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Doctoral school : ED 71 « Sciences pour l’Ingénieur » - UTC Université de technologie de Compiègne – Thesis proposal Part 1: Scientific sheet Thesis proposal title Polymerization of a liquid jet: Simulation of surgical glue embolization of blood vessels PhD grant Doctoral work contract based on a Ministry of Research Grant Research laboratory unité de recherche : UMR 7338 Biomechanics and Bioengineering (BMBI) research team: Biological Fluids Structures Interactions (IFSB) web site: www.utc.fr/bmbi/ Thesis supervisor(s) Dr. Badr Kaoui, CR2 CNRS Dr. Mathis Plapp, DR2 CNRS (HDR), Ecole Polytechique, Physics of Irregular Systems team, UMR 7643 Condensed Matter Physics (PMC), Palaiseau, France Scientific domain(s) Physics Biology, biomedical and health sciences Research work The importance of numerical modelling is rapidly increasing in the medical sciences, both for patient-specific treatments and for the improvement of medical techniques. The present project aims to apply modeling techniques developed in the domain of fluid-structure interactions to the simulation of surgical glue embolization of blood vessels. This is a novel technique used in surgery to stop bleeding. The modeling will yield insights that could help to improve this technique. Context and state-of-the-art: Intravascular injection of surgical glues is used as an alternative to open surgery to stop bleeding in case of hemorrhage or trauma, to occlude vessels presenting malformations or abnormal blood flow patterns, and to treat specific tumors. It consists in inserting and guiding a catheter through the arterial network via radiography, until reaching the site of administration of the glue (mixed with an oil). Even though glue embolization is largely used nowadays by clinicians, the mechanisms involved in the polymerization of the glue when it comes into contact with the blood flow are not yet understood. No systematic study has provided a detailed description of the physico-chemical mechanism of the polymerization or modeled the process. The polymerization at the glue-plasma interface is complex because of the many factors that influence it [1]: 1 - the multi-component fluid flow (here, the blood plasma and the glue-oil mixture), 2 - The phase transition phenomena (here, the glue polymerization), 3 - The fluid-structure interaction and free-moving interface (here, the plasma-glue interface and the polymerized glue bulk/film structure), 4 - The complex flow (here, the injection of the glue-oil into the blood stream). Despite the multitude of studies in the literature on liquid injection, drop formation and jetting, none of them has modeled numerically the polymerization of a liquid-liquid interface [2]. The objective of the project is to build a numerical simulation of glue injection coupled with its polymerization upon contact with blood. The project will be based on our strong experience in modeling of complex phenomena involving phase transitions and complex fluid dynamics. We will develop a code that will account for all the physico-chemical and hydrodynamic aspects involved in the process. To the best of our knowledge, such multi-physics simulations could not be achieved with conventional commercial software (e.g. Comsol and ANSYS Fluent). The PhD project will be conducted in tight collaboration with our colleagues Dr. Anne-Virginie Salsac from BMBI (who has the best knowledge of the glue embolization and who has initiated the first comprehensive in vitro study of glue injection and polymerization [1,3]) and Dr. Hervé Henry at Ecole Polytechnique (who will contribute with his expertise in modeling film formation at liquid-liquid interfaces [4]). Doctoral school : ED 71 « Sciences pour l’Ingénieur » - UTC Goals and milestones: We will develop a phenomenological model and study the glue polymerization kinetics as a function of the parameters of the problem. In the static case, we will consider the influence of plasma anion and protein concentration, temperature, and oil-to-glue fraction. We will then study the regimes of ejection of the glue mixture as a function of the glue injection flow rate and the surrounding plasma flow strength. Reporting a state diagram summarizing different regimes: 1 - Dripping, 2 - Liquid jet, 3 - Destabilization of the jet into droplets. The simulations will provide insight into how the blood composition alters the polymerization process of the injected glue. We will use our own in-house cutting edge codes, based on both the phase-field and the lattice-Boltzmann methods, which we