Research Group: Contrast Agents in Radiology (Radbruch)

Research Focus:

The research group “Contrast Agents in Radiology” investigates existing and potential contrast agents with a focus on oncologic applications. The group has a strong translational approach and collaborates with chemists, physicists, computational scientists and radiologists from many institutions in Europe (e.g. University of Münster, Rome, Paris, Barcelona, Zurich) and worldwide (e.g. Brigham Womens Hospital, Harvard, Medical University of South Carolina, Charleston). Aim of the group is on the one side to investigate new contrast agents and contrast agent mechanisms that potentially can improve diagnosis and treatment of oncologic patients. On the other side the group takes actively part in the safety assessment of existing contrast agents. The group has been at the forefront of the debate on gadolinium deposits in the brain following serial injections of gadolinium based contrast agents (GBCAs). The studies published by the group were the first showing that linear GBCAs release significantly more gadolinium in the brain than macrocyclic GBCAs.[1-7] As a consequence of the recent discussion, the European Medicines Agency decided in 2017 that all linear GBCAs will be withdrawn from the market (besides for the special indications of liver imaging).

Gadolinium Based Contrast Agents Safety Research

Gadolinium based contrast agents (GBCAs) are an indispensable part of daily clinical decision making and approximately 400 million dosages of GBCAs have been applied worldwide. GBCAs have an excellent safety profile with serious adverse reactions occurring in roughly 0.03% of all administrations.  However, the safety of GBCAs has become in the center of attention recently, since a japanese group [8] showed in 2014 that GBCAs can be stored in the brain, causing hyperintensities in deep brain nuclei, particularly the dentate nucleus. No clinical symptoms of these depositions are known, yet, however, common sense dictates to minimize the amount of gadolinium stored in our patients.

Measurement of Brain-Hyperintensities using quantitative MRI and automated lesion detection (Katherina Deike/Robert Haase/Alexander Radbruch)

© dkfz.de

Multiple retrospective patient studies and animal studies assessed the potential of the marketed GBCAs to cause hyperintensities or gadolinium deposits in the brain, respectively. The majority of studies provides evidence that linear GBCAs cause a SI increase (and hence gadolinium deposition) in the dentate nucleus and different deep brain nuclei, while macrocyclic do not. However, there are conflicting results for macrocyclic GBCAs. The discrepancy between these results might be explained with flawed methodology. Specifically, the results of the retrospective patient studies can be influenced by 1) MR imaging parameters and 2) the placement of the region of interest by the radiologist. The current study aimes to overcome these limitations by 1) performing quantitative MRI that is independent of MR-parameters and 2) application of an automatic evaluation software that is reader-independent in an optimized dataset of patients with serial injections of GBCAs.

Measurement of Gadolinium in different animal organs (Collaboration: University Münster, Prof. Karst (Chemistry), Prof. Paulus, PD Dr. Jeibmann (Neuropathology); Diagnostic Imaging Research Unit, University of Zurich, Dr. med. vet. Henning Richter (veterinarian)

Initial animal experiments provide evidence that gadolinium is not only stored in the brain but in a variety of organs. The collaboration of the Universities of Zurich, Münster and the DKFZ aims to investigate the extend and potential effects of GBCAs on a variety of organs in animal experiments.

New Contrast Agents: Glucose CEST MRI [9]

In Collaboration with the Research Group Chemical Exchange Saturated Transfer Imaging, new contrast mechanisms using glucose injections are investigated. For further details see 7 Tesla Imaging: Novel Biomarkers.

Literature:

1.            Radbruch, A., et al., Chelated or dechelated gadolinium deposition. Lancet Neurol, 2017. 16(12): p. 955.

2.            Radbruch, A., et al., Pediatric Brain: No Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-weighted MR Images after Consecutive Exposure to a Macrocyclic Gadolinium-based Contrast Agent. Radiology, 2017. 283(3): p. 828-836.

3.            Radbruch, A., et al., No Signal Intensity Increase in the Dentate Nucleus on Unenhanced T1-weighted MR Images after More than 20 Serial Injections of Macrocyclic Gadolinium-based Contrast Agents. Radiology, 2017. 282(3): p. 699-707.

4.            Radbruch, A., et al., Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology, 2015. 275(3): p. 783-91.

5.            Radbruch, A., et al., High-Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol. Invest Radiol, 2015. 50(12): p. 805-10.

6.            Weberling, L.D., et al., Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After Gadobenate Dimeglumine Administration. Invest Radiol, 2015. 50(11): p. 743-8.

7.            Radbruch, A., et al., Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents. Invest Radiol, 2016. 51(11): p. 683-690.

8.            Kanda, T., et al., High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology, 2014. 270(3): p. 834-41.

9.            Paech, D., et al., T1rho-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain. Radiology, 2017. 285(3): p. 914-922.

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