靜脈移植手術是臨床上最常見治療動脈阻塞相關疾病的方法之一，然而，在靜脈移植手術後，血管經常會發生再窄化的情形，這也是臨床最常見使靜脈移植手術失敗的原因。計算流體力學可以提供許多手術後血管的相關資訊，協助臨床預測可能會發生再窄化的區域。本研究中靜脈移植手術是利用外頸靜脈置換大鼠的頸總動脈，並使用30 MHz的高頻超音波系統觀察，在手術後的不同時間點，血管結構上改變。後續將藉由MATLAB軟體，從高頻超音波影像中重建不同時間點血管的3D幾何模型，並且利用有限元素法結合流固耦合的概念，模擬流力場與固力場相關的力學參數。血管管壁的剪切應力與流速將透過牛頓流體計算，血管管徑與壓力對管壁的影響將藉由此模形進行模擬。目前研究結果顯示，當血管管徑變小時，將會導致血管壁的剪切應力與流速增加，同時在靜脈移植區段可以發現最大的變形量與蒙麥斯應力產生，並且在手術兩周之後，血管再窄化的情況更加嚴重。綜合以上，結合高頻超音波系統與有限元素法進行流固耦合的模擬，能夠成功預測血流動力學因素引起的病理機制。

Restenosis usually occurs after patients underwent vein graft bypass surgery which is the common failure for vascular remodeling. Computational fluid dynamics (CFD) simulations can provide lots of important information of graft after surgery which can help to predict the occurrence of restenosis. In current study, the vein graft bypass surgery was created by replacing the common carotid artery with the external jugular vein in SD rats. The 30 MHz high frequency ultrasound (HFU) system was used to monitor the dynamic changes in vessel structures in vivo at different time points after surgery. Three dimensional geometry of vessel at different time points were reconstructed by HFU images using MATLAB. The mechanical properties of flow field and static structure field can be predicted with the application of fluid-structure interactive (FSI) finite element model. The shear stress on the vessel walls was directly calculated for Newtonian stress description and velocity field. The impacts of variations in vessel radii and pressure on vessel walls were predicted in this hemodynamic model. Our results showed decreases of the lumen area at the downstream of suture junction which lead to the increased of wall shear stress and velocity. And both of the maximum deformation and von-Mises stress could be observed in the vein graft segment. After two weeks of surgery, the narrowing of vein graft initiated seriously progresses of pathological remodeling. In summary, the combination of HFU imaging system and finite element methods for fluid-structure interactive estimation may predict the pathological mechanisms triggered by hemodynamic factors.

1. Mathers, C.D. and D. Loncar, Projections of global mortality and burden of disease from 2002 to 2030. PLoS medicine, 2006. 3(11): p. e442.
2. Ross, R., The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature, 1993. 362(6423): p. 801-9.
3. Libby, P. and M. Aikawa, Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med, 2002. 8(11): p. 1257-62.
4. Chyu, K.-Y. and P.K. Shah, Emerging therapies for atherosclerosis prevention and management. Cardiology clinics, 2011. 29(1): p. 123-135.
5. Mohrschladt, M.F., et al., Cardiovascular disease and mortality in statin-treated patients with familial hypercholesterolemia. Atherosclerosis, 2004. 172(2): p. 329-35.
6. Li, Z. and C. Kleinstreuer, Blood flow and structure interactions in a stented abdominal aortic aneurysm model. Med Eng Phys, 2005. 27(5): p. 369-82.
7. Wholey, M.H., N. Al-Mubarek, and M.H. Wholey, Updated review of the global carotid artery stent registry. Catheter Cardiovasc Interv, 2003. 60(2): p. 259-66.
8. Ener, R.A., et al., Carotid artery in-stent restenosis after carotid artery stenting. Journal of Invasive Cardiology, 2008. 20(6): p. 286.
9. Cosottini, M., et al., In stent restenosis predictors after carotid artery stenting. Stroke Res Treat, 2010. 2010.
10. Conte, M.S., et al., Results of PREVENT III: a multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery. J Vasc Surg, 2006. 43(4): p. 742-751; discussion 751.
11. Johnson, W.C. and K.K. Lee, A comparative evaluation of polytetrafluoroethylene, umbilical vein, and saphenous vein bypass grafts for femoral-popliteal above-knee revascularization: a prospective randomized Department of Veterans Affairs cooperative study. J Vasc Surg, 2000. 32(2): p. 268-77.
12. Leotta, D.F., et al., Remodeling in peripheral vein graft revisions: serial study with three-dimensional ultrasound imaging. J Vasc Surg, 2003. 37(4): p. 798-807.
