Jonathan P. Vande Geest

Biomechanical Determinants of Abdominal Aortic Aneurysm Rupture

Rupture of abdominal aortic aneurysm (AAA) represents a significant clinical event, having a mortality rate of 90% and being currently ranked as the 13th leading cause of death in the US. The ability to reliably evaluate the susceptibility of a particular AAA to rupture on a case-specific basis could vastly improve the clinical management of these patients. Because AAA rupture represents a mechanical failure of the degenerated aortic wall, biomechanical considerations are important to understand this process and to improve our predictions of its occurrence. Presented here is an overview of research to date related to the biomechanics of AAA rupture. This includes a summary of results related to ex vivo and in vivo mechanical testing, noninvasive AAA wall stress estimations, and potential mechanisms of AAA wall weakening. We conclude with a demonstration of a biomechanics-based approach to predicting AAA rupture on a patient-specific basis, which may ultimately prove to be superior to the widely and currently used maximum diameter criterion.

A biomechanics-based rupture potential index for abdominal aortic aneurysm risk assessment: Demonstrative application

Abstract:  Abdominal aortic aneurysms (AAAs) can typically remain stable until the strength of the aortic wall is unable to withstand the forces acting on it as a result of the luminal blood pressure, resulting in AAA rupture. The clinical treatment of AAA patients presents a dilemma for the surgeon: surgery should only be recommended when the risk of rupture of the AAA outweighs the risks associated with the interventional procedure. Since AAA rupture occurs when the stress acting on the wall exceeds its strength, the assessment of AAA rupture should include estimates of both wall stress and wall strength distributions. The present work details a method for noninvasively assessing the rupture potential of AAAs using patient‐specific estimations the rupture potential index (RPI) of the AAA, calculated as the ratio of locally acting wall stress to strength. The RPI was calculated for thirteen AAAs, which were broken up into ruptured (n= 8 and nonruptured (n= 5) groups. Differences in peak wall stress, minimum strength and maximum RPI were compared across groups. There were no statistical differences in the maximum transverse diameters (6.8 ± 0.3 cm vs. 6.1 ± 0.5 cm, p= 0.26) or peak wall stress (46.0 ± 4.3 vs. 49.9 ± 4.0 N/cm2, p= 0.62) between groups. There was a significant decrease in minimum wall strength for ruptured AAA (81.2 ± 3.9 and 108.3 ± 10.2 N/cm2, p= 0.045). While the differences in RPI values (ruptured = 0.48 ± 0.05 vs. nonruptured = 0.36 ± 0.03, respectively; p= 0.10) did not reach statistical significance, the p‐value for the peak RPI comparison was lower than that for both the maximum diameter (p= 0.26) and peak wall stress (p= 0.62) comparisons. This result suggests that the peak RPI may be better able to identify those AAAs at high risk of rupture than maximum diameter or peak wall stress alone. The clinical relevance of this method for rupture assessment has yet to be validated, however, its success could aid clinicians in decision making and AAA patient management.

Age Dependency of the Biaxial Biomechanical Behavior of Human Abdominal Aorta

BACKGROUND The biomechanical behavior of the human abdominal aorta has been studied with great interest primarily due to its propensity to develop such maladies as atherosclerotic occlusive disease, dissections, and aneurysms. The purpose of this study was to investigate the age-related biaxial biomechanical behavior of human infrarenal aortic tissue. METHODS OF APPROACH: A total of 18 samples (13 autopsy, 5 organ donor) were harvested from patients in each of three age groups: Group 1 (<30 years old, n=5), Group 2 (between 30 and 60 years old, n=7), and Group 3 (>60 years old, n=6). Each specimen was tested biaxially using a tension-controlled protocol which spanned a large portion of the strain plane. Response functions fit to experimental data were used as a tool to guide the appropriate choice of the strain energy function W. RESULTS Under an equibiaxial tension of 120 N/m, the average peak stretch values in the circumferential direction for Groups 1, 2, and 3 were (mean +/-SD) 1.46 +/- 0.07, 1.15 +/- 0.07, and 1.11 +/- 0.06, respectively, while the peak stretch values in the longitudinal direction were 1.41 +/- 0.03, 1.19 +/- 0.11, and 1.10 +/- 0.04, respectively. There were no significant differences between the average longitudinal and circumferential peak stretch within each group (p > 0.1), but both of these values were significantly less (p < 0.001) for Groups 2 and 3 when compared to Group 1. Patients in Group 1 were modeled using a polynomial strain energy function W, while patients in Groups 2 and 3 were modeled using an exponential form of W, suggesting an age-dependent shift in the mechanical response of this tissue. CONCLUSION The biaxial tensile testing results reported here are, to our knowledge, the first given for the human infrarenal aorta and reinforce the importance of determining the functional form of W from experimental data. Such information may be useful for the clinician or researcher in identifying key changes in the biomechanical response of abdominal aorta in the presence of an aneurysm.

