1) FINITE-ELEMENT MODELING AND PATIENT-SPECIFIC PREDICTION OF ANEURYSM GROWTH AND RUPTURE IN THE ASCENDING THORACIC AORTA
Keywords: Finite-element method, nonlinear mechanics, mechanobiology, aortic aneurysm, extracellular matrix degeneration, nonlocal mechanics, fluid-structure interactions.
Academic context: This PhD thesis is part of the interdisciplinary Biolochanics – Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicine – project (2015-2020) awarded to Stéphane Avril (http://www.mines-stetienne.fr/stephane-avril) under the European Research Council Consolidator Grant scheme (http://erc.europa.eu/consolidator-grants). His group at Mines Saint-Etienne leads major international research projects in the domain of soft tissue biomechanics, focused especially on aortic aneurysm through a longstanding collaboration with the Saint-Etienne University Hospital. The Biolochanics project also relies on collaborations with Yale University (USA).
Scientific context: The growth of aortic aneurysms is associated with several mechano-chemo-biological interactions leading to modifications of the tissue structure including the fragmentation of elastin and changes in the amount and organization of collagen. We have modeled these mechanisms in a constitutive model based on the constrained mixture approach, where each constituent has an elastic constitutive response governed by an anisotropic strain energy function and an inelastic constitutive response governed first by a scalar [1–d]-type damage formulation and second by a permanent deformation gradient related to the growth. The model is implemented as a user material in the Abaqus software.
Project summary: In this thesis, we will first start by performing different sensitivity studies on the numerical model, permitting to calibrate different parameters, including the different degradation rates of collagen and elastin and the related time evolution of stress and strain distribution. Calibration will be performed against experimental data acquired by another person working on the project. After this stage we will apply the model to simulate the growth of ATAA in patients for whom we have reconstructed the aortic geometry for several years (on going longitudinal study at the university hospital of Saint-Etienne). In addition to the geometry, we have also access to hemodynamics through 4D MRI also acquired longitudinally for these patients, and even stiffness of the wall through an inverse method developed by another student working also on the project. All these data will be used to calibrate the finite-element model on a cohort of +20 patients in order to better understand how aneurysms grow and how the damage localizes in the tissue. The final goal will be to simulate numerically the scenario of growth and possible rupture for any patient’s aneurysm, just from the 4D MRI data, thus aiding the surgeon to take important decision such as surgical repair.
Candidate profile: Candidates with strong backgrounds in engineering mechanics, biophysics, biomechanics, and/or applied mathematics are expected. Background in finite elements and nonlinear mechanics will be highly appreciated. Motivation for ground-breaking experimental work and interest in mechanobiology are recommended.
Administrative aspects: Situated in the dynamic Rhône-Alpes region (Lyon – France) in the heart of the European Union, Mines-Saint-Etienne is one of the oldest and most prestigious Grandes Ecoles, and has, since 1816, lived up to its motto “innovante par tradition – inspiring innovation“. Working in a culturally and scientifically most stimulating atmosphere, the successful candidate will earn
internationally competitive salaries. Employment durations is 3 years. The employer is Armines, linked by state-approved agreements to Mines Saint-Etienne. The thesis will start in October 2017.
If you are interested, send a curriculum vitae, a cover letter describing previous research experience and interests, the names and contact information of two references. Please, submit via email with “ERC Biolochanics D3” on the subject line to Prof Stéphane AVRIL, PhD (avril@emse.fr). Deadline for applications: 30th April 2017.
2) MULTISCALE CHARACTERIZATION OF PROTEOLYTIC REMODELING AND OF ITS BIOMECHANICAL EFFECTS IN THE AORTIC WALL
Keywords: Mechanobiology, aortic aneurysm, extracellular matrix degeneration, biomechanical tests, full-field measurements, digital image correlation, OCT, collagenase
Academic context: This PhD thesis is part of the interdisciplinary Biolochanics – Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicine – project (2015-2020) awarded to Stéphane Avril (http://www.mines-stetienne.fr/stephane-avril) under the European Research Council Consolidator Grant scheme (http://erc.europa.eu/consolidator-grants). His group at Mines Saint-Etienne leads major international research projects in the domain of soft tissue biomechanics, focused especially on aortic aneurysm through a longstanding collaboration with the Saint-Etienne University Hospital. The Biolochanics project also relies on collaborations with Yale University (USA).
Scientific context: The growth of aortic aneurysms is associated with several morphological abnormalities, particularly in the media. Two abnormalities standout from a mechanical standpoint: the fragmentation of elastin and changes in the amount and organization of collagen. Changes in the organization of these two load-bearing components signal that more than likely significant changes in the mechanical properties are occurring.
Project summary: In this project, we will focus on the contribution of collagen, as the fragmentation of elastin has been implicated in the normal aging process. In aneurysms the normal production and degradation rates of collagen are disturbed leading to enlargement and local weakening of the aortic wall. To investigate this localized weakening of the tissue through degradation of its collagen fibers we will develop a novel biochemically-based method to locally degrade the collagen fibers and characterize its biomechanical effects.
Sample will be cut from aortic tissue and tested in an inflation device. Using a digital image correlation system at the macro scale (developed by a post-doc also working on the project) and an optical coherence tomography (OCT) system at the micro scale (developed by another post-doc), images will be recorded during the inflation. While the pressure is held constant, a fine tipped syringe will be used to apply purified collagenase in buffered saline to a small region of the sample. After the application of collagenase the sample and testing device will be placed in a saline bath for incubation. The selected incubation times are short to ensure that the collagen fibers are only partially degraded. To verify that the enzymatic digestion of collagen occurred we will examine histological images. After the treatment, we will inflate the tissue to failure. We will subject a total of 30 ATAA wall specimens to this protocol.
The stress and strain fields at each pressure stage will be calculated using an inverse method based on the data of the digital image correlation system at the macro scale and of the optical coherence tomography system. The focus will be on determining if any novel local features are identified in the collagenase treated region, particularly at physiologic pressure. We will use the calculated mechanical properties to confirm that the collagenase treatment had the intended effect of weakening the mechanical properties at the application site. The experimental method is fully capable of capturing these local changes in material properties. By comparing the range of rupture stress, we will determine how localized collagen degradation impacts the final rupture stress.
Candidate profile: Candidates with strong backgrounds in engineering mechanics, biophysics, biomechanics, and/or applied mathematics are expected. Background in experimental mechanics
and optical measurement techniques will be appreciated. Motivation for ground-breaking experimental work and interest in mechanobiology are recommended.
Administrative aspects: Situated in the dynamic Rhône-Alpes region (Lyon – France) in the heart of the European Union, Mines-Saint-Etienne is one of the oldest and most prestigious Grandes Ecoles, and has, since 1816, lived up to its motto “innovante par tradition – inspiring innovation“. Working in a culturally and scientifically most stimulating atmosphere, the successful candidate will earn internationally competitive salaries. Employment durations is 3 years. The employer is Armines, linked by state-approved agreements to Mines Saint-Etienne. The thesis will start in October 2017.
If you are interested, send a curriculum vitae, a cover letter describing previous research experience and interests, the names and contact information of two references. Please, submit via email with “ERC Biolochanics D2” on the subject line to Prof Stéphane AVRIL, PhD (avril@emse.fr). Deadline for applications: 30th April 2017.
