Day 1

Pathophysiology

Basic Science and Clinical Understanding

Cardiovascular pathophysiology: atherosclerosis, vascular remodeling and blood clotting (9:30-11:00)

Gemma Vilahur (Catalan Institute of Cardiovascular Sciences - ICCC)

Cardiovascular disease is the leading cause morbidity and mortality Worldwide.  therosclerosis is a silent and chronic vascular pathology that is the main underlying cause of the majority of cardiovascular events. The evolution of vascular disease involves a combination of endothelial dysfunction, extensive lipid deposition in the vascular layers, exacerbated inflammatory response, proliferation of vascular smooth muscle cells and changes of the extracellular matrix components overall leading to vascular remodeling and the formation of an atherosclerotic plaque. “High-risk” plaques have a large lipid content covered by a thin fibrous cap infiltrated by inflammatory cells and diffuse calcification. The formation of new fragile and leaky vessels that invade the expanding atherosclerotic lesion contributes to increase the vulnerability of the plaque to rupture. In addition, biomechanical, haemodynamic and physical factors contribute to plaque destabilization. Upon erosion or rupture, these high-risk vulnerable plaques expose internal vascular structures and components to the blood flow which induces the activation of the coagulation cascade and, concomitantly, the recruitment and activation of circulating platelets eventually leading to thrombus formation (i.e. atherothrombosis). Thrombosis may compromise arterial blood flow supply leading to the presentation of oxygen deficiency and the presence of myocardial infarction.

Throughout my presentation I will describe the progression of the atherosclerotic vascular lesion along with the main morphological and haemodynamical features that predispose to atherosclerotic plaque rupture, and discuss the multifaceted mechanisms that drive coagulation/platelet activation and subsequent thrombus formation.

Bio: Dr. Gemma Vilahur (DVM, PhD, FESC) is a Senior I3P Researcher at the Catalan Institute of Cardiovascular Sciences (ICCC; Hospital Santa Creu and Sant Pau) in Barcelona, where she coordinates the Translational Research Department since her return from the United States in 2006. Her research activities have been focused on cardiovascular research, especially devoting to unraveling the basic mechanisms of vascular and heart disease pathology (from atherothrombosis to ischemic heart disease) and evaluating and discovering new potential therapeutic approaches. She has published over 100 peer-reviewed articles (citations: 1697 and Factor H: 24), has contributed to more than 30 book chapters and is co-author of several patents.

Dr. G. Vilahur is a current Nucleus member of the Working Group of Thrombosis of the European Society of Cardiology (ESC; 2014-2018) and Founder of the Scientists of Tomorrow (Council Basic Cardiovascular Science-ESC). She has been awarded with the Young Investigator Award (YIA) in Thrombosis by the European Society of Cardiology (Munich 20008) and has been YIA finalist in Thrombosis in ESC-Berlin 2002 and ESC-Vienna 2003 and YIA finalist in Basic Science in ESC-Vienna 2007. She has also been awarded twice with the First Research Prize in the National Congress of Cardiology (Madrid 2007; Seville 2012), First and second Prize in the National Congress of Atherosclerosis (Pamplona 2009 and Zaragoza 2013, respectively), and has received the Northwestern Cardiovascular Young Investigator's Forum and the Arteriosclerosis, Thrombosis, and Vascular Biology Merit Award of the American Heart Association (AHA; Chicago 2006). She has also won the L’Oreal-UNESCO Foundation Grant- for Women in Science (2012).

Cell biomechanics and collective migrations (11:30-12:30)

Xavier Trepat (ICREA, Institute for Bioengineering of Catalonia - IBEC)

Abstract

Bio: Xavier Trepat received a BSc in Physics in 2000 and a B.Sc in Engineering in 2001. In 2004 he obtained his PhD from the Medical School at the University of Barcelona. He then joined the Program in Molecular and Integrative Physiological Sciences at Harvard University as a postdoctoral researcher. In 2008 he became a Ramon y Cajal researcher at the University of Barcelona and the Institute for Bioengineering of Catalonia (IBEC), and in January 2011 he became an ICREA Research Professor. Trepat’s research aims to understand how cells and tissues grow, move, invade and regenerate in a variety of processes in health and disease. To achieve this, he has developed and patented different technologies to measure cellular properties at the micro- and nanoscales. He has then applied these technologies to identify fundamental mechanisms in cell biology and biophysics.

