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Research Focus

The functional imaging group of the Department of Radiology at the German Cancer Research Center focuses on the microscopic structure and vascular architecture of cancer tissue. Special emphasis is put on the development from the regular arrangement of cells and vessels in healthy tissue to its irregular arrangement in cancerous tissue and the corresponding changes in the measured signal in magnetic resonance imaging.  The projects are funded by the German Research Foundation (ZI 1295/2-1: 480.500 Euro and KU 3555/1-1: 55.505 Euro), the German National Merit Foundation (Studienstiftung des Deutschen Volkes), the physician-scientist program of Heidelberg University, and the Hoffmann-Klose Foundation (Heidelberg University). The group has been honored with several awards, e.g. with the scientist award of German Society for Medical Physics (DGMP), the Gorter award of German Chapter of the International Society of Magnetic Resonance Imaging and the PTW poster award in 2016.

Statistical tumor model and tumor entropy

Ansprechpartner: Christian Ziener und Artur Hahn

The aim of this project is the development of a statistical tumor model to characterize tumor architecture in terms of a plasma-model and to relate the measured MR-signal to the heterogeneity of the considered microscopic structure, i.e. the arrangement of cells and vessels. The microscopic arrangement of the relevant structures can be related to the entropy of the underlying tumor tissue. We obtain tumor entropy maps of cancer tissue from the measured MR-signal.

In close cooperation with the Department of Neuroradiology of Heidelberg University, the vessel architecture in glioma tissue is extracted from high-field magnetic resonance imaging (9.4 Tesla) of small animals. It is possible to relate the aggressive growth of glioblastoma multiforme with the new concept of entropy imaging.  Therefore, we perform numerical computations that include effects of diffusion in cellular organized and disorganized tissues and analyze the properties of the measured MR-signal. Specifically, we analyze spin dephasing in the local magnetic field of highly organized and disorganized capillaries and cells and their influence on the MR-signal. The numerical and analytical methods are validated in phantom experiments in close cooperation with the group of Prof. Peter Jakob at the Department of Experimental Physics V of the University of Würzburg. The implementation of response criteria for therapy-monitoring, which incorporate not only morphological aspects or signal intensities, but also functional parameters such as tumor entropy, will be performed with the National Center of Tumor Disease (NCT).

 

Vessel architectural imaging

Ansprechpartner: Ke Zhang und Felix Kurz

The imaging methodology Vessel Architectural Imaging (VAI) was first proposed by Emblem et al. (Nat Med 2013) to evaluate the treatment response of antiangiogenic therapy of glioblastoma patients. In principle, VAI is based on the simultaneous measurement of gradient echo relaxation time and spin echo relaxation time during contrast agent bolus injection. VAI shows a characteristic dependence on the vessel size, density, and oxygenation level in an MR imaging voxel. Our group developed magnetic resonance VAI sequences at 3 Tesla and 9.4 Tesla to quantify microstructural parameters during antiangiogenic therapy and relate them to treatment response criteria.

Quantitative characterization of lung tissue by MRI

Ansprechpartner: Lukas Buschle und Christian Ziener

A newly established area of research inside the Department of Radiology is the functional imaging of lung tissue. In contrast to other lung imaging methodologies, we make use of the intrinsic contrast of susceptibilities between air-filled alveoli and the surrounding interstitial tissue. The free induction decay or its corresponding line-shape strongly depend on susceptibility and diffusion around the alveoli. We analyze in collaboration with the Translational Lung Research Center (TLRC, Heidelberg) and Paul Scherrer Institute (PSI, Villigen, Switzerland) synchrotron-based micro-CT data sets of pathological lung tissue. Based on these results, we develop advanced mathematical algorithms to extract microscopic properties of lung tissue (alveolar diameter, alveolar density). The possibility to measure in inspiration and expiration at either 1.5 Tesla or 3 Tesla enables us to quantify additional intra-voxel specific parameters like susceptibility and diffusion inside peripheral lung tissue. The methods are applied to quantify the alveolar size in patients with emphysema. Currently, we investigate alveolar changes in patients with radiotherapy-induced pulmonal fibrosis.

Selected Publications

L. R. Buschle, F. T. Kurz, T. Kampf, W. L. Wagner, J. Duerr, W. Stiller, P. Konietzke, F. Wünnemann, M. A. Mall, M. O. Wielpütz, H. P. Schlemmer, and C. H. Ziener. Dephasing and diffusion on the alveolar surface, Phys. Rev. E 95, 022415 (2017).

F. T. Kurz, L. R. Buschle, T. Kampf, K. Zhang, H.-P. Schlemmer, S. Heiland, M. Bendszus, C. H. Ziener. Spin dephasing in a magnetic dipole field around large capillaries: Approximative and exact results, J. Magn. Reson. 273, 83-97 (2016).

L. R. Buschle, F. T. Kurz, T. Kampf, S. M. F. Triphan, H.-P. Schlemmer, C. H. Ziener. Diffusion-mediated dephasing in the dipole field around a single spherical magnetic object, Magn. Reson. Imaging 33, 1126-1145 (2015).

F. T. Kurz, T. Kampf, L. R. Buschle, H.-P. Schlemmer, S. Heiland, M. Bendszus, C. H. Ziener. Microstructural analysis of peripheral lung tissue through CPMG inter-echo time R2 dispersion, PLOS ONE 10, e0141894 (2015).

C. H. Ziener, F. T. Kurz, T. Kampf. Free induction decay caused by a dipole field, Phys. Rev. E 91, 032707 (2015).

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