Microstructural differences in the human posterior sclera as a function of age and race

PURPOSE The purpose of this study was to quantify the age and race-related differences in the microstructural organization of the human posterior sclera. Such differences may contribute to the predisposition of primary open-angle glaucoma in various high-risk populations. METHODS Posterior-temporal scleras from 75 right eyes were procured at an average distance of 3.5 mm from the center of the optic nerve head (ONH). A light-scattering device was used to investigate the matrix organization of posterior scleral fibers around the ONH. In addition to the degree of alignment (via eccentricity), the percentage occurrence of fiber angles within equatorial and meridionally aligned bins was quantified as a function of depth, sex, age, and race. There were 20 African Americans, 55 Caucasians, 49 males, 26 females, in this study, all falling within three age groups (<30, n = 8; 30-60, n = 33; and >60 years, n = 34). Three scleral layers, normalized for depth, were examined. RESULTS For all ages and both races, fibers were preferentially oriented equatorially at all layers (P < 0.001). The African Americans had a significantly higher percentage of occurrence of meridional fibers than did the Caucasians (P < 0.001). The percentage occurrence of meridional fibers decreased significantly from the inner to the outer layers of the posterior sclera (P < 0.001). CONCLUSIONS Statistically significant microstructural differences were found in the posterior sclera between African American and Caucasian donors. Ongoing work is focused on identifying whether such microstructural differences play a role in the higher prevalence of glaucoma in African American populations.

Determination of Coefficient of Friction for Self-Expanding Stent-Grafts

Migration of stent-grafts (SGs) after endovascular aneurysm repair of abdominal aortic aneurysms is a serious complication that may require secondary intervention. Experimental, analytical, and computational studies have been carried out in the past to understand the factors responsible for migration. In an experimental setting, it can be very challenging to correctly capture and understand the interaction between a SG and an artery. Quantities such as coefficient of friction (COF) and contact pressures that characterize this interaction are difficult to measure using an experimental approach. This behavior can be investigated with good accuracy using finite element modeling. Although finite element models are able to incorporate frictional behavior of SGs, the absence of reliable values of coefficient of friction make these simulations unreliable. The aim of this paper is to demonstrate a method for determining the coefficients of friction of a self-expanding endovascular stent-graft. The methodology is demonstrated by considering three commercially available self-expanding SGs, labeled as A, B, and C. The SGs were compressed, expanded, and pulled out of polymeric cylinders of varying diameters and the pullout force was recorded in each case. The SG geometries were recreated using computer-aided design modeling and the entire experiment was simulated in ABAQUS 6.8/STANDARD. An optimization procedure was carried out for each SG oversize configuration to determine the COF that generated a frictional force corresponding to that measured in the experiment. The experimental pullout force and analytically determined COF for SGs A, B, and C were in the range of 6-9 N, 3-12 N, and 3-9 N and 0.08-0.16, 0.22-0.46, and 0.012-0.018, respectively. The computational model predicted COFs in the range of 0.00025-0.0055, 0.025-0.07, and 0.00025-0.006 for SGs A, B, and C, respectively. Our results suggest that for SGs A and B, which are exoskeleton based devices, the pullout forces increase upto a particular oversize beyond which they plateau, while pullout forces showed a continuous increase with oversize for SG C, which is an endoskeleton based device. The COF decreased with oversizing for both types of SGs. The proposed methodology will be useful for determining the COF between self-expanding stent-grafts from pullout tests on human arterial tissue.

