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An In Vitro Evaluation of Emboli Trajectories Within a Three-Dimensional Physical Model of the Circle of Willis Under Cerebral Blood Flow Conditions

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Abstract

In vitro simulations of the trajectory and lodgement locations of emboli within the circle of Willis (CoW) are crucial in understanding the associated hemodynamic effects in stroke patients. A clot was fabricated from the hemolymph of a crustacean species. Clots were injected into the internal carotid artery via a cerebral flow facility housing a manufactured CoW human model. The trajectory of the clot was tracked and its hemodynamic effects monitored. The clots traveled with an average velocity of 88 mm/s along the ipsilateral side with momentary pauses along high curvature regions before finally lodging within the distal branches of the ipsilateral middle cerebral artery (MCA). These clots either elongated along the branching vessels or compressed against a bifurcation point. A blocked M1-segment of the MCA reduced the efferent blood pressure and flow rates by (15–77%) and (20–100%) respectively with a re-distribution of the flow towards the other efferent vessels. Mimicking blood clots with crustacean hemolymph provides a much lower biohazard risk than using human or mammalian blood clots and a superior alternative to synthetic materials. The geometry of the distal MCA vasculature will determine the end morphology of the lodged clot. Clotting severely reduces the distal flow rates and pressures.

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References

  1. Abou-Chebl, A. Endovascular treatment of acute ischemic stroke may be safely performed with no time window limit in appropriately selected patients. Stroke. 41:1996–2000, 2010.

    Article  PubMed  Google Scholar 

  2. Asakura, F., H. Yilmaz, G. Sekoranja, et al. Preclinical testing of a new clot-retrieving wire device using polyvinyl alcohol hydrogel vascular models. Neuroradiology. 49(3):243–251, 2007.

    Article  PubMed  Google Scholar 

  3. Buijs, P. C., M. J. Krabbe-Hartkamp, C. J. Bakker, E. E. de Lange, L. M. Ramos, M. M. Breteler, and W. P. Mali. Effect of age on cerebral blood flow: measurement with ungated two-dimensional phase-contrast MR angiography in 250 adults. Radiology. 209(3):667–674, 1998.

    Article  CAS  PubMed  Google Scholar 

  4. Cao, C., S. C. Ang, P. Indraratna, C. Manganas, P. Bannon, D. Black, D. Tian, and T. D. Yan. Systematic review and meta-analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis. Ann. Cardiothorac. Surg. 2(1):10–23, 2013.

    PubMed Central  PubMed  Google Scholar 

  5. Carlisle, C. R., E. A. Sparks, C. Der Loughlian, and M. Guthold. Strength and failure of fibrin fibre branchpoints. J. Thromb. Haemost. 8:1135–1138, 2010.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Chueh, J. K., A. K. Wakhloo, G. H. Hendricks, C. F. Silva, J. P. Weaver, and M. J. Gounis. Mechanical characterisation of thromboemboli in acute ischemic stroke and laboratory embolus analogs. Am. J. Neurodiol. 32:1237–1244, 2011.

    Article  CAS  Google Scholar 

  7. Chung, E. M. L., J. P. Hague, M.-A. Chanrion, K. V. Ramnarine, E. Katsogridakis, and D. H. Evans. Embolus trajectory through a physical replica of the major cerebral arteries. Stroke. 41(4):647–652, 2010.

    Article  PubMed  Google Scholar 

  8. Cloft, H. J., A. Rabinstein, G. Lanzino, and D. F. Kallmes. Intra-arterial stroke therapy: an assessment of demand and available work force. Am. J. Neuroradiol. 30(3):453–458, 2009.

    Article  CAS  PubMed  Google Scholar 

  9. Ene, F., C. Gachon, P. Delassus, R. Carroll, F. Stefanov, P. O’Flynn, and L. Morris. In vitro evaluation of the effects of intraluminal thrombus on abdominal aortic aneurysm wall dynamics. Med. Eng. Phys. 33(8):957–966, 2011.

    Article  PubMed  Google Scholar 

  10. Fahy, P., P. Delassus, P. McCarthy, S. Sultan, N. Hynes, and L. Morris. An in vitro assessment of the cerebral hemodynamcis through three patient specific circle of willis geometries. J. Biomech. Eng. 136(1):011007, 2013. doi:10.1115/1.402577.

