title: Wideband MRE and static mechanical indentation of human liver specimen: sensitivity of viscoelastic constants to the alteration of tissue structure in hepatic fibrosis.
abstract: Despite the success of elastography in grading hepatic fibrosis by stiffness related noninvasive markers the relationship between viscoelastic constants in the liver and tissue structure remains unclear. We therefore studied the mechanical properties of 16 human liver specimens with different degrees of fibrosis, inflammation and steatosis by wideband magnetic resonance elastography (MRE) and static indentation experiments providing the specimens׳ static Young׳s modulus (E), dynamic storage modulus (G') and dynamic loss modulus (G″). A frequency-independent shear modulus μ and a powerlaw exponent α were obtained by fitting G' and G″ using the two-parameter sprinpot model. The mechanical parameters were compared to the specimens׳ histology derived parameters such as degree of Fibrosis (F), inflammation score and fat score, amount of hydroxyproline (HYP) used for quantification of collagen, blood markers and presurgery in vivo function tests. The frequency averaged parameters G', G″ and μ were significantly correlated with F (G': R=0.762, G″: R=0.830; μ: R=0.744; all P<0.01) and HYP (G': R=0.712; G″: R=0.720; μ: R=0.731; all P<0.01). The powerlaw exponent α displayed an inverse correlation with F (R=-0.590, P=0.034) and a trend of inverse correlation with HYP (R=-0.470, P=0.089). The static Young׳s modulus E was less correlated with F (R=0.587, P=0.022) and not sensitive to HYP. Although inflammation was highly correlated with F (R=0.773, P<0.001), no interaction was discernable between inflammation and mechanical parameters measured in this study. Other histological and blood markers as well as liver function test were correlated with neither F nor the measured mechanical parameters. In conclusion, viscoelastic constants measured by wideband MRE are highly sensitive to histologically proven fibrosis. Our results suggest that, in addition to the amount of connective tissue, subtle structural changes of the viscoelastic matrix determine the sensitivity of mechanical tissue properties to hepatic fibrosis.
authors.affiliation: Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Reiter
authors.affiliation: Department of Pediatric Nephrology and Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Freise
authors.affiliation: Institute of Pathology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens
authors.affiliation: Clinic for Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Kamphues
authors.affiliation: Clinic for Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer
authors.affiliation: Clinic for Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stockmann
authors.affiliation: Interdisciplinary Rescue Center, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Rajan
authors.initials: R
authors.lastname: Somasundaram
authors.affiliation: Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Asbach
authors.affiliation: Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Braun
authors.affiliation: Department of Medical Biophysics, University of Western Ontario, Ontario, Canada; Department of Electrical and Computer Engineering, University of Western Ontario, Ontario, Canada.
authors.forename: Abbas
authors.initials: A
authors.lastname: Samani
authors.affiliation: Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: ingolf.sack@charite.de.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Sack
mesh_terms: D000818:Animals; D002417:Cattle; D024042:Collagen Type I / Q000378:metabolism; D004548:Elasticity; D054459:Elasticity Imaging Techniques; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D014783:Viscosity
chemical_list: D024042:Collagen Type I; D006909:Hydroxyproline
keywords: Collagen; Complex shear modulus dispersion; Elastography; Function; Liver fibrosis; Static indentation; Tissue matrix; Tissue structure; Viscoelasticity