Project

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Development of Highly Accelerated Magnetic Resonance Methods for Quantitative Analysis of Perfusion, Metabolism and Function in Cardiac Ischemia

English title Development of Highly Accelerated Magnetic Resonance Methods for Quantitative Analysis of Perfusion, Metabolism and Function in Cardiac Ischemia
Applicant Kozerke Sebastian
Number 132671
Funding scheme Interdisciplinary projects
Research institution Institut für Biomedizinische Technik Universität Zürich und ETHZ
Institution of higher education University of Zurich - ZH
Main discipline Biomedical Engineering
Start/End 01.02.2011 - 31.01.2014
Approved amount 667'626.00
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All Disciplines (4)

Discipline
Biomedical Engineering
Electrical Engineering
Cardiovascular Research
Clinical Cardiovascular Research

Keywords (15)

Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Dynamic Nuclear Polarization; Cardiovascular Magnetic Resonance; Sparse Sampling; Spatiotemporal Correlation; Transform Coding; Absolute Quantification; Ischemic Heart Disease; Reperfusion Injury; Coronary heart disease; Cardiac function; Perfusion; Metabolism; Hyperpolarized Magnetic Resonance

Lay Summary (English)

Lead
Lay summary
Despite significant progress in patient care coronary heart disease remains the leading cause of death worldwide. Considerable efforts have been directed towards timely detection and interventions in patients. As a result, management decisions are increasingly based on functional assessment reflecting the growing evidence that intervention convey no benefit or may even cause harm unless directed to viable and ischemic cardiac tissue. The role of diagnostic procedures including Cardiovascular Magnetic Resonance (CMR) imaging is therefore rapidly increasing.Today, the clinical value of CMR for the assessment of cardiac function and the detection of scarred tissue has been well established. Besides its place in a clinical environment CMR has also become invaluable in a pre-clinical setting and its potential for translational research within a "bench to bedside" strategy has started to unfold.Advances in magnetic resonance imaging methods have been and continue to be key drivers for the expanding role of CMR as a diagnostic tool. Moreover, the advent of dissolution Dynamic Nuclear Polarization methods has opened up a new window for observing metabolic processes in the in-vivo heart in real-time. In this context the perspective of obtaining detailed quantitative measures of perfusion, substrate metabolism and mechanical function of the entire heart with a single non-invasive imaging modality is highly appealing in both the pre-clinical and clinical realms.Current CMR methods for the assessment of perfusion, function and metabolism as available on standard clinical imaging systems lack sufficient scan efficiency and sensitivity and often provide only semi-quantitative information. The limited scan efficiency restricts both spatial and temporal resolution which is particularly critical when imaging transient signals as encountered in hyperpolarized metabolic imaging. Quantification methods have been proposed for conventional CMR perfusion and motion mapping methods, yet their analysis and adaptation to highly-accelerated imaging methods remains to be accomplished.Accordingly, the objectives of the present project are to develop and validate highly-accelerated and quantitative CMR imaging methods for assessing perfusion, metabolism and mechanical function of the ischemic heart. The work will serve a comprehensive description of the function of the in-vivo heart both in its healthy and its ischemic state and hence may constitute a novel and accurate diagnostic approach to monitor the heart's function in patients suffering from coronary heart disease.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Arterial, venous, and cerebrospinal fluid flow: simultaneous assessment with Bayesian multipoint velocity-encoded MR imaging.
Knobloch Verena, Binter Christian, Kurtcuoglu Vartan, Kozerke Sebastian (2014), Arterial, venous, and cerebrospinal fluid flow: simultaneous assessment with Bayesian multipoint velocity-encoded MR imaging., in Radiology, 270(2), 566-73.
