Skip to main content
SpringerLink
Log in

Three-Dimensional Reconstruction of Thrombus Formation during Photochemically Induced Arterial and Venous Thrombosis

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

We have selected a model of photochemically induced thrombosis in hamsters and mice in which thrombus formation is visualized via transillumination and quantified via image analysis. Applying a gray-compensation method, the images of developing thrombi were presently transformed and a three-dimensional (3D) reconstruction of thrombus evolution performed off line. To this end, a nondimensional Gray-compensated parameter Gc was calculated. The integrated Gc (IGc) correlated linearly (r=0.973) with the amount of light transilluminated and previously quantified as arbitrary light units. Matching Gc for reconstructed occlusive arterial and venous thrombi with the inner diameters of the hamster carotid artery and femoral vein, enabled the further conversion of IGc to real thrombus volumes, up to 0.14 mm3 in the carotid artery. In addition to enabling a graphical three-dimensional reconstruction of experimental thrombosis, via image subtraction, the kinetics of thrombus growth were visualized. Thus, platelet-mediated thrombus growth was found to occur randomly in small thrombi, but in larger thrombi, it occurred preferentially in its tailing vortex in areas of recirculating flow. The present study therefore confirms in vitro findings in an in vivo model. The 3D reconstruction and kinetics of thrombus growth may be helpful in the mechanistic and pharmacological study of experimental thrombosis. © 2003 Biomedical Engineering Society.

PAC2003: 8719Uv, 8750Hj, 8757Gg

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Angelillo-Scherrer, A., P. de Frutos, C. Aparicio, E. Melis, P. Savi, F. Lupu, J. Arnout, M. Dewerchin, M. F. Hoylaerts, J. Herbert, D. Collen, B. Dahlback, and P. Carmeliet. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat. Med.7:215–221, 2001.

    Google Scholar 

  2. Barstad, R. M., H. E. Roald, Y. Cui, V. T. Turitto, and K. S. Sakariassen. A perfusion chamber developed to investigate thrombus formation and shear profiles in flowing native human blood at the apex of well-defined stenoses. Arterioscler. Thromb.14:1984–1991, 1994.

    Google Scholar 

  3. Bernat, A., P. Hoffmann, and J. M. Herbert. Antagonism of SR 90107A/Org 31540–induced bleeding by protamine sulfate in rats and mice. Thromb. Haemostasis76:715–719, 1996.

    Google Scholar 

  4. Cho, J. H., C. H. Yun, H. S. Seo, T. Koga, T. Dan, B. A. Koo, and H. Y. Kim. The antithrombotic efficacy of AT-1459, a novel, direct thrombin inhibitor, in rat models of venous and arterial thrombosis. Thromb. Haemostasis86:1512–1520, 2001.

    Google Scholar 

  5. Davies, M. S., and A. C. Thomas. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br. Heart J.53:363–373, 1985.

    Google Scholar 

  6. Fay, W. P., J. G. Murphy, and W. G. Owen. High concentrations of active plasminogen activator inhibitor-1 in porcine coronary artery thrombi. Arterioscler., Thromb., Vasc. Biol.16:1277–1284, 1996.

    Google Scholar 

  7. Giles, A. R.Guidelines for the use of animals in biomedical research. Thromb. Haemostasis58:1078–1084, 1987.

    Google Scholar 

  8. Hartwell, D. W., and D. D. Wagner. New discoveries with mice mutant in endothelial and platelet selectins. Thromb. Haemostasis82:850–857, 1999.

    Google Scholar 

  9. Karino, T., and H. L. Goldsmith. Role of blood cell-wall interactions in thrombogenesis and atherogenesis: A microrheological study. Biorheology21:587–601, 1984.

    Google Scholar 

  10. Kawasaki, T., M. Dewerchin, H. R. Lijnen, J. Vermylen, and M. F. Hoylaerts. Vascular release of plasmiogen activator inhibitor-1 imparis fibrinolysis during acute arterial thrombosis in mice. Blood96:153–160, 2000.

    Google Scholar 

  11. Kawasaki, T., T. Kaida, J. Arnout, J. Vermylen, and M. F. Hoylaerts. A new animal model of thrombophilia confirms that high plasma factor VIII levels are thrombogenic. Thromb. Haemostasis81:306–311, 1999.

