Contribution of atherosclerotic plaque location and severity to the near-wall hemodynamics of the carotid bifurcation: an experimental study and FSI modeling

Abstract

Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index (OSI) and stress phase angle (SPA), which are more common in arterial bifurcations due to the complex structure. An experimental model of human carotid bifurcation with accurate geometrical and mechanical features was set up, and using realistic pulsatile flow rates, the inlet and outlet pressure pulses were measured for normal and stenosed models with 40% and 80% severities at common carotid (CCA), internal carotid (ICA) and external carotid (ECA) arteries. Based on the obtained experimental data, fluid–structure models were developed to obtain WSS, OSI, and SPA and evaluate pathological consequences at different locations. Mild severity had minor impact, however, inducing severe 80% stenosis in each branch led to considerable localized changes of hemodynamic parameters both in the stenosis site and other locations. This included sharp increases in WSS values accompanied by very low values close to zero before and after the peaks. Severe stenosis not only caused significant changes in the local artery, but also in other branches. OSI and SPA were less sensitive to stenosis, although high peaks were observed on bifurcation site for the stenosis at ECA. The interconnection of arteries at carotid bifurcation results in altered pressure/flow patterns in all branches when a stenosis is applied in any site. Such effect confirms pathological findings that atherosclerotic plaques are observed simultaneously in different carotid branches, although with different degrees of plaque growth and severity.

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References

  1. Amaya R, Pierides A, Tarbell JM (2015) The interaction between fluid wall shear stress and solid circumferential strain affects endothelial gene expression. PloS One 10(7):e0129952

    Article  Google Scholar 

  2. Amaya R, Cancel LM, Tarbell JM (2016) Interaction between the stress phase angle (SPA) and the oscillatory shear index (OSI) affects endothelial cell gene expression. PloS One 11(11):e0166569

    Article  Google Scholar 

  3. Amini S, Tafazzoli-Shadpour M, Haghighipour N, Golpayegani MRH , Shokrgozar MA (2008) Study of Tensile Cyclic Loading on Morphology of Endothelial Cell Line in Culture Medium: A Fractal and Topological Comparison. CMBES Proceedings, p. 31.

  4. Arzani A, Shadden SC (2018) Wall shear stress fixed points in cardiovascular fluid mechanics. J Biomech 73:145–152

    Article  Google Scholar 

  5. Assemat P, Armitage JA, Siu KK, Contreras KG, Dart AM, Chin-Dusting JP, Hourigan K (2014) Three-dimensional numerical simulation of blood flow in mouse aortic arch around atherosclerotic plaques. Appl Math Model 38(17–18):4175–4185

    MathSciNet  Article  Google Scholar 

  6. Atabek HB, Ling SC, Patel DJ (1975) Analysis of coronary flow fields in thoracotomized dogs. Circ Res 37(6):752–761

    Article  Google Scholar 

  7. Ballermann BJ, Dardik A, Eng E, Liu A (1998) Shear stress and the endothelium. Kidney Int Suppl 67:S100-108

    Article  Google Scholar 

  8. Berne RM, Winn HR, Rubio R (1981) The local regulation of cerebral blood flow. Prog Cardiovasc Dis 24(3):243–260

    Article  Google Scholar 

  9. Birchall D, Zaman A, Hacker J, Davies G, Mendelow D (2006) Analysis of haemodynamic disturbance in the atherosclerotic carotid artery using computational fluid dynamics. Eur Radiol 16(5):1074–1083

    Article  Google Scholar 

  10. Charkoudian N (2010) Mechanisms and modifiers of reflex induced cutaneous vasodilation and vasoconstriction in humans. J Appl Physiol 109(4):1221–1228

    Article  Google Scholar 

  11. Chistiakov DA, Orekhov AN, Bobryshev YV (2017) Effects of shear stress on endothelial cells: go with the flow. Acta Physiol 219(2):382–408

    Article  Google Scholar 

  12. Clemente G, Mancini M, Giacco R, Tornatore A, Ragucci M, Riccardi G (2015) Visceral adiposity and subclinical atherosclerosis in healthy young men. Int J Food Sci Nutr 66(4):466–470