    Article  Google Scholar 

  11. Fahy, P., P. Delassus, P. O’Flynn, and L. Morris. An experimental study of the effects anatomical variations have on collateral flows within the circle of willis. Farmington, VA: Proceedings of the ASME Summer Bioengineering Conference, 2011.

    Book  Google Scholar 

  12. Fahy, P., P. McCarthy, S. Sultan, N. Hynes, P. Delassus, and L. Morris. An experimental investigation of the hemodynamic variations due to aplastic vessels within three-dimensional phantom models of the circle of willis. Ann. Biomed. Eng. 42(1):123–128, 2014.

    Article  PubMed  Google Scholar 

  13. Ford, M. D., N. Alperin, S. H. Lee, D. W. Holdsworth, and D. A. Steinman. Characterization of volumetric flow rate waveforms in the normal internal carotid and vertebral arteries. Physiol. Meas. 26(4):477–488, 2005.

    Article  PubMed  Google Scholar 

  14. Gács, G., F. T. Mérei, and M. Bodosi. Balloon catheter as a model of cerebral emboli in humans. Stroke. 13(1):39–42, 1982.

    Article  PubMed  Google Scholar 

  15. Ghanem, A., J. Kocurek, J. M. Sinning, M. Weber, C. Hammersting, M. Wagner, M. Vasa-Nicotera, E. Grube, N. Werner, and G. Nickenig. Novel approaches for prevention of stroke related to transcather aortic valve implantation. Expert Rev. Cardiovasc. Ther. 11(10):1311–1320, 2013.

    Article  CAS  PubMed  Google Scholar 

  16. Gralla, J., M. Burkhardt, G. Schroth, M. EI-Koussy, M. Reinert, K. Nedeltchev, J. Slotboom, and C. Brekenfeld. Occlusion length is a crucial determinant of efficiency and complication rate in thrombectomy for acute ischemic stroke. Am. J. Neuroradiol. 29(2):247–252, 2008.

    Article  CAS  PubMed  Google Scholar 

  17. Hart, R. G., J. L. Halperin, L. A. Pearce, D. C. Anderson, R. A. Kronmal, et al. Lessons from the stroke prevention in atrial fibrillation trials. Ann. Intern. Med. 138(10):831–838, 2003.

    Article  PubMed  Google Scholar 

  18. Hauton, C. The scope of the crustacean immune system for disease control. J. Invertebr. Pathol. 110(2):251–260, 2012.

    Article  PubMed  Google Scholar 

  19. Hossmann, K. A. Experimental models for the investigation of brain ischemia. Cardiovasc. Res. 39:106–120, 1998.

    Article  CAS  PubMed  Google Scholar 

  20. Hussain, S. I., O. O. Zaidar, and B. F. M. Fitzsimmons. The penumbra system for mechanical thrombectomy in endovascular acute ischemic stroke therapy. Neurology. Suppl. 1:S135–S141, 2012.

    Article  Google Scholar 

  21. Hylek, E. M., A. S. Go, Y. Chang, N. G. Jensvold, L. E. Henault, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N. Engl. J. Med. 349:1019–1026, 2003.

    Article  CAS  PubMed  Google Scholar 

  22. Jou, L.-D., D. H. Lee, and M. E. Mawad. Cross-flow at the anterior communicating artery and its implication in cerebral aneurysm formation. J. Biomech. 43(11):2189–2195, 2010.

    Article  PubMed  Google Scholar 

  23. Krings, T., D. M. Mandell, T.-R. Kiehl, S. Geibprasert, M. Tymianski, H. Alvarez, K. G. Terbrugge, and F.-J. Hans. Intracranial aneurysms: from vessel wall pathology to therapeutic approach. Nat. Rev. Neurol. 7(10):547–559, 2011.

    Article  CAS  PubMed  Google Scholar 

  24. Leon, M. B., C. R. Smith, M. Mack, C. Miller, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N. Engl. J. Med. 363(17):1597–1607, 2010.

    Article  CAS  PubMed  Google Scholar 

  25. Lin, J. K., and W. C. Shyu. Middle cerebral artery occlusion compromising the sensory and motor cortices. Tzu Chi Med. 18:382–384, 2006.