Since his return to Spain from the USA in 2008, his research at the intersection between life and physical sciences has attracted ample support from the most prestigious funding agencies; Trepat is the one of the very few researchers in Europe ever to be awarded three grants from the European Research Council (ERC), one Starting, one Consolidator, and one Proof of Concept. He is also one of the few researchers – if not the only one – to ever publish his work as main author in five Nature family journals, namely Nature, Nature Physics, Nature Materials, Nature Methods, and Nature Cell Biology. The diversity of these journals captures the broad spectrum of topics in his laboratory. He has been awarded the Banc de Sabadell Award for Biomedical Research in 2015.

Cardiac haemodynamics (12:30-13:30)

Javier Bermejo (Gregorio Marañón Hospital)

Abstract

Presentation of sponsors and supporters

Presentation of VPHI, ESB and Chair UPF-QUAES (13:30 - 13:45)

Presentation Master Computational Biomedical Engineering (14:45 - 14:55)

Day 2

Input measurements

Acquisition processing, quantification

Whole-field optical metrology for vascular flow characterisation (9:30-11:00)

María Pilar Arroyo de Grandes (i3A - University of Zaragoza)

This seminar will present an overview of the advanced laser speckle based techniques, which we have been developing at the University of Zaragoza, for its application in a wide range of flows. The nonintrusive and simultaneous measurement in 2D or 3D flow regions with high spatial resolution and accuracy has always been our main goal.

Speckle is a random pattern appearing when a rough surface is illuminated with laser light. In fluid mechanics, the roughness is produced by seeding the fluid with particles. The surface is obtained by illuminating a fluid plane.

Particle Image Velocimetry (PIV) is nowadays a widely used technique for measuring two velocity component fields, from two time spaced speckle field images. Stereo PIV gives access to the third velocity component. We have been involved in the development of PIV from the very beginning, when it was just an idea. Some examples of its application to vascular flows will be shown.

Digital Speckle Pattern Interferometry (DSPI) as a fluid velocimetry technique, for measuring an out-of- plane velocity component, and its combination with PIV as an alternative to SteroPIV was proposed and developed in the frame of some European projects. The advantages and disadvantages of this proposal will be discussed.

Digital Image Plane Holography (DIPH) as a three component (3C) fluid velocimetry technique is based on an advanced analysis of the DSPI recordings, which reconstructs the complex speckle field. As such, PIV images are obtained from the speckle field intensity while DSPI images are obtained from the speckle field phase. Multiplexing techniques, developed to deal with the different order of magnitude of the time interval appropriated for a PIV or a DSPI analysis, will be discussed. They have also been used to simultaneously measure in more than one fluid plane. As a holographic technique, DIPH is dependent upon the laser coherence length which limits the width of the measured region. A method for improving this width limitation has been developed, improving the performance of the high speed lasers typical in fluid mechanic applications.

Digital inline Holography as a 3C-3D velocimetry technique is based on particle reconstruction and tracking. The main challenges of this technique, which is still under development, and some proposed improvements will be discussed. Over the past years, we have worked on a number of biomedical engineering applications. Some results on the flow in aneurysm models, in a carotid bifurcation model and in vessel models with endoscopic viewing will be presented.

Bio: Pilar Arroyo received her PhD in Physics from the University of Zaragoza (1987). She was a research fellow at the University of Edinburgh (1989-1990) and a postdoctoral Fulbright scholar at Stanford University (1990-1992). She worked for one year at Monash University (2000) and for six months at Worcester Polytechnic Institute (2014). She is currently a Full Professor at the Applied Physics Department of the University of Zaragoza and the Head of the Optical Laser Technologies group at the Aragon Institute of Engineering Research (I3A). Her research interest focuses on the development of experimental optical techniques for mechanical measurements, working with universities all over the world. She has published key papers in Particle Image Velocimetry (PIV), Holographic Interferometry, Digital Speckle Pattern Interferometry (DSPI) and Digital Holography with applications in a wide range of flows including convective, aerodynamic, turbomachinery and biological flows. She is currently involved in a number of biomedical engineering applications.

