Peter Verbrugghe

Human thoracic and abdominal aortic aneurysmal tissues: Damage experiments, statistical analysis and constitutive modeling.

Development of aortic aneurysms includes significant morphological changes within the tissue: collagen content increases, elastin content reduces and smooth muscle cells degenerate. We seek to quantify the impact of these changes on the passive mechanical response of aneurysms in the supra-physiological loading range via mechanical testing and constitutive modeling. We perform uniaxial extension tests on circumferentially and axially oriented strips from five thoracic (65.6 years ± 13.4, mean ± SD) and eight abdominal (63.9 years ± 11.4) aortic fusiform aneurysms to investigate both continuous and discontinuous softening during supra-physiological loading. We determine the significance of the differences between the fitted model parameters: diseased thoracic versus abdominal tissues, and healthy (Weisbecker et al., J. Mech. Behav. Biomed. Mater. 12, 93-106, 2012) versus diseased tissues. We also test correlations among these parameters and age, Body Mass Index (BMI) and preoperative aneurysm diameter, and investigate histological cuts. Tissue response is anisotropic for all tests and the anisotropic pseudo-elastic damage model fits the data well for both primary loading and discontinuous softening which we interpret as damage. We found statistically relevant differences between model parameters fitted to diseased thoracic versus abdominal tissues, as well as between those fitted to healthy versus diseased tissues. Only BMI correlated with fitted model parameters in abdominal aortic aneurysmal tissues.

A method for incorporating three-dimensional residual stretches/stresses into patient-specific finite element simulations of arteries.

The existence of residual stresses in human arteries has long been shown experimentally. Researchers have also demonstrated that residual stresses have a significant effect on the distribution of physiological stresses within arterial tissues, and hence on their development, e.g., stress-modulated remodeling. Through progress in medical imaging, image analysis and finite element (FE) meshing tools it is now possible to construct in vivo patient-specific geometries and thus to study specific, clinically relevant problems in arterial mechanics via FE simulations. Classical continuum mechanics and FE methods assume that constitutive models and the corresponding simulations start from unloaded, stress-free reference configurations while the boundary-value problem of interest represents a loaded geometry and includes residual stresses. We present a pragmatic methodology to simultaneously account for both (i) the three-dimensional (3-D) residual stress distributions in the arterial tissue layers, and (ii) the equilibrium of the in vivo patient-specific geometry with the known boundary conditions. We base our methodology on analytically determined residual stress distributions (Holzapfel and Ogden, 2010, J. R. Soc. Interface 7, 787-799) and calibrate it using data on residual deformations (Holzapfel et al., 2007, Ann. Biomed. Eng. 35, 530-545). We demonstrate our methodology on three patient-specific FE simulations calibrated using experimental data. All data employed here are generated from human tissues - both the aorta and thrombus, and their respective layers - including the geometries determined from magnetic resonance images, and material properties and 3-D residual stretches determined from mechanical experiments. We study the effect of 3-D residual stresses on the distribution of physiological stresses in the aortic layers (intima, media, adventitia) and the layers of the intraluminal thrombus (luminal, medial, abluminal) by comparing three types of FE simulations: (i) conventional calculations; (ii) calculations accounting only for prestresses; (iii) calculations including both 3-D residual stresses and prestresses. Our results show that including residual stresses in patient-specific simulations of arterial tissues significantly impacts both the global (organ-level) deformations and the stress distributions within the arterial tissue (and its layers). Our method produces circumferential Cauchy stress distributions that are more uniform through the tissue thickness (i.e., smaller stress gradients in the local radial directions) compared to both the conventional and prestressing calculations. Such methods, combined with appropriate experimental data, aim at increasing the accuracy of classical FE analyses for patient-specific studies in computational biomechanics and may lead to increased clinical application of simulation tools.

External aortic root support: a histological and mechanical study in sheep

OBJECTIVES Personalized external aortic root support has completed initial evaluation and has technology appraisal in the UK for patients with Marfan syndrome for use as an alternative to root replacement. Its long-term success in preventing aortic dissection remains uncertain. Here, we report a study in sheep to establish whether the externally supporting mesh, as used clinically, is biologically incorporated. The strength of the resulting mesh/artery composite has been tested. METHODS The carotid artery of growing sheep (n=6) was enclosed in a mesh sleeve made of a polymer, polyethylene terephthalate. After a predefined interval of 4-6 months, a length of the artery was excised, including the sleeved and unsleeved portions, and was stress tested and examined histologically. RESULTS One animal died of pneumonia 7 days after implantation. Comparing sleeved with normal segments, the overall thickness was increased and there was a fibrotic sheet in the periarterial space. The overall vessel wall architecture was preserved in all specimens. Although media thickness of ensleeved arteries was smaller and in one animal mild oedema was found in one quadrant of the outer part of the media. There was a significant increase in stiffness and maximum tensile strength of the supported segments compared with normal arterial tissue. CONCLUSIONS Polyethylene terephthalate mesh, as used for the external support of the dilated aortic root in Marfan syndrome, becomes incorporated in the periadventitial tissue of the carotid artery of sheep. Limited thinning of the media, without any signs of inflammation or medial necrosis, was visible. There was a significantly greater tensile strength in the carotid artery/mesh composite compared with the unsleeved carotid artery.