13. Mills, J.L., et al., The origin of infrainguinal vein graft stenosis: a prospective study based on duplex surveillance. J Vasc Surg, 1995. 21(1): p. 16-22; discussion 22-5.
14. Watson, H.R., et al., Incidence of stenoses in femorodistal bypass vein grafts in a multicentre study. Eur J Vasc Endovasc Surg, 2000. 20(1): p. 67-71.
15. Campbell, P.A., J.K. McGeachie, and F.J. Prendergast, Vein grafts for arterial repair: their success and reasons for failure. Ann R Coll Surg Engl, 1981. 63(4): p. 257-60.
16. Rosanio, S., et al., Prevention of restenosis after percutaneous coronary interventions: the medical approach. Thromb Haemost, 1999. 82 Suppl 1: p. 164-70.
17. Muto, A., et al., Mechanisms of vein graft adaptation to the arterial circulation: insights into the neointimal algorithm and management strategies. Circ J, 2010. 74(8): p. 1501-12.
18. Cox, J.L., D.A. Chiasson, and A.I. Gotlieb, Stranger in a strange land: the pathogenesis of saphenous vein graft stenosis with emphasis on structural and functional differences between veins and arteries. Prog Cardiovasc Dis, 1991. 34(1): p. 45-68.
19. Shier, e.a., Hole's Human Anatomy and Physiology. 7 ed. 1996.
20. Wesly, R.L., et al., Static linear and nonlinear elastic properties of normal and arterialized venous tissue in dog and man. Circ Res, 1975. 37(4): p. 509-20.
21. Selzer, R.H., et al., Improved common carotid elasticity and intima-media thickness measurements from computer analysis of sequential ultrasound frames. Atherosclerosis, 2001. 154(1): p. 185-93.
22. Fung, Y., Mechanical properties of blood vessels, in Biomechanics. 1981, Springer. p. 261-301.
23. Walden, R., et al., Matched elastic properties and successful arterial grafting. Arch Surg, 1980. 115(10): p. 1166-9.
24. Konig, G., et al., Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery. Biomaterials, 2009. 30(8): p. 1542-50.
25. Hecher, K., et al., Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies. Circulation, 1995. 91(1): p. 129-38.
26. Malek, A.M., S.L. Alper, and S. Izumo, Hemodynamic shear stress and its role in atherosclerosis. Jama, 1999. 282(21): p. 2035-2042.
27. Caro, C., J. Fitz-Gerald, and R. Schroter, Atheroma and arterial wall shear observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis. Proceedings of the Royal Society of London. Series B. Biological Sciences, 1971. 177(1046): p. 109-133.
28. Caro, C., J. Fitz-Gerald, and R. Schroter, Arterial wall shear and distribution of early atheroma in man. 1969.
29. Gibson, C.M., et al., Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries. Arteriosclerosis, Thrombosis, and Vascular Biology, 1993. 13(2): p. 310-315.
30. Cunningham, K.S. and A.I. Gotlieb, The role of shear stress in the pathogenesis of atherosclerosis. Laboratory investigation, 2004. 85(1): p. 9-23.
31. Davies, P.F., Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nature Clinical Practice Cardiovascular Medicine, 2008. 6(1): p. 16-26.
32. Chiu, J.-J. and S. Chien, Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiological reviews, 2011. 91(1): p. 327-387.
33. Tran-Son-Tay, R., et al., An experiment-based model of vein graft remodeling induced by shear stress. Annals of biomedical engineering, 2008. 36(7): p. 1083-1091.
34. de Sauvage Nolting, P.R., et al., Regression of carotid and femoral artery intima-media thickness in familial hypercholesterolemia: treatment with simvastatin. Arch Intern Med, 2003. 163(15): p. 1837-41.
35. Alexandrov, A.V., et al., Correlation of peak systolic velocity and angiographic measurement of carotid stenosis revisited. Stroke, 1997. 28(2): p. 339-42.
36. Mohler, E.R., 3rd, et al., High-frequency ultrasound for evaluation of intimal thickness. J Am Soc Echocardiogr, 2009. 22(10): p. 1129-33.
37. Faught, W.E., et al., Color-flow duplex scanning of carotid arteries: new velocity criteria based on receiver operator characteristic analysis for threshold stenoses used in the symptomatic and asymptomatic carotid trials. J Vasc Surg, 1994. 19(5): p. 818-27; discussion 827-8.
38. Steinman, D.A., Image-based computational fluid dynamics modeling in realistic arterial geometries. Annals of biomedical engineering, 2002. 30(4): p. 483-497.
39. Marshall, I., et al., MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models. J Biomech, 2004. 37(5): p. 679-87.