Flow imaging: from 1D Doppler measurements to 4D flow (11:30-12:30)

Alberto Gómez (King's College London)

The function of the cardiovascular system is to pump blood around the body. As such, being able to measure and visualize how blood moves is crucial for understanding cardiac function, and brings in important clinical information. The introduction of 2D  phased arrays ultrasound transducers and the development in phase-contrast MRI have enabled us to observe blood flow patterns in patients. In this talk I will cover from basic to advanced techniques and methods to measure cardiovascular blood flow using the most widely used techniques: Doppler ultrasound and magnetic resonance imaging. I will also introduce some of the current trends and active research lines and their potential implication in the future of flow imaging.

Bio: I hold a degree in Telecommunications Engineering from the Technical University of Madrid (Spain) and a degree in Biomedical Engineering from Telecom Bretagne (France). After a year working for General Electric Healthcare (Buc, Paris region, France) on interventional rasiology, in 2009 I obtained a Masters Degree in signal and image processing (SISEA). I did my Masters Thesis at Philips Research (Hamburg, Germany) on model based segmentation of CT images for radiotherapy planning.

At the end of 2009 I moved to King’s College London (UK), where I did my PhD on 3D intra-ventricular flow quantification using Doppler ultrasound images. After a post-doc on coupling of ventricular motion and flow at King’s in collaboration with University College London and Imperial College, in 2014 I started my second post-doc at King’s with the newly awarded iFIND project on fetal imaging.  In 2016 I became a Research Fellow at the Department of Biomedical Engineering at KC. My research interests cover ultrasound image acquisition, registration, segmentation and analysis for fetal and cardiac applications.

4D MRI for studying blood flow in heart and vessels (12:30-13:30)

José Rodríguez (Vall d'Hebron Hospital)

In recent years, 4D-flow MRI has emerged as an important tool to quantify complex flow in left ventricle and aorta. Due to the spatial resolution of MRI and its spatial distribution is has been crucial to understand flow dynamics in different aortic diseases like bicuspid aortic valve, Marfan syndrome and aortic dissection.

Information derived from 4D flow MRI can provide information about flow eccentricity, flow direction, wall share stress, oscillatory share index, pulse wave velocity and other important relevant parameters to understand aortic diseases.

The presentation will introduce the characteristics of 4D flow MRI, how the sequence works, the clinical application and also the main parameters derived from the sequence.

Bio: José F Rodríguez Palomares graduated in 1999 from the University Miguel Hernández (Alicante, Spain) with an Extraordinary Award Bachelor of Medicine. After that, he performed the cardiology training at Vall Hebrón Hospital (Barcelona, Spain) until 2004.

He performed an imaging Fellowship at the Imaging Department of Vall Hebrón Hospital from 2004-2006 by the supervision of Dr. Arturo Evangelista. Later, he did a research fellowship at the Department of MRI and Cardiac CT at Northwestern Memorial Hospital (Chicago. Illinois. USA) from 2006-2007. Since 2007, he had a position as an attending physician at the Cardiology Department of Vall Hebrón Hospital, being attached at the Imaging Unit directed by Dr. Arturo Evangelista and involved in echocardiography, cardiac-MR and cardiac CT. He is also an attending physician at the CMR/CT unit at Clínica-Pilar St Jordi, Clínica Quirón, Clínica Dexeus-Quiron and Clínica Sagrada Familia (all of them located in Barcelona).

He has also been responsible of the supervision of the residents and international Fellows in the field of CMR and CT at Vall Hebrón Hospital. He has also participated in all research projects in CMR/CT and published several papers in different journals (see attached publications). He got his PhD in 2016 by the Autonomous University of Barcelona with excellent-cum laude.

He is an aggregate professor of the Autonomous University of Barcelona teaching 4th year medical students.

Since 2015, he is a Fellow of the European Society of Cardiology (FESC). He has also been vice chair of the Working Group on CMR and CT of the Spanish Society of Cardiology from 2010-2012, and chair from 2013 to 2016. Thus, every year, he has participated in different National and International meetings. He also serves as a reviewer for the Revista Española de Cardiología and numerous other journals.

Day 3

Multiphysics / Multiscale Models

Organ, cell, molecular

Walking on water – why cartilage is hydrated (9:30-11:00)

René van Donkelaar (Eindhoven University of Technology)

Articular cartilage is the thin, shiny cover of long bones in our articulating joints. Healthy cartilage allows painless motion of bones, while subject to significant mechanical loading. Only when cartilage becomes damaged, we literally feel its importance. Joints in which cartilage is worn away are very painful, and osteoarthritis is one of the most common disabling diseases. Unfortunately, treatment is very difficult because of the limited intrinsic repair capacity of cartilage.