Porohyperelastic finite element modeling of abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is the gradual weakening and dilation of the infrarenal aorta. This disease is progressive, asymptomatic, and can eventually lead to rupture--a catastrophic event leading to massive internal bleeding and possibly death. The mechanical environment present in AAA is currently thought to be important in disease initiation, progression, and diagnosis. In this study, we utilize porohyperelastic (PHE) finite element models (FEMs) to investigate how such modeling can be used to better understand the local biomechanical environment in AAA. A 3D hypothetical AAA was constructed with a preferential anterior bulge assuming both the intraluminal thrombus (ILT) and the AAA wall act as porous materials. A parametric study was performed to investigate how physiologically meaningful variations in AAA wall and ILT hydraulic permeabilities affect luminal interstitial fluid velocities and wall stresses within an AAA. A corresponding hyperelastic (HE) simulation was also run in order to be able to compare stress values between PHE and HE simulations. The effect of AAA size on local interstitial fluid velocity was also investigated by simulating maximum diameters (5.5 cm, 4.5 cm, and 3.5 cm) at the baseline values of ILT and AAA wall permeability. Finally, a cyclic PHE simulation was utilized to study the variation in local fluid velocities as a result of a physiologic pulsatile blood pressure. While the ILT hydraulic permeability was found to have minimal affect on interstitial velocities, our simulations demonstrated a 28% increase and a 20% decrease in luminal interstitial fluid velocity as a result of a 1 standard deviation increase and decrease in AAA wall hydraulic permeability, respectively. Peak interstitial velocities in all simulations occurred on the luminal surface adjacent to the region of maximum diameter. These values increased with increasing AAA size. PHE simulations resulted in 19.4%, 40.1%, and 81.0% increases in peak maximum principal wall stresses in comparison to HE simulations for maximum diameters of 35 mm, 45 mm, and 55 mm, respectively. The pulsatile AAA PHE FEM demonstrated a complex interstitial fluid velocity field the direction of which alternated in to and out of the luminal layer of the ILT. The biomechanical environment within both the aneurysmal wall and the ILT is involved in AAA pathogenesis and rupture. Assuming these tissues to be porohyperelastic materials may provide additional insight into the complex solid and fluid forces acting on the cells responsible for aneurysmal remodeling and weakening.

Adaptation of a planar microbiaxial optomechanical device for the tubular biaxial microstructural and macroscopic characterization of small vascular tissues.

Murine models of disease are a powerful tool for researchers to gain insight into disease formation, progression, and therapies. The biomechanical indicators of diseased tissue provide a unique insight into some of these murine models, since the biomechanical properties in scenarios such as aneurysm and Marfan syndrome can dictate tissue failure and mortality. Understanding the properties of the tissue on the macroscopic scale has been shown to be important, as one can then understand the tissues ability to withstand the high stresses seen in the cardiac pulsatile cycle. Alterations in the biomechanical response can foreshadow prospective mechanical failure of the tissue. These alterations are often seen on the microstructural level, and obtaining detailed information on such changes can offer a better understanding of the phenomena seen on the macroscopic level. Unfortunately, mouse models present problems due to the size and delicate features in the mechanical testing of such tissues. In addition, some smaller arteries in large-animal studies (e.g., coronary and cerebral arteries) can present the same issues, and are sometimes unsuitable for planar biaxial testing. The purpose of this paper is to present a robust method for the investigation of the mechanical properties of small arteries and the classification of the microstructural orientation and degree of fiber alignment. This occurs through the cost-efficient modification of a planar biaxial tester that works in conjunction with a two-photon nonlinear microscope. This system provides a means to further investigate how microstructure and mechanical properties are modified in diseased transgenic animals where the tissue is in small tube form. Several other hard-to-test tubular specimens such as cerebral aneurysm arteries and atherosclerotic coronary arteries can also be tested using the described modular device.

