Project

Back to overview

Hyperpolarized Magnetic Resonance Metabolic Imaging - From Bench to Bedside

English title Hyperpolarized Magnetic Resonance Metabolic Imaging - From Bench to Bedside
Applicant Kozerke Sebastian
Number 145007
Funding scheme R'EQUIP
Research institution Institut für Biomedizinische Technik Universität Zürich und ETHZ
Institution of higher education University of Zurich - ZH
Main discipline Biomedical Engineering
Start/End 01.08.2013 - 31.12.2014
Approved amount 1'000'000.00
Show all

All Disciplines (4)

Discipline
Biomedical Engineering
Clinical Cardiovascular Research
Neurophysiology and Brain Research
Cardiovascular Research

Keywords (6)

Hyperpolarisation; Multi-modal Imaging; Magnetic Resonance Imaging; Metabolic Imaging; Diagnostic Imaging; Dynamic Nuclear Polarization

Lay Summary (German)

Lead
Ziel des vorliegenden Projektes ist die Installation und Anwendung des schweizweit ersten sterilen Hyperpolarisierers zur Erfassung von Stoffwechselvorgängen mittels Magnetresonanzbildgebung (MR) im lebenden Organismus. Potentielle Applikationen im Bereich der Diagnostik von kardiovaskulären Erkrankungen und in der Tumorbildgebung am Menschen werden untersucht.
Lay summary

Besides imaging anatomical details and tissue properties in-vivo, there is significant interest in quantifying metabolic activity to characterize organ function in humans. Information about cell metabolism is of key importance in assessing the state, progression and success of intervention in many diseases including disorders of the cardiovascular system and in cancer.

Among the diagnostic imaging modalities available today, Magnetic Resonance (MR) is the only non-invasive and radiation-free method for mapping metabolic activity in the living subject. The spatial and temporal resolution of the measurement is, however, hampered by a relatively low sensitivity of the underlying imaging principle. The limited sensitivity is of particular concern when imaging substances other than tissue water. For example, carbon containing substrates play key roles in cell metabolism and are central to producing energy in the life cell but are hardly accessible by MR imaging. The low sensitivity of MR is due to the fact that at only a small fraction of carbon nuclei are polarized at body temperature. At very low temperature near absolute zero, however, the degree of polarization can be significantly increased using so-called Dynamic Nuclear Polarization (DNP) techniques. It has been shown that this hyperpolarized state remains preserved upon rapid dissolution of the compound for injection.

With recent break-through advances in dissolution hyperpolarization technology, it has become possible to enhance the MR sensitivity of relevant metabolic molecules to be administered in live subjects by more than 30’000-fold. Pilot studies have already indicated great potential of using hyperpolarized MR methods to study real-time metabolism in cardiovascular and oncology applications. It is the aim of the present project to translate the technology to humans and explore applications in various diagnostic fields.

Direct link to Lay Summary Last update: 14.03.2013

Responsible applicant and co-applicants

Collaboration

Group / person Country
Types of collaboration
Dr. Thomas Eykyn - King's College London and Institute of Cancer Research, Sutton Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Roger Schibli - Pharmaceutical Sciences, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Markus Rudin - Animal Imaging Centre, University and ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Matthias Ernst - Physical Chemistry, ETH Zurich Switzerland (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
EU COST Talk given at a conference Accelerating Hyperpolarized MRI 27.06.2014 Zürich, Switzerland Kozerke Sebastian;
International Diagnostic Course Davos – Excellence in Teaching Talk given at a conference All you Need to Know about Hyperpolarized Magnetic Resonance 01.04.2014 Davos, Switzerland Kozerke Sebastian;
Pi-Net Talk given at a conference Beyond Nyquist – Accelerated Imaging of Hyperpolarized Spin Systems 02.10.2013 Bordeaux, France Kozerke Sebastian;


Associated projects

Number Title Start Funding scheme
132935 Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: insulin resistance, ageing, and physical activity 01.12.2010 Project funding (Div. I-III)
128625 A multimodal approach to cerebral blood flow and metabolism 01.04.2010 SNSF Professorships
126230 Muscle Precursor Cells for the treatment of Urinary Incontinence 01.10.2009 Ambizione
153014 Translational Microstructural and Metabolic Magnetic Resonance Imaging for Cardiac Regeneration Therapy 01.05.2014 Project funding (Div. I-III)
127604 Entwicklung einer neuen Hybrid-Bildgebungs-Methode zur nicht invasiven kardialen Diagnostik 01.11.2009 Project funding (Div. I-III)
132671 Development of Highly Accelerated Magnetic Resonance Methods for Quantitative Analysis of Perfusion, Metabolism and Function in Cardiac Ischemia 01.02.2011 Interdisciplinary projects

