Advertisement

Annals of Biomedical Engineering

, Volume 45, Issue 11, pp 2494–2508 | Cite as

Review of Mechanical Testing and Modelling of Thrombus Material for Vascular Implant and Device Design

  • S. Johnson
  • S. Duffy
  • G. Gunning
  • M. Gilvarry
  • J. P. McGarry
  • P. E. McHugh
Article

Abstract

A thrombus or blood clot is a solid mass, made up of a network of fibrin, platelets and other blood components. Blood clots can form through various pathways, for example as a result of exposed tissue factor from vascular injury, as a result of low flow/stasis, or in very high shear flow conditions. Embolization of cardiac or vascular originating blood clots, causing an occlusion of the neurovasculature, is the major cause of stroke and accounts for 85% of all stroke. With mechanical thrombectomy emerging as the new standard of care in the treatment of acute ischemic stroke (AIS), the need to generate a better understanding of the biomechanical properties and material behaviour of thrombus material has never been greater, as it could have many potential benefits for the analysis and performance of these treatment devices. Defining the material properties of a thrombus has obvious implications for the development of these treatment devices. However, to-date this definition has not been adequately established. While some experimentation has been performed, model development has been extremely limited. This paper reviews the previous literature on mechanical testing of thrombus material. It also explores the use of various constitutive and computational models to model thrombus formation and material behaviour.

Keywords

Clot material Mechanical characterization Computational modelling Mechanical thrombectomy Material behaviour Experimental testing 

Notes

Acknowledgments

The authors would like to acknowledge the support of Neuravi Ltd, the Irish Research Council Enterprise Partnership Scheme and the NUI Galway Hardiman Research Scholarship for this research.