Gender-related differences in the tensile strength of abdominal aortic aneurysm

Abstract:  A recent study investigated the association of gender with the growth rate of AAAs and found a significant increase in the growth rate of AAAs in women than in men. On the basis of these observations, we hypothesize that there are gender‐associated differences in AAA wall integrity and mechanical strength. The purpose of this study was to explore this hypothesis by comparing the tensile strength of freshly resected AAA tissue specimens between women and men. Seventy‐six rectangular specimens (20 mm long × 5 mm wide) from 34 patients (24 male, 10 female) were excised from the anterior wall of patients undergoing open repair of their abdominal aortic aneurysm and tested in a uniaxial tensile tester. Ultimate tensile strength (UTS) was taken as the peak stress obtained before specimen failure. While there were no statistical differences in strength between specimens taken from male and female patients, there was a trend toward a decrease in strength in females as compared to males (87.6 ± 6.7 N/cm2 vs. 67.6 ± 8.1 N/cm2, p = 0.09). To the authors knowledge this work represents the first report of differences in biomechanical properties as a function of gender. The nearly significant decrease in UTS in women versus men reported here may be important in assessing the risk of rupture in AAA. Further testing is warranted to confirm the current trends.

Differences in the Region- and Depth-Dependent Microstructural Organization in Normal Versus Glaucomatous Human Posterior Sclerae

PURPOSE This study quantitatively investigated differences in the regional- and depth-dependent human posterior scleral microstructure in glaucomatous (G) and nonglaucomatous (NG) donors. METHODS Twenty-five posterior poles from six G and seven NG donors were analyzed using small angle light scattering (SALS) to investigate the organization of scleral fibers around the optic nerve head. Eccentricity (Ecc), fiber splay (FS), and percent equatorial fibers (PEF) were quantified. RESULTS Regional statistically significant differences between G and NG groups existed in Ecc (P < 0.0001), FS (P < 0.005), and PEF (P < 0.005). Distinct and substantial variation through the depth occurred in all three end points. Region-specific differences in Ecc existed at the episcleral surface; however, by 40% into the depth, all regions converged to a similar value. Fiber splay increased in all regions by an average of 0.14 from the episcleral surface to the intraocular surface. The percentage of equatorial fibers decreased universally through the depth from approximately 61% to 33%. Generally, the inferior and superior regions had a lower Ecc and PEF compared to the nasal and temporal regions. CONCLUSIONS Region and depth of the posterior sclera are important factors that should be included when comparing scleral microstructure of G and NG tissue in experimental and computational work. The dramatic changes in the depth of the sclera may represent baseline properties that affect predisposition to primary open angle glaucoma (POAG), and necessitate that further research include depth as a factor in assessing how observed structural differences contribute to or are a result of POAG.

Design and demonstration of a microbiaxial optomechanical device for multiscale characterization of soft biological tissues with two-photon microscopy.

The biomechanical response of tissues serves as a valuable marker in the prediction of disease and in understanding the related behavior of the body under various disease and age states. Alterations in the macroscopic biomechanical response of diseased tissues are well documented; however, a thorough understanding of the microstructural events that lead to these changes is poorly understood. In this article we introduce a novel microbiaxial optomechanical device that allows two-photon imaging techniques to be coupled with macromechanical stimulation in hydrated planar tissue specimens. This allows that the mechanical response of the microstructure can be quantified and related to the macroscopic response of the same tissue sample. This occurs without the need to fix tissue in strain states that could introduce a change in the microstructural configuration. We demonstrate the passive realignment of fibrous proteins under various types of loading, which demonstrates the ability of tissue microstructure to reinforce itself in periods of high stress. In addition, the collagen and elastin response of tissue during viscoelastic behavior is reported showing interstitial fluid movement and fiber realignment potentially responsible for the temporal behavior. We also demonstrate that nonhomogeneities in fiber strain exist over biaxial regions of assumed homogeneity.