Assessment of ischaemic burden in angiographic three-vessel coronary artery disease with high-resolution myocardial perfusion cardiovascular magnetic resonance imaging.
Motwani Manish, Maredia Neil, Fairbairn Timothy A, Kozerke Sebastian, Greenwood John P, Plein Sven (2014), Assessment of ischaemic burden in angiographic three-vessel coronary artery disease with high-resolution myocardial perfusion cardiovascular magnetic resonance imaging., in European heart journal cardiovascular Imaging, 0.
Multimodal functional evaluation of severe kinking of an ascending aortic prosthesis in a patient with embolic stroke.
Gotschy Alexander, Binter Christian, Niemann Markus, Alkadhi Hatem, Kana Veronika, Czerny Martin, Tanner Felix C, Kozerke Sebastian, Manka Robert (2014), Multimodal functional evaluation of severe kinking of an ascending aortic prosthesis in a patient with embolic stroke., in European heart journal, 0.
Quantitative three-dimensional cardiovascular magnetic resonance myocardial perfusion imaging in systole and diastole.
Motwani Manish, Kidambi Ananth, Sourbron Steven, Fairbairn Timothy A, Uddin Akhlaque, Kozerke Sebastian, Greenwood John P, Plein Sven (2014), Quantitative three-dimensional cardiovascular magnetic resonance myocardial perfusion imaging in systole and diastole., in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Ma, 16, 19-19.
Accelerating hyperpolarized metabolic imaging of the heart by exploiting spatiotemporal correlations.
Weiss Kilian, Sigfridsson Andreas, Wissmann Lukas, Busch Julia, Batel Michael, Krajewski Marcin, Ernst Matthias, Kozerke Sebastian (2013), Accelerating hyperpolarized metabolic imaging of the heart by exploiting spatiotemporal correlations., in NMR in biomedicine, 26(11), 1380-6.
Advanced cardiovascular magnetic resonance myocardial perfusion imaging: high-spatial resolution versus 3-dimensional whole-heart coverage.
Motwani Manish, Jogiya Roy, Kozerke Sebastian, Greenwood John P, Plein Sven (2013), Advanced cardiovascular magnetic resonance myocardial perfusion imaging: high-spatial resolution versus 3-dimensional whole-heart coverage., in Circulation. Cardiovascular imaging, 6(2), 339-48.
Cardiac proton spectroscopy using large coil arrays.
Weiss Kilian, Martini Nicola, Boesiger Peter, Kozerke Sebastian (2013), Cardiac proton spectroscopy using large coil arrays., in NMR in biomedicine, 26(3), 276-84.
Compensation of signal loss due to cardiac motion in point-resolved spectroscopy of the heart.
Weiss Kilian, Summermatter Severin, Stoeck Christian T, Kozerke Sebastian (2013), Compensation of signal loss due to cardiac motion in point-resolved spectroscopy of the heart., in Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine /, 0.
Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres.
Jogiya Roy, Makowski Markus, Phinikaridou Alkystsis, Patel Ashish S, Jansen Christian, Zarinabad Nelly, Chiribiri Amedeo, Botnar Rene, Nagel Eike, Kozerke Sebastian, Plein Sven (2013), Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres., in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Ma, 15(1), 62-62.
Iterative k-t principal component analysis with nonrigid motion correction for dynamic three-dimensional cardiac perfusion imaging.
Schmidt Johannes F M, Wissmann Lukas, Manka Robert, Kozerke Sebastian (2013), Iterative k-t principal component analysis with nonrigid motion correction for dynamic three-dimensional cardiac perfusion imaging., in Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine /, 0.
Pre- and post-operative assessment of valvular and aortic flow using 4D flow magnetic resonance imaging.
Manka Robert, Busch Julia, Crelier Gerard, Lüscher Thomas F, Kozerke Sebastian (2013), Pre- and post-operative assessment of valvular and aortic flow using 4D flow magnetic resonance imaging., in European heart journal, 1.
Reconstruction of divergence-free velocity fields from cine 3D phase-contrast flow measurements.
Busch Julia, Giese Daniel, Wissmann Lukas, Kozerke Sebastian (2013), Reconstruction of divergence-free velocity fields from cine 3D phase-contrast flow measurements., in Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine /, 69(1), 200-10.
A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.
