Abstract Number ‐ 56: Investigation of Aneurysmal Initiation Factor with Experimental Animal Model by Computational Fluid Dynamics Analysis
Authors: Kasai Tomoki , Koseki Hirokazu , Takao Hiroyuki , Fujimura Soichiro , Kato Naoki , Kan Issei , Sunami Shota , Yuzawa Kazuya , Uchikawa Hayato , Ishibashi Toshihiro , Fukudome Koji , Yamamoto Makoto , Murayama Yuichi 
Published: April 2023

Introduction
Hemodynamics has been reported to be involved in the pathophysiology of the initiation of intracranial aneurysms. Computational fluid dynamics (CFD) simulation has been widely used to investigate what kind of hemodynamics is related to intracranial aneurysm development or rupture. However, in the case of humans, it is difficult to obtain cerebrovascular images before the aneurysm formation because most of them are detected incidentally by magnetic resonance angiography (MRA) or computed tomography angiography (CTA). Therefore, the mechanism of aneurysm initiation has not been elucidated yet. In this study, CFD analysis was conducted with experimental animal models. Furthermore, immunostainings and Elastica van Gieson (EvG) staining were also performed to investigate the relationship between hemodynamics and aneurysm initiation.

Methods
We selected the experimental aneurysm model of a rat proposed by Shimizu et al.[1] With this model, aneurysms can be induced with a certain probability at the artificial bifurcation site created by end‐to‐side anastomosis of bilateral common carotid arteries and induced hypertension. Among the 50 rats surgically manipulated, 5 de novo cases and 14 cases without aneurysm initiation defined as stable cases were included in this study. The other 31 cases were excluded because of death or lack of imaging quality. MRA was conducted weekly until 4 weeks after manipulation. Acquired images were processed for the CFD analysis and various kinds of hemodynamic parameters were calculated. Among them, we regarded dimensionless wall shear stress divergence (WSSD*) and pressure loss coefficient (PLc) as the hemodynamic parameters previously suggested to be related to aneurysm initiation[2]. Vessels were collected after 2 weeks of follow‐up, and we observed endothelial cells (EC), smooth muscle cells (SMC), and the internal elastic lamina (IEL) at the apex of the bifurcationby immunostaining and EvG staining.

Results
The CFD results showed that a high WSSD* area existed at the apex of bifurcation in both de novo cases and stable cases. The averaged WSSD* of the de novo cases was 18.2% higher than that of the stable cases (de novo: 0.577 ± 0.243, stable: 0.488 ± 0.235). Likewise, the average PLc of the de novo cases was 11.5% higher than that of the stable cases (de novo: 8.22 ± 1.76, stable: 7.37 ± 2.49). The immunostaining images demonstrated that EC and SMC were more degenerated in de novo cases than in stable cases. Furthermore, the EvG staining images showed that IEL degenerated only in the de novo cases. Therefore, because WSSD* and PLc indicate a stretching force and flow impingement on the vessel wall, respectively, the elevation of those parameters may contribute to damage of EC, SMC, and IEL known as pathological features of an intracranial aneurysm.

Conclusions
CFD analysis and tissue observation were conducted with the vessels of the experimental animal model (5 de novo cases and 14 stable cases). Our results indicate that high WSSD* and high PLc are the factors related to aneurysm initiation.