The question then becomes: how is it possible that this very important tissue is able to sustain the severe mechanical demands for your entire life, without developing any damage? The answer lies in its structural organization and its high fluid content. Cartilage contains 70% fluid, entrapped in a solid matrix that contains an organized collagen network filled with amorphous, electrically charged proteoglycans. Through Donnan osmosis, the proteoglycans attract environmental water and stretches the matrix when the tissue swells. The tight collagen network resists this expansion, leaving the cartilage with an unmet swelling potential. It turns out that the resultant osmotic pressure is highly effective in load bearing. This load bearing function is further enhanced by the particular structural organization of the collagen network.

This presentation will explain the mechanics of cartilage in more detail and elucidate the importance of the fluid content for the mechanical performance of the healthy tissue. It will also be demonstrated why early degenerative changes in the tissue may be detrimental for healthy load bearing, and are therefore prone to result in progressive cartilage degeneration.

Bio: René van Donkelaar obtained his PhD degree in 1999 at the Maastricht University. As of 1998 he was already appointed at the Biomedical Engineering Department of the Eindhoven University of Technology, where he was one of the first faculty members. He worked at this department in the groups of prof Frank Baaijens, prof Rik Huiskes, and eventually prof Keita Ito, where he is currently appointed associate professor in cartilage mechanics.

The central theme in his research is cartilage, which he approaches from a biomechanical point of view. Using fundamental insights on the mechanical behavior of cartilage, he established a well-recognized computational model of cartilage mechanics. The main asset of this model is that it directly links biochemical contents (distributions of proteoglycans and collagen) and structural features (collagen fiber orientation), to mechanical properties. The focus of his work has now shifted from fundamental to applied cartilage research in two main research areas. First, he aims to develop improved loading protocols for cartilage tissue engineering. Second, he aims to understand how adverse mechanical loading leads to progression of osteoarthritis, ultimately leading to the development of diagnostic tools. All topics are studied by means of experimental work using cell cultures and explant systems, in conjunction with numerical modeling using the aforementioned cartilage mechanics model. The latter is being adapted such that cartilage growth and developmental as well as cartilage degeneration can be computed and predicted.

Mechanobiology and mathematical modeling of atheroma plaque initiation and development (11:30-12:30)

Miguel Ángel Martínez Barca (University of Zaragoza)

Atherosclerosis is the process in which plaques - consisting of deposits of cholesterol and other lipids, calcium and large inflammatory cells called macrophages - are built up in the walls of the arteries causing narrowing, hardening of the arteries and loss of elasticity. This process is commonly referred to as plaque formation. The mechanical factors which could initiate the atherosclerosis lesion have been widely explored by many authors: cyclic stretch, laminar and oscillatory shear stress, effects of vessel compliance, curvature, pulsatile blood flow or cardiac motion are considered the main mechanical triggers of atherosclerosis initiation. This talk presents a review of some 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. Furthermore, experimental data taken from the literature have been used in order to physiologically determine model parameters. Finally, the role of the hypertension on the atheroma plaque growth is included by means of the mechanical deformation on the wall artery. Our current approach is based on the process on plaque initiation and intimal thickening rather than in severe plaque progression and rupture phenomena. The results show that the mathematical model is able to qualitatively capture the atheroma plaque development observed in the intima layer.

Bio: M.A. Martínez has been a Professor of Structural Mechanics of the Department of Mechanical Engineering, University of Zaragoza, Spain since 2010. From 1996 to 2002, he was an assistant professor and from 2003 to 2010 he worked as an associate professor. He achieved his PhD in Computational Mechanics at the University of Zaragoza in 1999 and did a post-doctoral stay at the Laboratoire de Rhéologie et Thermodynmique des Matériaux Macromoléculaires of the Conservatoire National des Arts et Métiers (CNAM) in Paris in 2000. His teaching activities include Continuum Mechanics, Materials Strength, Structural Mechanics, Advanced Numerical Methods and Cardiovascular Biomechanics.

He is coordinator of the Applied Mechanics and Bioengineering Group (http://amb.unizar.es/). AMB belongs to the Aragón Institute of Engineering Research (I3A) and comprises more than 20 researchers, 3 full professors, 8 associate professors and several post and pre doctoral researchers and technical assistants. In addition to the research activity, AMB is involved in teaching undergraduate and graduate courses in the School of Engineering and Architecture (Escuela de Ingeniería y Arquitectura, EINA) at the University of Zaragoza.