References

  1. 1.
    Akbik, F., J. A. Hirsch, P. T. Cougo-Pinto, R. V. Chandra, C. Z. Simonsen, and T. Leslie-Mazwi. The evolution of mechanical thrombectomy for acute stroke. Curr. Treat. Options Cardiovasc. Med. 18:32, 2016.CrossRefPubMedGoogle Scholar
  2. 2.
    Ashton, J. H., J. P. Vande Geest, B. R. Simon, and D. G. Haskett. Compressive mechanical properties of the intraluminal thrombus in abdominal aortic aneurysms and fibrin-based thrombus mimics. J. Biomech. 42:197–201, 2009.CrossRefPubMedGoogle Scholar
  3. 3.
    Babushkina, E. S., N. M. Bessonov, F. I. Ataullakhanov, and M. A. Panteleev. Continuous modeling of arterial platelet thrombus formation using a spatial adsorption equation. PLoS ONE 10:e0141068, 2015.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Berkhemer, O. A., et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N. Engl. J. Med. 372:11–20, 2014.CrossRefPubMedGoogle Scholar
  5. 5.
    Bodnár, T., and A. Sequeira. Numerical simulation of the coagulation dynamics of blood. Comput. Math. Methods Med. 9:83–104, 2008.CrossRefGoogle Scholar
  6. 6.
    Brown, A. E. X., R. I. Litvinov, D. E. Discher, P. K. Purohit, and J. W. Weisel. Multiscale mechanics of fibrin polymer: gel stretching with protein unfolding and loss of water. Science 325:741–744, 2009.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Burghardt, W. R., T. K. Goldstick, J. Leneschmidt, and K. Kempka. Nonlinear viscoelasticity and the thrombelastograph: 1. Studies on bovine plasma clots. Biorheology 32:621–630, 1995.CrossRefPubMedGoogle Scholar
  8. 8.
    Carr, M. E., and S. L. Carr. Fibrin structure and concentration alter clot elastic modulus but do not alter platelet mediated force development. Blood Coagul. Fibrinolysis 6:79–86, 1995.CrossRefPubMedGoogle Scholar
  9. 9.
    Center for Devices and Radiological Health. Guidance for Industry and FDA Staff Pre-Clinical and Clinical Studies for Neurothrombectomy Devices. 2007Google Scholar
  10. 10.
    Center for Devices and Radiological Health. Guidance for Industry and FDA Staff—Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems. Center for Devices and Radiological Health, 2010Google Scholar
  11. 11.
    Chandran, V. D., O. E. Kadri, and R. S. Voronov. Thrombus yield stress calculation from LBM based on intravital laser injury images in mice. In: Northeast Bioengineering Conference (NEBEC), 2017. http://nebec.njit.edu/PDFfiles/NEBEC2017-000272.pdf
  12. 12.
    Chen, E. J., J. Novakofski, W. K. Jenkins, and W. D. O’Brien. Young’s modulus measurements of soft tissues with application to elasticity imaging. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43:191–194, 1996.CrossRefGoogle Scholar
  13. 13.
    Chueh, J. Y., A. K. Wakhloo, G. H. Hendricks, C. F. Silva, J. P. Weaver, and M. J. Gounis. Mechanical characterization of thromboemboli in acute ischemic stroke and laboratory embolus analogs. AJNR. Am. J. Neuroradiol. 32:1237–1244, 2011.CrossRefPubMedGoogle Scholar
  14. 14.
    Dempfle, C.-E., T. Kälsch, E. Elmas, N. Suvajac, T. Lücke, E. Münch, and M. Borggrefe. Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots. Blood Coagul. Fibrinolysis 19:765–770, 2008.CrossRefPubMedGoogle Scholar
  15. 15.
    Di Martino, E., S. Mantero, F. Inzoli, G. Melissano, D. Astore, R. Chiesa, and R. Fumero. Biomechanics of abdominal aortic aneurysm in the presence of endoluminal thrombus: Experimental characterisation and structural static computational analysis. Eur. J. Vasc. Endovasc. Surg. 15:290–299, 1998.CrossRefPubMedGoogle Scholar
  16. 16.
    Duffy, S., M. Farrell, K. McArdle, J. Thornton, D. Vale, E. Rainsford, L. Morris, D. S. Liebeskind, E. MacCarthy, and M. Gilvarry. Novel methodology to replicate clot analogs with diverse composition in acute ischemic stroke. J. Neurointerv. Surg. 2016. doi: 10.1136/neurintsurg-2016-012308.Google Scholar
  17. 17.
    Fang, J., Y.-L. Wan, C.-K. Chen, and P.-H. Tsui. Discrimination between newly formed and aged thrombi using empirical mode decomposition of ultrasound B-scan image. Biomed Res. Int. 1–9:2015, 2015.Google Scholar
  18. 18.
    Ferry, J. D., and P. R. Morrison. Chemical, clinical, and immunological studies on the products of human plasma fractionation. XVI. fibrin clots, fibrin films, and fibrinogen plastics. J. Clin. Invest. 23:566–572, 1944.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Fogelson, A. L., and R. D. Guy. Immersed-boundary-type models of intravascular platelet aggregation. Comput. Methods Appl. Mech. Eng. 197:2087–2104, 2008.CrossRefGoogle Scholar
  20. 20.
    Fukada, E., Y. Sugiura, M. Date, and M. Kaibara. Methods to study rheological properties of blood during clotting. Biorheology Suppl. 1:9–14, 1984.PubMedGoogle Scholar
  21. 21.
    Furie, B., and B. C. Furie. Mechanisms of thrombus formation. N. Engl. J. Med. 359:938–949, 2008.CrossRefPubMedGoogle Scholar
  22. 22.
