scholarly journals Linking Aortic Mechanical Properties, Gene Expression and Microstructure: A New Perspective on Regional Weakening in Abdominal Aortic Aneurysms

2021 ◽  
Vol 8 ◽  
Author(s):  
Arianna Forneris ◽  
Jacob Kennard ◽  
Alina Ismaguilova ◽  
Robert D. Shepherd ◽  
Deborah Studer ◽  
...  

Background: Current clinical practice for the assessment of abdominal aortic aneurysms (AAA) is based on vessel diameter and does not account for the multifactorial, heterogeneous remodeling that results in the regional weakening of the aortic wall leading to aortic growth and rupture. The present study was conducted to determine correlations between a novel non-invasive surrogate measure of regional aortic weakening and the results from invasive analyses performed on corresponding ex vivo aortic samples. Tissue samples were evaluated to classify local wall weakening and the likelihood of further degeneration based on non-invasive indices.Methods: A combined, image-based fluid dynamic and in-vivo strain analysis approach was used to estimate the Regional Aortic Weakness (RAW) index and assess individual aortas of AAA patients prior to elective surgery. Nine patients were treated with complete aortic resection allowing the systematic collection of tissue samples that were used to determine regional aortic mechanics, microstructure and gene expression by means of mechanical testing, microscopy and transcriptomic analyses.Results: The RAW index was significantly higher for samples exhibiting lower mechanical strength (p = 0.035) and samples classified as low elastin content (p = 0.020). Samples with higher RAW index had the greatest number of genes differentially expressed compared to any constitutive metric. High RAW samples showed a decrease in gene expression for elastin and a down-regulation of pathways responsible for cell movement, reorganization of cytoskeleton, and angiogenesis.Conclusions: This work describes the first AAA index free of assumptions for material properties and accounting for patient-specific mechanical behavior in relation to aneurysm strength. Use of the RAW index captured biomechanical changes linked to the weakening of the aorta and revealed changes in microstructure and gene expression. This approach has the potential to provide an improved tool to aid clinical decision-making in the management of aortic pathology.

2012 ◽  
Vol 9 (74) ◽  
pp. 2047-2058 ◽  
Author(s):  
J. S. Wilson ◽  
S. Baek ◽  
J. D. Humphrey

Complementary advances in medical imaging, vascular biology and biomechanics promise to enable computational modelling of abdominal aortic aneurysms to play increasingly important roles in clinical decision processes. Using a finite-element-based growth and remodelling model of evolving aneurysm geometry and material properties, we show that regional variations in material anisotropy, stiffness and wall thickness should be expected to arise naturally and thus should be included in analyses of aneurysmal enlargement or wall stress. In addition, by initiating the model from best-fit material parameters estimated for non-aneurysmal aortas from different subjects, we show that the initial state of the aorta may influence strongly the subsequent rate of enlargement, wall thickness, mechanical behaviour and thus stress in the lesion. We submit, therefore, that clinically reliable modelling of the enlargement and overall rupture-potential of aneurysms may require both a better understanding of the mechanobiological processes that govern the evolution of these lesions and new methods of determining the patient-specific state of the pre-aneurysmal aorta (or correlation to currently unaffected portions thereof) through knowledge of demographics, comorbidities, lifestyle, genetics and future non-invasive or minimally invasive tests.


Author(s):  
Amirhossein Arzani ◽  
Shawn C. Shadden

Abdominal aortic aneurysms (AAA) are characterized by disturbed flow patterns, low and oscillatory wall shear stress with high gradients, increased particle residence time, and mild turbulence. Diameter is the most common metric for rupture prediction, although this metric can be unreliable. We hypothesize that understanding the flow topology and mixing inside AAA could provide useful insight into mechanisms of aneurysm growth. AAA morphology has high variability, as with AAA hemodynamics, and therefore we consider patient-specific analyses over several small to medium sized AAAs. Vortical patterns dominate AAA hemodynamics and traditional analyses based on the Eulerian fields (e.g. velocity) fail to convey the complex flow structures. The computation of finite-time Lyapunov exponent (FTLE) fields and underlying Lagrangian coherent structures (LCS) help reveal a Lagrangian template for quantifying the flow [1].


Author(s):  
David M. Pierce ◽  
Thomas E. Fastl ◽  
Hannah Weisbecker ◽  
Gerhard A. Holzapfel ◽  
Borja Rodriguez-Vila ◽  
...  

Through progress in medical imaging, image analysis and finite element (FE) meshing tools it is now possible to extract patient-specific geometries from medical images of, e.g., abdominal aortic aneurysms (AAAs), and thus to study clinically relevant problems via FE simulations. Medical imaging is most often performed in vivo, and hence the reconstructed model geometry in the problem of interest will represent the in vivo state, e.g., the AAA at physiological blood pressure. However, classical continuum mechanics and FE methods assume that constitutive models and the corresponding simulations start from an unloaded, stress-free reference condition.


2010 ◽  
Vol 43 (7) ◽  
pp. 1408-1416 ◽  
Author(s):  
Barry J. Doyle ◽  
Aidan J. Cloonan ◽  
Michael T. Walsh ◽  
David A. Vorp ◽  
Timothy M. McGloughlin

2010 ◽  
Vol 40 (1) ◽  
pp. 47-53 ◽  
Author(s):  
F. Helderman ◽  
I.J. Manoch ◽  
M. Breeuwer ◽  
U. Kose ◽  
H. Boersma ◽  
...  

Author(s):  
Ender A. Finol ◽  
Shoreh Hajiloo ◽  
Keyvan Keyhani ◽  
David A. Vorp ◽  
Cristina H. Amon

Abdominal Aortic Aneurysms (AAAs) are characterized by a continuous dilation of the infrarenal segment of the abdominal aorta. Despite significant improvements in surgical procedures and imaging techniques, the mortality and morbidity rates associated with untreated ruptured AAAs are still outrageously high. AAA disease is a health risk of significant importance since this kind of aneurysm is mostly asymptomatic until its rupture, which is frequently a lethal event with an overall mortality rate in the 80% to 90% range. From a purely biomechanical viewpoint, aneurysm rupture is a phenomenon that occurs when the mechanical stress acting on the dilating inner wall exceeds its failure strength. Since the internal mechanical forces are maintained by the dynamic action of blood flowing in the aorta, the quantification of the hemodynamics of AAAs is essential for the characterization of their biomechanical environment.


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