On the interplay between hemodynamics and biochemsitry of the normal and aneurysmatic abdominal aorta

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On the interplay between

hemodynamics and

biochemistry of the normal

and aneurysmatic

abdominal aorta

Jacopo B i ase t ti

Licentiate thesis in solid Mechanics

stockholm, sweden 2011

www.kth.se TRITA HFL-0512 ISSN 1654-1472 ISRN KTH/HFL/R-11/14-SE ISBN 978-91-7501-139-4

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Preface

The work presented in this thesis has been carried out at the department of Solid Mechanics, Royal Institute of Technology (KTH), Stockholm.

The work has been financially supported by the Young Faculty grant no. 2006-7568 provided by the Swedish Research Council, VINNOVA and the Swedish Foundation for Strategic Research, which are gratefully acknowledged.

Stockholm, October 2011 Jacopo Biasetti

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Introduction

Overview

The arterial system consists of a number of arteries through which blood ﬂows carrying, for example, oxygen and nutrients to the different organs. One of the most important arteries in the human body is the aorta, a vessel consisting of three segments, the ascending aorta, also called aortic arch, the descending thoracic and the abdominal aorta, the last one being the focus of the present work.

Abdominal Aortic Aneurysm

An abdominal aortic aneurysm (AAA) is a focal dilatation of the abdominal aorta, see Figure 1, frequently observed in the aging population [3] and thought to be the end result of irreversible pathological remodeling of the arterial connective tissue [2]. In principle any aortic section can become aneurysmatic, yet the infrarenal segment (the aortic region between the renal arteries and the iliac arteries) is the more prone to develop an AAA. Abdominal aortic aneurysm is frequently characterized by the presence of an Intra-Luminal Thrombus (ILT), a soft tissue composed mainly of ﬁbrin, blood cells, platelets, blood proteins and cellular debris [1]. The ILT exert a series of biochemical and biomechanical effects on AAA’s evolution, see [10] [7] [6] [9] [11] [5] [8].

Objective

The aim of this study is twofold: understand the complex flow fields peculiar to the healthy and diseased human aortas, and develop an integrated fluido-chemical framework able to model the coagulation cascade in blood flow.

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Figure 1: Localization of the aorta in the human body and comparison between a normal and an aneurysmatic aorta.

Numerical Modeling

Computational models and post-processing routines have been developed, as detailed in Papers A, B, and C. The Finite Volume (FV) software ANSYS CFX (ANSYS Inc.), the Finite Element (FE) software COMSOL (COMSOL AB), MATLAB (MATLAB Inc.), and the visualization and post-processing software Tecplot (Tecplot Inc.) were used.

Result

Numerical results of the flow field revealed marked differences between normal and aneurys-matic aortas; this result lead to the postulation of a theory of fluid-driven ILT growth, see Paper A. The analysis of the flow field using the concept of Vortical Structures (VS) helped refining the proposed theory of driven ILT growth, see paper B. The coupling between the fluid-dynamical field with a model of the coagulation cascade, see Paper C, helped elucidating the complex interaction between fluid-dynamics and biochemistry.

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Discussion

Flow ﬁelds between normal and diseased aortas differ markedly; the Newtonian assumption has been found to be inappropriate in the case of diaseased aortas, where lower shear rates dictates a higher viscosity. Vortical Structures form in the neck region (proximal) and travels down the lumen until burst occurs in the distal region of the aneurysm; their motion and burst location correlates with the region of thickest ILT. The distribution of chemicals is linked to the behavior of VSs, in particular thrombin accumulates in the distal region of the AAA.

Conclusion

The detailed analysis of blood flow represents one of the major challenges in modern compu-tational vascular biomechanics due to the complex intertwined phenomena characterizing the cardiovascular system. The ability to model blood flow within a certain degree of accuracy and the availability of an integrated fluido-chemical model able to capture the significant features of the coagulation cascade in flowing blood and to link them to ILT growth is of paramount importance since in serving as guidance both for experiments and for future modeling efforts.

