Periodic Reporting for period 4 - AArteMIS (Aneurysmal Arterial Mechanics: Into the Structure)
Periodo di rendicontazione: 2019-10-01 al 2020-10-31
Current knowledge on the microscopic determinants of arterial tissues’ mechanical response and rupture is limited and prevents from understanding rupture, and organizing adapted treatments of rupture-prone vascular diseases. The present project aimed to fill this gap.
The rupture of arterial tissue is a mechanical phenomenon that occurs when the wall stress state exceeds the local strength of the tissue. Detailed characterization of damage and rupture mechanics of arteries requires developing suitable experimental approaches, and their analyses. In particular, damage progression in large arteries is believed to be initiated in the intimal-medial layer of the arterial wall (the innermost layer), through a dissection event in most cases. The adventitial layer (the outermost) would support the load until it fails in turn, causing the complete rupture of the vessel.
The AArteMIS project, in its final form, aimed at describing and analyzing the rupture mechanisms of both medial and adventitial layers, these mechanisms being necessarily different due to different composition and structure. A large effort (larger than initially planned) was put on experimental characterization as this aspect is still insufficient in the current state of the art, though it represents the starting point for all subsequent research.
The rupture of arterial tissue is a mechanical phenomenon that occurs when the wall stress state exceeds the local strength of the tissue. Detailed characterization of damage and rupture mechanics of arteries requires developing suitable experimental approaches, and their analyses. In particular, damage progression in large arteries is believed to be initiated in the intimal-medial layer of the arterial wall (the innermost layer), through a dissection event in most cases. The adventitial layer (the outermost) would support the load until it fails in turn, causing the complete rupture of the vessel.
The AArteMIS project, in its final form, aimed at describing and analyzing the rupture mechanisms of both medial and adventitial layers, these mechanisms being necessarily different due to different composition and structure. A large effort (larger than initially planned) was put on experimental characterization as this aspect is still insufficient in the current state of the art, though it represents the starting point for all subsequent research.
From a general point of view, the project was marked by the development of unique, original and relevant experimental approaches, along with their analyses.
• Experiments combining multi-photon microscopy and a bulge inflation test were developed to observe deforming microstructure under increasing load, focusing on the rupture of the adventitial layer;
• a setup was designed to measure thickness maps of arterial samples with very high accuracy, in order to answer the crucial question of the role of thickness in assessing areas which are more at risk of rupture;
• a complete approach based on tension-inflation testing of tubular arterial segments in a X-ray microtomography setup was developed to study in vitro the onset of dissection in the medial layer of arterial tissue and the influence of intimal defects’ characteristics;
• a study of the effect of propylene-glycol (a chemical used to make tissue more transparent in optical observations like Optical Coherence Tomography, OCT) was performed to evaluate its effects on elastic and rupture properties of tissues. Similarly, the effect of other chemical specifically degrading mechanically-essential components of the extracellular matrix (elastin, collagen) is being investigated to assess the influence of these components if the failure properties of arterial tissue;
• an OCT experiment was developed to observe the progress of dissection-like cracks in the media of an arterial sample, by investigating the 3D deformation state around medial cracks.
In addition to these experimental investigations, numerical analysis methodologies were developed to provide quantitative data in relationship with common models, and deeper understanding than what could be observed in the experiments. They include:
• numerical reconstruction of discrete fiber networks to model and study adventitial rupture, in order improve the understanding of the mechanics of such networks, and to quantify fiber-based adventitial rupture criteria using our experimental data;
• numerical modeling of dissection onset and propagation in the medial layer, in order to understand the influence of mechanical or geometrical properties on the critical pressure triggering dissection and its early propagation, and to identify medial rupture model parameters based on our experiments;
• development and implementation in a Finite Element code of a multi-scale homogenization model taking into account microstructural information in order to include the micro-scale physics and mechanics in a model describing the macroscopic mechanical response of arterial tissue. It was used to elucidate and quantify micro-scale deformation and mechanical state of tissues, and in patient-specific simulation applications where micro-scale information may be the key for remodeling or rupture-risk estimates.
In terms of results, the implementation of these methodologies proved successful and led to results which are of high importance for the community, and for future research.
• Experiments combining multi-photon microscopy and a bulge inflation test were developed to observe deforming microstructure under increasing load, focusing on the rupture of the adventitial layer;
• a setup was designed to measure thickness maps of arterial samples with very high accuracy, in order to answer the crucial question of the role of thickness in assessing areas which are more at risk of rupture;
• a complete approach based on tension-inflation testing of tubular arterial segments in a X-ray microtomography setup was developed to study in vitro the onset of dissection in the medial layer of arterial tissue and the influence of intimal defects’ characteristics;
• a study of the effect of propylene-glycol (a chemical used to make tissue more transparent in optical observations like Optical Coherence Tomography, OCT) was performed to evaluate its effects on elastic and rupture properties of tissues. Similarly, the effect of other chemical specifically degrading mechanically-essential components of the extracellular matrix (elastin, collagen) is being investigated to assess the influence of these components if the failure properties of arterial tissue;
• an OCT experiment was developed to observe the progress of dissection-like cracks in the media of an arterial sample, by investigating the 3D deformation state around medial cracks.
