Quantitative assessment of hepatic fibrosis in an animal model with magnetic resonance elastography

Chronic liver disease is a world‐wide problem that causes progressive hepatic fibrosis as a hallmark of progressive injury. At present, the gold standard for diagnosing hepatic fibrosis is liver biopsy, which is an invasive method with many limitations, including questionable accuracy and risks of complications. MR elastography (MRE), a phase‐contrast MRI technique for quantitatively assessing the mechanical properties of soft tissues, is a potential noninvasive diagnostic method to assess hepatic fibrosis. In this work, MRE was evaluated as a quantitative method to assess the in vivo mechanical properties of the liver tissues in a knockout animal model of liver fibrosis. This work demonstrates that the shear stiffness of liver tissue increases systematically with the extent of hepatic fibrosis, as measured by histology. A linear correlation between liver stiffness and fibrosis extent was well‐defined in this animal model. An additional finding of the study was that fat infiltration, commonly present in chronic liver disease, does not significantly correlate with liver stiffness at each fibrosis stage and thus does not appear to interfere with the ability of MRE to assess fibrosis extent. In conclusion, MRE has the potential not only for assessing liver stiffness, but also for monitoring potential therapies for hepatic fibrosis. Magn Reson Med 58:346–353, 2007. © 2007 Wiley‐Liss, Inc.

[1]  V. de Lédinghen,et al.  Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. , 2005, Gastroenterology.

[2]  L. Guay-Woodford,et al.  Autosomal recessive polycystic kidney disease: the clinical experience in North America. , 2003, Pediatrics.

[3]  K. Zerres,et al.  Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender , 1996, Acta paediatrica.

[4]  V. de Lédinghen,et al.  Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study , 2005, Gut.

[5]  Stephen L. Chen,et al.  The Natural History of Hepatitis C Virus (HCV) Infection , 2006, International journal of medical sciences.

[6]  G. Glover Multipoint dixon technique for water and fat proton and susceptibility imaging , 1991, Journal of magnetic resonance imaging : JMRI.

[7]  E. Mezey,et al.  Sampling variability on percutaneous liver biopsy. , 1979, Archives of internal medicine.

[8]  M. Beaugrand How to assess liver fibrosis and for what purpose? , 2006, Journal of hepatology.

[9]  R. D. de Knegt,et al.  Non-invasive measurement of liver fibrosis: Application of the FibroScan® in hepatology , 2006, Scandinavian journal of gastroenterology. Supplement.

[10]  Armando Manduca,et al.  Spatio-temporal Directional Filtering for Improved Inversion of MR Elastography Images , 2002, MICCAI.

[11]  S. Friedman,et al.  Liver fibrosis -- from bench to bedside. , 2003, Journal of hepatology.

[12]  Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperative Study Group. , 1994, Hepatology.

[13]  X. Forns,et al.  Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[14]  Christopher J. Parsons,et al.  Mechanisms of liver fibrosis. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[15]  P. Kamath,et al.  Clinical and Molecular Characterization Defines a Broadened Spectrum of Autosomal Recessive Polycystic Kidney Disease (ARPKD) , 2006, Medicine.

[16]  J. Bruzzi,et al.  Liver biopsy. , 2001, The New England journal of medicine.

[17]  D. Schuppan,et al.  Hepatic fibrosis: From bench to bedside , 2002, Journal of gastroenterology and hepatology.

[18]  Laura Marelli,et al.  A systematic review of the quality of liver biopsy specimens. , 2006, American journal of clinical pathology.

[19]  M. Ziol,et al.  Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. , 2003, Ultrasound in medicine & biology.

[20]  Dieter Klatt,et al.  In Vivo Determination of Hepatic Stiffness Using Steady-State Free Precession Magnetic Resonance Elastography , 2006, Investigative radiology.

[21]  N. Yamanaka,et al.  Consistency of human liver. , 1985, The Journal of surgical research.

[22]  R L Ehman,et al.  Tissue characterization using magnetic resonance elastography: preliminary results. , 2000, Physics in medicine and biology.

[23]  Mickael Tanter,et al.  Viscoelastic shear properties of in vivo breast lesions measured by MR elastography. , 2005, Magnetic resonance imaging.

[24]  P. Schlichting,et al.  Reproducibility of liver biopsy diagnosis in relation to the size of the specimen. , 1980, Scandinavian journal of gastroenterology.

[25]  G. Brosnahan,et al.  Volume progression in polycystic kidney disease. , 2006, The New England journal of medicine.

[26]  R. Ehman,et al.  Needle shear wave driver for magnetic resonance elastography , 2006, Magnetic resonance in medicine.

[27]  M. Fink,et al.  Shear elasticity probe for soft tissues with 1-D transient elastography , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[28]  Richard L Ehman,et al.  MR elastography of the liver: preliminary results. , 2006, Radiology.

[29]  J. F. Greenleaf,et al.  Magnetic resonance elastography: Non-invasive mapping of tissue elasticity , 2001, Medical Image Anal..

[30]  A. Manduca,et al.  Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. , 1995, Science.

[31]  G. H. Rose,et al.  Magnetic resonance elastography of skeletal muscle , 2001, Journal of magnetic resonance imaging : JMRI.

[32]  A. Manduca,et al.  MR elastography of breast cancer: preliminary results. , 2002, AJR. American journal of roentgenology.

[33]  Vicente E. Torres,et al.  The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein , 2002, Nature Genetics.

[34]  D. Capron,et al.  Noninvasive diagnosis of liver fibrosis by ultrasonic transient elastography (Fibroscan) , 2006, European journal of gastroenterology & hepatology.

[35]  P. Bedossa,et al.  Intraobserver and Interobserver Variations in Liver Biopsy Interpretation in Patients with Chronic Hepatitis C , 1994 .

[36]  J. Bosch,et al.  Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension. , 2005, Journal of clinical gastroenterology.

[37]  K. Parker,et al.  "Sonoelasticity" images derived from ultrasound signals in mechanically vibrated tissues. , 1990, Ultrasound in medicine & biology.

[38]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[39]  M. Colombo,et al.  Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. , 1986, Journal of hepatology.

[40]  Wen-Chun Yeh,et al.  Elastic modulus measurements of human liver and correlation with pathology. , 2002, Ultrasound in medicine & biology.

[41]  G H Glover,et al.  Three‐point dixon technique for true water/fat decomposition with B0 inhomogeneity correction , 1991, Magnetic resonance in medicine.

[42]  B. V. Van Beers,et al.  Liver fibrosis: non‐invasive assessment with MR elastography , 2006, NMR in biomedicine.

[43]  S. Friedman,et al.  Reversal of hepatic fibrosis — Fact or fantasy? , 2006, Hepatology.

[44]  E. Avner,et al.  PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. , 2002, American journal of human genetics.

[45]  R. Pérez Tamayo Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis? , 1983, Hepatology.

[46]  R. P. Tamayo Is Cirrhosis of the Liver Experimentally Produced by CC14 an Adequate Model of Human Cirrhosis? , 2007 .

[47]  Johannes Bernarding,et al.  Analysis of wave patterns in MR elastography of skeletal muscle using coupled harmonic oscillator simulations. , 2002, Magnetic resonance imaging.

[48]  J. Iredale,et al.  Emerging Therapies for Liver Fibrosis , 2006, Digestive Diseases.

[49]  Raymond H. Myers,et al.  Probability and Statistics for Engineers and Scientists. , 1973 .