Correlation of biomechanics to tissue reaction in aortic aneurysms assessed by finite elements and [18F]–fluorodeoxyglucose–PET/CT

Mechanobiological interactions are essential for the adaption of the cardiovascular system to altered environmental and internal conditions, but are poorly understood with regard to abdominal aortic aneurysm (AAA) pathogenesis, growth and rupture. In the present study, we therefore calculated mechanical AAA quantities using nonlinear finite element methods and correlated these to [18F]-fluorodeoxyglucose (FDG)-metabolic activity in the AAA wall detected by positron emission tomography/computed tomography (PET/CT). The interplay between mechanics and FDG-metabolic activity was analyzed in terms of maximum values and the three-dimensional spatial relationship, respectively. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) data sets of n = 18 AAA patients were studied. Maximum FDG-uptake (SUV max ) in the AAA wall varied from 1.32 to 4.60 (average SUV max 3.31 ± 0.87). Maximum wall stresses and strains ranged from 10.0 to 64.0 N∕cm(2) (38.2 ± 13.8  N∕cm(2)) and from 0.190 to 0.260 (0.222 ± 0.023), respectively. SUV max was significantly correlated to maximum wall stress and strain (SUV max to stress: r = 0.71, p = 0.0005; SUV max to strain: r = 0.66, p = 0.0013). To evaluate the three-dimensional spatial interaction between FDG-uptake and acting wall stress, element-wise correlations were performed. In all but 2 AAAs, positive element-wise correlation of FDG-uptake to wall stress was obtained, with the Pearson's correlation coefficient ranging from -0.168 to 0.738 ( 0.372 ± 0.263). The results indicate that mechanical stresses are correlated quantitatively and spatially to FDG-uptake in the AAA wall. It is hypothesized that unphysiologically increased loading in the AAA wall triggers biological tissue reaction, such as inflammation or regenerative processes, causing elevated FDG-metabolic activity. These findings strongly support experimental hypotheses of mechanotransduction mechanisms in vivo.

[1]  W. Wall,et al.  A Comparison of Diameter, Wall Stress, and Rupture Potential Index for Abdominal Aortic Aneurysm Rupture Risk Prediction , 2010, Annals of Biomedical Engineering.

[2]  W A Wall,et al.  Impact of calcifications on patient-specific wall stress analysis of abdominal aortic aneurysms , 2010, Biomechanics and modeling in mechanobiology.

[3]  Jay D Humphrey,et al.  Mechanisms of arterial remodeling in hypertension: coupled roles of wall shear and intramural stress. , 2008, Hypertension.

[4]  J Swedenborg,et al.  The impact of intraluminal thrombus failure on the mechanical stress in the wall of abdominal aortic aneurysms. , 2011, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[5]  Frans van de Vosse,et al.  Biomechanical properties of abdominal aortic aneurysms assessed by simultaneously measured pressure and volume changes in humans. , 2008, Journal of vascular surgery.

[6]  David A. Vorp,et al.  Towards A Noninvasive Method for Determination of Patient-Specific Wall Strength Distribution in Abdominal Aortic Aneurysms , 2006, Annals of Biomedical Engineering.

[7]  R Fumero,et al.  Biomechanics of abdominal aortic aneurysm in the presence of endoluminal thrombus: experimental characterisation and structural static computational analysis. , 1998, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[8]  L Speelman,et al.  Patient-specific AAA wall stress analysis: 99-percentile versus peak stress. , 2008, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[9]  W. Wall,et al.  Impact of Model Complexity on Patient Specific Wall Stress Analyses of Abdominal Aortic Aneurysms , 2009 .

[10]  T Christian Gasser,et al.  Failure properties of intraluminal thrombus in abdominal aortic aneurysm under static and pulsating mechanical loads. , 2008, Journal of vascular surgery.

[11]  S. Doll,et al.  On the Development of Volumetric Strain Energy Functions , 2000 .

[12]  L Speelman,et al.  Importance of initial stress for abdominal aortic aneurysm wall motion: dynamic MRI validated finite element analysis. , 2009, Journal of biomechanics.

