SFB 1340: In vivo Visualization of Extracellular Matrix Pathology „Matrix in Vision“

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All biological tissues react to inflammation, injury, or tumor invasion by an adaptive response of the local extracellular matrix (ECM) with a loss of equilibrium. This process is known as ECM remodeling and involves changes in the biochemical composition, architecture, and physicomechanical properties. Quantitative and qualitative modification of matrix proteins, proteoglycans, and glycosaminoglycans (GAGs) begins in the early phase of disease development and continues with disease progression. Because of the fundamental quantitative and qualitative changes the ECM components undergo in diseased tissue, the ECM has attracted our interest as an vivo imaging target for the detection, characterization, and monitoring of disease. During the first funding period CRC „Matrix in Vision“ confirmed this using models of atherosclerosis, aortic aneurysm, uremic cardiomyopathy, multiple sclerosis, inflammatory conditions of the bowel and liver, and peritumoral inflammation using methods of molecular and biophysical ex vivo and in vivo MR imaging. During the second funding period, the aims are to investigate how the methods of in vivo imaging established so far are suitable to detect treatment responses in established disease models and what information imaging can provide on ECM composition and its changes during treatment. To this end, the CRC will further advance physical and biochemical analytical techniques including element microscopy. A central aim is to analyze interactions between molecular imaging probes (gadolinium (Gd)-based nonspecific and specific contrast agents, iron oxide nanoparticles) and ECM components. The focus here is on GAGs, which are an important target because they can form complexes with positively charged imaging probes or their positively charged components. The expected insights into mechanisms underlying the enhancement of inflammatory tissue in MR imaging using clinically approved Gd-based imaging probes will affect the interpretation of clinical contrast-enhanced MRI. Imaging studies will include multiscale quantification of mechanical structural elements of the ECM, ranging from microscopic protein and GAG networks to macroscopic mechanical parameters investigated by clinical diagnostic elastography. The results will also translate into immediate clinical applications.In this way, CRC 1340 for the first time combines biological molecular methods in radiology with new insights into the role of mechanical tissue parameters in the development of disease and the monitoring of treatment responses. Also for the first time, CRC 1340 will thus enable the investigation of relationships of ECM structure and signal generation in molecular and biophysical medical imaging towards the development of new imaging approaches allowing quantitative, disease-specific diagnosis in radiology.