## 4 Discussion  
In IAC for oral cancer, the flow of anticancer agents into the tumor-feeding arteries directly influences the success of the treatment. Therefore, clinicians should understand how the anticancer agent flows in the carotid artery. However, no measure provides clinicians with direct observation of the flow of the anticancer agent in vessels. Hence, this study utilized a CFD analysis to develop a new simulation system to predict the distribution of anticancer agents in patients with oral cancer. Only a few studies have analyzed the flow of anticancer agents using CFD. [PERSON] et al. (2018) analyzed the anticancer agent flow in the carotid artery with the linguofacial trunk assuming [PERSON]'s method. However, in their analysis model, the STA, OA, and MA, which are the main ECA branches, were excluded. Because the catheter was placed in the CCA, the anticancer agent flowed into the ICA, which can cause brain dysfunction in actual practice. Furthermore, the boundary condition was determined by setting the distribution rate of the blood among the ECA branches, which cannot reproduce the patient-specific blood flow field in vessels. In contrast, the analysis model included all the main ECA branches in the present study, and the catheter was placed in the ECA or linguofacial trunk. The boundary condition was patient-specific using the 0D resistance model, which can reproduce an accurate blood flow field in the numerical analysis ([PERSON] et al., 2018). Moreover, in the present study, convergence was achieved within a reasonable time considering the clinical application of this analysis method. In all analyses with the boundary condition assuming injection with a syringe driver, the agent was delivered into the outlets for which the streamlines that flowed in the vicinity of the catheter headed. In the present study, the mass fraction of the agent was calculated by solving the convection-diffusion equation of the species (Equation (1)), which consists of the terms for convection and diffusion. Therefore, it is clear that the convection term is more effective than the diffusion term on the solutions, judging from the scales of the space (cm), time (s), and diffusion coefficient between blood and agent (\(1\times 10^{-9}\) m\({}^{2}\)/s). Furthermore, the velocity of the blood was significantly higher than that of the anticancer agent. Therefore, the agent was transferred by the blood flow immediately after the injection. The volume-rendering images and streamlines in Figure 9a,d,e and Figures 10a-c and 11a,d represent this phenomenon. Moreover, in all models for both patients A and B, the distribution rate of the anticancer agent was inconsistent with that of blood. This suggests that the distribution of agents between the LA and FA in the ECA with the linguofacial trunk is not determined by the amount of blood but by how blood flows in the vicinity of the catheter. In addition to these findings, this CFD study revealed that the blood flow within a 2-mm radius from the catheter tip plays an important role in determining the agent flow because higher agent gradients were observed in the catheter tip zones in all models compared to the LA and FA zones. There was a discrepancy in the distribution rates of the agent between the two boundary conditions in models A0 and B0. In the analysis with the boundary condition assuming manual injection, streamlines that directly moved toward the LA and FA from the catheter tip were observed (Figures 8c and 10d). This indicates that the blood flow field was significantly changed by the higher velocity at the catheter tip than that made by syringe driver injection. Higher gradients of the agent in the LA and FA zones than those in other analyses were thought to be caused by this distinct flow field. In model B0, less discrepancy in the distribution rates of the agent was observed between two boundary conditions than that in model A0. This was due to the difference of the distribution of streamlines of the fluid around the catheter tip between the two models.