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Biomechanics of abdominal aortic aneurysm:Experimental evidence and multiscale constitutive modeling
KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics. (vascuMECH)
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. , 48 p.
Series
Trita-HFL. Report / Royal Institute of Technology, Solid mechanics, ISSN 1654-1472 ; 0530
National Category
Mechanical Engineering Medical Engineering Materials Engineering Applied Mechanics
Identifiers
URN: urn:nbn:se:kth:diva-101990OAI: oai:DiVA.org:kth-101990DiVA: diva2:550186
Public defence
2012-09-20, Sal L1, Drottning Kristinas väg 30, KTH, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20120907

Available from: 2012-09-07 Created: 2012-09-06 Last updated: 2013-01-14Bibliographically approved
List of papers
1. Multidimensional growth measurements of abdominal aortic aneurysms
Open this publication in new window or tab >>Multidimensional growth measurements of abdominal aortic aneurysms
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2013 (English)In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 58, no 3, 748-755 p.Article in journal (Refereed) Published
Abstract [en]

Background: Monitoring the expansion of abdominal aortic aneurysms (AAAs) is critical to avoid aneurysm rupture in surveillance programs, for instance. However, measuring the change of the maximum diameter over time can only provide limited information about AAA expansion. Specifically, regions of fast diameter growth may be missed, axial growth cannot be quantified, and shape changes of potential interest for decisions related to endovascular aneurysm repair cannot be captured. Methods: This study used multiple centerline-based diameter measurements between the renal arteries and the aortic bifurcation to quantify AAA growth in 51 patients from computed tomography angiography (CTA) data. Criteria for inclusion were at least 1 year of patient follow-up and the availability of at least two sufficiently high-resolution CTA scans that allowed an accurate three-dimensional reconstruction. Consequently, 124 CTA scans were systematically analyzed by using A4clinics diagnostic software (VASCOPS GmbH, Graz, Austria), and aneurysm growth was monitored at 100 cross-sections perpendicular to the centerline. Results: Monitoring diameter development over the entire aneurysm revealed the sites of the fastest diameter growth, quantified the axial growth, and showed the evolution of the neck morphology over time. Monitoring the development of an aneurysm's maximum diameter or its volume over time can assess the mean diameter growth (r = 0.69, r = 0.77) but not the maximum diameter growth (r = 0.43, r = 0.34). The diameter growth measured at the site of maximum expansion was similar to 16%/y, almost four times larger than the mean diameter expansion of 4.4%/y. The sites at which the maximum diameter growth was recorded did not coincide with the position of the maximum baseline diameter (rho = 0.12; P = .31). The overall aneurysm sac length increased from 84 to 89 mm during the follow-up (P < .001), which relates to the median longitudinal growth of 3.5%/y. The neck length shortened, on average, by 6.2% per year and was accompanied by a slight increase in neck angulation. Conclusions: Neither maximum diameter nor volume measurements over time are able to measure the fastest diameter growth of the aneurysm sac. Consequently, expansion-related wall weakening might be inappropriately reflected by this type of surveillance data. In contrast, localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements over the entire aneurysm sac. This information might further reinforce the quality of aneurysm surveillance programs.

Keyword
Randomized Controlled-Trial, Early Elective Surgery, Ultrasonographic Surveillance, Endovascular Repair, Expansion Rate, Rupture Risk, Wall Stress, Diameter, Size, Enlargement
National Category
Surgery
Identifiers
urn:nbn:se:kth:diva-101989 (URN)10.1016/j.jvs.2012.11.070 (DOI)000323616800026 ()2-s2.0-84883176627 (Scopus ID)
Note

QC 20130930

Available from: 2012-09-06 Created: 2012-09-06 Last updated: 2017-12-07Bibliographically approved
2. 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
Open this publication in new window or tab >>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
2011 (English)In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 44, no 14, 2544-2550 p.Article in journal (Refereed) Published
Abstract [en]

A fundamental understanding of the mechanical properties of the extracellular matrix (ECM) is critically important to quantify the amount of macroscopic stress and/or strain transmitted to the cellular level of vascular tissue. Structural constitutive models integrate histological and mechanical information, and hence, allocate stress and strain to the different microstructural components of the vascular wall. The present work proposes a novel multi-scale structural constitutive model of passive vascular tissue, where collagen fibers are assembled by proteoglycan (PG) cross-linked collagen fibrils and reinforce an otherwise isotropic matrix material. Multiplicative kinematics account for the straightening and stretching of collagen fibrils, and an orientation density function captures the spatial organization of collagen fibers in the tissue. Mechanical and structural assumptions at the collagen fibril level define a piece-wise analytical stress-stretch response of collagen fibers, which in turn is integrated over the unit sphere to constitute the tissue's macroscopic mechanical properties. The proposed model displays the salient macroscopic features of vascular tissue, and employs the material and structural parameters of clear physical meaning. Likewise, the constitutive concept renders a highly efficient multi-scale structural approach that allows for the numerical analysis at the organ level. Model parameters were estimated from isotropic mean-population data of the normal and aneurysmatic aortic wall and used to predict in-vivo stress states of patient-specific vascular geometries, thought to demonstrate the robustness of the particular Finite Element (FE) implementation. The collagen fibril level of the multi-scale constitutive formulation provided an interface to integrate vascular wall biology and to account for collagen turnover.