plan to upgrade and merge within this project. The developed code will help understand the glue embolization mechanism. It will help predict different polymerization-induced scenarios and patterns and thus, control the phenomena to prevent any clinical complication afterwards. Methods of investigation: We master the knowledge and we are pioneers in the development and use of the phase-field method (for the modeling of phase transitions and front capturing of free-moving boundaries) [5-7] and the lattice-Boltzmann method (for computational fluid dynamics in complex geometries and for front tracking, when combined with the immersed boundary method) [7-9], which are two key state-of-the-art numerical methods. We will use phase-field modeling to track the glue-plasma interface and handle the polymerization phase transition that takes place at the interface (by solving the diffusion-advection-reaction equations). The study will be carried out in a fully three-dimensional domain. This permits to model the complete process and to capture irregular patterns observed in experiments (see the figure), and which could not be obtained with 2D or 3D axisymmetric simulations (largely used to study liquid jets and droplets generation [10]). The production High Performance Computing simulations will be run on large machines, PILCAM2 of the UTC, and we will ask access to other clusters such as IDRIS of the CNRS. Plan for the PhD: Development of polymerization model in absence of flow, polymerization starting at the glue-plasma interface in a stagnant blood plasma (1st year), coupling the polymerization model with the co-flowing device geometry (2nd year) and coupling the polymerization with both plasma and red blood cells motion in a microcirculatory network (3rd year). References: [1] M.-C. Sandulache, P. Paullier, R. Bouzerar, T. Yzet, O. Balédent, A.-V Salsac, Liquid injection in confined coflow: application to portal vein embolization by glue injection, Physics of Fluids. 24, 081902 (2012) [2] J. Eggers, E. Villermaux, Physics of liquid jets, Rep. Prog. Phys. 71, 036601 (2008) [3] Y. Li, D. Barthès-Biesel, A.-V. Salsac, Embolization of blood vessels by glue injection: an in vitro study of polymerization kinetics, Journal of the Mechanical Behavior of Biomedical Materials. In Press (2016) [4] M. Ardré, H. Henry, C. Douarche, M. Plapp, An individual-based model for biofilm formation at liquid surfaces, Physical Biology 12 (6), 066015 (2015) [5] M. Plapp, A. Karma, Multiscale random-walk algorithm for simulating interfacial pattern formation, Physical Review Letters. 84, 1740 (2000) [6] B. Kaoui, M. Noureddine, R. Nassif and Y. Boughaleb, Phase-field modelling of dendritic growth behaviour towards the cooling/heating of pure nickel, M. J. Condensed Matter 6, 109 (2005) [7] A. Cartalade, A. Younsi, M. Plapp: Lattice Boltzmann simulations of 3D crystal growth: Numerical schemes for a phase-field model with anti-trapping Doctoral school : ED 71 « Sciences pour l’Ingénieur » - UTC current, Computers and Mathematics with Applications 71, 1784-1798 (2016). [8] T. Krüger, B. Kaoui and J. Harting, Interplay of inertia and deformability on rheological properties of a suspension of capsules, Journal of Fluid Mechanics 751, 725-745 (2014) [9] Z. Shen, G. Coupier, B. Kaoui, B. Polack, J. Harting, C. Misbah, T. Podgorski, Inversion of hematocrit partition at microcirculatory bifurcations, Microvascular Research 105, 40-46 (2016) [10] Kaoui et al., Generation of ultrapure droplets using a mesh nebulizer, Proceedings of the Workshop Physics with Industry 2016, Leiden, The Netherlands (2017) Key words Glue embolization, blood flow, polymerization phase transition, liquid glue injection Requirements MSc in physics, mathematics, chemical engineering, or mechanical engineering, knowledge in scientific computing. We seek candidates who are result-oriented, self-motivated, who like challenges and are ready to work in collaboration and communicate effectively. Starting time September 2017 Location Compiègne and Palaiseau Part 2: Job description Duration 36 months Additional missions available Possibility of teaching Research laboratory BMBI is one of the leading and pioneering laboratory in France and worldwide in biomechanics and bioengineering Material resources Access to the computing facilities (PILCAM2 and others) National collaborations Dr. Anne-Virginie Salsac from BMBI and Dr. Hervé Henry at Ecole Polytechnique. Contact [email protected] Please contact first the thesis supervisor before applying online on https://webapplis.utc.fr/admissions/doctorants/accueil.jsf