[13]  J. Gillard,et al.  Impact of calcification and intraluminal thrombus on the computed wall stresses of abdominal aortic aneurysm. , 2008, Journal of vascular surgery.

[14]  J Swedenborg,et al.  Biomechanical rupture risk assessment of abdominal aortic aneurysms: model complexity versus predictability of finite element simulations. , 2010, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[15]  Manuel Doblaré,et al.  Mechanical stresses in abdominal aortic aneurysms: influence of diameter, asymmetry, and material anisotropy. , 2008, Journal of biomechanical engineering.

[16]  S. Carding,et al.  Abdominal aortic aneurysms: an autoimmune disease? , 2008, Trends in molecular medicine.

[17]  K. Birukov,et al.  Cyclic stretch, reactive oxygen species, and vascular remodeling. , 2009, Antioxidants & redox signaling.

[18]  W. Buurman,et al.  Biomarkers of AAA progression. Part 1: extracellular matrix degeneration , 2009, Nature Reviews Cardiology.

[19]  N. Cheshire,et al.  Fluid structure interaction of patient specific abdominal aortic aneurysms: a comparison with solid stress models , 2006, Biomedical engineering online.

[20]  Marcel Breeuwer,et al.  Towards patient-specific risk assessment of abdominal aortic aneurysm , 2008, Medical & Biological Engineering & Computing.

[21]  W. Wall,et al.  Interaction of biomechanics and metabolic activity in abdominal aortic aneurysm wall , 2009 .

[22]  F. Jaffer,et al.  The year in molecular imaging. , 2009, JACC. Cardiovascular imaging.

[23]  Christian Reeps,et al.  A continuum description of the damage process in the arterial wall of abdominal aortic aneurysms , 2012, International journal for numerical methods in biomedical engineering.

[24]  M. L. Raghavan,et al.  Inverse method of stress analysis for cerebral aneurysms , 2008, Biomechanics and modeling in mechanobiology.

[25]  D. Vorp,et al.  The effects of aneurysm on the biaxial mechanical behavior of human abdominal aorta. , 2006, Journal of biomechanics.

[26]  W A Wall,et al.  Prestressing in finite deformation abdominal aortic aneurysm simulation. , 2009, Journal of biomechanics.

[27]  W. Oyen,et al.  In Vivo Imaging of Abdominal Aortic Aneurysms: Increased FDG Uptake Suggests Inflammation in the Aneurysm Wall , 2008, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[28]  Wolfgang A. Wall,et al.  Coupling strategies for biomedical fluid–structure interaction problems , 2010 .

[29]  X. Y. Xu,et al.  High levels of 18F-FDG uptake in aortic aneurysm wall are associated with high wall stress. , 2010, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[30]  W. Wall,et al.  Truly monolithic algebraic multigrid for fluid–structure interaction , 2011 .

[31]  F. Jaffer,et al.  The year in molecular imaging. , 2010, JACC. Cardiovascular imaging.

[32]  Michael J Fagan,et al.  Peak wall stress measurement in elective and acute abdominal aortic aneurysms. , 2008, Journal of vascular surgery.

[33]  M. Dobritz,et al.  Imaging of Acute and Chronic Aortic Dissection by 18F-FDG PET/CT , 2010, Journal of Nuclear Medicine.

[34]  M. Webster,et al.  Effect of intraluminal thrombus on wall stress in patient-specific models of abdominal aortic aneurysm. , 2002, Journal of vascular surgery.

[35]  A. Tedgui,et al.  Mechanisms of blood flow-induced vascular enlargement. , 2002, Biorheology.

[36]  H. Sillesen,et al.  Molecular pathology in vulnerable carotid plaques: correlation with [18]-fluorodeoxyglucose positron emission tomography (FDG-PET). , 2009, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[37]  K Y Volokh,et al.  A model of growth and rupture of abdominal aortic aneurysm. , 2008, Journal of biomechanics.

[38]  T. Murohara,et al.  Uptake of 18F-FDG in Acute Aortic Dissection: A Determinant of Unfavorable Outcome , 2010, Journal of Nuclear Medicine.

