(E-184) A Heterogeneous Model of Murine Aorta Derived from Micro-Computed Tomography

Introduction:: The aorta is the main artery in the body, and it is composed of three layers: the intima, media, and externa/adventitia. The media is mostly composed of collagen and elastin, where collagen is the dominant contributor to the strength and structural stability of the aorta. Aortic aneurysm diseases lead to deformation and weakening of the aortic wall and increases the risk of life-threatening aortic rupture. Our goal is to demonstrate that the heterogeneous distribution of collagen and elastin affects the local biomechanics of the aortic wall and that the local responses to stress are not necessarily the same as the global response. We propose a model of collagen and elastin behavior in murine aorta at different geometric points by utilizing high resolution micro-computed tomography (microCT) imaging in order to allow us to study how the aorta deforms to blood pressure at the local level.


Materials and Methods:: Aorta samples were obtained from careful dissection and removal of the thoraco-abdominal aorta from ten weeks-old C57BL/6 mice, with some mice being injected via tail vein with an in vivo collagen hybridizing peptide (CHP) to reform the triple-helix structure of denatured collagen. The aortas were pressurized with formalin at varying distensions. The samples underwent a heavy metal staining procedure and fixed in epoxy resin. Tomographs of the samples were obtained using the University of Chicago PaleoCT scanner and 2-BM-B beamline at the Advanced Photon Source at Argonne National Laboratory to obtain multi-scale views of the tissue. The PaleoCT scanner provided global 20-microns resolution images of the aortic wall and the 2-BM-B images provided 0.35 to 0.70 micron resolution images to clearly detect the collagen and elastin layers in the aortic wall. Sections of the aortas were segmented, smoothed and meshed using Simpleware ScanIP (Synopsys) to create 3D models for finite element modeling (FEM, Abaqus, Dassault Systemes) where stress-strain relationships were extracted from uniaxial loading conditions.

Results, Conclusions, and Discussions:: The elastin layers in the aortas of mice without CHP were clearly seen in microCT images obtained from 2-BM-B. Images of aortas from mice that received CHP show increased contrast between the elastin layers confirming the presence of collagen in the interstitial layers. The elastin layers were segmented and the interstitial regions were segmented to represent the collagen. This 3D model was smoothed and meshed and generated over 12 million elements. The aortic ring was thus divided into sections with 1-2 million elements each for FEM. In our simulations, we defined the collagen as either being equal to (1X), ten times stiffer (10X), or one hundred times stiffer (100X) than elastin. In general, as the collagen stiffness increases, the pressure gradient is well-distributed along the length of the elastin fibers. The stresses generated in the radial direction are greater than the stresses in the hoop direction. Young’s moduli were calculated from linear fits of the stress-strain data with significant variability in the 10X and 100X systems. This provides preliminary evidence that local structure is important in aortic biomechanics. Pathogenesis of aneurysmal disease is dependent on collagen and elastin turnover. Aneurysm rupture results from mechanical failure: peak wall stress exceeds local tissue strength. This is exemplified in Marfan’s syndrome where altered collagen architecture leads to an incoherent mechanical network.


Acknowledgements (Optional): : This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.


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