His current research is related to Computational Biomechanics, mainly in the field of Mechanics of Soft Tissues, Blood Vessels, Heart, Ligament, Tendons and Cartilage. He is currently focused in the numerical-experimental study of the vascular system, its mechanical behavior, remodeling processes and different vascular pathologies, such as atherosclerosis or atheroma plaque stability. He has also worked in the study of different intravascular devices, such as stents, balloons or vena cava filters.

He is the author of more than 70 JCR indexed papers, 200 conference proceedings, different book chapters, reports and oral presentations. He has been responsible for several research projects and contracts with the industry and has been advisor of nine Doctoral Theses.

The multiscale heart: From models to clinical decision support (12:30-13:30)

Kristin McLeod (Simula Research)

The heart is an organ comprised of a complex structure that is able to sustain billions of beats in a lifetime through intricate coupling of electrical activation, mechanical function, and hemodynamic load. Naturally, when disease or lifestyle affects one or more of these aspects, the longterm sustainability of the pumping action is compromised. While advances in management and treatment of heart disease have been substantial, cardiovascular disease remains the number one cause of death worldwide. In light of this, cardiac modelling and analysis have become increasingly popular in recent years to improve understanding of heart disease, and to better stratify patients for treatment. In this talk, an entry-level introduction to multiscale modelling of cardiac electrophysiology will be given, describing how multiscale models are being translated into clinical decision support tools. Complementing this, I will present methods to predict outcomes to therapy and thus to drive therapy decision making, via analysis of groups and populations. Finally, I will discuss how we can take the best of both worlds and incorporate patient-specific modelling with group-wise analysis.

Bio: Kristin McLeod has primary research interests in medical image processing, statistical cardiac modeling, population-based modeling, reduced order modeling, and machine learning. She completed a PhD in 2013 with first class honours (mention trés honorable) at the National Research Institute of Computer Science and Mathematics (Inria), through the Université de Nice Sophia Antipolis. She has been working as a postdoctoral fellow since then at Simula Research Laboratory in the Scientific Computing department as a part of the Center for Cardiological Innovation. During this time, she has also worked as an external postdoctoral fellow at Inria, France. The main aim of her research (past and present) is to bridge the gap between modellers and clinicians by developing models that can be easily understood and interpreted from a clinical point of view, with the main objective being to derive models of cardiac phenomena to complement clinical measures to provide indicators to aid with diagnosis and therapy planning. Kristin is actively involved in the medical imaging community, as a co-organiser of the Statistical Atlases and Computational Modelling of the Heart workshop of the Medical Image Computing and Computer Assisted Interventions (MICCAI) conference, and as a founding member of the MICCAI student board.

Towards Credible Modeling and Simulation at the FDA:  Virtual Patients for Regulatory Decision Making. (18:00-19:00).

HONORARY VPH LECTURE

Tina Morrison (Deputy Director, ision of Applied Mechanics, FDA)

To address the requests from both the healthcare industry and patients for getting access to new and improved treatments faster, the FDA investigates various strategies to accelerate the regulatory process while further increasing patient safety.  Computational Modeling and Simulation is a very promising avenue that the FDA is considering.

In a 2011 report, FDA recognized an important role for modeling and simulation to advance regulatory science and its strategic priorities.  In that document, FDA identified eight Regulatory Science Priority Areas, four of which had a specific method or approach for modeling and simulation.  See the table below for details.

FDA develops and reviews a broad range of modeling and simulation: chemical exposure models, knowledge-based models, mechanistic models, physics-based models, and statistical models and methods.  Additionally, simulation results are used to support regulatory evaluation in different phases of the product’s life cycle, which can vary based on the Center and product area.  To advance the use of modeling and simulation to support the development and evaluation of the products that FDA regulates, FDA has formed a Committee on Modeling and Simulation.   The main goals of the Committee are to:

• Raise awareness of the successes, challenges and opportunities for modeling and simulation to advance regulatory science at the FDA;
• Promote consistent regulatory review across isions, Offices, and Centers for technical matters pertaining to modeling and simulation through collaborative communication and unified messaging;
• Promote consistent decision making related to modeling and simulation across the FDA by developing credibility principles that can be applied to a wide-range of disciplines; and
• Serve as a resource of and for expertise on modeling and simulation on current and emerging technologies for the FDA.

