Content

Invited Speakers

Opening Lecture

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Ajit P. Yoganathan is the Wallace H. Coulter Distinguished Faculty Chair, Associate Chair for Translational Research,  and Regents’ professor in the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University. He is also the founder and the Director of the Center for Innovative Cardiovascular Technologies. For more than 40 years Dr. Yoganathan has been a stalwart in the field of basic and translational cardiovascular research, especially on experimental and computational fluid mechanics as it pertains to artificial heart valves, the whole heart, and congenital heart diseases. In his effort to take an interdisciplinary and translational approach to his research, Dr. Yoganathan has established collaborations with clinicians, scientists, and industry professionals world-wide. Over the past decade Dr. Yoganathan has also been active in inventing and developing a variety of medical devices and has been issued seven patents, three of which have been licensed to companies and/or have direct clinical use/impact on patients.  Dr. Yoganathan has published over 350 peer reviewed journal articles and more than 40 book chapters in leading biomedical journals and books.  His career has also been distinguished by a number of high honors.  Most recently, in recognition of his significant contributions to the field of engineering, he was elected to the prestigious National Academy of Engineers in Washington, D.C.


 COMPUTATIONAL CHALLENGES IN CARDIOVASCULAR FLUID MECHANICS
The challenges in computational cardiovascular fluid mechanics address a cross-section of problems when using the computational fluid dynamics or fluid-structure interaction techniques to simulate cardiovascular related processes, such as blood flow with or without cardiovascular devices, blood damage, surgical planning, inverse characterization of soft tissue properties, and other applications. This opening lecture gives an overview of the computational challenges encountered in 35 years of the existence of Cardiovascular Fluid Mechanics laboratory at Wallace H. Coulter Department of Biomedical Engineering.

 

Keynotes/Plenary Lectures

Francisco_Chinesta.jpgFrancisco Chinesta, born in 1966 in Valencia (Spain), is currently Professor of Computational Mechanics at the Ecole Centrale of Nantes (France), titular from 2008 to 2012 of the EADS Corporate Foundation International Chair on Advanced Modeling of Composites Manufacturing Processes and titular from 2013 of the ESI International Chair on Advanced Simulation Strategies. He is associate member of the University of Wales Institute of Non-Newtonian Fluid Mechanics. In 2011 he was nominated senior member of the “Institut Universitaire de France” – IUF –. He was nominated in 2013 fellow of the Spanish Royal Academy of Engineering. He is authors of more than 200 papers in international peer reviewed journals and his main research topic concerns advanced simulation based on the use of model order reduction for the real time simulation, optimization, inverse analysis and simulation based control in engineering sciences.


 REDUCED ORDER MODELING BASED REAL TIME COMPUTATIONAL SURGERY
Computational surgery has been defined recently as "the application of mathematics and algorithm design, enabling imaging, robotics, informatics, and simulation technologies, incorporating biological and physical principles, to improve surgery'". It has been since the early times of development of computers that their promising use in the field of medicine has been investigated. With the irruption of endoscopical and minimally invasive procedures, on one side, and robot-operated surgery, on the other, training of surgeons has becoming a task in which computer simulation has acquired a preeminent role in recent years. In essence, surgeons have begun to access organs during surgery in an indirect way, through a screen, and this needs for real time feedback as well as a period of intensive training to avoid costly errors.
In this talk we revisit the concept of computational vademecum, analyzed in detail when applied for the real-time simulation in the field of computational surgery. In essence, a computational vademecum is an off-line computer simulation of a physical process in which different parameters have been considered as coordinates, thus giving rise to a high-dimensional problem. To avoid the numerical difficulties associated to meshing high-dimensional domains, and also their respective post-processing, Proper Generalized Decomposition (PGD) methods have been employed. These allow to express the high-dimensional solution as a finite sum of separable functions, that can be post-processed on-line at tremendously high feedback rates, even on the order of kHz. These vademecums allows real time haptic feedbacks, real time simulation of contact problems, simulation of cutting, … and even patient-specific computational surgery. These works are developed in very close collaboration with the Elias Cueto's research group at the University of Zaragoza in Spain.