    Google Scholar 

  26. Liu, W., C. R. Carlisle, E. A. Sparks, and M. Guthold. The mechanical properties of single fibrin fibres. J. Thromb. Haemost. 8:1030–1036, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Maas, S. J., and J. E. Safdieh. Ischemic stroke: pathophysiology and principles of localization. Hosp. Physician Neurol. Board Rev. Man. 13(2):1–17, 2009.

    Google Scholar 

  28. Makkar, R. R., P. G. Fontana, H. Jilaihawi, S. Kapadia, et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N. Engl. J. Med. 366(18):1696–1704, 2012.

    Article  CAS  PubMed  Google Scholar 

  29. Marder, V. J., D. J. Chute, S. Starkman, A. M. Abolian, et al. Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke. 37(8):2086–2093, 2006.

    Article  PubMed  Google Scholar 

  30. Masuda, J., C. Yutani, J. Ogata, Y. Kuriyama, and T. Yamaguchi. Atheromatous embolism in the brain: a clinicopathologic analysis of 15 autopsy cases. Neurology. 44:1231–1237, 1994.

    Article  CAS  PubMed  Google Scholar 

  31. Monson, K. L., W. Goldsmith, N. M. Barbaro, and G. T. Manley. Axial mechanical properties of fresh human cerebral blood vessels. J Biomech. Eng. 125(2):288–294, 2003.

    Article  PubMed  Google Scholar 

  32. Monson, K. L., W. Goldsmith, N. M. Barbaro, and G. T. Manley. Significance of source and size in the mechanical response of human cerebral blood vessels. J. Biomech. 38(4):737–744, 2005.

    Article  PubMed  Google Scholar 

  33. Moore, S., T. David, J. G. Chase, J. Arnold, and J. Fink. 3D models of blood flow in the cerebral vasculature. J. Biomech. 39(8):1454–1463, 2006.

    Article  CAS  PubMed  Google Scholar 

  34. Morris, L., P. O’Donnell, P. Delassus, and T. McGloughlin. Experimental assessment of stress patterns in abdominal aortic aneurysms using the photoelastic method. Strain. 40(4):165–172, 2004.

    Article  Google Scholar 

  35. Morris, L., F. Stefanov, and T. McGloghlin. Stent graft performance in the treatment of abdominal aortic aneurysms: the influence of compliance and geometry. J. Biomech. 46(2):383–395, 2013.

    Article  PubMed  Google Scholar 

  36. Ng, Y. S., J. Stein, M. M. Ning, and R. M. Black-Schaffer. Comparison of clinical characteristics and functional outcomes of ischemic stroke in different vascular territories. Stroke. 38:2309–2314, 2007.

    Article  PubMed  Google Scholar 

  37. Nogueira, R. G., L. H. Schwamm, and J. Hirsch. Endovascular approaches to acute stroke, part 1: drugs, devices, and data. Am. J. Neuroradiol. 30(4):649–661, 2009.

    Article  CAS  PubMed  Google Scholar 

  38. O’Brien, T., L. Morris, M. O’Donnell, M. Walsh, and T. McGloughlin. Injection-moulded models of major and minor arteries: the variability of model wall thickness owing to casting technique. Proc. Inst. Mech. Eng. H. 219(H5):381–386, 2005.

    Article  PubMed  Google Scholar 

  39. Ringelstein, E. B., R. Biniek, C. Weiller, B. Ammeling, P. N. Nolte, and A. Thorn. Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology. 42:289–298, 1992.

    Article  CAS  PubMed  Google Scholar 

  40. Ruland, S., and A. Venkatesh. Cerebral autoregulation and blood pressure lowering. Hypertension. 49:977–978, 2007.

    Article  CAS  PubMed  Google Scholar 

  41. Schwaigner, B. J., F. Kober, A. S. Gersing, J. F. Kleine, S. Wunderlich, C. Zimmer, H. Poppert, and S. Prothmann. The pREset stent retriever for endovascular treatment of stroke caused by MCA occlusion: safety and clinical outcome. Clin. Neuroradiol. 2014. doi:10.1007/s00062-014-0329-z.

    Google Scholar 

  42. Seitz, R. J., P. Hoflick, F. Binkofski, L. Tellmann, H. Herzog, and H. J. Freund. Role of the premotor cortex in recover from middle cerebral artery infarction. Arch. Neurol. 55:1081–1088, 1998.