40. Frauenfelder, T., et al., Flow and wall shear stress in end-to-side and side-to-side anastomosis of venous coronary artery bypass grafts. Biomed Eng Online, 2007. 6: p. 35.
41. Lee, S.E., et al., Direct numerical simulation of transitional flow in a stenosed carotid bifurcation. J Biomech, 2008. 41(11): p. 2551-61.
42. Mut, F., et al., Fast Numerical Solutions of Patient-Specific Blood Flows in 3D Arterial Systems. Int j numer method biomed eng, 2010. 26(1): p. 73-85.
43. Clough, R.W., The finite element method in plane stress analysis. 1960.
44. Kock, S.A., et al., Mechanical stresses in carotid plaques using MRI-based fluid-structure interaction models. J Biomech, 2008. 41(8): p. 1651-8.
45. Gao, H., et al., Carotid arterial plaque stress analysis using fluid-structure interactive simulation based on in-vivo magnetic resonance images of four patients. J Biomech, 2009. 42(10): p. 1416-23.
46. Takizawa, K., et al., Space–time finite element computation of arterial fluid–structure interactions with patient‐specific data. International Journal for Numerical Methods in Biomedical Engineering, 2010. 26(1): p. 101-116.
47. Yang, C., D. Tang, and S.Q. Liu, A multi-physics growth model with fluid–structure interactions for blood flow and re-stenosis in rat vein grafts: A growth model for blood flow and re-stenosis in grafts. Computers & structures, 2003. 81(8): p. 1041-1058.
48. Volokh, K., Prediction of arterial failure based on a microstructural bi-layer fiber–matrix model with softening. Journal of biomechanics, 2008. 41(2): p. 447-453.
49. Stemper, B.D., N. Yoganandan, and F.A. Pintar, Methodology to study intimal failure mechanics in human internal carotid arteries. Journal of biomechanics, 2005. 38(12): p. 2491-2496.
50. Wang, X. and X. Li, Biomechanical behaviors of curved artery with flexible wall: A numerical study using fluid–structure interaction method. Computers in biology and medicine, 2011. 41(11): p. 1014-1021.
51. Fillinger, M.F., et al., Prediction of rupture risk in abdominal aortic aneurysm during observation: wall stress versus diameter. Journal of Vascular Surgery, 2003. 37(4): p. 724-732.
52. Chaichana, T., Z. Sun, and J. Jewkes, Computational fluid dynamics analysis of the effect of plaques in the left coronary artery. Computational and mathematical methods in medicine, 2012. 2012.
53. Lee, C.-J., et al., A comparison of estimation methods for computational fluid dynamics outflow boundary conditions using patient-specific carotid artery. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 2013. 227(6): p. 663-671.
54. Bandyk, D.F., et al., Hemodynamics of vein graft stenosis. Journal of vascular surgery, 1988. 8(6): p. 688-695.
55. McGah, P.M., et al., A longitudinal study of remodeling in a revised peripheral artery bypass graft using 3D ultrasound imaging and computational hemodynamics. Journal of biomechanical engineering, 2011. 133(4): p. 041008.
56. Kamenskiy, A.V., et al., Comparative analysis of the biaxial mechanical behavior of carotid wall tissue and biological and synthetic materials used for carotid patch angioplasty. Journal of biomechanical engineering, 2011. 133(11): p. 111008.
57. Ilic, D., et al. Measurement of Elastic Properties of Blood Vessels. in Engineering in Medicine and Biology Society, 2005. IEEE-EMBS 2005. 27th Annual International Conference of the. 2006. IEEE.
58. Yu, J., et al., The effect of stromal cell-derived factor-1alpha/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration. Biomaterials, 2012. 33(32): p. 8062-74.
59. Liu, B., The influences of stenosis on the downstream flow pattern in curved arteries. Medical engineering & physics, 2007. 29(8): p. 868-876.
60. Berger, S. and L. Jou, Flows in stenotic vessels. Annual Review of Fluid Mechanics, 2000. 32(1): p. 347-382.
61. Chien, S., Effects of disturbed flow on endothelial cells. Annals of biomedical engineering, 2008. 36(4): p. 554-562.
62. Liu, S., et al., A possible role of initial cell death due to mechanical stretch in the regulation of subsequent cell proliferation in experimental vein grafts. Biomechanics and modeling in mechanobiology, 2002. 1(1): p. 17-27.
63. Fry, D.L., Certain histological and chemical responses of the vascular interface to acutely induced mechanical stress in the aorta of the dog. Circulation Research, 1969. 24(1): p. 93-108.
64. Shuhaiber, J.H., et al., Mechanisms and future directions for prevention of vein graft failure in coronary bypass surgery. European journal of cardio-thoracic surgery, 2002. 22(3): p. 387-396.