Summary of appended papers

Paper A: Hemodynamics of the normal aorta compared to fusiform and saccular abdominal

aortic aneurysms with emphasis on a potential thrombus formation mechanism

In this paper the blood flow in normal aortas, fusiform AAAs and saccular AAAs has been simulated. Patient-specific luminal geometries were reconstructed from Computerized Tomog-raphy AngiogTomog-raphy data and blood flow simulated using physiological boundary conditions. To capture the non-Newtonian behavior of blood, the Carreau-Yasuda model for shear-thinning has been used. From the analysis of the solution fields a possible mechanism of shear-induced

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v platelets activation has been detailed, which in turn forms the basis for a theory of ﬂuid-driven ILT growth.

Paper B: Blood ﬂow and coherent vortices in the normal and aneurysmatic aortas: a ﬂuid

dy-namical approach to intra-luminal thrombus formation

In this paper the theory of ﬂuid-driven ILT growth proposed in Paper A has been extended. The powerful concept of Vortical Structures (VSs) has been exploited and a correlation between VSs educed with theλ2-method and ILT formation in AAAs delineated. VSs proved to be key in un-derstading the complex phenomena occurring in blood ﬂow. A clear correlation between VSs and wall shear stress has been found, while the motion of VSs (from formation to break-up) correlates well with the location of thickest ILT. The results showed to be strongly dependent from the constituted model and the non-Newtonian assumption proved to be the most accurate one.

Paper C: An integrated ﬂuido-chemical model towards modeling the formation of intra-luminal

thrombus in abdominal aortic aneurysms

In this paper the coagulation cascade in flowing blood has been modeled. A fluido-chemical model in which the tissue factor pathway is implemented as a series of convection-diffusion-reaction (CDR) equations coupled to the fluid-dynamical field modeled via the Navier-Stokes equations with the assumption of non-Newtonian behavior has been developed. A link between the chemical fields (in particular thrombin, the main quantity of interest) and Vortical Structures (VSs) has been found. Thrombin accumulates in the distal portion of the abdominal aortic aneurysm, a finding that correlates with the position of the thickest ILT.

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References

[1] R. Adolph, D. A. Vorp, D. L. Steed, M. W. Webster, M. V. Kameneva, and S. C. Watkins. Cellular content and permeability of intraluminal thrombus in Abdominal Aortic Aneurysm. J. Vasc. Surg., 25:916–926, 1997.

[2] E. Choke, G. Cockerill, W. R. Wilson, S. Sayed, J. Dawson, I. Loftus, and M. M. Thomp-son. A review of biological factors implicated in Abdominal Aortic Aneurysm rupture.

Eur. J. Vasc. Endovasc. Surg., 30:227–244, 2005.

[3] C. Fleming, E. P. Whitlock, T. Beil, and F. A. Lederle. Review: Screening for Abdominal Aortic Aneurysm: A best-evidence systematic review for the U.S. Preventive Services Task Force. Ann. Intern. Med., 142:203–211, 2005.

[4] J. D. Humphrey. Cardiovascular Solid Mechanics. Cells, Tissues, and Organs. Springer-Verlag, New York, 2002.

[5] F. Inzoli, F. Boschetti, M. Zappa, T. Longo, and R. Fumero. Biomechanical factors in Abdominal Aortic Aneurysm rupture. Eur. J. Vasc. Surg., 7:667–74, 1993.

[6] M. Kazi, J. Thyberg, P. Religa, J. Roy, P. Eriksson, U. Hedin, and J. Swedenborg. Inﬂu-ence of intraluminal thrombus on structural and cellular composition of Abdominal Aortic Aneurysm wall. J. Vasc. Surg., 38:1283–1292, 2003.

[7] M. Kazi, C. Zhu, J. Roy, G. Paulsson-Berne, A. Hamsten, J. Swedenborg, U. Hedin, and P. Eriksson. Difference in matrix-degrading protease expression and activity between thrombus-free and thrombus-covered wall of Abdominal Aortic Aneurysm. Arterioscler.

