Project

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Magnetic Resonance Imaging-Guided Computational Mechanics of Growth and Remodeling of the Failing Heart

English title Magnetic Resonance Imaging-Guided Computational Mechanics of Growth and Remodeling of the Failing Heart
Applicant Kozerke Sebastian
Number 166485
Funding scheme Interdisciplinary projects
Research institution Institut für Biomedizinische Technik Universität Zürich und ETHZ
Institution of higher education ETH Zurich - ETHZ
Main discipline Biomedical Engineering
Start/End 01.07.2016 - 30.06.2020
Approved amount 648'688.00
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All Disciplines (3)

Discipline
Biomedical Engineering
Clinical Cardiovascular Research
Mechanical Engineering

Keywords (5)

Heart Failure; Computational Modelling; Computational Mechanics; Magnetic Resonance Imaging; Cardiovascular Magnetic Resonance

Lay Summary (German)

Lead
Das vorliegende Projekt hat das Ziel, patientenspezifische Computermodelle des Herzens zu entwickeln, um die Remodellierung des Herzens hinzu einer Herzinsuffizienz ausgehend von nicht-invasiven Magnetresonanzbildgebungsdaten vorherzusagen. Zu diesem Zweck werden modernste Magnetresonanzverfahren, die neben anatomischen und funktionellen Parametern auch die Erfassung der Mikrofaserstruktur des Herzens erlauben, implementiert und validiert. Ausgehend von diesen Daten werden biomechanische Modelle entwickelt und an die in-vivo Daten angepasst. Anhand dieser Modelle werden in der Folge Vorhersagen zur Veränderung des Herzens berechnet und diese durch weitere Magnetresonanzmessungen optimiert. Die Ergebnisse und Werkzeuge, die im Rahmen dieser Forschungsarbeit entstehen, sollen zukünftig dazu beitragen, optimale Therapieverfahren für Patienten mit einer Herzinsuffizienz zu entwickeln.
Lay summary

While advances in diagnostics and therapy have improved survival after heart failure diagnosis, 50% of the patients die within five years upon diagnosis. In heart failure, the heart remodels and cardiac function deteriorates. Without timely treatment and intervention, fatal consequences develop.
Current non-invasive diagnostic tests provide an assessment of the overall function of the heart. However, they do not reveal insights into microstructural changes and fail to predict outcome. Critically, alterations at microstructural level are seen as early hallmarks of deteriorating cardiac function. Detailed insights potentially enable the prediction of the structural and mechanical state of the heart given diagnostic image information in a patient. To this end, a framework will be developed in the present project which ultimately permits improved risk stratification of an individual patient’s heart by the combination of advanced non-invasive Magnetic Resonance imaging and patient-specific and image-guided computational modelling of the heart. The project involves data collection in pig models of chronic cardiac infarction using advanced non-invasive Magnetic Resonance imaging methods. Thereby information of the anatomy, function and microstructure can be obtained and used to develop and build computational models of the heart. Using these models future state and function of the heart will be predicted. These prediction will subsequently validated by repeated Magnetic Resonance imaging. Once the predictive performance of the models is established, the methodology will be translated into a clinical setting to the benefits of patients suffering from heart failure.

Direct link to Lay Summary Last update: 30.06.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Analysis and correction of off‐resonance artifacts in echo‐planar cardiac diffusion tensor imaging
Gorkum Robbert J. H., Deuster Constantin, Guenthner Christian, Stoeck Christian T., Kozerke Sebastian (2020), Analysis and correction of off‐resonance artifacts in echo‐planar cardiac diffusion tensor imaging, in Magnetic Resonance in Medicine.
Motion and eddy current-induced signal dephasing in in vivo cardiac DTI
Stoeck Christian T., von Deuster Constantin, van Gorkum Robbert J. H., Kozerke Sebastian (2020), Motion and eddy current-induced signal dephasing in in vivo cardiac DTI, in Magn Reson Med, 84(1), 277-288.
Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging
Stoeck Christian T., Scott Andrew D., Ferreira Pedro F., Tunnicliffe Elizabeth M., Teh Irvin, Nielles-Vallespin Sonia, Moulin Kevin, Sosnovik David E., Viallon Magalie, Croisille Pierre, Kozerke Sebastian, Firmin David N., Ennis Daniel B., Schneider Jurgen E. (2020), Motion-Induced Signal Loss in In Vivo Cardiac Diffusion-Weighted Imaging, in J Magn Reson Imaging, 51(1), 319-320.
Validation of Finite Element Image Registration‐based Cardiac Strain Estimation from Magnetic Resonance Images
Berberoğlu Ezgi, Stoeck Christian, Moireau Philippe, Kozerke Sebastian, Genet Martin (2019), Validation of Finite Element Image Registration‐based Cardiac Strain Estimation from Magnetic Resonance Images, in PAMM, 19(1), 1-4.
3D Medical Image Synthesis by Factorised Representation and Deformable Model Learning
Joyce Thomas, Kozerke Sebastian (2019), 3D Medical Image Synthesis by Factorised Representation and Deformable Model Learning, in MICCAI, 110-119.
On probing intravoxel incoherent motion in the heart-spin-echo versus stimulated-echo DWI
Spinner Georg R., Stoeck Christian T., Mathez Linda, von Deuster Constantin, Federau Christian, Kozerke Sebastian (2019), On probing intravoxel incoherent motion in the heart-spin-echo versus stimulated-echo DWI, in Magn Reson Med, 82(3), 1150-1163.
Equilibrated warping: Finite element image registration with finite strain equilibrium gap regularization
Genet M., Stoeck C. T., von Deuster C., Lee L. C., Kozerke S. (2018), Equilibrated warping: Finite element image registration with finite strain equilibrium gap regularization, in Med Image Anal, 50, 1-22.
Bayesian intravoxel incoherent motion parameter mapping in the human heart
Spinner Georg R., von Deuster Constantin, Tezcan Kerem C., Stoeck Christian T., Kozerke Sebastian (2017), Bayesian intravoxel incoherent motion parameter mapping in the human heart, in J Cardiovasc Magn Reson, 19(1), 85-85.
Maximum likelihood estimation of cardiac fiber bundle orientation from arbitrarily spaced diffusion weighted images
Nagler Andreas, Bertoglio Cristóbal, Stoeck Christian T., Kozerke Sebastian, Wall Wolfgang A. (2017), Maximum likelihood estimation of cardiac fiber bundle orientation from arbitrarily spaced diffusion weighted images, in Med Image Anal, 39, 56-77.