    Article  Google Scholar 

  13. Dancu MB, Tarbell JM (2006) Large negative stress phase angle (SPA) attenuates nitric oxide production in bovine aortic endothelial cells. J Biomech Eng 128(3):329–334

    Article  Google Scholar 

  14. De Nisco G, Hoogendoorn A, Chiastra C, Gallo D, Kok AM, Morbiducci U, Wentzel JJ (2020a) The impact of helical flow on coronary atherosclerotic plaque development. Atherosclerosis 300:39–46

    Article  Google Scholar 

  15. De Nisco G, Tasso P, Calo K, Mazzi V, Gallo D, Condemi F, Farzaneh S, Avril S, Morbiducci U (2020b) Deciphering ascending thoracic aortic aneurysm hemodynamics in relation to biomechanical properties. Med Eng Phys 82:119–129

    Article  Google Scholar 

  16. Dejana E, Hirschi KK, Simons M (2017) The molecular basis of endothelial cell plasticity. Nat Commun 8(1):14361

    Article  Google Scholar 

  17. DiCarlo AL, Holdsworth DW, Poepping TL (2019) Study of the effect of stenosis severity and non-Newtonian viscosity on multidirectional wall shear stress and flow disturbances in the carotid artery using particle image velocimetry. Med Eng Phys 65:8–23

    Article  Google Scholar 

  18. Domanin M, Gallo D, Vergara C, Biondetti P, Forzenigo LV, Morbiducci U (2019) Prediction of long term restenosis risk after surgery in the carotid bifurcation by hemodynamic and geometric analysis. Ann Biomed Eng 47(4):1129–1140

    Article  Google Scholar 

  19. Donea J, Huerta A, Ponthot JP, Rodríguez-Ferran A (2017) Arbitrary L agrangian–E ulerian Methods. Encycl Comput Mech Second Edn. https://doi.org/10.1002/9781119176817.ecm2009

    Article  Google Scholar 

  20. Eikendal AL, Groenewegen KA, Bots ML, Peters SA, Uiterwaal CS, den Ruijter HM (2016) Relation between adolescent cardiovascular risk factors and carotid intima-media echogenicity in healthy young adults: the atherosclerosis risk in young adults (ARYA) study. J Am Heart Assoc 5(5):e002941

    Article  Google Scholar 

  21. Gallo D, Steinman DA, Morbiducci U (2016) Insights into the co-localization of magnitude-based versus direction-based indicators of disturbed shear at the carotid bifurcation. J Biomech 49(12):2413–2419

    Article  Google Scholar 

  22. Gallo D, Bijari PB, Morbiducci U, Qiao Y, Xie Y, Etesami M, Habets D, Lakatta EG, Wasserman BA, Steinman DA (2018) Segment-specific associations between local haemodynamic and imaging markers of early atherosclerosis at the carotid artery: an in vivo human study. J R Soc Interface 15(147):20180352

    Article  Google Scholar 

  23. Giacomin AJ, Dealy JM (1993) Large-amplitude oscillatory shear. In: Collyer AA (ed) Techniques in rheological measurement. Springer, Dordrecht, pp 99–121

    Google Scholar 

  24. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (1987) Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316(22):1371–1375

    Article  Google Scholar 

  25. Gutierrez-Chico JL, Zhao S, Chatzizisis YS (2018) Vorticity: at the crossroads of coronary biomechanics and physiology. Atherosclerosis 273:115–116

    Article  Google Scholar 

  26. Hatami J, Tafazzoli-Shadpour M, Haghighipour N, Shokrgozar MA, Janmaleki M (2013) Influence of cyclic stretch on mechanical properties of endothelial cells. Exp Mech 53(8):1291–1298

    Article  Google Scholar 

  27. Hennerici M, Aulich A, Sandmann W, Freund HJ (1981) Incidence of asymptomatic extracranial arterial disease. Stroke 12(6):750–758

