hepFib-ECM
The extracellular matrix as a target for biophysical and molecular imaging of inflammation and fibrosis of the liver
Quantitative biophysical imaging, biochemical and histological analyses will be used to (i) elucidate suitability of hyaluronic acid (glycosaminoglycan) and lumican (inflammatory marker) in ECM as early predictors for NAFLD/NASH; (ii) clarify the progression of ECM changes in inflammation related to dysbiotic gut microbiota; and (iii) investigate the translational potential of ECM-targeted imaging.
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Motivation
During inflammation and fibrosis in the course of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), the extracellular matrix (ECM) of the liver undergoes specific structural changes. Tissue viscoelastic parameters sensitive to this show that liver stiffness is mainly determined by hepatocytes, whereas viscoelastic dispersion can be attributed to the ECM.
Innovations and perspectives
Insights will be gained on (i) hepatic ECM in inflammation, (ii) disease-related glycosaminoglycans in progression and treatment of NAFLD and NASH, (iii) gut microbiota and pro-inflammatory lumican in ECM changes related to susceptibility to NAFLD and disease severity, and (iv) translational potential of ECM-targeted imaging.
Selected publications
- Reiter R, Loch FN, Kamphues C, Bayerl C, Marticorena Garcia SR, Siegmund B, Kühl AA, Hamm B, Braun J, Sack I, Asbach P. Feasibility of Intestinal MR Elastography in Inflammatory Bowel Disease. J Magn Reson Imaging. 2022;55:815-822.
- Reiter R, Shahryari M, Tzschätzsch H, Haas M, Bayerl C, Siegmund B, Hamm B, Asbach P, Braun J, Sack I. Influence of fibrosis progression on the viscous properties of in vivo liver tissue elucidated by shear wave dispersion in multifrequency MR elastography. J Mech Behav Biomed Mater. 2021;121:104645.
- Everwien H., Ariza de Schellenberger A., Haep N., Tzschätzsch H., Pratschke J., Sauer I.M., Braun J., Hillebrandt K.H., Sack I.: Magnetic resonance elastography quantification of the solid-to-fluid transition of liver tissue due to decellularization. J Mech Behav Biomed. 2020;104:103640.
- Sauer F., Oswald L., Ariza de Schellenberger A., Tzschätzsch H., Schrank F., Fischer T., Braun J., Mierke CT., Valiullin R., Sack I., Käs JA.: Collagen networks determine viscoelastic properties of connective tissues yet do not hinder diffusion of the aqueous solvent. Soft Matter. 2019;15:3055-3064.
- Ariza de Schellenberger A., Tzschätzsch H., Polchlopek B., Bertalan G., Schrank F., Garczynska K., Janmey P.A., Braun J., Sack I.: Sensitivity of multifrequency magnetic resonance elastography and diffusion-weighted imaging to cellular and stromal integrity of liver tissue. J Biomech. 2019;88:201-208.