[39]  K. Cunningham,et al.  The role of shear stress in the pathogenesis of atherosclerosis , 2005, Laboratory Investigation.

[40]  Calum Gray,et al.  Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide: A Pilot Study , 2011, Circulation. Cardiovascular imaging.

[41]  Roland Hustinx,et al.  Contribution of PET scanning to the evaluation of abdominal aortic aneurysm. , 2004, Seminars in vascular surgery.

[42]  M M Thompson,et al.  A review of biological factors implicated in abdominal aortic aneurysm rupture. , 2005, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[43]  Yannis Papaharilaou,et al.  Computational Evaluation of Aortic Aneurysm Rupture Risk: What Have We Learned So Far? , 2011, Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists.

[44]  T Christian Gasser,et al.  Analysis of aortic wall stress and rupture risk in patients with abdominal aortic aneurysm with a gender perspective. , 2011, Journal of vascular surgery.

[45]  W. Wall,et al.  Glucose metabolism in the vessel wall correlates with mechanical instability and inflammatory changes in a patient with a growing aneurysm of the abdominal aorta. , 2009, Circulation. Cardiovascular imaging.

[46]  Michael S Sacks,et al.  A planar biaxial constitutive relation for the luminal layer of intra-luminal thrombus in abdominal aortic aneurysms. , 2006, Journal of biomechanics.

[47]  V. Fuster,et al.  Relationships Among Regional Arterial Inflammation, Calcification, Risk Factors, and Biomarkers: A Prospective Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Imaging Study , 2009, Circulation. Cardiovascular imaging.

[48]  M L Raghavan,et al.  Toward a biomechanical tool to evaluate rupture potential of abdominal aortic aneurysm: identification of a finite strain constitutive model and evaluation of its applicability. , 2000, Journal of biomechanics.

[49]  Christian Reeps,et al.  The impact of model assumptions on results of computational mechanics in abdominal aortic aneurysm. , 2010, Journal of vascular surgery.

[50]  R. Ogden.  Large deformation isotropic elasticity – on the correlation of theory and experiment for incompressible rubberlike solids , 1972, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[51]  B. Krause,et al.  Increased 18F-fluorodeoxyglucose uptake in abdominal aortic aneurysms in positron emission/computed tomography is associated with inflammation, aortic wall instability, and acute symptoms. , 2008, Journal of vascular surgery.

[52]  A. Groves,et al.  What is the relationship between 18F-FDG aortic aneurysm uptake on PET/CT and future growth rate? , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[53]  Shmuel Einav,et al.  Patient-Based Abdominal Aortic Aneurysm Rupture Risk Prediction with Fluid Structure Interaction Modeling , 2010, Annals of Biomedical Engineering.

[54]  D A Vorp,et al.  Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening. , 2001, Journal of vascular surgery.

[55]  K. J. Grande-Allen,et al.  Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells. , 2006, Cardiovascular research.

[56]  Madhavan L Raghavan,et al.  Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm. , 2006, Journal of biomechanics.

[57]  Mark F Fillinger,et al.  Prediction of rupture risk in abdominal aortic aneurysm during observation: wall stress versus diameter. , 2003, Journal of vascular surgery.

[58]  Barry J Doyle,et al.  A comparison of modelling techniques for computing wall stress in abdominal aortic aneurysms , 2007, Biomedical engineering online.

[59]  F. N. van de Vosse,et al.  Patient-specific initial wall stress in abdominal aortic aneurysms with a backward incremental method. , 2007, Journal of biomechanics.

[60]  Mark F Fillinger,et al.  In vivo analysis of mechanical wall stress and abdominal aortic aneurysm rupture risk. , 2002, Journal of vascular surgery.

[61]  A. Groves,et al.  Increased metabolic activity in abdominal aortic aneurysm detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). , 2009, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[62]  Jürgen Weese,et al.  A comparison of similarity measures for use in 2-D-3-D medical image registration , 1998, IEEE Transactions on Medical Imaging.

[63]  Wolfgang A. Wall,et al.  A computational strategy for prestressing patient‐specific biomechanical problems under finite deformation , 2010 .