Biomechanics of abdominal aortic aneurysm:Experimental evidence and multiscale constitutive modeling Giampaolo Martufi Doctoral thesis no. 80, 2012 KTH School of Engineering Sciences Department of Solid Mechanics Royal Institute of Technology SE-100 44 Stockholm Sweden TRITA HFL-0530 ISSN 1654-1472 ISRN KTH/HFL/R-12/0014-SE Akademisk avhandling som med tillstånd av Kungliga Tekniska Högskolan i Stockholm framlägges till offentlig granskning för avläggande av teknisk doktorsexamen torsdagen den 20 september kl. 10.00 i sal L1, Kungliga Tekniska Högskolan, Drottning Kristinasvägen 30, Stockholm. A mia madre Abstract The reliable assessment of Abdominal Aortic Aneurysm (AAA) rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. A multi-disciplinary approach including vascular biomechanics and constitutive modeling is needed to better understand and more effectively treat these diseases. AAAs are formed through irreversible pathological remodeling of the vascular wall and integrating this biological process in the constitutive description could improve the current understanding of this disease as well as the predictability of biomechanical simulations. First in this thesis, multiple centerline-based diameter measurements between renal arteries and aortic bifurcation have been used to monitor aneurysm growth of in total 51 patients from Computer Tomography-Angiography (CT-A) data. Secondly, the thesis proposes a novel multi-scale constitutive model for the vascular wall, where collagen fibers are assembled by proteoglycan cross-linked collagen fibrils and reinforce an otherwise isotropic matrix (elastin). Collagen fibrils are dynamically formed by a continuous stretch-mediated process, deposited in the current configuration and removed by a constant degradation rate. The micro-plane concept is then used for the Finite Element (FE) implementation of the constitutive model. Finally, histological slices from intra-luminal thrombus (ILT) tissue were analyzed using a sequence of automatic image processing steps. Derived microstructural data were used to define Representative Volume Elements (RVEs), which in turn allowed the estimation of microscopic material properties using the non-linear FE. The thesis showed that localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements all over the AAA sac. Consequently, this information might further reinforce the quality of aneurysm surveillance programs. The novel constitutive model proposed in the thesis has a strong biological motivation and provides an interface with biochemistry. Apart from modeling the tissue’s passive response, the presented model is helpful to predict saline feature of aneurysm growth and remodeling. Finally, the thesis provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture. Preface The research presented in this doctoral thesis has been carried out at the Department of Solid Mechanics, Royal Institute of Technology (KTH), Stockholm between July 2008 and July 2012. The work was financially supported by the Young Faculty Grant No. 2006-7568 provided by the Swedish Research Council, VINNOVA and the Swedish Foundation for Strategic Research, and the EC Seventh Framework Programme, fighting Aneurysmal Disease (FAD- 200647), which is sincerely acknowledged. First of all I would like to express my sincere gratitude to my supervisor T. Christian Gasser for giving me the opportunity to work with a very interesting and challenging topic. I am thankful for his support, for the fruitful discussions and excellent guidance through these four years at KTH. Further I would like to thank Ender Finol for introducing me to the field of biomechanics and Elena Di Martino for her valuable advices and knowledge in AAA biomechanics. I would also like to thank my colleagues and friends at KTH Solid Mechanics for making the working environment enjoyable. Finally, I would like to extend my gratitude to my dad, my sister and my brother in law for all the encouragement and support I received. Stockholm, August 2012 Giampaolo Martufi List of appended papers Paper A: Growth of small abdominal aortic aneurysms: A multidimensional analysis G. Martufi, M. Auer, J. Roy, J.Swedenborg, N. Sakalihasan, G. Panuccio and T.C. Gasser Report 529, Department of Solid Mechanics, KTH Engineering Sciences, Royal Institute of