Collaboration

Group / person Country
Types of collaboration
Prof. Julius Guccione / UCSF United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. Wolfgang Wall / TU Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Martin Genet / Ecole Polytechnique Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference 3D sub-millimeter personalized estimation of cardiomyocyte orientation using dimensionality reduction 08.08.2020 Virtual conference, France Buoso Stefano; Kozerke Sebastian;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference An MR image-guided left-ventricular shape model embedding local physiological coordinates and directions 08.08.2020 Virtual conference, France Buoso Stefano; Kozerke Sebastian;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference A Machine Learning Approach to Left Ventricle Mesh Prediction from Multi-Slice MR Images 08.08.2020 Virtual conference, France Buoso Stefano; Kozerke Sebastian;
DFG Nachwuchsakademie Talk given at a conference Imaging Across Spatiotemporal Scales - Probing flow, diffusion and metabolism in the heart 10.09.2019 Berlin, Germany Kozerke Sebastian;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference On Probing Intravoxel Incoherent Motion in the Heart using Spin Echo versus Stimulated Echo Diffusion Weighted Imaging 11.05.2019 Montreal, Canada Kozerke Sebastian; von Deuster Constantin Karl Viktor;
World Congress of Biomechanics Talk given at a conference Validation of cardiac strain estimation from 3D-tagged magnetic resonance images using finite element image correlation 08.07.2018 Dublin, Ireland Berberoglu Ezgi; Kozerke Sebastian;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference Assessment of Myocardial Fibre Architecture in Cardiac Amyloidosis Patients using In-Vivo Cardiac Diffusion Tensor Imaging 16.06.2018 Paris, France Kozerke Sebastian; van Gorkum Robbert; Manka Robert; von Deuster Constantin Karl Viktor;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference Analysis of cardiac motion induced error for in-vivo cardiac DTI in different heart phases - a comparison of second-order motion compensated SE versus STEAM 16.06.2018 Paris, France Kozerke Sebastian; von Deuster Constantin Karl Viktor; van Gorkum Robbert;
Meeting of the Swiss Society of Anatomy, Histology and Embryology Talk given at a conference From Spin to Picture to Computational Models - Biomedical Imaging of Failing Hearts 08.09.2017 Zurich, Switzerland Kozerke Sebastian;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference Intravoxel Incoherent Motion Model in the Heart of Patients under Adenosine Induced Stress 22.04.2017 Honolulu, United States of America Manka Robert; Kozerke Sebastian; von Deuster Constantin Karl Viktor;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Talk given at a conference Free-breathing Black-blood Prepared Cardiac Diffusion Tensor Imaging 22.04.2017 Honolulu, United States of America von Deuster Constantin Karl Viktor; Kozerke Sebastian; van Gorkum Robbert;
Annual Meeting of the International Socierty of Magnetic Resonance in Medicine Poster Impact of eddy-currents and cardiac motion in DTI of the in-vivo heart - a comparison of second-order motion compensated SE versus STEAM 22.04.2017 Honolulu, United States of America von Deuster Constantin Karl Viktor; Kozerke Sebastian; van Gorkum Robbert;
NIH NHLBI Seminar Individual talk From Spin to Picture to Computational Models – Biomedical Imaging of Failing Hearts 22.02.2017 Bethesda, United States of America Kozerke Sebastian;
Young Swiss Cardiac Surgeons Individual talk MRI Herzdiagnostik in Klinik und Forschung 27.01.2017 Lucerne, Switzerland Manka Robert; Kozerke Sebastian;
MRI Erasmus Course Cardiovascular MRI and CT Talk given at a conference CMR - new developments 06.10.2016 Zurich, Switzerland Kozerke Sebastian; Manka Robert;
Seminar Series Institute for Regenerative Medicine Individual talk From Spin to Picture to Computational Models – Biomedical Imaging of Failing Hearts 30.08.2016 Zurich, Switzerland Kozerke Sebastian;
M3DISIM Seminar Individual talk From Spin to Picture to Computational Models 13.07.2016 Paros, Switzerland Kozerke Sebastian;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
ETH Industry Day Talk 29.08.2017 Zurich, Switzerland Kozerke Sebastian;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Digital Health Day German-speaking Switzerland 2018