    Gasser, T. C., G. Görgülü, M. Folkesson, and J. Swedenborg. Failure properties of intraluminal thrombus in abdominal aortic aneurysm under static and pulsating mechanical loads. J. Vasc. Surg. 48:179–188, 2008.CrossRefPubMedGoogle Scholar
  23. 23.
    Goyal, M., et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N. Engl. J. Med. 372:1019–1030, 2015.CrossRefPubMedGoogle Scholar
  24. 24.
    Gralla, J., G. Schroth, L. Remonda, K. Nedeltchev, J. Slotboom, and C. Brekenfeld. Mechanical thrombectomy for acute ischemic stroke: thrombus-device interaction, efficiency, and complications in vivo. Stroke. 37:3019–3024, 2006.CrossRefPubMedGoogle Scholar
  25. 25.
    Gunning, G. M., K. Mcardle, M. Mirza, S. Duffy, M. Gilvarry, and P. A. Brouwer. Clot friction variation with fibrin content; implications for resistance to thrombectomy. J. Neurointerventioal Surg. 372:1019–1030, 2016.Google Scholar
  26. 26.
    Hinnen, J. W., D. J. Rixen, O. H. J. Koning, J. H. van Bockel, and J. F. Hamming. Development of fibrinous thrombus analogue for in vitro abdominal aortic aneurysm studies. J. Biomech. 40:289–295, 2007.CrossRefPubMedGoogle Scholar
  27. 27.
    Hrapko, M., J. A. W. van Dommelen, G. W. M. Peters, and J. S. H. M. Wismans. The mechanical behaviour of brain tissue: large strain response and constitutive modelling. Biorheology 43:623–636, 2006.PubMedGoogle Scholar
  28. 28.
    Huang, C.-C., P.-Y. Chen, and C.-C. Shih. Estimating the viscoelastic modulus of a thrombus using an ultrasonic shear-wave approach. Med. Phys. 40:42901, 2013.CrossRefGoogle Scholar
  29. 29.
    Huang, C. C., Y. H. Lin, T. Y. Liu, P. Y. Lee, and S. H. Wang. Review: study of the blood coagulation by ultrasound. J. Med. Biol. Eng. 31:79–86, 2011.CrossRefGoogle Scholar
  30. 30.
    Humphrey, J. D., and G. A. Holzapfel. Mechanics, mechanobiology and modeling of human abdominal aorta and aneurysms. J. Biomech. 45:805–815, 2012.CrossRefPubMedGoogle Scholar
  31. 31.
    Karsaj, I., and J. D. Humphrey. A mathematical model of evolving mechanical properties of intraluminal thrombus. Biorheology 46:509–527, 2009.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Kim, E., O. V. Kim, K. R. Machlus, X. Liu, T. Kupaev, J. Lioi, A. S. Wolberg, D. Z. Chen, E. D. Rosen, Z. Xu, and M. Alber. Correlation between fibrin network structure and mechanical properties: an experimental and computational analysis. Soft Matter 7:4983, 2011.CrossRefGoogle Scholar
  33. 33.
    Kim, O. V., R. I. Litvinov, J. W. Weisel, and M. S. Alber. Structural basis for the nonlinear mechanics of fibrin networks under compression. Biomaterials 35:6739–6749, 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Krasokha, N. W., S. Theisen, P. Reese, C. Mordasini, J. Brekenfeld, J. Gralla, G. Slotboom Schrott, and H. Monstadt. Mechanical properties of blood clots—a new test method. Mechanische Eigenschaften von Thromben - Neue Untersuchungsmethoden. Materwiss. Werksttech. 41:1019–1024, 2010.CrossRefGoogle Scholar
  35. 35.
    Liu, K., M. R. VanLandingham, and T. C. Ovaert. Mechanical characterization of soft viscoelastic gels via indentation and optimization-based inverse finite element analysis. J. Mech. Behav. Biomed. Mater 2:355–363, 2009.CrossRefPubMedGoogle Scholar
  36. 36.
    Mozaffarian, D. Heart disease and stroke statistics—2016 update. Circulation 133:e38–e360, 2015.CrossRefPubMedGoogle Scholar
  37. 37.
    Noailly, J., H. Van Oosterwyck, W. Wilson, T. M. Quinn, and K. Ito. A poroviscoelastic description of fibrin gels. J. Biomech. 41:3265–3269, 2008.CrossRefPubMedGoogle Scholar
  38. 38.
    O’Leary, S. A., E. G. Kavanagh, P. A. Grace, T. M. McGloughlin, and B. J. Doyle. The biaxial mechanical behaviour of abdominal aortic aneurysm intraluminal thrombus: classification of morphology and the determination of layer and region specific properties. J. Biomech 47:1430–1437, 2014.CrossRefPubMedGoogle Scholar
  39. 39.
    Pivkin, I. V., P. D. Richardson, and G. Karniadakis. Blood flow velocity effects and role of activation delay time on growth and form of platelet thrombi. Proc. Natl. Acad. Sci. U. S. A. 103:17164–17169, 2006.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Polzer, S., T. Gasser, B. Markert, J. Bursa, and P. Skacel. Impact of poroelasticity of intraluminal thrombus on wall stress of abdominal aortic aneurysms. Biomed. Eng. Online 11:62, 2012.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Robinson, R. A., L. H. Herbertson, S. Sarkar Das, R. A. Malinauskas, W. F. Pritchard, and L. W. Grossman. Limitations of using synthetic blood clots for measuring in vitro clot capture efficiency of inferior vena cava filters. Med. Devices (Auckl) 6:49–57, 2013.PubMedCentralGoogle Scholar
  42. 42.
    Ryan, E. A., L. F. Mockros, J. W. Weisel, and L. Lorand. Structural origins of fibrin clot. Rheology. 77:2813–2826, 1999.Google Scholar
  43. 43.