    Article  Google Scholar 

  28. Himburg HA, Grzybowski DM, Hazel AL, LaMack JA, Li X-M, Friedman MH (2004) Spatial comparison between wall shear stress measures and porcine arterial endothelial permeability. Am J Physiol-Heart Circul Physiol 286(5):H1916–H1922

    Article  Google Scholar 

  29. Hoi Y, Zhou YQ, Zhang X, Henkelman RM, Steinman DA (2011) Correlation between local hemodynamics and lesion distribution in a novel aortic regurgitation murine model of atherosclerosis. Ann Biomed Eng 39(5):1414–1422

    Article  Google Scholar 

  30. Howard VJ, McClure LA, Meschia JF, Pulley L, Orr SC, Friday GH (2006) High prevalence of stroke symptoms among persons without a diagnosis of stroke or transient ischemic attack in a general population: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Arch Intern Med 166(18):1952–1958

    Article  Google Scholar 

  31. Ku DN, Giddens DP (1983) Pulsatile flow in a model carotid bifurcation. Arterioscler Thromb Vasc Biol 3(1):31–39

    Google Scholar 

  32. Langille BL, O’Donnell F (1986) Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 231(4736):405–407

    Article  Google Scholar 

  33. Lee S-W, Antiga L, Steinman DA (2009) Correlations among indicators of disturbed flow at the normal carotid bifurcation. J Biomech Eng 131(6):061013

    Article  Google Scholar 

  34. Lehoux S, Jones EA (2016) Shear stress, arterial identity and atherosclerosis. Thromb Haemost 115(3):467–473

    Article  Google Scholar 

  35. Li Z, Xu X, Xia J, Deng X, Zeng T (2017) Quantitative evaluation between wall shear stress and artery angle in three-dimensional atherosclerotic carotid bifurcation model. J Med Imag Health Inform 7(4):805–809

    Article  Google Scholar 

  36. Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Song WL, Doran AC , Vickers KC (2019) The role of lipids and lipoproteins in atherosclerosis. Endotext [Internet], MDText. com, Inc.

  37. Maurits N, Loots G, Veldman A (2007) The influence of vessel wall elasticity and peripheral resistance on the carotid artery flow wave form: a CFD model compared to in vivo ultrasound measurements. J Biomech 40(2):427–436

    Article  Google Scholar 

  38. Mazzi V, Gallo D, Calo K, Najafi M, Khan MO, De Nisco G, Steinman DA, Morbiducci U (2020) A Eulerian method to analyze wall shear stress fixed points and manifolds in cardiovascular flows. Biomech Model Mechanobiol 19(5):1403–1423

    Article  Google Scholar 

  39. Mendieta JB, Fontanarosa D, Wang J, Paritala PK, McGahan T, Lloyd T, Li Z (2020) The importance of blood rheology in patient-specific computational fluid dynamics simulation of stenotic carotid arteries. Biomech Model Mechanobiol 19(5):1477–1490

    Article  Google Scholar 

  40. Moore JE Jr (2009) Biomechanical issues in endovascular device design. J Endovasc Ther 16(Suppl 1):1–11

    Google Scholar 

  41. Morbiducci U, Kok AM, Kwak BR, Stone PH, Steinman DA, Wentzel JJ (2016) Atherosclerosis at arterial bifurcations: evidence for the role of haemodynamics and geometry. Thromb Haemost 115(3):484–492

    Article  Google Scholar 

  42. Moyle KR, Antiga L, Steinman DA (2006) Inlet conditions for image-based CFD models of the carotid bifurcation: is it reasonable to assume fully developed flow? J Biomech Eng 128(3):371–379

    Article  Google Scholar 

  43. Nasu K, Tsuchikane E, Katoh O, Vince DG, Virmani R, Surmely JF, Murata A, Takeda Y, Ito T, Ehara M, Matsubara T, Terashima M, Suzuki T (2006) Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology. J Am Coll Cardiol 47(12):2405–2412