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Alberto Figueroa is the Edward B. Diethrich Associate Professor of Biomedical Engineering and Surgery at the University of Michigan. He completed his PhD in Mechanical Engineering at Stanford University in 2006, focusing on computational methods to perform fluid-structure interaction simulations of blood flow in patient-specific cardiovascular models. He moved to King’s College London in England where he was Senior Lecturer in Biomedical Engineering from 2011 to 2014. Dr. Figueroa’s current research interests include: Methods to predict the growth & remodeling of blood vessels in response to changes in their biomechanical environment; Methods to predict the short-term response (auto-regulation) of the arterial system in response to changes in pressure and flow; and Computational tools to evaluate and predict the performance of abdominal and thoracic endografts. Dr. Figueroa has published extensively in the fields of Biomedical Engineering, Applied Mechanics, Life Sciences, and Vascular and Endovascular Surgery.

 

 CRIMSON: AN INTEGRATED COMPUTER MODELLING FRAMEWORK FOR SUBJECT-SPECIFIC CARDIOVASCULAR SIMULATION 

Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Research efforts have been focused mainly on three areas: i) pathogenesis of vascular disease, ii) development of medical devices, and iii) virtual surgical planning. However, despite great initial promise, the actual use of patient-specific computer modelling in the clinic has been very limited. Clinical diagnosis still relies on traditional methods based on imaging and invasive measurements. The same invasive trial-and-error paradigm is often seen in vascular disease research, where animal models are used profusely to quantify simple metrics that could perhaps be evaluated via non-invasive computer modelling techniques. Lastly, medical device manufacturers rely mostly on in-vitro models to investigate the anatomic variations, arterial deformations, and biomechanical forces needed for the design of medical devices.

In this project, our aim is to develop an integrated image-based computer modelling framework for subject-specific cardiovascular simulation (CRIMSON) that can successfully bridge the gap between the research world and the clinic. The main features of the CRIMSON simulation environment are: A parallel blood flow solver based on the academic code SimVascular; A modern GUI for medical image data segmentation based on the Medical Imaging Interaction Toolkit (MITK); Libraries for automatic estimation of parameters required for boundary and material parameter specification. These parameter estimation routines are based on Kalman-filtering theory; and Routines to enable the automatic simulation of transitional cardiovascular stages. These routines mimic the action of key cardiovascular functions such as the baroreflex, and local auto-regulations such as those in the coronary and cerebral circulations. In this talk, we will provide an overview of the most novel features for the software, specifically the functions for parameter estimation and simulation of transitional stages, and highlight a series of future developments for the project.

 

 

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Marie-Christine Ho Ba Tho is Full Professor in Mechanics since 1998 at UTC (Université de Technologie de Compiègne) and currently Head of Biomechanics and Bioengineering Laboratory associated with CNRS (Centre National de Rercherches Scientifiques). She received a Master in Physics in 1985, Post Diploma in Radiological Physics in 1986 and PhD in Biomechanics in 1989 from Université Paul Sabatier (UPS) at Toulouse, France. Since 2006, she is also a member of the World Council for Biomechanics, and she is nominated at the Scientific Board at the Institute for Engineering and Systems Sciences (INSIS) of CNRS since 2010. Her research interest concerns biomechanics of the musculoskeletal system especially children, adult bone and joints deformities. Methodologies developed are bone and joints modeling and characterization coupled with medical imaging techniques. She introduced the development of numerical models with individualized mechanical and geometric properties derived from medical images and the multiscale characterization of the musculo-skeletal system. Most of her research are performed in collaboration with national and international companies and clinicians (orthopaedics and radiologists). Recently her work is focused in the modelling of uncertainties of the biomechanics data and their propagation in the development of medical computer aided system diagnosis.

 

subject-specific NUMERICAL models with material properties and boundary conditions derived from medical imaging

The objective is to address the methodology developed to model musculoskeletal systems with personalised geometric and material properties and boundary conditions derived from medical image data. For hard tissue, from Computed Tomography (CT) personalized bone mechanical properties could be extracted and moreover its follow up could provided data for validation of patient specific predictions. For soft tissue advanced MRI such as dynamic MRI and Magnetic Resonance Elastography (MRE) allowed respectively to analyse the in vivo forces generated by the muscles in movement but also its mechanical properties in passive and active behavior. Based on these knowledges, patient specific geometry, mechanical properties and forces are assessed derived from advanced medical imaging techniques. These data are of importance for developing patient specific computer modelling for prediction and evaluation of therapeutic, surgical or functional rehabilitation treatments.