Additionally, FDA is seeking partnership with national and international organizations pursuing similar activities.  The presentation from FDA will provide details on modeling and simulation initiatives to support medical products and an update on the Committee.

Table 1: FDA’s key science priorities areas that will rely on modeling and simulation to advance regulatory science

Bio: Dr. Tina Morrison is the chair of the new FDA-wide working group on Modeling and Simulation, sponsored by the Office of the Chief Scientists, which will launch in the Fall of 2016.  She has been serving as the Regulatory Advisor of Computational Modeling for the Office of Device Evaluation since 2013.  In that capacity, she leads the Regulatory Review of Computational Modeling working group at CDRH, which has developed guidance documents on the use of modeling and simulation in the regulatory evaluation of medical devices.  She dedicates much of her energy towards advancing regulatory science through modeling and simulation because she believes the future of medical device design and evaluation, and thus enhanced patient care, lies with computation and enhanced visualization.  She serves as chair of the ASME V&V40 Subcommittee on Computational Modeling of Medical Devices, where she is leading the development of a strategy to assess the credibility of computational models.  She is working with a team at CDRH to implement this strategy into the review of premarket submissions that leverage computational modeling.  For seven years, she was a scientific reviewer on a variety of medical device premarket submissions in Cardiovascular Devices.  She received her PhD in Theoretical and Applied Mechanics from Cornell University in 2006. Profile in Figshare. 

Day 4

Computational Aspects

Implementation, validation, coupling

Computational analysis of particulate flows. Applications in bio-mechanics (9:30-11:00)

Eugenio Oñate (International Center for Numerical Methods in Engineering - CIMNE)

The talk presents an overview of the computational mechanics of particulate flows. Details of a numerical formulation combining the finite element method for fluid flow analysis with an embedded approach for treating suspended and floating particles of different sizes is described. The talk concludes with examples of applications of the coupled numerical procedure to the analysis of a number of particulate flow problems of interest to biomechanics

Bio: Prof. EUGENIO OÑATE, Civil Engineer and PhD by University of Swansea, Wales, (1979), Professor of Structural and Continuum Mechanics at Technical University of Catalonia (UPC), founder and director of the International Center for Numerical Methods in Engineering (CIMNE, www.cimne.com), founder and Honorary President of the Spanish Society of Numerical Methods in Engineering (SEMNI), founder and Past-President of the  European Community on Computational Methods in Applied Sciences (ECCOMAS) and Past-President of the International for Association Computational Mechanics (IACM) . He has received a number of awards from universities and scientific and technological organisations worldwide. He is editor of three international journals and author of three text books and some 350 scientific papers on developments and applications of finite element and particle-based methods for structural mechanics, fluid dynamics, fluid-soil-structure interaction, bio-mechanics and industrial forming processes

Identifying faulty valves in the heart (11:30-12:30)

Pablo Lamata (King's College London)

When the heart beats, blood is squeezed from the heart into the aorta. As it leaves the heart, it crosses the valve, and the pressure of the blood drops.  The amount the blood pressure drops can tell doctors a lot about how the valve is functioning and is a powerful diagnostic technique. Cardiologists currently use non-invasive images to measure a peak velocity value in the jet of blood leaving the heart, and then use a physical principle (called Bernoulli’s Principle) to estimate for the pressure drop when the jet leaves the heart through the aortic valve. And, if this information is not sufficient, invasive pressure sensors can be placed inside the heart through a catheterised surgical procedure.

In this talk I will describe how to create additional clinical value by bringing more physics and maths into the hospital. I will present an improved method for measuring the presence of an obstruction when the blood flows out of the heart. I will motivate the need of this method through a detailed analysis of the Bernoulli principle in the human aortic valve, which reveals that it can cause inaccuracies in blood pressure measurements when the valves are narrowed, irregularly shaped or where the valve doesn’t work properly. By taking the right mathematical and physical assumptions, a more accurate and precise non-invasive estimation of the peak pressure drop, beyond Bernoulli’s principle, is now possible. And using advanced imaging technology we can assess a more comprehensive examination of blood velocity, and thus control for the variations in speed caused by faulty valves.

These results are hoped to enable a better risk stratification, and reduction of risks and costs of catheterised procedures, in conditions where the flow of blood from the heart is constricted such as in valve stenosis. I will also discuss how further research could identify more suitable pressure biomarkers, better characterising the impact of constriction severity and better predicting clinical outcomes.