    Article  Google Scholar 

  44. NIROOMANDOSCUII H, Tafazzoli-Shadpour M, Ghalichi F (2007) Biomechanical analysis of wall remodeling in elastic arteries with application of fluid–solid interaction methods. J Mech Med Biol 7(04):433–447

    Article  Google Scholar 

  45. Niu L, Meng L, Xu L, Liu J, Wang Q, Xiao Y, Qian M, Zheng H (2015) Stress phase angle depicts differences in arterial stiffness: phantom and in vivo study. Phys Med Biol 60(11):4281–4294

    Article  Google Scholar 

  46. Or S (1997) Do plaques grow upstream or downstream? An angiographic study in the femoral artery. Arterioscler Thromb Vasc Biol 17(5):912–918

    Article  Google Scholar 

  47. Peiffer V, Sherwin SJ, Weinberg PD (2013) Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? Syst Rev Cardiovasc Res 99(2):242–250

    Article  Google Scholar 

  48. Qiu Y, Tarbell JM (2000) Numerical simulation of pulsatile flow in a compliant curved tube model of a coronary artery. J Biomech Eng 122(1):77–85

    Article  Google Scholar 

  49. Razavi A, Shirani E, Sadeghi M (2011) Numerical simulation of blood pulsatile flow in a stenosed carotid artery using different rheological models. J Biomech 44(11):2021–2030

    Article  Google Scholar 

  50. Rezvani-Sharif A, Tafazzoli-Shadpour M, Avolio A (2019) Progressive changes of elastic moduli of arterial wall and atherosclerotic plaque components during plaque development in human coronary arteries. Med Biol Eng Comput 57(3):731–740

    Article  Google Scholar 

  51. Salzar RS, Thubrikar MJ, Eppink RT (1995) Pressure-induced mechanical stress in the carotid artery bifurcation: a possible correlation to atherosclerosis. J Biomech 28(11):1333–1340

    Article  Google Scholar 

  52. Samaee M, Tafazzoli-Shadpour M, Alavi H (2017) Coupling of shear–circumferential stress pulses investigation through stress phase angle in FSI models of stenotic artery using experimental data. Med Biol Eng Comput 55(8):1147–1162

    Article  Google Scholar 

  53. Selzer RH, Mack WJ, Lee PL, Kwong-Fu H, Hodis HN (2001) Improved common carotid elasticity and intima-media thickness measurements from computer analysis of sequential ultrasound frames. Atherosclerosis 154(1):185–193

    Article  Google Scholar 

  54. Sharma S, Singh U, Katiyar VK (2015) Magnetic field effect on flow parameters of blood along with magnetic particles in a cylindrical tube. J Magn Magn Mater 377:395–401

    Article  Google Scholar 

  55. Shoajei S, Tafazzoli-Shahdpour M, Shokrgozar MA, Haghighipour N (2014) Alteration of human umbilical vein endothelial cell gene expression in different biomechanical environments. Cell Biol Int 38(5):577–581

    Article  Google Scholar 

  56. Shojaei S, Tafazzoli-Shadpour M, Shokrgozar MA, Haghighipour N, Jahromi FH (2018) Stress phase angle regulates differentiation of human adipose-derived stem cells toward endothelial phenotype. Prog Biomater 7(2):121–131

    Article  Google Scholar 

  57. Stone PH, Saito S, Takahashi S, Makita Y, Nakamura S, Kawasaki T, Takahashi A, Katsuki T, Nakamura S, Namiki A (2012) Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study. Circulation 126(2):172–181

    Article  Google Scholar 

  58. Suarez-Cunqueiro MM, Duker J, Liebehenschel N, Schon R, Schmelzeisen R (2002) Calcification of the branches of the external carotid artery detected by panoramic radiography: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94(5):636–640

    Article  Google Scholar 

  59. Sugiyama S, Niizuma K, Nakayama T, Shimizu H, Endo H, Inoue T, Fujimura M, Ohta M, Takahashi A, Tominaga T (2013) Relative residence time prolongation in intracranial aneurysms: a possible association with atherosclerosis. Neurosurgery 73(5):767–776