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vii [8] W. R. Mower, W. J. Qui˜nones, and S. S. Gambhir. Effect of intraluminal thrombus on

Abdominal Aortic Aneurysm wall stress. J. Vasc. Surg., 33:602–608, 1997.

[9] J. Swedenborg and P. Eriksson. The Intraluminal Thrombus as a source of proteolytic activity. Ann. N.Y. Acad. Sci., 1085:133–138, 2006.

[10] D. A. Vorp, P. C. Lee, D. H. Wang, M. S. Makaroun, E. M. Nemoto, S. Ogawa, and M. W. Webster. Association of intraluminal thrombus in Abdominal Aortic Aneurysm with local hypoxia and wall weakening. J. Vasc. Surg., 34:291–299, 2001.

[11] D. H. Wang, M. S. Makaroun, M. W. Webster, and D. A. Vorp. Effect of intraluminal thrombus on wall stress in patient-speciﬁc models of Abdominal Aortic Aneurysm. J.

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Paper A:

Hemodynamics of the normal aorta compared to fusiform and saccular abdominal aortic aneurysms with emphasis on a potential thrombus formation mechanism.

Biasetti J, Gasser T.C, Auer M, Hedin U, Labruto F. Ann Biomed Eng. 2010 Feb; 38(2):380-390

Paper B:

Blood flow and coherent vortices in the normal and aneurysmatic aortas: a fluid dynamical approach to intra-luminal thrombus formation.

Biasetti J, Hussain F, Gasser T.C.

J R Soc Interface. 2011 Oct 7;8(63):1449-61. Epub 2011 Apr 6.

Paper C:

An integrated fluido-chemical model towards modeling the formation of intra-luminal thrombus in abdominal aortic aneurysms.

Biasetti J, Spazzini PG, Gasser T.C. Submitted for publication, 2011

In addition to the appended papers, the work has resulted in the following conference contributions:

Biomechanical determinants of Abdominal Aortic Aneurysms – fusiform versus pseudo(saccular) formations

Biasetti J, Auer M, Gasser T.C, Hedin U, Swedenborg J.

WCCM8 and ECCOMAS, Venice, Italy, June 30 – July 5, 2008

Hemodynamic simulations towards a biomechanical model of thrombus formation in Abdominal Aortic Aneurysm

Biasetti J, Gasser T.C, Auer M, Hedin U, Labruto F.

Endovascular Surgery – Bringing Basic Science into Clinical Practice, Stockholm,

Sweden, March 19-21, 2009

Hemodynamic simulations in Abdominal Aortic Aneurysms – Insights into thrombus formation

Biasetti J, Gasser T.C, Auer M, Hedin U, Labruto F.

10th US National Congress on Computational Mechanics, Columbus, Ohio, US, July

16-19, 2009

Structural and hemodynamical analysis of Aortic Aneurysms from Computerized Tomography Angiography data

Gasser T.C, Auer M, Biasetti J

Proceedings of the World Congress 2009 – Medical Physics and Biomedical Engineering, Munich, Germany, September 7-12, 2009

Coherent structure and blood flow dynamics in the normal and aneurysmatic aorta

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Biasetti J, Hussain F, Gasser T.C.

ECCOMAS CFD 2010 – Fifth European Conference on Computational Fluid Dynamics, Lisbon, Portugal, June 14-17, 2010

A blood flow based model for platelet activation in Abdominal Aortic Aneurysms

Biasetti J, Gasser T.C.

WCB 2010 – 6th World Congress on Biomechanics, Singapore, Singapore, August

1-6, 2010

A fluido-chemical model of thrombus formation

CMBE 2011 – 2nd International Conference on Mathematical and Computational Biomedical Engineering, Washington D.C., USA, March 30 – April 1, 2011

The intra-luminal thrombus in abdominal aortic aneurysms: a fluido-chemical approach to explain its development

6th International Symposium on Biomechanics in Vascular Biology and Cardiovascular Disease, Rotterdam, The Netherland, April 14-15, 2011

On the interplay between hemodynamics and biochemsitry of the normal and aneurysmatic abdominal aorta