Progress in the imaging of metabolic processes

A research team in Kiel has developed new contrast agents for magnetic resonance imaging in order to be able to make biochemical processes visible.

Magnetic resonance imaging (MRI) has enormous potential for diagnostics and research. It not only enables the illustration of coarse structures, but also biochemical processes too, in principle. However, conventional machines are not sensitive enough for this. MRI machines used in hospitals are perfect for providing images of anatomic structures in the brain, for example, determining a slipped disc or measuring a tumor. But they reach their limits when trying to illustrate metabolic processes that are of medical interest. “The concentration of many extremely interesting metabolic products is far too low to measure them,” explained Professor Jan-Bernd Hövener, who is interested in chemical analysis using MRI and is establishing this technique at the Cluster of Excellence "Precision Medicine in Chronic Inflammation” (PMI). His working group developed new methods to increase the sensitivity of MRI and enable biochemical analyses. They came one major step closer to achieving this goal in their current paper. The findings were published in the high profile Journal of the American Chemical Society.

Hyperpolarization increases the sensitivity in MRI

“The signal from a normal MRI is usually far too weak, unfortunately, to be able to measure the metabolism, the fundamental processes of life,” explained the professor of translational MRI at the Faculty of Medicine at Kiel University (CAU) and head of the Section Biomedical Imaging of the Department of Diagnostic Radiology at the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel and the Molecular Imaging North Competence Center (MOIN CC). The medical physicist uses what are known as hyperpolarization methods to amplify the signals. These are physical methods which cause the nuclear spins – a kind of compass needle – to increasingly align in one direction, making them more visible in MRI. Magnetic resonance can only be measured if the spins align and don’t cancel each other out. “The application of hyperpolarized contrast agents is a promising approach for the imaging of metabolic processes. Hereby, endogenous (the body’s own) substances like glucose are processed quantum mechanically before being applied, so that they ‘light up’ in MRI,” said Hövener. This could help us detect cancer cells which increasingly convert glucose at an early stage. The technique has only been used experimentally to date, plus it is slow and very expensive. The equipment needed, a so-called Dynamic Nuclear Polarizer (DNP), costs over €2 million.

New procedure combines the advantages of various technologies

“We have developed a new method that is much cheaper and works within a few seconds,” reported lead author Dr. Kolja Them, post-doctoral researcher in Hövener’s working group. “We have managed to combine two previously separate methods with each other and thereby achieved an increase in signal amplification of up to 50,000 times.” Parahydrogen-Induced Polarization via proton exchange (PHIP-X) enables a broad application spectrum because it amplifies the MR signals of many biomolecules. “We hope to be able to use this to produce new contrast agents for precision medicine more quickly and more cheaply than was possible up to now,” said Kolja Them. However, there is still lots to do before application. More research into the basic principles is required, the materials need to be made compatible and the signal amplification needs to be maintained for longer. The Cluster of Excellence PMI has advanced the development of PHIP-X with funding via Kolja Them. According to Hövener, “This funding is an excellent tool to support promising projects by our young colleagues. The funding gives us the opportunity to bring new technologies into application.”

Location for unique imaging and hyperpolarization research

Since his appointment at Kiel University in 2017, Hövener has gathered several pieces of equipment in order to build up a unique location for imaging and hyperpolarization research. In addition to machines for producing metabolic contrast agents and lung imaging, these also include various experimental set ups to investigate the quantum mechanics of hyperpolarization and the associated MRI machines. The highlights are the especially strong 7 Tesla and 9.4 Tesla MRI machines. In comparison: machines used in hospitals typically have magnets with a strength of 1.5 to 3 Tesla.

The MOIN CC is essential for Hövener’s research. “With this facility, the federal state of Schleswig-Holstein, the Faculty of Medicine and Kiel University have created an excellent infrastructure which permits us to attract talent from around the world. Innovation frequently originates from basic science, and Kiel has recognized this fact!”

Man in front of MRI
© MOIN CC, Kiel University

Dr. Kolja Them uses this powerful MRI machine to research the application of the new contrast agents.

Man in Lab coat and safety goggles
© pur.pur

Professor Jan-Bernd Hövener

Original publication:

Kolja Them, Frowin Ellermann, Andrey N. Pravdivtsev, Oleg G. Salnikov, Ivan V. Skovpin, Igor V. Koptyug, Rainer Herges, and Jan-Bernd Hövener. Parahydrogen-Induced Polarization Relayed via Proton Exchange. J. Am. Chem. Soc. 2021, 143, 34, 13694–13700.

Scientific Contact:

Dr. Kolja Them
Section Biomedical Imaging
Molecular Imaging North Competence Center (MOIN CC), CAU, UKSH
Department of Diagnostic Radiology, UKSH Kiel,
0431 880-5854

Prof. Dr. Jan-Bernd Hövener
Section Biomedical Imaging
Molecular Imaging North Competence Center (MOIN CC), CAU, UKSH
Department of Diagnostic Radiology, UKSH Kiel,
0431 880-5833
Twitter/Instagram: @theMOINCC

About the Cluster of Excellence PMI

The Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI) is being funded from 2019 to 2025 through the German Excellence Strategy (ExStra). It succeeds the "Inflammation at Interfaces” Cluster, which was already funded in two periods of the Excellence Initiative (2007-2018). Around 300 members from eight institutions at four locations are involved: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH), Muthesius University of Fine Arts and Design, Kiel Institute for the World Economy (IfW), Leibniz Institute for Science and Mathematics Education (IPN)), Lübeck (University of Lübeck, University Medical Center Schleswig-Holstein (UKSH)), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel - Leibniz Lung Center).

The goal is to translate interdisciplinary research findings on chronic inflammatory diseases of barrier organs to healthcare more intensively, as well as to fulfil previously unsatisfied needs of the patients. Three points are important in the context of successful treatment, and are therefore at the heart of PMI research: the early detection of chronic inflammatory diseases, the prediction of disease progression and complications, and the prediction of individual responses to treatment.

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