Manka Robert, Kozerke Sebastian, Rutz Andrea K, Stoeck Christian T, Boesiger Peter, Schwitter Juerg (2012), A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy., in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Ma, 14, 47-47.
A multi-sample 94GHz dissolution dynamic-nuclear-polarization system.
Batel Michael, Krajewski Marcin, Weiss Kilian, With Oliver, Däpp Alexander, Hunkeler Andreas, Gimersky Martin, Pruessmann Klaas P, Boesiger Peter, Meier Beat H, Kozerke Sebastian, Ernst Matthias (2012), A multi-sample 94GHz dissolution dynamic-nuclear-polarization system., in Journal of magnetic resonance (San Diego, Calif. : 1997), 214(1), 166-174.
Developing Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart
Weiss K, Mariotti E, Hill DK, Orton MR, Dunn JT, Medina RA, Southworth R, Kozerke S, Eykyn TR (2012), Developing Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart, in Applied Magnetic Resonance, 43(1-2), 275-288.
Dissolution dynamic nuclear polarization efficiency enhanced by Hartmann-Hahn cross polarization
Batel M, Krajewski M, Däpp A, Hunkeler A, Meier BH, Kozerke S, Ernst M (2012), Dissolution dynamic nuclear polarization efficiency enhanced by Hartmann-Hahn cross polarization, in Chemical Physics Letters, 554, 72-76.
High-resolution versus standard-resolution cardiovascular MR myocardial perfusion imaging for the detection of coronary artery disease.
Motwani Manish, Maredia Neil, Fairbairn Timothy A, Kozerke Sebastian, Radjenovic Aleksandra, Greenwood John P, Plein Sven (2012), High-resolution versus standard-resolution cardiovascular MR myocardial perfusion imaging for the detection of coronary artery disease., in Circulation. Cardiovascular imaging, 5(3), 306-13.
Metabolic MR imaging of regional triglyceride and creatine content in the human heart.
Weiss Kilian, Martini Nicola, Boesiger Peter, Kozerke Sebastian (2012), Metabolic MR imaging of regional triglyceride and creatine content in the human heart., in Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine /, 68(6), 1696-704.
MRI temporal acceleration techniques.
Tsao Jeffrey, Kozerke Sebastian (2012), MRI temporal acceleration techniques., in Journal of magnetic resonance imaging : JMRI, 36(3), 543-60.
Sparsity transform k-t principal component analysis for accelerating cine three-dimensional flow measurements.
Knobloch Verena, Boesiger Peter, Kozerke Sebastian (2012), Sparsity transform k-t principal component analysis for accelerating cine three-dimensional flow measurements., in Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine /, 1.
Undersampled Cine 3D tagging for rapid assessment of cardiac motion.
Stoeck Christian T, Manka Robert, Boesiger Peter, Kozerke Sebastian (2012), Undersampled Cine 3D tagging for rapid assessment of cardiac motion., in Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Ma, 14, 60-60.
Validation of dynamic 3-dimensional whole heart magnetic resonance myocardial perfusion imaging against fractional flow reserve for the detection of significant coronary artery disease.
Jogiya Roy, Kozerke Sebastian, Morton Geraint, De Silva Kalpa, Redwood Simon, Perera Divaka, Nagel Eike, Plein Sven (2012), Validation of dynamic 3-dimensional whole heart magnetic resonance myocardial perfusion imaging against fractional flow reserve for the detection of significant coronary artery disease., in Journal of the American College of Cardiology, 60(8), 756-65.
Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location.
Manka Robert, Paetsch Ingo, Kozerke Sebastian, Moccetti Marco, Hoffmann Rainer, Schroeder Joerg, Reith Sebastian, Schnackenburg Bernhard, Gaemperli Oliver, Wissmann Lukas, Wyss Christophe A, Kaufmann Philipp A, Corti Roberto, Boesiger Peter, Marx Nikolaus, Lüscher Thomas F, Jahnke Cosima (2012), Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location., in European heart journal, 33(16), 2016-24.
Hybrid cardiac magnetic resonance/computed tomographic imaging: first fusion of three-dimensional magnetic resonance perfusion and low-dose coronary computed tomographic angiography.
Manka Robert, Kuhn Felix P, Kuest Silke M, Gaemperli Oliver, Kozerke Sebastian, Kaufmann Philipp A (2011), Hybrid cardiac magnetic resonance/computed tomographic imaging: first fusion of three-dimensional magnetic resonance perfusion and low-dose coronary computed tomographic angiography., in European Heart Journal, 32(21), 2625-2625.

