The human aorta is susceptible to both atherosclerotic plaque deposition and aneurysmal enlargement. While the specific causal mechanisms are unclear, biomechanical factors are thought to play an important role, particularly in the differing susceptibility of the thoracic and abdominal aorta to these degenerative changes. We developed a non-invasive magnetic resonance method to quantify aortic wall biomechanics in vivo and found that aortic wall motion and strain vary around the aortic circumference with significant local variation in aortic structure. This is consistent with clinical observations of eccentric plaque localization and focal aneurysm formation. Furthermore, aortic biomechanics are impacted by implanted endovascular devices such as stents and stent grafts which are used to treat occlusive disease and aneurysms of the aorta with unknown long term consequences. During this grant, we will relate varying aortic strain patterns measured in vivo to the 3-dimensional microarchitecture of normal porcine aortas. We will then implant endovascular aortic stents and stent grafts in experimental animals to modify aortic wall biomechanics. We will assess the acute and chronic impact on in vivo aortic wall biomechanics and long-term changes in aortic microstructure. We will utilize the same in vivo magnetic resonance imaging technique to assess aortic wall motion and cyclic strain in humans and quantitate the differences about the circumference and along the length of the aorta. We will study both young and elderly healthy volunteers in order to discern age and gender related differences in aortic wall biomechanics. These data will provide valuable insights into our understanding of the structure and compostition of the aorta in relation to biomechanical strain and will provide a means of assessing the impact on the aortic wall of interventional treatments using implanted aortic devices. Further, these studies will provide a framework to understand normal age-related and degenerative changes affecting the human aorta. Finally, it will provide a quantitative basis for application of aortic magnetic resonance imaging in larger human clinical trials involving patients with aneurysmal or occlusive disease of the aorta, both before and after endovascular treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064327-07
Application #
7056772
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Wassef, Momtaz K
Project Start
1999-09-30
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
7
Fiscal Year
2006
Total Cost
$354,724
Indirect Cost
Name
Stanford University
Department
Surgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Figueroa, C Alberto; Taylor, Charles A; Yeh, Victoria et al. (2010) Preliminary 3D computational analysis of the relationship between aortic displacement force and direction of endograft movement. J Vasc Surg 51:1488-97; discussion 1497
Figueroa, C Alberto; Taylor, Charles A; Yeh, Victoria et al. (2009) Effect of curvature on displacement forces acting on aortic endografts: a 3-dimensional computational analysis. J Endovasc Ther 16:284-94
Morrison, Tina M; Choi, Gilwoo; Zarins, Christopher K et al. (2009) Circumferential and longitudinal cyclic strain of the human thoracic aorta: age-related changes. J Vasc Surg 49:1029-36
Figueroa, C Alberto; Taylor, Charles A; Chiou, Allen J et al. (2009) Magnitude and direction of pulsatile displacement forces acting on thoracic aortic endografts. J Endovasc Ther 16:350-8
O'Connell, Mary K; Murthy, Sushila; Phan, Samson et al. (2008) The three-dimensional micro- and nanostructure of the aortic medial lamellar unit measured using 3D confocal and electron microscopy imaging. Matrix Biol 27:171-81
Goergen, Craig J; Johnson, Bonnie L; Greve, Joan M et al. (2007) Increased anterior abdominal aortic wall motion: possible role in aneurysm pathogenesis and design of endovascular devices. J Endovasc Ther 14:574-84
Draney, Mary T; Arko, Frank R; Alley, Marcus T et al. (2004) Quantification of vessel wall motion and cyclic strain using cine phase contrast MRI: in vivo validation in the porcine aorta. Magn Reson Med 52:286-95
Xu, Chengpei; Zarins, Christopher K; Glagov, Seymour (2002) Biphasic response of tropoelastin at the poststenotic dilation segment of the rabbit aorta. J Vasc Surg 36:605-12
Xu, Chengpei; Lee, Sheila; Shu, Chang et al. (2002) Expression of TGF-beta1 and beta3 but not apoptosis factors relates to flow-induced aortic enlargement. BMC Cardiovasc Disord 2:11
Xu, Chengpei; Zarins, Christopher K; Glagov, Seymour (2002) Gene expression of tropoelastin is enhanced in the aorta proximal to the coarctation in rabbits. Exp Mol Pathol 72:115-23

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