Strain assessment in the carotid artery wall using ultrasound speckle tracking: validation in a sheep model

The aim of this study was to validate carotid artery strain assessment in-vivo using ultrasound speckle tracking. The left carotid artery of five sheep was exposed and sonomicrometry crystals were sutured onto the artery wall to obtain reference strain. Ultrasound imaging was performed at baseline and stress, followed by strain estimation using an in-house speckle tracking algorithm tuned for vascular applications. The correlation between estimated and reference strain was r = 0.95 (p < 0.001) and r = 0.87 (p < 0.01) for longitudinal and circumferential strain, respectively. Moreover, acceptable limits of agreement were found in Bland-Altman analysis (longitudinally: -0.15 to 0.42%, circumferentially: -0.54 to 0.50%), which demonstrates the feasibility of estimating carotid artery strain using ultrasound speckle tracking. However, further studies are needed to test the algorithm on human in-vivo data and to investigate its potential to detect subclinical cardiovascular disease and characterize atherosclerotic plaques.

Reconstruction of atrioventricular valves with photo-oxidized bovine pericardium

Repair of complex valve pathological processes often requires the use of leaflet tissue or pericardium. The use of bovine photo-oxidized pericardium may be an alternative, a tissue less prone to calcification. The aim of this study is to evaluate the use of photo-oxidized bovine pericardial tissue in the reconstruction of atrioventricular valves in humans. Between July 2001 and September 2006, 21 patients with complex valve pathology underwent a reconstruction with photo-oxidized pericardium. The pericardial patch was used for the reconstruction of a tricuspid valve leaflet in two patients, the reconstruction of a mitral valve leaflet in six patients, the reconstruction of the tricuspid annulus in one patient and the reconstruction of the mitral annulus in 12 patients. The follow-up ranged from 13.9 to 43.2 months. There were five perioperative deaths. Four patients developed failure of the reconstruction, in one patient there was thinning and perforation of the pericardial patch without signs of infection or abrasion. The other patients were free from thromboembolism, endocarditis, hemorrhagic complications or echocardiographic signs of failure of the reconstruction. Photo-oxidized bovine pericardium is a versatile material for complex reconstruction of the atrioventricular valvular structures. Its durability should, however, be investigated in comparison with alternative tissues in a randomized trial.

Electro-actuation of biocompatible Pluronic/methacrylic acid hydrogel in blood-plasma and in blood-mimicking buffers

The electro-responsiveness in blood plasma and in blood mimicking fluids of methacrylic acid modified Pluronic (P127) hydrogel is investigated. It is observed that the hydrogels response to an applied potential, in all buffer solutions, is very high, and comparable in amplitude and time response to classic polyelectrolyte gels. The highest actuation amplitude is achieved in PBS, which is directly related to the largest current value obtained for that buffer. The electro-actuation achieved in blood plasma is comparable to that in KREBS and KCl buffers. The good performance in blood plasma is attributed to the low protein adhesion to hydrogel surface. Preliminary biocompatibility studies demonstrate that the investigated hydrogel can be considered biocompatible.

Support of the aortic wall: a histological study in sheep comparing a macroporous mesh with low-porosity vascular graft of the same polyethylene terephthalate material

OBJECTIVES Wrapping with various materials was an early treatment for aortic aneurysms. Wrapping with low-porosity vascular grafts has been associated with graft migration and vascular erosion. An alternative is to use a macroporous mesh (MPM) made of the same polymer (polyethylene terephalate). We compared the histological outcome 1 year after wrapping sheep aortas with low-porosity grafts versus MPM fabrics. METHODS The 2 different fabrics were wrapped around the aorta of 3 sheep. After 1 year the aortas were excised. The 2 wrapped segments of aorta were compared with each other and control aorta. Histological examinations and measurements were made of the layers of the aortic wall in 36 prespecified locations in each of the 3 sheep. RESULTS Both fabrics were consistently surrounded by foreign body reaction and well-vascularized fibrosis. This was more pronounced with the low-porosity vascular graft material which was poorly incorporated and caused buckling at the transition between wrapped and unwrapped aorta. Conversely, the MPM was fully incorporated, resulting in a composite mesh/biological aortic wall. There was reduction of medial thickness with both materials but it was locally more extreme due to the corrugations in the vascular graft material. The findings were consistent between sampled locations and were similar in the 3 animals. CONCLUSIONS The different porosity and rigidity of the materials influences their incorporation into the aortic wall. The incorporation of the pliable MPM precludes the complications of migration and erosion which are seen after wrapping with low-porosity prosthetic vascular graft material.