Abstract

Among the diagnostic imaging modalities available today, Magnetic Resonance (MR) is the only non-invasive and radiation-free method for mapping multiple metabolic pathways in the living subject. The spatial and temporal resolution of the measurement is, however, hampered by a relatively low sensitivity of the underlying imaging principle. Improving the sensitivity has therefore been a primary target of methodological and technological developments since the inception of MR as a diagnostic tool in the early 80s. Improved antennae designs, parallel signal reception and the availability of stronger magnets have led to significant gains in sensitivity. Despite the advantages in technology, MR remains a relatively insensitive technique when probing nuclei other than protons. Metabolically active molecules contain for example carbon. The carbon-13 isotope, which occurs at 1.1% natural abundance, is an MR-visible nucleus and lends itself for assessing metabolic substrate uptake and conversion in the live object, in particular as individual metabolites can be identified based on their specific MR resonance frequencies. Unfortunately, their low concentration and the limited MR sensitivity of carbon relative to protons prohibit sufficient spatial and temporal resolution in-vivo.The low sensitivity of MR is due to the fact that at room temperature only a small fraction of the nuclei are polarized. At very low temperature of about 1 Kelvin, however, the degree of polarization can be significantly increased using so-called Dynamic Nuclear Polarization (DNP) techniques. It has been shown that this hyperpolarized state remains preserved over a short period upon rapid dissolution of the compound and subsequent injection. With recent break-through advances in dissolution hyperpolarization technology, it has become possible to enhance the MR sensitivity of relevant metabolic molecules to be administered in live subjects by more than 30’000-fold. These achievements are about to transform an entire field. Pilot studies have indicated great potential of using hyperpolarized MR methods to study metabolism in cardiovascular and oncology applications non-invasively and in real-time. Preliminary data also indicate the feasibility and safety of the method in humans and promising applications in the cardiovascular field and oncology are within reach.Switzerland has taken a lead role in developing dynamic nuclear polarization equipment and imaging techniques. Considerable attention has been attracted with the recent presentation of the first multi-sample DNP system developed at the Institute for Biomedical Engineering at the University and ETH Zurich. In view of the promises of imaging metabolism in-vivo and in real-time as well as Switzerland’s leading role in the field, translation of the technology towards use in humans is indicated. This move requires DNP technology beyond experimental designs including sterile equipment and streamlined operation. Based on previous work and studies it is without doubt that hyperpolarized MR imaging has great potential in assessing alterations of metabolic function associated with a wide range of very relevant diseases in both animals and humans. It has been recognized that changes in metabolic substrate utilization present a cause rather than a consequence in many situations. As metabolic changes occur early during disease onset and progression, the approach caters to the early detection paradigm that has been formulated in view of identifying patients at risk and in guiding targeted treatment. Accordingly, significant potential exists to develop the method into a clinical, day-to-day diagnostic imaging tool.A key prerequisite for achieving this goal concerns further development of the DNP technology and its efficient and sterile implementation for use in animals and humans. The manufacturing tasks required clearly go beyond the capabilities of academic institutions. Accordingly, support is sought to purchase one of the first sterile, multi-sample DNP systems developed by General Electric and make it accessible to a user consortium of experts in metabolic imaging at the University and ETH Zurich, the University Hospital Zurich and the University of Berne. With the present proposal the consortium aims to install Switzerland’s first sterile, multi-sample DNP system and to develop a world-leading metabolic MR imaging program targeting• Cardiovascular research (ischemic heart disease, heart failure, diabetes)• Oncology research (prostate cancer, oxidative stress, drug response)• Hepatic and musculoskeletal research (fatty liver, aging, stem cell differentiation)The program proposed herein significantly extends the current research foci pursued in the field of non-invasive imaging. Based on the worldwide reputation the consortium has gained in fundamental and applied research of diagnostic imaging, the DNP device and the associated program will strengthen the leading role Switzerland plays in the field. Timely implementation will place the consortium at the forefront of exploring and translating Hyperpolarized Magnetic Resonance Imaging as a novel non-invasive diagnostic tool. The program bears considerable potential to aid early detection in patients at risk and therapy response by providing real-time access to metabolic “footprints” in-vivo.
-