Regional biomechanical characterization of human ascending aortic aneurysms: Microstructure and biaxial mechanical response.

The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel et al. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. STATEMENT OF SIGNIFICANCE: Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity.

Predictive constitutive modelling of arteries by deep learning.

The constitutive modelling of soft biological tissues has rapidly gained attention over the last 20 years. Current constitutive models can describe the mechanical properties of arterial tissue. Predicting these properties from microstructural information, however, remains an elusive goal. To address this challenge, we are introducing a novel hybrid modelling framework that combines advanced theoretical concepts with deep learning. It uses data from mechanical tests, histological analysis and images from second-harmonic generation. In this first proof of concept study, our hybrid modelling framework is trained with data from 27 tissue samples only. Even such a small amount of data is sufficient to be able to predict the stress-stretch curves of tissue samples with a median coefficient of determination of R2 = 0.97 from microstructural information, as long as one limits the scope to tissue samples whose mechanical properties remain in the range commonly encountered. This finding suggests that deep learning could have a transformative impact on the way we model the constitutive properties of soft biological tissues.

Constitutive modeling using structural information on collagen fiber direction and dispersion in human superficial femoral artery specimens of different ages.

Arterial mechanics plays an important role in vascular pathophysiology and repair, and advanced imaging can inform constitutive models of vascular behavior. We have measured the mechanical properties of 14 human superficial femoral arteries (SFAs) (age 12-70, mean 48±19 years) using planar biaxial extension, and determined the preferred collagen fiber direction and dispersion using multiphoton microscopy. The collagen fiber direction and dispersion were evaluated using second-harmonic generation imaging and modeled using bivariate von Mises distributions. The microstructures of elastin and collagen were assessed using two-photon fluorescence imaging and conventional bidirectional histology. The mechanical and structural data were used to describe the SFA mechanical behavior using two- and four-fiber family invariant-based constitutive models. Older SFAs were stiffer and mechanically more nonlinear than younger specimens. In the adventitia, collagen fibers were undulated and diagonally-oriented, while in the media, they were straight and circumferentially-oriented. The media was rich in collagen that surrounded the circumferentially-oriented smooth muscle cells, and the elastin was present primarily in the internal and external elastic laminae. Older SFAs had a more circumferential collagen fiber alignment, a decreased circumferential-radial fiber dispersion, but the same circumferential-longitudinal fiber dispersion as younger specimens. Both the two- and the four-fiber family constitutive models were able to capture the experimental data, and the fits were better for the four-fiber family formulation. Our data provide additional details on the SFA intramural structure and inform structurally-based constitutive models.

Failure properties and microstructure of healthy and aneurysmatic human thoracic aortas subjected to uniaxial extension with a focus on the media.

Current clinical practice for aneurysmatic interventions is often based on the maximum diameter of the vessel and/or on the growth rate, although rupture can occur at any diameter and growth rate, leading to fatality. For 27 medial samples obtained from 12 non-aneurysmatic (control) and 9 aneurysmatic human descending thoracic aortas we examined: the mechanical responses up to rupture using uniaxial extension tests of circumferential and longitudinal specimens; the structure of these tissues using second-harmonic imaging and histology, in particular, the content proportions of collagen, elastic fibers and smooth muscle cells in the media. It was found that the mean failure stresses were higher in the circumferential directions (Control-C 1474kPa; Aneurysmatic-C 1446kPa), than in the longitudinal directions (Aneurysmatic-L 735kPa; Control-L 579kPa). This trend was the opposite to that observed for the mean collagen fiber directions measured from the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C), thus suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. The difference in the mean values of the out-of-plane dispersion in the radial/longitudinal plane between the control and aneurysmatic groups was significant. The difference in the mean values of the mean fiber angle from the circumferential direction was also significantly different between the two groups. Most specimens showed delamination zones near the ruptured region in addition to ruptured collagen and elastic fibers. This study provides a basis for further studies on the microstructure and the uniaxial failure properties of (aneurysmatic) arterial walls towards realistic modeling and prediction of tissue failure. STATEMENT OF SIGNIFICANCE: A data set relating uniaxial failure properties to the microstructure of non-aneurysmatic and aneurysmatic human thoracic aortic medias under uniaxial extension tests is presented for the first time. It was found that the mean failure stresses were higher in the circumferential directions, than in the longitudinal directions. The general trend for the failure stresses was Control-C > Aneurysmatic-C > Aneurysmatic-L > Control-L, which was the opposite of that observed for the mean collagen fiber direction relative to the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C) suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. This study provides a first step towards more realistic modeling and prediction of tissue failure.

