The extracellular matrix (ECM) provides cells with positional information and a mechanical scaffold for adhesion and migration. It consists of collagens, glycoproteins, proteoglycans, glycosaminoglycans and molecules that are bound specifically by the ECM, such as certain growth factors/cytokines, matrix metalloproteinases (MMPs) and processing enzymes such as tissue transglutaminase and procollagen propeptidases. This finely tuned ecosystem is dysbalanced in chronic fibrogenesis, which can be regarded as a continuous wound-healing process and which results in scar formation. Importantly, the ECM directs cellular differentiation, migration, proliferation, and fibrogenic activation or deactivation. Partially via defined oligopeptide sequences or structural domains, the ECM transfers specific signals to cells that act in concert with growth factors/cytokines. These signals either confer stress activation, with a resultant fibrogenic response, or stress relaxation, with a fibrolytic response. Alternatively, ECM-derived peptides can modulate angiogenesis, or growth factor and MMP availability and activity. Current ECM-related antifibrotic strategies are based on the identification and in vivo application of ECM-derived biomodulatory peptides, peptide sequences, or their nonpeptidic mimetics. The latter open the opportunity of oral application and an extended biological half-life. Examples are peptides derived from collagens VI (stress activation) and XIV (stress relaxation), or collagenous consensus peptides that remove ECM-bound MMPs and growth factors. Furthermore, certain peptides can be used as targeting structures to the fibrogenic lesion.

MR elastography (MRE) allows the noninvasive assessment of the viscoelastic properties of human organs based on the organ response to oscillatory shear stress. Shear waves of a given frequency are mechanically introduced and the propagation is imaged by applying motion-sensitive gradients. An experiment was set up that introduces multifrequency shear waves combined with broadband motion sensitization to extend the dynamic range of MRE from one given frequency to, in this study, four different frequencies. With this approach, multiple wave images corresponding to the four driving frequencies are simultaneously acquired and can be evaluated with regard to the dispersion of the complex modulus over the respective frequency. A viscoelastic model based on two shear moduli and one viscosity parameter was used to reproduce the experimental wave speed and wave damping dispersion. The technique was applied in eight healthy volunteers and eight patients with biopsy-proven high-grade liver fibrosis (grade 3-4).

The diagnostic performance of multifrequency MR elastography in determining the degree of hepatic fibrosis increases with stage of fibrosis. Metrics obtained at the higher frequencies provide better diagnostic performance compared with the lower frequencies. Results of the AUROC analysis demonstrate the high accuracy of frequency-independent cutoff values for staging higher grades of hepatic fibrosis.

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bSSFP combined with fractional MRE enables rapid measurement of liver stiffness in vivo. The used actuation principle supports a 2-dimensional analysis of the strain wave field captured by axial wave images. The measured data indicate individual variations of hepatic stiffness in healthy volunteers.