Keyword
Collagen, Microfiber, Aneurysm, Aorta, Finite Element, Multiscale
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-47994 (URN)10.1016/j.jbiomech.2011.07.015 (DOI)000295754800004 ()2-s2.0-80052408016 (Scopus ID)
Funder
Swedish Research Council, 2006-7568
Note

QC 20111116

Available from: 2011-11-16 Created: 2011-11-15 Last updated: 2017-12-08Bibliographically approved
3. Turnover of fibrillar collagen in soft biological tissue with application to the expansion of abdominal aortic aneurysms
Open this publication in new window or tab >>Turnover of fibrillar collagen in soft biological tissue with application to the expansion of abdominal aortic aneurysms
2012 (English)In: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, no 77, 3366-3377 p.Article in journal (Refereed) Published
Abstract [en]

A better understanding of the inherent properties of vascular tissue to adapt to its mechanical environment is crucial to improve the predictability of biomechanical simulations. Fibrillar collagen in the vascular wall plays a central role in tissue adaptation owing to its relatively short lifetime. Pathological alterations of collagen turnover may fail to result in homeostasis and could be responsible for abdominal aortic aneurysm (AAA) growth at later stages of the disease. For this reason our previously reported multiscale constitutive framework (Martufi, G. & Gasser, T. C. 2011 J. Biomech. 44, 2544-2550 (doi:10.1016/j.jbiomech.2011.07.015)) has been enriched by a collagen turnover model. Specifically, the framework's collagen fibril level allowed a sound integration of vascular wall biology, and the impact of collagen turnover on the macroscopic properties of AAAs was studied. To this end, model parameters were taken from the literature and/or estimated from clinical follow-up data of AAAs (on average 50.7 mm-large). Likewise, the in vivo stretch of the AAA wall was set, such that 10 per cent of collagen fibres were engaged. Results showed that the stretch spectrum, at which collagen fibrils are deposed, is the most influential parameter, i.e. it determines whether the vascular geometry grows, shrinks or remains stable over time. Most importantly, collagen turnover also had a remarkable impact on the macroscopic stress field. It avoided high stress gradients across the vessel wall, thus predicted a physiologically reasonable stress field. Although the constitutive model could be successfully calibrated to match the growth of small AAAs, a rigorous validation against experimental data is crucial to further explore the model's descriptive and predictive capabilities.

Keyword
remodelling, aneurysm, growth, rupture, constitutive modelling, vascular tissue
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-101983 (URN)10.1098/rsif.2012.0416 (DOI)000310573100020 ()2-s2.0-84868575742 (Scopus ID)
Funder
Swedish Research Council, 2006-7568VinnovaSwedish Foundation for Strategic Research EU, FP7, Seventh Framework Programme, FAD-200647
Note

QC 20121207

Available from: 2012-09-06 Created: 2012-09-06 Last updated: 2017-12-07Bibliographically approved
4. Micromechanical Characterization of Intra-luminal Thrombus Tissue from Abdominal Aortic Aneurysms
Open this publication in new window or tab >>Micromechanical Characterization of Intra-luminal Thrombus Tissue from Abdominal Aortic Aneurysms
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2010 (English)In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 38, no 2, 371-379 p.Article in journal (Refereed) Published
Abstract [en]

The reliable assessment of Abdominal Aortic Aneurysm rupture risk is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. Intra-luminal thrombus (ILT) has multiple biomechanical and biochemical impacts on the underlying aneurysm wall and thrombus failure might be linked to aneurysm rupture. Histological slices from 7 ILTs were analyzed using a sequence of automatic image processing and feature analyzing steps. Derived microstructural data was used to define Representative Volume Elements (RVE), which in turn allowed the estimation of microscopic material properties using the non-linear Finite Element Method. ILT tissue exhibited complex microstructural arrangement with larger pores in the abluminal layer than in the luminal layer. The microstructure was isotropic in the abluminal layer, whereas pores started to orient along the circumferential direction towards the luminal site. ILT's macroscopic (reversible) deformability was supported by large pores in the microstructure and the inhomogeneous structure explains in part the radially changing macroscopic constitutive properties of ILT. Its microscopic properties decreased just slightly from the luminal to the abluminal layer. The present study provided novel microstructural and micromechanical data of ILT tissue, which is critically important to further explore the role of the ILT in aneurysm rupture. Data provided in this study allow an integration of structural information from medical imaging for example, to estimate ILT's macroscopic mechanical properties.

Keyword
Intra-luminal thrombus, Abdominal Aortic Aneurysm (AAA), Finite element, method (FEM), Microscale, Constitutive modeling, wall stress, rupture
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-19175 (URN)10.1007/s10439-009-9837-4 (DOI)000274237000013 ()2-s2.0-77249089737 (Scopus ID)
Funder
Swedish Research Council, 2006-7568
Note
QC 20110124Available from: 2010-08-05 Created: 2010-08-05 Last updated: 2017-12-12Bibliographically approved

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