Bio: Dr. Pablo Lamata is a Lecturer and Sir Henry Dale Fellow at King’s College of London. His research interest focuses in the combination of imaging and computational modelling techniques for the development of new biomarkers to improve the management of cardiovascular diseases. He has 15 years of experience in the development and clinical adoption of image analysis, physiological modelling, and surgical simulation and navigation solutions. He was previously worked at University of Oxford, and as a Marie Curie Fellow at Siemens. He obtained his PhD at Universidad Politécnica de Madrid, and his MSc from the Universidad de Zaragoza.

Particle based fluid modelling (12:30-13:30)

Hernán Morales (Philips)

Numerical modelling in biophysics is evolving from pure academic research towards practical industrial applications. The choice of a numerical approach to solve the assumed governing equations is intimately related to the scientific question, the type of biological problem, as well as the available clinical data. In this talk, computational fluid dynamics based on an Euler method is first presented for a neurovascular application. The goal is to show how this particular computational approach can be used to support the quantification of intra-aneurysmal flow that is based on image analysis. The second part of the presentation introduces a Lagrangian meshless scheme for cardiac flow modeling. The purpose is to explain why a meshless method can fit better this particular biological problem and available data to answer specific scientific questions. The second part of this talk is linked to one of the hand-on sessions, where more details of the meshless method are provided.

Bio: Hernán G. Morales was born in the city of La Serena, Chile. He graduated of Mechanical Engineering at the University of Chile in 2006. He obtained his PhD in 2012 from the Universitat Pompeu Fabra (UPF), Barcelona in the field of biomechanics. During his thesis, he investigated vascular hemodynamics, especially in cerebral aneurysms with endovascular therapies, by computational fluid dynamics. Currently, he works as scientist at Philips Research in Paris, where numerical modeling helps to understand human cardiovascular pathophysiology and treatment outcomes. His main interests are now oriented towards the use of meshless methods for cardiac mechanics (flow, solid and their interaction).

Day 5

Applications

Understanding decision-support therapy support

Understanding fetal cardiovascular changes and the role of modelling (9:30-11:00)

Bart Bijnens (ICREA & DTIC, Universitat Pompeu Fabra)

Altered working conditions (such as pressure or volume loading) induce remodelling of the heart and circulation in order to maintain adequate perfusion of the organs. While these structural changes, when induced in adult life, lead to acquired heart disease, they are often reversible with adequate therapy. However, when working conditions change during the (in-utero) development of the fetal heart, these changes might be permanent and predispose the newborn to increased risks of developing cardiovascular diseases in adult life. Therefore, understanding how altered conditions in fetal life influence the development of the cardiovascular system are crucial for assessing risk and suggesting preventive therapies.

For this, animal models provide ways for comprehensive studies of fetal cardiac remodelling while in clinical practice, non-invasive imaging (such as echocardiography) is the only option. To enrich clinical data as well as to separate determining factors, computational models offer novel possibilities. 

In this lecture, we will present several changes in the cardiovascular system during fetal life that induce permanent structural and functional remodelling. Using (simplified) modelling of the determining factors can provide insight in the underlying mechanisms as well as approaches towards the assessment of personalised information that is difficult to obtain in clinical practice.

Bio: ICREA Research Professor at UPF (Universitat Pompeu Fabra). Technology MSc in Electronic Engineering and PhD in Medical Sciences (1997, Catholic University of Leuven, Belgium). Since 1998 he is an Associate Professor of Cardiovascular Imaging and Cardiac Dynamics at the Faculty of Medicine in Leuven. Since 2007, he is also a Visiting Professor at the University of Zagreb, Croatia, where he resided during 1 year. He has also stayed at St George's Hospital in London (2005-2006), supervising clinical research. Since Sept 2008, he is an ICREA researcher at the Department of Information and Communication Technologies of the Universitat Pompeu Fabra.

Works on translational Cardiovascular Pathophysiology, focussing on assessing cardiac function and understanding and recognising the changes induced by disease and how treatment strategies can be used to modulate these. This is approached by integrating information handling and processing techniques, combined with basic knowledge on cardiovascular pathophysiology, in order to advance clinical sciences. This implies defining the research approach from the basic understanding of the disease towards the clinical study; selecting/designing the appropriate investigational tools to assess the relevant clinical parameters; quantifying the diagnostic information (from clinical information to imaging data) to extract the most pertinent information and interpreting the results and relate them to the pathophysiological knowledge.