    Article  Google Scholar 

  60. Tada S, Tarbell J (2005) A computational study of flow in a compliant carotid bifurcation–stress phase angle correlation with shear stress. Ann Biomed Eng 33(9):1202–1212

    Article  Google Scholar 

  61. Taghizadeh H, Tafazzoli-Shadpour M, Shadmehr MB (2015) Analysis of arterial wall remodeling in hypertension based on lamellar modeling. J Am Soc Hypertens 9(9):735–744

    Article  Google Scholar 

  62. Tang BT, Cheng CP, Draney MT, Wilson NM, Tsao PS, Herfkens RJ, Taylor CA (2006) Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling. Am J Physiol Heart Circ Physiol 291(2):H668-676

    Article  Google Scholar 

  63. Tang D, Yang C, Mondal S, Liu F, Canton G, Hatsukami TS, Yuan C (2008) A negative correlation between human carotid atherosclerotic plaque progression and plaque wall stress: In vivo MRI-based 2D/3D FSI models. J Biomech 41(4):727–736

    Article  Google Scholar 

  64. Taylor CA, Hughes TJ, Zarins CK (1998) Finite element modeling of three-dimensional pulsatile flow in the abdominal aorta: relevance to atherosclerosis. Ann Biomed Eng 26(6):975–987

    Article  Google Scholar 

  65. Thomas JB, Antiga L, Che SL, Milner JS, Steinman DA, Spence JD, Rutt BK, Steinman DA (2005) Variation in the carotid bifurcation geometry of young versus older adults: implications for geometric risk of atherosclerosis. Stroke 36(11):2450–2456

    Article  Google Scholar 

  66. Yamamoto E, Siasos G, Zaromytidou M, Coskun AU, Xing L, Bryniarski K, Zanchin T, Sugiyama T, Lee H, Stone PH, Jang IK (2017) Low endothelial shear stress predicts evolution to high-risk coronary plaque phenotype in the future: a serial optical coherence tomography and computational fluid dynamics study. Circ Cardiovasc Interv 10(8):e005455

    Article  Google Scholar 

  67. Yang C, Canton G, Yuan C, Ferguson M, Hatsukami TS, Tang D (2010a) Advanced human carotid plaque progression correlates positively with flow shear stress using follow-up scan data: an in vivo MRI multi-patient 3D FSI study. J Biomech 43(13):2530–2538

    Article  Google Scholar 

  68. Yang C, Canton G, Yuan C, Ferguson M, Hatsukami TS, Tang D (2010b) Advanced human carotid plaque progression correlates positively with flow shear stress using follow-up scan data: An< i> in vivo</i> MRI multi-patient 3D FSI study. J Biomech 43(13):2530–2538

    Article  Google Scholar 

  69. Yang S, Wang Q, Shi W, Guo W, Jiang Z, Gong X (2019) Numerical study of biomechanical characteristics of plaque rupture at stenosed carotid bifurcation: a stenosis mechanical property-specific guide for blood pressure control in daily activities. Acta Mech Sin 35(6):1279–1289

    Article  Google Scholar 

  70. Yousif MY, Holdsworth DW, Poepping TL (2010) A blood-mimicking fluid for particle image velocimetry with silicone vascular models. Exp Fluids 50(3):769–774

    Article  Google Scholar 

  71. Zarins CK, Giddens DP, Bharadvaj B, Sottiurai VS, Mabon RF, Glagov S (1983) Carotid bifurcation atherosclerosis Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circul Res 53(4):502–514

    Article  Google Scholar 

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Ahmadpour-B, M., Nooraeen, A., Tafazzoli-Shadpour, M. et al. Contribution of atherosclerotic plaque location and severity to the near-wall hemodynamics of the carotid bifurcation: an experimental study and FSI modeling. Biomech Model Mechanobiol (2021). https://doi.org/10.1007/s10237-021-01431-x

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Keywords

  • Cross-bifurcation stenosis
  • Wall shear stress
  • Oscillatory shear index
  • Stress phase angle
  • Endothelial cell function