Project overview and content

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 through disease progression as well upon healing. Because of the fundamental quantitative and qualitative changes the ECM components undergo in diseased tissue, the ECM has attracted interest as an vivo imaging target for the detection, characterization, and monitoring of disease. The proposed „Matrix in Vision“ Collaborative Research Center (CRC) aims at using inflammation as a pathologic case in point to experimentally investigate how the different ECM components might be targeted by in vivo imaging. This involves the use of models of atherosclerosis, abdominal aortic aneurysm, various cardiomyopathies, multiple sclerosis, and inflammatory conditions of the bowel and liver to elucidate specific ECM alterations associated with these diseases in terms of histologic, analytic, and biomechanical properties. To advance imaging approaches, the CRC will analyze interactions between molecular imaging probes (gadolinium-based nonspecific contrast agents and specific probes based on iron oxide nanoparticles) and ECM components. The focus here is on GAGs, which are the primary target because they can form complexes with positively charged imaging probes or their positively charged components. Imaging studies will include the multiscale quantification of mechanical structural elements of the ECM, ranging from microscopic protein and glycosaminoglycan networks to macroscopic mechanical parameters investigated by clinical diagnostic elastography. In summary, “Matrix in Vision” for the first time combines biological molecular methods in radiology with new biophysical insights into the role of mechanical tissue parameters in the development of disease. Also for the first time, the proposed CRC will thus enable the investigation of relationships of the ECM structure and signal generation in molecular and biophysical medical imaging for the development of new imaging approaches allowing quantitative, disease-specific diagnosis in radiology.