EPeña2.jpgEstefanía Peña became Associate Professor of the Department of Mechanical Engineering of the University of Zaragoza (Spain) in 2008 where she still teaches. From 2001 to 2004 she was lecturer and from 2004 to 2008 Assistant Professor of Structural Mechanics at the UZ. She got the degree of Mechanical Engineering at the University of Zaragoza (Spain) in 2000. She achieved his Ph.D. in Computational Mechanics at the University of Zaragoza in 2004 and spent a post-doctoral stay at the Universities of Southampton in U.K. in 2004 and Joseph Fourier of Grenoble in France in 2005. She is member of Applied Mechanics and Bioengineering Group of the I3A (Aragón Institute of Engineering Research). She is member of different national and international scientific associations and she has published more than 70 papers. She is Associate Editor of Annals Biomedical Enginnering and Applied Bionics and Biomechanics Journals. Her current research is related to Biomechanics, mainly in the field of Mechanics of Soft Tissues as blood vessels, muscle, ligament and tendons,– mechanical behaviors of biomaterials and prostheses for clinical applications and experimental methods to characterize biological tissues.


Mechanobiology and modeling of atheroma plaque formation and development

Atherosclerosis is a vascular disease caused by inflammation of the arterial wall, which results in the accumulation of low-density lipoprotein (LDL) cholesterol, monocytes, macrophages and fat-laden foam cells at the place of the inflammation. This process is commonly referred to as plaque formation. The evolution of the atherosclerosis disease, and in particular the influence of wall shear stress on the growth of atherosclerotic plaques, is still a poorly understood phenomenon. This talk presents a review of mathematical models of atheroma plaque and presents a new mathematical model to reproduce atheroma plaque growth in coronary arteries. This model uses the Navier–Stokes equations and Darcy’s law for fluid dynamics, convection–diffusion–reaction equations for modelling the mass balance in the lumen and intima, and the Kedem–Katchalsky equations for the interfacial coupling at membranes, i.e. endothelium. The volume flux and the solute flux across the interface between the fluid and the porous domains are governed by a three-pore model. The main species and substances which play a role in early atherosclerosis development have been considered in the model, i.e. LDL, oxidized LDL, monocytes, macrophages, foam cells, smooth muscle cells, cytokines and collagen.  Our current approach is on the process on plaque initiation and intimal thickening rather than in severe plaque progression and rupture phenomena.

 


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Michael Sacks is the W. A. “Tex” Moncrief, Jr. Simulation-Based Engineering Science Chair and a world authority on cardiovascular biomechanics. His research focuses on the quantification and modeling of the structure-mechanical properties of native and engineered cardiovascular soft tissues. He is a leading international authority on the mechanical behavior and function of the native and replacement heart valves. He is also active in the biomechanics of engineered tissues, and in understanding the in-vitro and in-vivo remodeling processes from a functional biomechanical perspective. Dr. Sacks is currently director of the ICES Center for Cardiovascular Simulation and Professor of Biomedical Engineering. His research includes multi-scale studies of cell/tissue/organ mechanical interactions in heart valves and is particularly interested in determining the local stress environment for heart valve interstitial cells. Recent research has included developing novel multi-scale models of the mitral valve and bioprosthetic heart valves, as well as constitutive models of ventricular myocardium that allow for the separation of the individual contributions of the myocyte and connective tissue networks.

 

ON THE DEVELOPMENT OF AN ANATOMICAL, STRUCTURAL, AND BIOMECHANICAL INTEGRATED MODEL OF THE MITRAL VALVE

The mitral valve (MV) is one of the four heart valves which locates in between the left atrium and left ventricle and regulates the unidirectional blood flow and normal functioning of the heart during cardiac cycles. Alternation of any component of the MV apparatus will typically lead to abnormal MV function. Currently 40,000 patients in the United States receive MV repair or replacement annually according to the American Heart Association. Clinically, this can be achieved iteratively by surgical repair that reinstate normal annular geometry (size and shape) and restore mobile leaflet tissue, resulting in reduced annular and chordae force distribution. High-fidelity computer simulations provide a means to connect the cellular function with the organ-level MV tissue mechanical responses, and to help the design of optimal MV repair strategy. As in many physiological systems, one can approach heart valve biomechanics from using multiscale modeling (MSM) methodologies, since mechanical stimuli occur and have biological impact at the organ, tissue, and cellular levels. Yet, MSM approaches of heart valves are scarce, largely due to the major difficulties in adapting conventional methods to the areas where we simply do not have requisite data. There also re-mains both theoretical and computational challenges to applying traditional MSM techniques to heart valves. Moreover, existing physiologically realistic computational models of heart valve function make many assumptions, such as a simplified micro-structural and anatomical representation of the MV apparatus, and thorough validations with in-vitro or in-vivo data are still limited. We present the details of the state-of-the-art of mitral valve modeling techniques, with an emphasis on what is known and investigated at various length scales.

