The project area for basic research includes three subject domains:
- Imaging Methods
- Analytical Methods
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Project A01 (Braun/Sack)
Multiscale Elastography for Characterization of Pathologic Extracellular Matrix Changes
Magnetic resonance elastography (MRE) can quantify mechanical properties of soft tissues for clinical diagnosis. A01 aims at developing multiscale MRE for measuring the shear modulus of biological samples ranging from submillimeter volumes, to mouse models, to the full-organ clinical scale for the detection of changes in the biophysical properties of the extracellular matrix (ECM). Applying multiscale MRE and viscoelastic model identification to generic phantoms, composed of ECM components as well as to biological tissue samples will allow us to identify relationships between biophysical imaging markers and disease-related microscopic ECM changes and to thus establish this method for diagnostic purposes.
Project A02 (Wiekhorst/Trahms/Taupitz)
Magnetic Particle Imaging of the Extracellular Matrix
Magnetic Particle Imaging (MPI) is a novel quantitative imaging technique for the specific visualization of magnetic nanoparticles (MNPs). Our preliminary experimental investigations indicate that MNPs have the potential to be used as specific imaging probes for glycosaminoglycans (GAGs) of the extracellular matrix. This experimental project tests the hypothesis that MPI can be used to indirectly monitor and quantify biomolecular processes in a deregulated extracellular matrix, with high spatial and temporal resolution, based on the detection of the dynamic magnetic behavior of MNPs. Quantitative physical and biochemical analytical methods will be used as references.
Project A03 (Teutloff/Bittl)
Electron Paramagnetic Resonance to Investigate Gadolinium-Glycosaminoglycan Complexes
Preliminary work within the Clinical Study Center KFO 213 showed a transfer of gadolinium ions from gadolinium-based MRI contrast agents to heavily sulfated glycosaminoglycans, which occur at higher levels in inflamed tissue. The possible effect of this transchelation process on contrast enhancement in glycosaminoglycan-containing tissue needs to be adressed due to its potential as a tissue-type-specific marker, even though it occurs only to a small extent. In the proposed CRC, we will use electron paramagnetic resonance spectroscopy to identify and characterize gadolinium-binding motifs in glycosaminoglycans.
Project A04 (Kanngießer)
X-Ray Microscopy and Spectroscopy for Speciation of the Chemical Environment of Metal-Based Imaging Probes
In this project, we will use different X-ray-based analytical techniques for the localization and chemical speciation of intravenously injected metal-based imaging probes in tissues with a pathologically altered extracellular matrix (ECM). These techniques include laboratory soft X-ray microscopy, enabling nanoscale three-dimensional (3D) localization of the probes in relation to tissue components, correlative fluorescence microscopy, linking this structural information to functional data, and synchrotron-based scanning X-ray spectroscopy, enabling sub-micron spatially resolved chemical speciation of metal-based nanoprobes in tissue. To specifically establish an analytical workflow within the CRC, extensive instrument development is indispensable in order to ensure adequate analysis of the interactions of imaging probes with the ECM.
Project A05 (Pagel)
Unraveling the Structures of Glycosaminoglycans and their Binding Characteristics with Cationic Imaging Probes
Glycosaminoglycans (GAGs) are a diverse class of polysaccharides, which perform a broad range of functions. Depending on their molecular structure, GAGs bind to metal components of cationic imaging probes with different affinity, which makes them attractive candidates as targets for the in vivo imaging of diseases. In this project, techniques based on ion mobility-mass spectrometry and gas-phase spectroscopy will be developed to characterize the structure and cation-binding affinity of GAGs. The obtained results will help us to improve our understanding of the role of GAGs in diseases.
Project A06 (Seeberger/Tauber)
Synthesis of Defined Glycosaminoglycans and Development of Glycosaminoglycan-Targeting Antibodies
Glycosaminoglycans (GAGs) bind cationic metal ions due to their complexing activity. The molecular basis of complex formation is largely unknown. A06 examines the relationship between the binding affinity of cationic imaging probes and the chemical structure of GAGs. GAG sequences of defined chemical structure identified in disease models will be synthesized and employed to study the binding of cationic imaging probes to GAGs using in vitro binding assays. Moreover, binding of these GAG sequences to the corresponding metal-based imaging probes in tissue sections will be examined in co-localization experiments using monoclonal antibodies (mAb) generated against synthesized GAG sequences. mAb conjugated with Gd-chelate will be used for in vivo imaging. The results will contribute to our understanding of the binding principles of cationic imaging probes to GAGs on the molecular level.