Technology, Stockholm, Sweden. Submitted to international journal for publication. Paper B: A constitutive model for vascular tissue that integrates fibril, fiber and continuum levels with application to the isotropic and passive properties of the infrarenal aorta G. Martufi and T.C. Gasser Journal of Biomechanics, 44(14):2544-2550, 2011. Paper C: Turnover of fibrillar collagen in soft biological tissue with application to the expansion of abdominal aortic aneurysms G. Martufi and T.C. Gasser Journal of the Royal Society Interface, published online, doi:10.1098/rsif.2012.0416, 2012. Paper D: Micromechanical characterization of intra-luminal thrombus tissue from abdominal aortic aneurysms T.C. Gasser, G. Martufi, M. Auer, M. Folkesson and J.Swedenborg Annals of Biomedical Engineering, 38(2):371-379, 2010. In addition to the appended paper, the work has resulted in the following publications in conference proceedings fully reviewed prior to publication: Remodeling of fibrillar collagen applied to aneurysm growth G. Martufi and T.C. Gasser Proceedings of the Word Congress on Computational Mechanics, Sao Paulo, Brazil, July 8 – 13, 2012. Histo-mechanical modeling of the wall of abdominal aorta aneurysms G. Martufi and T.C. Gasser Proceedings of MATHMOD 2012 - 7th Vienna International Conference on Mathematical Modelling, Vienna, Austria, February 15-17, 2012. (6 pages paper) Remodeling of abdominal aortic aneurysm wall: A multi-scale structural approach G. Martufi and T.C. Gasser Proceedings of the 4th International Conference on the Mechanics of Biomaterials and Tissues, Hawaii, USA, December 11-15, 2011. A multi-scale collagen turn-over model for soft biological tissues with application to abdominal aortic aneurysms growth G. Martufi, T.C. Gasser and M. Auer Proceedings of ASME 2011 Summer Bioengineering Conference, Farmington, Pennsylvania, USA , June 22 - 25, 2011. Progression of abdominal aortic Aneurysm: Clinical evidence and multiscale modeling G. Martufi, T.C. Gasser, M. Labruto and J. Swedenborg Proceedings of the 6th International Symposium on Biomechanics in Vascular Biology and Cardiovascular Disease, Rotterdam, The Netherlands, April 14 – 15, 2011. A constitutive model for vascular tissue that integrates fibril, fiber and continuum levels T.C. Gasser, G. Martufi and M. Auer Proceedings of 2nd International Conference on Computational & Mathematical Biomedical Engineering, George Mason University, Washington D.C., USA March 30 - April 1, 2011. Abdominal aortic aneurysm development over time: Experimental evidence and constitutive modeling G. Martufi, T.C. Gasser, M. Auer, M. Labruto and J. Swedenborg Proceedings of the 6th World Congress on Biomechanics, Singapore, August 1 – 6, 2010. A growth model for abdominal aortic aneurysms based on continuous collagen turn-over G. Martufi,T.C. Gasser and M. Auer Proceedings of the IV European Conference on Computational Mechanics, Paris, France, May 16 – 21, 2010. Micro-structural and micro-mechanical characterization of thrombus tissue from abdominal aortic aneurysms G. Martufi, T.C. Gasser, M. Folkesson and J. Swedenborg Proceedings of the 10th US National Congress on Computational Mechanics, Columbus, Ohio, US, July 16-19, 2009. Micro-structural and micro-mechanical analysis of thrombus tissue from abdominal aortic aneurysms G. Martufi, T.C. Gasser, M. Folkesson and J. Swedenborg Endovascular Surgery - Bringing Basic Science into Clinical Practice, March 19- 21, Stockholm, Sweden, 2009. Contents 1. INTRODUCTION 11 1.1. Background 11 1.2. Pathophysiology of AAA 13 1.3. Rupture criteria in a clinical setting 14 1.4. Biomechanical rupture risk assessment 15 1.5. AAA biomechanics 16 1.5.1. AAA wall histology 16 1.5.2. AAA wall mechanics 17 1.5.3. AAA wall expansion 18 1.5.4. AAA thrombus mechanics 20 2. METHODS 23 2.1. Experimental evidence of AAA growth 23 2.2. Multiscale constitutive modeling 23 2.3. Micromechanical characterization of ILT 24 3. RESULTS 25 3.1. Clinical study 25 3.2. Numerical predictions of the passive and active responses of the AAA wall 26 3.3. Microstructural and micromechanical characterization of ILT 28 4. DISCUSSION 31 5. CONCLUSIONS 33 6. REFERENCES 35 Paper A Paper B Paper C Paper D 9 Biomechanics of Abdominal Aortic Aneurysm 10
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