title: Distinguishing between Hepatic Inflammation and Fibrosis with MR Elastography.
abstract: Purpose To investigate the utility of magnetic resonance (MR) elastography-derived mechanical properties in the discrimination of hepatic inflammation and fibrosis in the early stages of chronic liver diseases. Materials and Methods All studies were approved by the institutional animal care and use committee. A total of 187 animals were studied, including 182 mice and five pigs. These animals represented five different liver diseases with a varying combination and extent of hepatic inflammation, fibrosis, congestion, and portal hypertension. Multifrequency three-dimensional MR elastography was performed, and shear stiffness, storage modulus, shear loss modulus, and damping ratio were calculated for all animals. Necroinflammation, fibrosis, and portal pressure were either histologically scored or biochemically and physically quantified in all animals. Two-sided Welch t tests were used to evaluate mean differences between disease and control groups. Spearman correlation analyses were used to evaluate the relationships between mechanical parameters and quantitative fibrosis extent (hydroxyproline concentration) and portal pressure. Results Liver stiffness and storage modulus increased with progressively developed fibrosis and portal hypertension (mean stiffness at 80 Hz and 48-week feeding, 0.51 kPa ± 0.12 in the steatohepatitis group vs 0.29 kPa ± 0.01 in the control group; P = .02). Damping ratio and shear loss modulus can be used to distinguish inflammation from fibrosis at early stages of disease, even before the development of histologically detectable necroinflammation and fibrosis (mean damping ratio at 80 Hz and 20-week feeding, 0.044 ± 0.012 in the steatohepatitis group vs 0.014 ± 0.008 in the control group; P < .001). Damping ratio and liver stiffness vary differently with respect to cause of portal hypertension (ie, congestion- or cirrhosis-induced hypertension). These differentiation abilities have frequency-dependent variations. Conclusion Liver stiffness and damping ratio measurements can extend hepatic MR elastography to potentially enable assessment of necroinflammatory, congestive, and fibrotic processes of chronic liver diseases.©RSNA, 2017 Online supplemental material is available for this article.
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Meng
authors.initials: M
authors.lastname: Yin
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Glaser
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Armando
authors.initials: A
authors.lastname: Manduca
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Taofic
authors.initials: T
authors.lastname: Mounajjed
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Harmeet
authors.initials: H
authors.lastname: Malhi
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Simonetto
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Ruisi
authors.initials: R
authors.lastname: Wang
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Shennen A
authors.initials: SA
authors.lastname: Mao
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Glorioso
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Faysal M
authors.initials: FM
authors.lastname: Elgilani
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ward
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Nyberg
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Shah
authors.affiliation: From the Departments of Radiology (M.Y., K.J.G., A.M., R.L.E.) and Physiology and Biomedical Engineering (A.M.) and the Divisions of Anatomic Pathology (T.M.), Gastroenterology and Hepatology (H.M., D.A.S., R.W., L.Y., V.H.S.), Transplantation Surgery (S.A.M., J.M.G., F.M.E., S.L.N.), and Nephrology and Hypertension (C.J.W., P.C.H.), Mayo Clinic, 200 First St SW, Rochester, MN 55905.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Ehman
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005260:Female; D006505:Hepatitis / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D013552:Swine
chemical_list: D002251:Carbon Tetrachloride