    Article  CAS  PubMed  Google Scholar 

  43. Shrive, A. K., A. M. Metcalfe, J. R. Cartwright, and T. J. Greenhough. C-reactive protein and SAP-like pentraxin are both present in Limulus polyphemus hemolymph: crystal structure of Limulus SAP. J. Mol. Biol. 290(5):997–1008, 1999.

    Article  CAS  PubMed  Google Scholar 

  44. Steinman, D. A., Y. Hoi, P. Fahy, L. Morris, et al. Variability of CFD solutions for pressure and flow in a giant aneurysm: the SBC2012 CFD challenge. J. Biomech. Eng. 135(2):021016, 2013. doi:10.1115/1.4023382.

    Article  PubMed  Google Scholar 

  45. Tanaka, H., N. Fujita, T. Enoki, et al. Relationship between variations in the circle of Willis and flow rates in internal carotid and basilar arteries determined by means of magnetic resonance imaging with semiautomated lumen segmentation: reference data from 125 healthy volunteers. Am. J. Neuroradiol. 27:1770–1775, 2006.

    CAS  PubMed  Google Scholar 

  46. Taussky, P., R. G. Tawk, W. P. Daugherty, and R. A. Hanel. Medical therapy for ischemic stroke: review of intravenous and intra-arterial treatment methods. World Neurosurg. 76(6):S9–S15, 2011.

    Article  PubMed  Google Scholar 

  47. Tennuci, C., G. Pearce, J. Wong, S. Nayak, T. Jones, F. Lally, and C. Roffe. Comparison of the effectiveness of three methods of recanalization in a model of the middle cerebral artery: thrombus aspiration via a 4F Catheter, thrombus aspiration via the GP thromboaspiration device, and mechanical thrombectomy using the solitaire thrombectomy device. Stroke Res. Treat. 2011:186424, 2011.

    PubMed Central  PubMed  Google Scholar 

  48. Tenser, M. S., A. P. Amar, and W. J. Mack. Mechanical thrombectomy for acute ischemic stroke using the MERCI retriever and penumbra aspiration systems. World Neurosurg. 76(6):S16–S23, 2011.

    Article  PubMed  Google Scholar 

  49. Torvik, A., and K. Skullerud. Watershed infarcts in the brain caused by microemboli. Clin. Neuropathol. 1:99–105, 1982.

    CAS  PubMed  Google Scholar 

  50. Weisel, J. W. Structure of fibrin: impact on clot stability. J. Thromb. Haemost. 5(1):116–124, 2007.

    Article  CAS  PubMed  Google Scholar 

  51. Zhu, L., D. S. Liebeskind, R. Jahan, S. Starkman, N. Salamon, G. Duckwiler, et al. Thrombus branching and vessel curvature are important determinants of middle cerebral artery trunk recanalization with merci thrombectomy devices. Stroke. 43:787–792, 2014.

    Article  Google Scholar 

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Acknowledgments

This research was funded by Strands I and III from the Department of Education in Ireland.

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We have no conflict of interest issues.

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Authors and Affiliations

  1. Galway Medical Technologies Centre, Department of Mechanical and Industrial Engineering, Galway Mayo Institute of Technology, Galway, Ireland

    Paul Fahy, Fiona Malone, Eugene McCarthy & Liam Morris

  2. Department of Diagnostic Radiology, University Hospital, Galway, Ireland

    Peter McCarthy

  3. Neuroradiology Department, Beaumont Hospital, Dublin, Ireland

    John Thornton, Paul Brennan, Alan O’Hare & Seamus Looby

  4. Department of Vascular and Endovascular Surgery, Western Vascular Institute, University Hospital, Galway, Ireland

    Sherif Sultan

  5. Department of Vascular & Endovascular Surgery, Galway Clinic, Galway, Ireland

    Sherif Sultan & Niamh Hynes

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  1. Paul Fahy
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  2. Fiona Malone
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  3. Eugene McCarthy
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Correspondence to Liam Morris.

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Associate Editor Andreas Anayiotos oversaw the review of this article.

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Fahy, P., Malone, F., McCarthy, E. et al. An In Vitro Evaluation of Emboli Trajectories Within a Three-Dimensional Physical Model of the Circle of Willis Under Cerebral Blood Flow Conditions. Ann Biomed Eng 43, 2265–2278 (2015). https://doi.org/10.1007/s10439-015-1250-6

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