 

 

Qiwang2012-portrait.jpgQi Wang is currently the College of Arts and Sciences Distinguished Professor at the Department of Mathematics, University of South Carolina. He graduated with a BS degree in Mathematics from Nankai University, China in 1982 and obtained his PhD in Applied Mathematics from The Ohio State University, USA in 1991. He has held tenure-track and tenured faculty positions at Indiana University-Purdue University Indianapolis, Florida State University and University of South Carolina. He is research area is in applied and computational mathematics with focus on multiscale modeling and simulation of complex fluid flows. He has Published over 120 peer-reviewed journal papers and served on the editorial board for four journals. He is the thrust leader for the Theory, Modeling, and Simulation thrust in the NanoCenter at USC and for the modeling team in the South Carolina biofabrication consortium. He is also affiliated with Beijing Computational Science Research Center, China and Nankai University currently.

 

MODELING ACTIVE LIQUID CRYSTAL SOLUTIONS AND GELS WITH APPLICATIONS TO COMPLEX BIOLOGICAL SYSTEMS

Active liquid crystals solutions and gels are complex fluids whose anisotropic molecules undergo self-propelled motion by either burning ATP or reacting with the host matrix. The self-propelled motion introduces new active stresses to the momentum balance together with self-propelled velocity. , which can lead to spontaneous flows and symmetry breaking flow patterns. In this talk, I will first present a systematic development of hydrodynamic theories for the active matter system using the generalized Onsager relation. Then, I will study a specific system for polar active liquid crystals in confined geometries with physical boundary conditions aiming at exploring flow instabilities due to the flow-activity interaction. Finally, I will discuss the employment of this active liquid crystal model in the development of a whole cell model to simulation cell mitosis and motility. 3D numerical simulations of cytokinesis and cell motion will be presented.



YX.jpgXiao Yun Xu is a Professor of Biofluid Mechanics in the Department of Chemical Engineering at Imperial College London. She joined the Department of Chemical Engineering at Imperial College in 1998 as a Lecturer, and was promoted to full Professor in 2009. She received her BSc and MSc degrees in Thermo-Fluids Engineering from Dalian University of Technology in China, and her PhD (1992) in Mechanical Engineering from the City University, London. Her research is mainly focused on transport processes in biological and physiological systems, and examples of her current research include: image-based analysis of cardiovascular fluid mechanics and mass transport, multi-scale modelling of drug delivery to solid tumour, nanoparticle-mediated drug delivery in cancer and thrombolytic therapies, rheological behaviour of biomass suspensions and solid-liquid mixing in bioreactors for the production of fuels from energy crops. She has co-authored 116 articles in peer-reviewed journals, and supervised 38 PhD students. In 2009, she received the Imperial College Rector’s Award for Excellence in Research Supervision for her exceptional contributions in providing a supportive learning environment for postgraduate research students.

TOWARDS AN INTEGRATED MULTIPHYSICS MODELLING FRAMEWORK FOR DRUG DELIVERY TO SOLID TUMOUR

Effective delivery of therapeutic agents to tumour cells is essential to the success of most cancer treatment therapies. The transport of anticancer drugs and their effects on tumour cells involve multiple physical and biochemical processes. Mathematical modelling provides a tool to help us understand the interaction of these complex processes, thereby contributing to the improvement and optimisation of drug delivery. In this talk, a Computational modelling framework will be described which incorporates the key physical and biochemical processes involved in drug transport in solid tumour and drug uptake by tumour cells, as well as real tumour geometry reconstructed from magnetic resonance images. Our most recent work on computational modelling of thermosensitive liposomal delivery of anticancer drugs activated by high intensity focused ultrasound will also be discussed.