    Google Scholar 

  12. Keller, J. W., and J. D. Folts. Combined inhibitory effects of aspirin and ethanol on adrenaline exacerbation of acute platelet thrombus formation in stenosed canine coronary arteries. Cardiovasc. Res.24:191–197, 1990.

    Google Scholar 

  13. Lassila, R., J. J. Badimon, S. Vallabhajosula, and L. Badimon. Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood. Effects of different stenoses on thrombus growth. Arteriosclerosis (Dallas)10:306–315, 1990.

    Google Scholar 

  14. Libby, P.Current concepts of the pathogenesis of the acute coronary syndromes. Circulation104:365–372, 2001.

    Google Scholar 

  15. Liu, S. Q., L. Zhong, and J. Goldman. Control of the shape of a thrombus-neointima-like structure by blood shear stress. J. Biomech. Eng.124:30–36, 2002.

    Google Scholar 

  16. Marchese, P., E. Saldívar, J. Ware, and Z. M. Ruggeri. Adhesive properties of the isolated amino-terminal domain of platelet glycoprotein Iba in a flow field. Proc. Natl. Acad. Sci. U.S.A.96:7837–7842, 1999.

    Google Scholar 

  17. Matsuno, H., T. Uematsu, S. Nagashima, and M. Nakashima. Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. J. Pharmacol. Methods25:303–317, 1991.

    Google Scholar 

  18. Nemmar, A., M. F. Hoylaerts, E. Verbeken, P. H. M. Hoet, and B. Nemery. Utrafine particles affect experimental thrombosis. Am. J. Respir. Crit. Care Med.166:998–1004, 2002.

    Google Scholar 

  19. Ni, H., C. V. Denis, S. Subbarao, J. L. Degen, T. N. Sato, R. O. Hynes, and D. D. Wagner. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J. Clin. Invest.106:385–392, 2000.

    Google Scholar 

  20. Sprawls P. In: Physical Principles of Medical Imaging, Madison, WI: Medical Physics, 1995.

    Google Scholar 

  21. Stockmans, F., J. M. Stassen, J. Vermylen, M. F. Hoylaerts, and å. Nyström. A technique to investigate mural thrombus formation in small arteries and veins: I. Comparative morphometric and histological analysis. Ann. Plast. Surg.38:56–62, 1997.

    Google Scholar 

  22. Stockmans, F., J. M. Stassen, J. Vermylen, M. F. Hoylaerts, and å. Nyström. A technique to investigate mural thrombus formation in small arteries and veins: II. Effects of aspirin, heparin, r-hirudin and G-4120. Ann. Plast. Surg.38:63–68, 1997.

    Google Scholar 

  23. Takiguchi, Y., K. Wada, H. Matsuno, and M. Nakashima. Effect of diabetes on photochemically induced thrombosis in femoral artery and platelet aggregation in rats. Thromb. Res.63:445–456, 1991.

    Google Scholar 

  24. Umemura, K., Y. Kohno, H. Matsuno, T. Uematsu, and M. Nakashima. A new model for photochemically induced thrombosis in the inner ear microcirculation and the use of hearing loss as a measure for microcirculatory disorders. Eur. Arch. Otorhinolaryngol.248:105–108, 1990.

    Google Scholar 

  25. Wu, D., M. Meiring, H. F. Kotze, H. Deckmyn, and N. Cauwenberghs. Inhibition of platelet glycoprotein Ib, glycoprotein IIb/IIIa, or both by monoclonal antibodies prevents arterial thrombosis in baboons. Arterioscler., Thromb., Vasc. Biol.22:323–328, 2002.

    Google Scholar 

  26. Yamamoto, H., I. Vreys, J. M. Stassen, R. Yoshimoto, J. Vermylen, and M. F. Hoylaerts. Antagonism of vWF inhibits both injury induced arterial and venous thrombosis in the hamster. Thromb. Haemostasis79:202–210, 1998.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium

    Ting Zhu & Marc F. Hoylaerts

  2. Biomechanics Laboratory, Department of Engineering Mechanics, Tsinghua University, Beijing, People's Republic of China

    Ting Zhu, HuCheng Zhao & Jia Wu

Authors
  1. Ting Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. HuCheng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jia Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marc F. Hoylaerts
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, T., Zhao, H., Wu, J. et al. Three-Dimensional Reconstruction of Thrombus Formation during Photochemically Induced Arterial and Venous Thrombosis. Annals of Biomedical Engineering 31, 515–525 (2003). https://doi.org/10.1114/1.1566771

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.1566771

Search

Navigation