In addition to these experimental investigations, numerical analysis methodologies were developed to provide quantitative data in relationship with common models, and deeper understanding than what could be observed in the experiments. They include:
• numerical reconstruction of discrete fiber networks to model and study adventitial rupture, in order improve the understanding of the mechanics of such networks, and to quantify fiber-based adventitial rupture criteria using our experimental data;
• numerical modeling of dissection onset and propagation in the medial layer, in order to understand the influence of mechanical or geometrical properties on the critical pressure triggering dissection and its early propagation, and to identify medial rupture model parameters based on our experiments;
• development and implementation in a Finite Element code of a multi-scale homogenization model taking into account microstructural information in order to include the micro-scale physics and mechanics in a model describing the macroscopic mechanical response of arterial tissue. It was used to elucidate and quantify micro-scale deformation and mechanical state of tissues, and in patient-specific simulation applications where micro-scale information may be the key for remodeling or rupture-risk estimates.
In terms of results, the implementation of these methodologies proved successful and led to results which are of high importance for the community, and for future research.
The main achievements beyond the state of the art that can be highlighted in AArteMIS can be divided into the following three categories:
Most important results include advances regarding adventitial failure:
• in a bulging aneurysmal sample, neither the minimum thickness nor the maximum strain nor the maximum stress locations are good indicators of the rupture location in a tissue. This confirms that the intrinsic strength of the tissue is of crucial importance.
• Microstructural observations of bulging aneurysmal tissue showed that adventitial fiber structures undergo progressive straightening with quasi-null rotations under inflation providing further insight into the micro-architectural changes to help in understanding the determinants of remodeling and rupture.
• Important structure–function relationships that control the mechanical response of adventitial tissue were evidenced thanks numerical reconstruction of the collagen fiber networks. They quantified the uncramping process of fibers under uniaxial tension, and showed that at loads close to rupture, the probability of failure occurring at the fiber level is up to 2%. Combined to uniaxial and bi-axial rupture data the model was used to demonstrate that fiber-based damage can strongly shape the macroscopic failure response of the tissue, and identified values of collagen fiber failure strain were in the range of 8.8 % to 29.3 % for bulge inflation samples, while 18.7 % to 25.5 % for uniaxial samples.
Results include major advances regarding medial failure:
• Combined experimental and numerical approaches on the rupture of media underlined the importance of shear delamination in medial dissection-like failure.
• A model using X-FEM method was used in a numerical design of experiment approach to assess the most important factors in initiating a dissection, and its likely direction of propagation.
• The development of a setup based on OCT raised the need to investigate the influence of PG and other enzymes degrading targeted proteins on the rupture mechanics of medial tissue. The results revealed that strain-based failure criteria do govern rupture of such tissue and are not affected by such chemical.
• A setup enabling OCT observations around the crack tip in medial samples was developed, demonstrating the importance of shear strain in this area, and its likely predominance in the onset of dissection propagation.
Results include elements for integration of those data in a patient-specific application process:
• We implemented a multi-scale homogenization constitutive model in a FEM code. Employing constitutive parameters supported by histological examinations, the results validated the model’s ability to predict the micro- and macroscopic mechanical behavior.
• Its application to patient-specific geometries proved essential as it detailed the microstructural mechanisms involved in a given geometry under pressure, as well as the effect of altered constituent as found in some diseases, paving the way for remodeling models based on the actual mechanics at the scale of cells and relevant constituents.
Most important results include advances regarding adventitial failure:
• in a bulging aneurysmal sample, neither the minimum thickness nor the maximum strain nor the maximum stress locations are good indicators of the rupture location in a tissue. This confirms that the intrinsic strength of the tissue is of crucial importance.
• Microstructural observations of bulging aneurysmal tissue showed that adventitial fiber structures undergo progressive straightening with quasi-null rotations under inflation providing further insight into the micro-architectural changes to help in understanding the determinants of remodeling and rupture.
• Important structure–function relationships that control the mechanical response of adventitial tissue were evidenced thanks numerical reconstruction of the collagen fiber networks. They quantified the uncramping process of fibers under uniaxial tension, and showed that at loads close to rupture, the probability of failure occurring at the fiber level is up to 2%. Combined to uniaxial and bi-axial rupture data the model was used to demonstrate that fiber-based damage can strongly shape the macroscopic failure response of the tissue, and identified values of collagen fiber failure strain were in the range of 8.8 % to 29.3 % for bulge inflation samples, while 18.7 % to 25.5 % for uniaxial samples.
Results include major advances regarding medial failure:
• Combined experimental and numerical approaches on the rupture of media underlined the importance of shear delamination in medial dissection-like failure.
• A model using X-FEM method was used in a numerical design of experiment approach to assess the most important factors in initiating a dissection, and its likely direction of propagation.
• The development of a setup based on OCT raised the need to investigate the influence of PG and other enzymes degrading targeted proteins on the rupture mechanics of medial tissue. The results revealed that strain-based failure criteria do govern rupture of such tissue and are not affected by such chemical.
• A setup enabling OCT observations around the crack tip in medial samples was developed, demonstrating the importance of shear strain in this area, and its likely predominance in the onset of dissection propagation.
Results include elements for integration of those data in a patient-specific application process:
• We implemented a multi-scale homogenization constitutive model in a FEM code. Employing constitutive parameters supported by histological examinations, the results validated the model’s ability to predict the micro- and macroscopic mechanical behavior.
• Its application to patient-specific geometries proved essential as it detailed the microstructural mechanisms involved in a given geometry under pressure, as well as the effect of altered constituent as found in some diseases, paving the way for remodeling models based on the actual mechanics at the scale of cells and relevant constituents.