Collaboration

Group / person Country
Types of collaboration
King's College London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
University of Leeds Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
RWTH Aachen Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
German Heart Institute Berlin Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Society for Cardiovascular Magnetic Resonance Talk given at a conference Accelerated CMR – Changing the Imaging Paradigm 10.07.2014 Hong Kong, China Kozerke Sebastian;
TMII Symposium Talk given at a conference Beyond Nyquist – Accelerated Cardiovascular Imaging 29.05.2014 New York, United States of America Kozerke Sebastian;
International Society for Magnetic Resonance in Medicine Talk given at a conference Myocardial Perfusion Imaging 10.05.2014 Mailand, Italy Kozerke Sebastian;
Society for Cardiovascular Magnetic Resonance Talk given at a conference Breaking the Speed Limit 16.01.2014 New Orleans, United States of America Kozerke Sebastian;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Hyperempfindliche Kernspintomografie - Scharfe Bilder dank stark polarisierten Atomkernen NZZ International 2014
Media relations: print media, online media Blitzschnelle Herzbilder UZH Magazin German-speaking Switzerland 2013
New media (web, blogs, podcasts, news feeds etc.) Bilder des Stoffwechsels in Echtzeit UZH News German-speaking Switzerland 2012
Media relations: print media, online media Revolution in der Roehre ETH Globe German-speaking Switzerland 2012

Awards

Title Year
Outstanding Teacher Award International Society of Magnetic Resonance in Medicine 2013
Summa cum Laude Awards International Society of Magnetic Resonance in Medicine 2013

Associated projects

Number Title Start Funding scheme
145007 Hyperpolarized Magnetic Resonance Metabolic Imaging - From Bench to Bedside 01.08.2013 R'EQUIP
197702 Learning Physics-Based Optimal Design of Cardiovascular MRI 01.09.2021 Project funding
153014 Translational Microstructural and Metabolic Magnetic Resonance Imaging for Cardiac Regeneration Therapy 01.05.2014 Project funding