Associated projects

Number Title Start Funding scheme
197702 Learning Physics-Based Optimal Design of Cardiovascular MRI 01.09.2021 Project funding
174144 MR guided biomechanical modelling of the heart - a novel tool to predict remodelling in heart failure 01.02.2018 Ambizione
153014 Translational Microstructural and Metabolic Magnetic Resonance Imaging for Cardiac Regeneration Therapy 01.05.2014 Project funding

Abstract

In spite of significant advances in diagnosis and treatment, ischemic heart disease remains a leading cause of death worldwide. The loss of functional cardiac muscle tissue due to myocardial infarction causes ventricular remodeling including myofiber disarray, myocardial wall thinning and dilatation, compromising the overall pump function of the heart. Without timely treatment these conditions often lead to heart failure. At a global level 26 million patients suffer from heart failure with an incidence that is steadily increasing with age. While survival has improved over the last decades, 50% of heart failure patients still die within five years upon diagnosis.Critical aspects of the heart failure management are early diagnosis and long-term prognosis, which define the patients’ risk stratification and associated preventative therapy options. To improve early diagnosis, treatment efficiency and ultimately long-term prognosis, it is essential to better understand the cascade of events during disease onset and progression. Computational modeling, in combination with modern simulation tools and new imaging and experimental modalities, now offer the potential to provide greater insight into structural and functional changes of tissue growth and remodeling.The overall objective of the present proposal is to develop image-guided and experimentally validated computational models of cell aggregate-level structural and tissue-level mechanical changes in pathologic cardiac growth and remodeling. To this end, a growth and remodeling law is formulated and implemented, which will be calibrated and validated using longitudinal in-vivo Magnetic Resonance (MR) imaging data and ex-vivo experimental data of cardiac microstructure, tissue and functional parameters in pig models of chronic myocardial infarction and left ventricular volume overload. The proposed program is highly interdisciplinary as it combines in-vivo and ex-vivo imaging in a translational setting, mechanical modeling and numerical simulation. The key work packages of the project are defined as follows:WP1. In-vivo tissue- and organ-level MR and pressure data collection in pig models of chronic myocardial infarction and volume overload•MR cine, displacement and diffusion imaging to quantify cardiac kinematics and microstructure•Application of MR extracellular volume mapping to quantify tissue viability and extracellular volume•Adaptation of our data analysis and processing pipeline to derive kinematic and parametric maps•Longitudinal control study in healthy pigs without intervention to establish reference values •Longitudinal comprehensive MR and pressure measurements during chronic myocardial infarction•Longitudinal comprehensive MR and pressure measurements during chronic volume overloadWP2. Formulation, implementation and calibration of cardiac mechanical model relating cell aggregate, tissue and organ level properties of remodeling heart•Implementation of microstructure-based constitutive law for the myocardium•Formulation of microstructure-based growth evolution law within our existing framework•Formulation and implementation of remodeling law to describe structural change of myofibers•Building of animal-specific bi-ventricular models based on longitudinal in-vivo data •Calibration and validation of growth & remodeling law based on longitudinal in-vivo dataWP3. Validation of the proposed structure-properties relationship using high-resolution ex-vivo imaging and histology •Post-mortem high-resolution MR diffusion tensor imaging for detailed tissue analysis•Implementation and application of ex-vivo MR elastography to quantify mechanical tissue stiffness•Histological staining to quantify distribution of collagen and cardiac muscle•Correlation of model prediction with longitudinal in-vivo and experimental post-mortem data•Validation of proposed structure-properties relationship in health and diseaseThe project proposed herein addresses the lack of data and understanding of cardiac growth and remodeling upon infarction and ventricular volume overload. Using a novel computational modeling framework to combine data from comprehensive MR imaging, a bridge between the remodeling mechanisms taking place at the cell aggregate level over time and the tissue level, which can be probed non-invasively in-vivo, will be established. The concept is expected to pave the way towards quantitative diagnosis and prognostic tools to optimize and personalize treatment strategies in heart failure patients.
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