Biomechanical Characterization of Ascending Aortic Aneurysms

Ascending thoracic aortic aneurysms (ATAAs) are a silent disease, ultimately leading to dissection or rupture of the arterial wall. There is a growing consensus that diameter information is insufficient to assess rupture risk, whereas wall stress and strength provide a more reliable estimate. The latter parameters cannot be measured directly and must be inferred through biomechanical assessment, requiring a thorough knowledge of the mechanical behaviour of the tissue. However, for healthy and aneurysmal ascending aortic tissues, this knowledge remains scarce. This study provides the geometrical and mechanical properties of the ATAA of six patients with unprecedented detail. Prior to their ATAA repair, pressure and diameter were acquired non-invasively, from which the distensibility coefficient, pressure–strain modulus and wall stress were calculated. Uniaxial tensile tests on the resected tissue yielded ultimate stress and stretch values. Parameters for the Holzapfel–Gasser–Ogden material model were estimated based on the pre-operative pressure–diameter data and the post-operative stress–stretch curves from planar biaxial tensile tests. Our results confirmed that mechanical or geometrical information alone cannot provide sufficient rupture risk estimation. The ratio of physiological to ultimate wall stress seems a more promising parameter. However, wall stress estimation suffers from uncertainties in wall thickness measurement, for which our results show large variability, between patients but also between measurement methods. Our results also show a large strength variability, a value which cannot be measured non-invasively. Future work should therefore be directed towards improved accuracy of wall thickness estimation, but also towards the large-scale collection of ATAA wall strength data.

Biomechanical evaluation of a personalized external aortic root support applied in the Ross procedure

A commonly heard concern in the Ross procedure, where a diseased aortic valve is replaced by the patients own pulmonary valve, is the possibility of pulmonary autograft dilatation. We performed a biomechanical investigation of the use of a personalized external aortic root support or exostent as a possibility for supporting the autograft. In ten sheep a short length of pulmonary artery was interposed in the descending aorta, serving as a simplified version of the Ross procedure. In seven of these cases, the autograft was supported by an external mesh or so-called exostent. Three sheep served as control, of which one was excluded from the mechanical testing. The sheep were sacrificed six months after the procedure. Samples of the relevant tissues were obtained for subsequent mechanical testing: normal aorta, normal pulmonary artery, aorta with exostent, pulmonary artery with exostent, and pulmonary artery in aortic position for six months. After mechanical testing, the material parameters of the Gasser-Ogden-Holzapfel model were determined for the different tissue types. Stress-strain curves of the different tissue types show significantly different mechanical behavior. At baseline, stress-strain curves of the pulmonary artery are lower than aortic stress-strain curves, but at the strain levels at which the collagen fibers are recruited, the pulmonary artery behaves stiffer than the aorta. After being in aortic position for six months, the pulmonary artery tends towards aorta-like behavior, indicating that growth and remodeling processes have taken place. When adding an exostent around the pulmonary autograft, the mechanical behavior of the composite artery (exostent + artery) differs from the artery alone, the non-linearity being more evident in the former.

Aortic wall thickness in patients with ascending aortic aneurysm versus acute aortic dissection

OBJECTIVES Recent studies have shown that aortic diameter alone is an insufficient parameter to identify patients at risk for aortic dissection. The aim of this study was to determine the value of the ratio of aortic diameter to medial wall thickness as a new marker of risk. METHODS We obtained data from 181 patients with an ascending aortic aneurysm (n = 94) or an acute type A aortic dissection (n = 87), surgically treated at our institution (1996-2012). Measurements of the maximum aortic diameter and the medial wall thickness were conducted by retrospective review of preoperative imaging studies and histological specimens, respectively. RESULTS Nearly 60% of the dissection patients had aortic diameters smaller than 50 mm. There was a significant negative linear correlation between medial wall thickness and aortic diameter (P = 0.01) in the dissection group only. Among patients with aortic diameters above 50 mm, dissection patients had significantly thinner aortic media (P = 0.04). Among patients with a mildly dilated aorta (>45 mm), the aortic diameter to medial wall thickness ratio was significantly higher in the dissection group (P = 0.04). CONCLUSIONS Among patients with a dilatation of the ascending aorta of more than 45 and 49 mm, patients experiencing aortic dissection have a significantly higher aortic diameter to wall thickness ratio and a thinner aortic media, respectively. In the subset of patients with mild aortic dilatation, wall thickness might in the future serve as an additional parameter to help identify those patients who would benefit from prophylactic aortic surgery.