Abstract

Despite significant progress in patient care coronary heart disease (CHD) remains the leading cause of death worldwide. Considerable efforts have been directed towards timely detection and interventions in patients with CHD. Management decisions are increasingly based on functional assessment reflecting the growing evidence that intervention in CHD convey no benefit or may even cause harm unless directed to viable and ischemic myocardium. The role of diagnostic procedures including Cardiovascular Magnetic Resonance (CMR) imaging is therefore rapidly increasing. Today, the clinical value of CMR for the assessment of global ventricular function and the detection of myocardial scar has been well established. Besides its place in a clinical environment CMR has also become invaluable in a pre-clinical setting and its potential for translational research within a “bench to bedside” strategy has started to unfold.Advances in magnetic resonance imaging methods have been and continue to be key drivers for the expanding role of CMR as a diagnostic tool. Seminal work in parallel imaging and prior knowledge-driven methods has successfully relaxed the hitherto tight interrelation between spatiotemporal resolution and scan time. Moreover, the advent of dissolution Dynamic Nuclear Polarization (DNP) methods has opened up a new window for observing metabolic processes in the in-vivo heart in real-time. In this context the perspective of obtaining detailed quantitative measures of perfusion, substrate metabolism and contractile function of the entire heart with a single non-invasive imaging modality is highly appealing in both the pre-clinical and clinical realms.Perfusion, metabolism and contractile function are tightly coupled and well regulated within bounds. In ischemia, continuous supply of oxygen is reduced or disrupted and the fine balance of metabolic substrates utilization is disturbed. In the event of persistent ischemia, reperfusion intervention can restore myocardial blood supply and hence potentially recovers contractile function. It has, however, been recognized that reperfusion intervention can cause damage to functioning myocardium and the controversy about the underlying mechanisms of reperfusion injury and its treatment is still ongoing. To this end, an integrated non-invasive approach to quantifying perfusion, metabolism and contractile function can help addressing this debate. Current CMR methods for the assessment of perfusion, function and metabolism as available on standard imaging systems lack sufficient scan efficiency and sensitivity and often provide only semi-quantitative information. The limited scan efficiency restricts spatial-temporal resolution which is particularly critical when imaging transient signals in bolus perfusion and hyperpolarized metabolic imaging. Quantification methods have been proposed for conventional CMR perfusion and motion mapping methods, yet their analysis and adaptation to highly-accelerated methods remains to be accomplished.The objectives of the present project are to develop and validate highly-accelerated and quantitative CMR imaging methods for assessing perfusion, metabolism and contractile function of the ischemic heart. In addressing the limited scan efficiency, prior knowledge driven methods will be developed to provide highly-accelerated imaging of perfusion and function of the beating heart. Owing to the significant increase in scan efficiency we will also be able to translate this technology to the small animal heart which will permit bolus perfusion and functional imaging at high heart rates and during ischemia-reperfusion interventions. Starting from the accelerated imaging technology developed for perfusion imaging, two- and three-dimensional methods for spatially resolved metabolic imaging of hyperpolarized compounds will be implemented. This project is based on our recently developed multi-sample DNP system for carbon polarization. This system is designed to provide up to six bolus injections for repeated assessment of metabolic information during interventions in the animal heart. To validate and assess clinical utility of the methods we aim to apply the perfusion and contractile imaging methods to patients with CHD together with national and international partners.The overall program consists of four work packages exploiting the power of accelerated imaging methods for assessing perfusion, metabolism and function of the ischemic heart:• Development of highly accelerated CMR imaging methods for perfusion, metabolic and tissue tagged imaging including- extension of the k-t imaging framework to constrain temporal signal evolution and spatial confinement- evaluation of reconstruction error and noise properties • Analysis and adaptation of quantitative processing algorithms comprising- definition of suitable deconvolution strategies for quantitative perfusion and metabolic imaging- introduction of joint modulus and phase processing for myocardial tagging data• Study of perfusion, metabolism and function of ischemia-reperfusion in animal model including- implementation of accelerated quantitative perfusion, metabolic and contractile imaging on animal imager- feasibility study of quantitative perfusion, metabolism and motion in occlusion/reperfusion scenarios • Application of accelerated three-dimensional perfusion and motion quantification in patients involving- perfusion and functional imaging in patients with chronic CHD undergoing revascularization procedures- clinical studies of ischemia-reperfusion injury in patients with acute myocardial infarctionThe methodological work proposed herein aims to develop a single non-invasive tool to study the correlation of perfusion, metabolism and contraction in a quantitative manner with high spatial and temporal resolution. The project addresses two main drawbacks of current CMR methods in preclinical and clinical research - scan efficiency and sensitivity. Scan efficiency plays a pivotal role in cardiac applications since a moving target is imaged. Moreover, contrast enhanced perfusion imaging as well as hyperpolarization methods provide a transient signal demanding very efficient data sampling. Hyperpolarization methods offer a new approach to boost sensitivity for metabolic imaging. Even though this method is currently only applicable in a preclinical setting, its translation into humans is anticipated in the near future. In its entirety a non-invasive single-modality imaging approach for quantitative assessment of perfusion, metabolism and function offers intriguing possibilities to study the correlation of energy supply, conversion and work of the heart under normal and ischemic conditions.
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