Multiscale integrative modelling of asthmatic airway mechanobiology (11:30-12:30)

Bindi Brook (University of Nottingham)

Asthma is characterised by inflammation, airway hyper-responsiveness (rapid and excessive airway smooth muscle (ASM) contraction to low doses of contractile agent) and airway remodelling (involving long-term structural changes to the epithelium, collagenous basement membrane and ASM bundles). The mechanisms underlying these characteristics and how they interact is not well-understood. In this talk I will describe the multiscale models that we have developed, that capture ASM force generation cell-matrix adhesion in a dynamic environment at the cellular scale and its effect on tissue-level processes such as broncho-constriction/dilation of whole airways. Additionally I will illustrate how we are coupling these models to morphoelastic models of inflammation-driven airway remodelling, informed by experimental data, to understand the influence of remodelling on hyper-responsiveness and vice versa. These models have been developed in close collaboration with experimental biologists and respiratory clinicians with the ultimate aim of developing novel therapies driven by improved understanding of the underlying mechanobiology.

Bio: Bindi Brook’s MRC- and EU-funded research is focussed on developing multiscale mathematical and computational models of airway hyper-responsiveness and remodelling that is characteristic of asthma. Her group develops models in close collaboration with experimental biologists and clinicians, that integrate experimental data, that in turn generate new hypotheses and inform design of novel experiments. She uses a variety of approaches including discrete-stochastic models at the sub-cellular scale through to deterministic-continuum nonlinear (morpho)elastic models at the tissue scale. The aim of her work is to address specific fundamental questions associated with asthma patho-physiology as well as investigate potential interventional therapies.

Chicken wings, cactus, windsocks and cauliflowers in cardiology (12:30-13:30)

Óscar Cámara (DTIC, Universitat Pompeu Fabra)

The influence of the left atrial appendage (LAA) and its different possible morphologies in atrial haemodynamics and thrombus formation is not fully known yet. In this talk I will present our most recent work analysing blood flow characteristics in relation with LA/LAA morphologies to better understand conditions that may lead to thrombus formation. We constructed several patient-specific computational meshes of left atrial geometries from medical imaging data. Subsequently, Computational Fluid Dynamics (CFD) methods were run with boundary conditions based on pressure and velocity measurements from literature. Relevant indices characterizing the resulting simulated flows such as local maps of vorticity were related to simple LAA shape parameters. Our in silico study estimates different 3D haemodynamics patterns dependent on the patients-pecific atrial geometry. It also suggests that areas near the LAA ostium and with presence of lobes are more prone to coagulation due to the presence of low velocities and vortices.

Bio: Dr. Oscar Camara is an Associate Professor at the Information and Communication Technologies Department (DTIC) at Universitat Pompeu Fabra (UPF). He obtained his Degree in Telecommunications Engineering from ETSETB in the Universitat Politècnica de Catalunya (UPC), in Barcelona, in 1999. He completed his Master and PhD in Image Processing in the École Nationale Supérieure des Télécommunications in Paris, under the supervision of Prof. Isabelle Bloch, in 2000 and 2003, respectively. In 2004, he joined the group of Prof. David Hawkes and Prof. Derek Hill in London as postdoctoral researcher, first at the King´s College London and last at the University College London until 2007. From July 2007 to September 2011, he was a member of the CISTIB group lead by Dr. Alejandro Frangi at the DTIC of the UPF as Ramón y Cajal postdoctoral researcher. From October 2011, he is coordinating Physense, a research group at the DTIC. He is also coordinating, together with Dr. Javier Macía, the undergraduate degree of Biomedical Engineering at the UPF.

My research has mainly been focused on developing new signal and image processing and computational science methods for medical applications. Within classical signal and image processing fields, I have methodological contributions on multimodal image object recognition and fusion and motion analysis with knowledge-based constraints. Another field in which I have been strongly involved is computational modelling of different organs of the human body within the "Virtual Physiological Human" framework. Methodologies for improving computational imaging and computational models through its validation with controlled ground-truth data or through its personalization with patient-specific data will be presented. These methodological developments were applied in different clinical applications in the fields of oncology, neurology and cardiology.

Presentation of awards (16:30 - 17:00)

Best Poster Award by Simula

Best Hands-on Award by Chair UPF-QUAES