    Saldívar, E., J. N. Orje, and Z. M. Ruggeri. Tensile destruction test as an estimation of partial proteolysis in fibrin clots. Am. J. Hematol. 71:119–127, 2002.CrossRefPubMedGoogle Scholar
  44. 44.
    Schmitt, C., A. Hadj Henni, and G. Cloutier. Characterization of blood clot viscoelasticity by dynamic ultrasound elastography and modeling of the rheological behavior. J. Biomech. 44:622–629, 2011.CrossRefPubMedGoogle Scholar
  45. 45.
    Slaboch, C. L., M. S. Alber, E. D. Rosen, and T. C. Ovaert. Mechano-rheological properties of the murine thrombus determined via nanoindentation and finite element modeling. J. Mech. Behav. Biomed. Mater. 10:75–86, 2012.CrossRefPubMedGoogle Scholar
  46. 46.
    Stary, H. Atlas of Atherosclerosis Progression and Regression. New York/London: Parthenon Publishing, 1999.Google Scholar
  47. 47.
    Teng, Z., J. Feng, Y. Zhang, Y. Huang, M. P. F. Sutcliffe, A. J. Brown, Z. Jing, J. H. Gillard, and Q. Lu. Layer- and direction-specific material properties, extreme extensibility and ultimate material strength of human abdominal aorta and aneurysm: a uniaxial extension study. Ann. Biomed. Eng. 43:2745–2759, 2015.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    van Dam, E. A., S. D. Dams, G. W. M. Peters, M. C. M. Rutten, G. W. H. Schurink, J. Buth, and F. N. van de Vosse. Determination of linear viscoelastic behavior of abdominal aortic aneurysm thrombus. Biorheology 43:695–707, 2006.PubMedGoogle Scholar
  49. 49.
    van Dam, E. A., S. D. Dams, G. W. M. Peters, M. C. M. Rutten, G. W. H. Schurink, J. Buth, and F. N. van de Vosse. Non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus. Biomechan Model Mechanobiol 7:127–137, 2008.CrossRefGoogle Scholar
  50. 50.
    van Kempen, T. H. S., A. C. B. Bogaerds, G. W. M. Peters, and F. N. van de Vosse. A constitutive model for a maturing fibrin network. Biophys. J. 107:504–513, 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    van Kempen, T. H. S., W. P. Donders, F. N. van de Vosse, and G. W. M. Peters. A constitutive model for developing blood clots with various compositions and their nonlinear viscoelastic behavior. Biomech. Model. Mechanobiol. 2015. doi: 10.1007/s10237-015-0686-9.Google Scholar
  52. 52.
    van Kempen, T. H. S., G. W. M. Peters, and F. N. van de Vosse. A constitutive model for the time-dependent, nonlinear stress response of fibrin networks. Biomech. Model. Mechanobiol. 14:995–1006, 2015.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Vande Geest, J. P., M. S. Sacks, D. A. Vorp, B. Ray, G. Kuhan, I. C. Chetter, and P. T. McCollum. A planar biaxial constitutive relation for the luminal layer of intra-luminal thrombus in abdominal aortic aneurysms. J. Biomech. 39:2347–2354, 2006.CrossRefPubMedGoogle Scholar
  54. 54.
    Vidmar, J., I. Serša, E. Kralj, and P. Popovič. Unsuccessful percutaneous mechanical thrombectomy in fibrin-rich high-risk pulmonary thromboembolism. Thromb. J. 13:30, 2015.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Wang, D. H., M. Makaroun, M. W. Webster, and D. A. Vorp. Mechanical properties and microstructure of intraluminal thrombus from abdominal aortic aneurysm. J. Biomech. Eng. 123:536–539, 2001.CrossRefPubMedGoogle Scholar
  56. 56.
    Weisel, J. W. The mechanical properties of fibrin for basic scientists and clinicians. Biophys. Chem. 112:267–276, 2004.CrossRefPubMedGoogle Scholar
  57. 57.
    Weisel, J. W. Structure of fibrin: impact on clot stability. J. Thromb. Haemost. 5(Suppl 1):116–124, 2007.CrossRefPubMedGoogle Scholar
  58. 58.
    Weisel, J. W. Biophysics. Enigmas of blood clot elasticity. Science 320:456–457, 2008.CrossRefPubMedGoogle Scholar
  59. 59.
    Weisel, J. W. Biomechanics in haemostasis and thrombosis. J. Thromb. Haemost. 8:1027–1029, 2010.PubMedGoogle Scholar
  60. 60.
    Xie, H., K. Kim, S. R. Aglyamov, S. Y. Emelianov, M. O’Donnell, W. F. Weitzel, S. K. Wrobleski, D. D. Myers, T. W. Wakefield, and J. M. Rubin. Correspondence of ultrasound elasticity imaging to direct mechanical measurement in aging DVT in rats. Ultrasound Med. Biol. 31:1351–1359, 2005.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Xu, Z., N. Chen, M. M. Kamocka, E. D. Rosen, and M. Alber. A multiscale model of thrombus development. J. R. Soc. Interface 5:705–722, 2008.CrossRefPubMedGoogle Scholar
  62. 62.
    Xu, Z., M. Kamocka, M. Alber, and E. D. Rosen. Computational approaches to studying thrombus development. Arterioscler. Thromb. Vasc. Biol. 31:500–505, 2011.CrossRefPubMedGoogle Scholar
  63. 63.
    Xu, Z., O. Kim, M. Kamocka, E. D. Rosen, and M. Alber. Multiscale models of thrombogenesis. Wiley Interdiscip. Rev. Syst. Biol. Med. 4:237–246, 2012.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2017

Authors and Affiliations

  1. 1.Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and InformaticsNational University of IrelandGalwayIreland
  2. 2.Galway-Mayo Institute of TechnologyGalwayIreland
  3. 3.Neuravi LtdGalwayIreland

Personalised recommendations