of this study is to clarify the role of hemodynamic and pathological damage on the mechanisms of IAs formation and growth through investigating hemodynamic characteristics of unruptured intracranial aneurysms (IAs) using computational fluid dynamics (CFD) and histopathology of these aneurysms, and analyzing the relevance of hemodynamic parameters and pathological damage of IAs.Methods:Eight patients of unruptured IAs clipped by microsurgery were enrolled in this study. The data and aneurysmal specimens of these patients were collected. Three-dimensional model were reconstructed with Mimics 17.0 software. Fluid-solid coupled model were simulated and the relevant hemodynamics parameters (Wall shear stress (WSS), von mises stress, total pressure, velocity and streamline and total deformation) were analyzed with Ansys 14.5 software. In order to nicely recover the aneurysmal specimens,3D model was printed by 3D printing technology. The regions of highest and lowest value of these parameters were located. Immunohistochemical staining was used to detect the expression of interleukin-1γ(IL-1β), tumor necrosis factor-alpha (TNF-a), matrix metalloproteinase-2 (MMP-2), MMP-9, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) on the aneurysm wall of these regions. Results:The distribution of total pressure on aneurysm wall was uneven, but not quite difference. WSS on aneurysm neck was higher than that on aneurysm body and dome. Von mises stress on aneurysm neck was higher than that on aneurysm, the distribution of which was also uneven. Immunohistochemistry showed the expression of IL-1β, TNF-a, MMP-2, MMP-9, iNOS and eNOS on aneurysm wall.The expression of IL-1(3, TNF-a, MMP-2, MMP-9 and iNOS between the regions of highest and lowest value of WSS, von mises stress, total pressure and total deformation was no statistical significance (P>0.05). But the expression of eNOS on high WSS region was higher than that on low WSS region. The difference was statistically significant (P<0.05). Conclusion:IL-1β, TNF-a, MMP-2, MMP-9, iNOS and eNOS all play a role on the mechanisms of IAs formation and growth. High WSS may facilitate the formation and growth of IAs by upregulating the expression of eNOS on aneurysm wall.Part Ⅱ Analysis of hemodynamic and histopathology on ruptured intracranial aneurysmsObjective:The aim of this study is to clarify the role of hemodynamic and pathological damage on the mechanisms of IAs rupture through investigating hemodynamic characteristics of ruptured IAs using CFD and histopathology of these aneurysms, and analyzing the relevance of hemodynamic parameters and pathological damage of IAs. Methods:Ten patients of ruptured IAs clipped by microsurgery were enrolled in this study. The data and aneurysmal specimens of these patients were collected. Three-dimensional model were reconstructed with Mimics 17.0 software. Fluid-solid coupled model were simulated and the relevant hemodynamics parameters (WSS, von mises stress, total pressure, velocity and streamline and total deformation) were analyzed with Ansys 14.5 software. In order to nicely recover the aneurysmal specimens,3D model was printed by 3D printing technology. Immunohistochemical staining was used to detect the expression of IL-1β, TNF-α, MMP-2, MMP-9, eNOS and iNOS on the aneurysm wall of rupture point region and aneurysm body. Results: Rupture point was at the dome of IAs in 8 cases and on the aneurysm body in 2 cases. Most of the rupture points were located on the region of low WSS and high total pressure. Immunohistochemistry showed the positive expression of IL-1β, TNF-α, MMP-2, MMP-9, iNOS and eNOS on aneurysm wall of rupture region and aneurysm body. But the expression of IL-1β and TNF-α on rupture region was higher than that on aneurysm body. The difference was statistically significant (P<0.05). Conclusion:Most of aneurysm rupture points are located on the region of low WSS and high total pressure and not directly associated with von mises stress and total deformation. Low WSS may facilitate inflammatory reaction on the aneurysm wall by increasing proinflammatory factor IL-1β and TNF-α, degrade extracellular matrix protein, finally lead to IAs rupture.