The Biolochanics project
Biolochanics is the name of a 5 years project which started in May 2015 and which has the ambitious objective of preventing aortic aneurysm from being a cause of mortality. Remember that the rupture of Aortic Aneurysms (AA) kills more than 30000 persons every year in Europe and the USA.
The project is led by Prof Stéphane Avril and gathers together a team of about 20 researchers involving permanent faculty, postdocs and PhD students.
It has the financial support of the European Research Council (ERC) which attributed a grant of 2 million euros to Prof Stéphane Avril in 2015 (ERC-2014-CoG BIOLOCHANICS).
The Biolochanics vision
The rupture of an aortic aneurysm is a complex phenomenon that occurs when the wall stress exceeds the local strength of the aorta due to degraded properties of the tissue. Our vision is that the evolution of the strength and of the wall stress of the aorta during the growth of an aneurysm can be predicted on a patient-specific basis by a computational model. We plan to develop this computational model and to validate it on different cohorts during the course of the Biolochanics project. The use of the computational model will be proposed to cardiac and vascular surgeons for a prediction of the mid-term and long-term fate of every aortic aneurysm. This will permit to plan surgical intervention more securely and more timely for the benefit of all the patients.
The Biolochanics roadmap
An aortic aneurysm may be considered as a mechanobiological instability. While the tissue is healthy, uniform stress and stiffness properties are maintained across the aorta according to the principle of homeostasis. The tissue is mechanobiologically stable. But when the mechanosensitivity of cells in the tissue is impaired or when the regulation of structural proteins is chemically disturbed, a mechanical heterogeneity may develop irreversibly in the tissue and may initiate an aneurysm.
Our aim is to develop finite-element models of aortas that intrinsically account for the regional variations of material properties in the tissue. These regional variations of material properties will be determined for every patient at the moment of their examination. They will constitute the initial conditions of a model that will predict their evolution and its consequences on the integrity of the tissue.
The important stages of the project are the following:
- Development of the computational model. The local effects of proteolytic remodeling in the aortic tissue are first investigated in vitro using full-field optical measurements and inverse identification of the distribution of material properties. Then, the changes in the regional distribution of material properties occurring at different stages of aneurysm progression are identified combining biaxial testing, full-field optical measurements and inverse identification on a model of mice aneurysm. Finally, a new constitutive model able to account for local tissue remodeling is implemented in a finite-element environment. It takes into account internal length-scales controlling localization mechanisms involved in the development of the mechanobiological instability. This resorts to the nonlocal continuum damage theory.
- Patient-specific calibration of the computational model. Based on a new approach combining 4D phase-contrast magnetic resonance imaging (PC-MRI), fluid-structure interaction (FSI) finite element simulations and inverse identification, we perform a complete patient-specific reconstruction of the distribution of material properties in the wall of the aorta and of the blood action applied on it. All the patients diagnosed with an aneurysm of the ascending thoracic aorta at the Saint-Etienne University hospital and in other hospitals willing to collaborate are invited to take a 4D MRI exam. The distribution of their aortic material properties is reconstructed from these MRI data using the new approach. Two groups of patients are considered: i. patients having a surgical intervention after the exam: their excised tissue is collected and tested mechanically in order to determine if the material properties determined from the MRI are correct; ii. patients remaining under surveillance: they are invited to take the exam six months later in order to characterize the kinetics of growth and remodeling. The data are used to calibrate the model predictions.
- Clinical validation. An user-friendly interface will be developed and tested by a group of clinicians. For patients willing to take a PC-MRI exam, it will permit: 1. reconstructing automatically the model of each patient’s aneurysm, 2. visualizing the existing heterogeneities of material properties at the date of the exam, 3. predicting the growth of the aneurysm and the remodeling of the material properties over the next 12 months.
The Biolochanics team
Faculty and permanent staff
|Stéphane AVRIL||Directeur du CIS|
|Pierre BADEL||Responsable du département STBio|
|Nicolas CURT||Technicien de laboratoire|
|Jérôme MOLIMARD||Adjoint au directeur du CIS|
|Baptiste PIERRAT||Ingénieur de recherche|
- Nele Famaey is a research associate at KUL, Belgium. She visits our group for 3 months in 2016 and works on computational modeling of aneurysm growth.
- Mirunalini Thirugnanasambandam is a PhD student at the University of Texas San Antonio, USA, under the supervision of Prof Ender Finol. She works on the Clinical Management of Abdominal Aortic Aneurysms (AAA) using Patient-Specific Tissue Mechanics. She visited our group from September to December 2015. We are developing together a method of stress analysis for aortic aneurysms which does not require running a finite element model.
- Matthew Bersi is a PhD student at Yale, USA, under the supervision of Prof Jay Humphrey. He works on the mechanical properties of the aorta of different mouse models of aneurysms. We developed together a method able to derive regional variations of these material properties. He visited our group in December 2015.
- Magalie Viallon is a physicist and engineer at CHUSE. She is a specialist of MRI. With Prof Pierre Croisille, head of radiology at CHUSE, they play a key role in acquiring the best image data possible on the recruited patients.
- Jay Humphrey is John C. Malone Professor and Chair of Biomedical Engineering at Yale, USA. He has 30 years of experience in the field of continuum biomechanics, with primary interest in vascular mechanics and mechanobiology. Stéphane Avril visited his group from May to August 2014 and continues visiting regularly. The collaboration is on an inverse method able to derive regional variations of mechanical properties in the aorta of different mouse models of aneurysms.
- Jia Lu is Professor at the University of Iowa, USA. He is an expert in inverse problems for soft membranes. The collaboration is on the local identification of mechanical and rupture properties in aneurysm samples tested with a bulge inflation system.