Biomechanics of aortic wall failure with a focus on dissection and aneurysm: A review.

Aortic dissections and aortic aneurysms are fatal events characterized by structural changes to the aortic wall. The maximum diameter criterion, typically used for aneurysm rupture risk estimations, has been challenged by more sophisticated biomechanically motivated models in the past. Although these models are very helpful for the clinicians in decision-making, they do not attempt to capture material failure. Following a short overview of the microstructure of the aorta, we analyze the failure mechanisms involved in the dissection and rupture by considering also traumatic rupture. We continue with a literature review of experimental studies relevant to quantify tissue strength. More specifically, we summarize more extensively uniaxial tensile, bulge inflation and peeling tests, and we also specify trouser, direct tension and in-plane shear tests. Finally we analyze biomechanically motivated models to predict rupture risk. Based on the findings of the reviewed studies and the rather large variations in tissue strength, we propose that an appropriate material failure criterion for aortic tissues should also reflect the microstructure in order to be effective. STATEMENT OF SIGNIFICANCE: Aortic dissections and aortic aneurysms are fatal events characterized by structural changes to the aortic wall. Despite the advances in medical, biomedical and biomechanical research, the mortality rates of aneurysms and dissections remain high. The present review article summarizes experimental studies that quantify the aortic wall strength and it discusses biomechanically motivated models to predict rupture risk. We identified contradictory observations and a large variation within and between data sets, which may be due to biological variations, different sample sizes, differences in experimental protocols, etc. Based on the findings of the reviewed literature and the rather large variations in tissue strength, it is proposed that an appropriate criterion for aortic failure should also reflect the microstructure.

On fibre dispersion modelling of soft biological tissues: a review.

Collagen fibres within fibrous soft biological tissues such as artery walls, cartilage, myocardiums, corneas and heart valves are responsible for their anisotropic mechanical behaviour. It has recently been recognized that the dispersed orientation of these fibres has a significant effect on the mechanical response of the tissues. Modelling of the dispersed structure is important for the prediction of the stress and deformation characteristics in (patho)physiological tissues under various loading conditions. This paper provides a timely and critical review of the continuum modelling of fibre dispersion, specifically, the angular integration and the generalized structure tensor models. The models are used in representative numerical examples to fit sets of experimental data that have been obtained from mechanical tests and fibre structural information from second-harmonic imaging. In particular, patches of healthy and diseased aortic tissues are investigated, and it is shown that the predictions of the models fit very well with the data. It is straightforward to use the models described herein within a finite-element framework, which will enable more realistic (and clinically relevant) boundary-value problems to be solved. This also provides a basis for further developments of material models and points to the need for additional mechanical and microstructural data that can inform further advances in the material modelling.

Mechanical strength of aneurysmatic and dissected human thoracic aortas at different shear loading modes.

Rupture of aneurysms and acute dissection of the thoracic aorta are life-threatening events which affect tens of thousands of people per year. The underlying mechanisms remain unclear and the aortic wall is known to lose its structural integrity, which in turn affects its mechanical response to the loading conditions. Hence, research on such aortic diseases is an important area in biomechanics. The present study investigates the mechanical properties of aneurysmatic and dissected human thoracic aortas via triaxial shear and uniaxial tensile testing with a focus on the former. In particular, ultimate stress values from triaxial shear tests in different orientations regarding the aorta׳s orthotropic microstructure, and from uniaxial tensile tests in radial, circumferential and longitudinal directions were determined. In total, 16 human thoracic aortas were investigated from which it is evident that the aortic media has much stronger resistance to rupture under 'out-of-plane' than under 'in-plane' shear loadings. Under different shear loadings the aortic tissues revealed anisotropic failure properties with higher ultimate shear stresses and amounts of shear in the longitudinal than in the circumferential direction. Furthermore, the aortic media decreased its tensile strength as follows: circumferential direction >longitudinaldirection> radial direction. Anisotropic and nonlinear tissue properties are apparent from the experimental data. The results clearly showed interspecimen differences influenced by the anamnesis of the donors such as aortic diseases or connective tissue disorders, e.g., dissected specimens exhibited on average a markedly lower mechanical strength than aneurysmatic specimens. The rupture data based on the combination of triaxial shear and uniaxial extension testing are unique and build a good basis for developing a 3D failure criterion of diseased human thoracic aortic media. This is a step forward to more realistic modeling of mechanically induced tissue failure i.e. rupture of aneurysms or progression of aortic dissections.