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CONQUER – Innovative Contrast Agents for a Clear View in Medicine

Radically new diagnostic procedures and therapeutic treatment methods – those are the key factors for ensuring that people will be able to live a healthy life in future too. Scientists in the Field of Expertise Human & Biotechnology at TU Graz are developing a smart contrast agent in cooperation with an international consortium. The intended application is medical imaging by means of magnetic resonance so as to visualise organs and tissue at the molecular level. Molecular imaging is playing an increasingly important role in diagnostics, understanding diseases, and developing effective treatment methods.

Looking inside the Body

In addition to laboratory tests, imaging procedures such as CT and MRI count among routine examinations. MRI offers a particularly wide range of contrast mechanisms that not only allow us to visualise the form, position and structure of body parts, organs and tissue, but also provide details of functioning. Yet these procedures have certain limits – particularly when it comes to visualising molecular and metabolic changes at a high resolution and with a high level of reliability, e.g. in cases of cancer, Alzheimer’s and heart diseases. Sensitivity – the percentage of patients in which the particular disease is actually detected by applying the test – plays a significant role in this context.

Under the research project “CONQUER – Contrast by Quadrupole Enhanced Relaxation”, scientists at TU Graz are developing completely new “smart” contrast agents. The aim is to enable greatly improved molecular imaging in magnetic resonance tomography. With the aid of the newly developed contrast agents, it would be possible to visualise molecular functions of tissues and organs that have so far remained invisible in MRI. This would allow us to identify diseases earlier and with greater reliability and to better understand their pathogenesis.

We see our idea as an opportunity to develop great new contrast agents with extremely desirable properties. One possible application, for example, could be selective activation and deactivation of contrasts in the tissue being examined, as well as sensitivity to the pH value and other biomarkers, explains Hermann Scharfetter from the Institute of Medical Engineering at TU Graz.

Making Even More Differentiated Images Possible

Magnetic resonance imaging works with a strong magnetic field and high-frequency electromagnetic fields. The latter excites the nuclear magnetic moments of hydrogen atoms, for a short time knocking them out of equilibrium. The weak signals thus created in the radiofrequency coils of the MRI scanner are converted into images that visualise the composition and structure of tissue.

Magnetic resonance imaging can produce high-resolution tomographic images of the inside of the body. This clinical imaging tool is still far from complete, however, both in terms of method and technology, the project manager notes. The aim is therefore to create even enriched images of the inside of the body. To this end, the scientists at TU Graz are making use of an effect found in quantum mechanics known as quadrupole relaxation.

Quadrupole Relaxation – When Atoms Report Back Differently

Contrast agents can increase the information value of the images created. The scientists’ basic assumption is that cross-relaxation (an interaction between different nuclei that causes them to return to their equilibrium states at a different speed compared to non-interacting nuclei) presents an extremely versatile contrast mechanism.

Hermann Scharfetter explains: If there are molecules with quadrupole nuclei in a certain tissue, this allows us to selectively modify the signal generated and thus image contrast. Unlike conventional contrast agents, the effect of quadrupole nuclei can be activated or deactivated by means of appropriate measurement, but also by means of chemical processes. 
The scientists are facing the challenge of designing the chemical compounds containing quadrupole nuclei so that their resonance frequency is close to the target frequency for clinical magnetic resonance imaging.

Source: Lunghammer – TU Graz

With the aid of a gutted microwave oven, a repurposed cat food tin, and what looks like electronic waste, the trio of scientists Stefan Spirk, Hermann Scharfetter and Andreas Petrovic (from left to right) spent months of great effort at TU Graz building the first prototype for a special nuclear quadrupole resonance spectrometer for measuring the weak atomic signal. 

Source: Hermann Scharfetter
Hermann Scharfetter, associate professor at the Institute of Medical Engineering

There is hardly anything more exciting for me than to retreat to the lab with my outstanding team in order to think up our next challenging experiment at our leisure.

Source: Lunghammer – TU Graz
Andreas Petrovic, project collaborator

The project requires excellent scientific expertise in quantum physics, chemistry, biomedical engineering and even toxicology, and is only possible in an interdisciplinary team such as we were able to establish in this case.

Source: Hermann Scharfetter – TU Graz

CONQUER-related TU Graz researchers Christian Gösweiner, Roland Fischer and Michaela Flock (from left) are discussing the spectrum of a recently synthetised quadrupole compound in the quadrupole-resonance laboratory of the Institute of Medical Engineering.

Source: Lunghammer – TU Graz
Stefan Spirk, project collaborator

One of the driving forces of this team is the sheer curiosity in breaking completely new ground in science.

Experiments with the MRI device, source: Lunghammer – TU Graz

The scientists and their international partners

  • design quantum-mechanical and quantum-chemical models.
  • graft quadrupolar core compounds onto nanoparticles.
  • characterise core compounds and nanoparticles in detail.
  • test the results on cell cultures in the 3-Tesla high-field MRI scanner at TU Graz

Further Information

Institute of Medical Engineering
Stremayrgasse 16/III
8010 Graz, Austria
www.tugraz.at/institute/imt

Hermann SCHARFETTER
Ao.Univ.-Prof. Dipl.-Ing. Dr.techn.
Coordinator FETopen project CONQUER
Phone: +43 316 873 35404
hermann.scharfetternoSpam@tugraz.at

Source: Lunghammer – TU Graz

Success through collaboration

To reach the research goals, the CONQUER scientists in the Field of Expertise Human & Biotechnology at TU Graz cooperate with numerous national and international research facilities.

International Cooperation

  • Heinz Amenitsch, Austrian Synchrotron Beamline of Elettra in Trieste, Italy
  • Danuta Kruk, University of Warmia and Mazury, Poland
  • Karin Stana-Kleinschek, University of Maribor
  • Per Olof Westlund, University of Umea, Sweden 

 

 

National Cooperation

  • Institute of Inorganic Chemistry, TU Graz
  • Institute for Chemistry and Technology of Materials, TU Graz
  • Institute of Medical Engineering, TU Graz
  • NAWI Graz
  • Center for Medical Research, Core Facility Microscopy, Medical University of Graz