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Diagnosis and Measurement of Liver Fibrosis by MRI in Bile Duct Ligated Rats

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Abstract

The noninvasive evaluation of liver fibrosis is a major clinical goal in liver diseases. Our aim was to identify MRI parameters to quantify liver fibrosis in vivo in an animal model of liver fibrosis with slight inflammation. We evaluated serum hyaluronate, liver hydroxyproline, area of liver fibrosis (image analysis), and 1.5-T MRI in 10 sham rats and 24 bile duct ligated rats with different stages of liver fibrosis. Liver signal intensity (SI)/muscle SI ratio and liver relaxation times (rT) were measured on T1 and T2 weighted sequences at different echo (TE) or recovery (RT) times of MRI. Among the 66 MRI parameters tested, the highest correlation with the area of fibrosis was observed for rT2 (r=0.78, P < 0.01). The area of liver fibrosis was independently predicted by five MRI variables (adjusted R 2=0.78, with R 2=0.64 for rT2 and rT1). Diagnostic accuracy for liver fibrosis was 100% using two variables: liver/muscle SI ratio on T2 at 30-ms TE and liver/muscle SI ratio on T1 at 50-ms RT. We conclude that in this animal model, fibrosis could be diagnosed with an accuracy of 100% using two MRI parameters. The quantification of liver fibrosis was very accurate either with only one MRI parameter (r=0.78 for rT2) or with five parameters (r=0.90) in this cholestatic model.

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References

  1. Gandon Y, Olivié D, Guyader D, Aubé C, Oberti F, Sebille V, Deugnier Y (2004) Noninvasive assessment of hepatic iron store by MRI. Lancet 363(9406):357–362

    Article  PubMed  CAS  Google Scholar 

  2. Stark DD, Bass NM, Moss AA, Bacon BR, McKerrow JH, Cann CE, Brito A, Goldberg HI (1983) Nuclear magnetic resonance imaging of experimentally induced liver disease. Radiology 148:743–751

    PubMed  CAS  Google Scholar 

  3. Stark DD, Goldberg HI, Moss AA, Bass NM (1984) Chronic liver disease: Evaluation by magnetic resonance. Radiology 150:149–151

    PubMed  CAS  Google Scholar 

  4. Aisen AM, Doi K, Swanson SD (1994) Detection of liver fibrosis with magnetic cross-relaxation. MRM 31:551–556

    CAS  Google Scholar 

  5. Chalumeau RA, Creyghton JH, De Nie I, Moerland MA, Van Der Lende OR, Smidt J (1988) Is the magnetic resonance imaging proton spin-lattice relaxation time a reliable noninvasive parameter of developing liver fibrosis? Hepatology 8:217–221

    Article  Google Scholar 

  6. Golderg HI, Moss AA, Stark DD, Mckerrow J, Engelstad B, Brito A (1984) Hepatic cirrhosis: Magnetic resonance imaging. Radiology 153:737–739

    Google Scholar 

  7. Kreft B, Dombrowski F, Block W, Bachmann R, Pfeifer U, Schild H (1999) Evaluation of different models of experimentally induced liver cirrhosis for MRI research with correlation to histopathologic findings. Invest Radiol 35:360–366

    Article  Google Scholar 

  8. Kreft B, Block W, Dombrowski F, Fackeldey A, Bachmann R, Muhlhauser J, Traber F, Oksendal A, Pfeifer U, Schild HH (1998) Diagnostic value of a superparamagnetic iron oxide in MR imaging of chronic liver disease in an animal model. Am J Roentgenol 170:661–668

    CAS  Google Scholar 

  9. Amano Y, Kumazaki T, Ishihara M (1998) Single-shot diffusion-weighted echo-planar imaging of normal and cirrhotic livers using a phased-array multicoil. Acta Radiol 39:440–442

    PubMed  CAS  Google Scholar 

  10. Alanen A, Komu M, Leino R, Toikkanen S (1998) MR and magnetisation transfer imaging in cirrhotic and fatty livers. Acta Radiol 39:434–439

    PubMed  CAS  Google Scholar 

  11. Yamashita Y, Yamamoto H, Hirai A, Yoshimatsu S, Baba Y, Takahashi M (1996) MR imaging enhancement with sperparamagnetic iron oxide in chronic liver disease: Influence of liver dysfunction and parenchymal pathology. Abdom Imaging 21:318–323

    Article  PubMed  CAS  Google Scholar 

  12. Kita K, Kita M, Sato M, Ooshima A, Yamada R (1996) MR imaging of liver cirrhosis. Role of fibrous septa in vizualization of regenerating nodules. Acta Radiol 37:198–203

    CAS  Google Scholar 

  13. Murakami T, Baron RL, Federle MP, Peterson MS, Oliver JH 3rd, Davis PL, Confer SR (1996) Cirrhosis of the liver: MR imaging with mangafodipir trisodium (Mn–DPDP). Radiology 198:567–572

    PubMed  CAS  Google Scholar 

  14. Keevil SF, Alstead EM, Dolke G, Brooks AP, Armstrong P, Farthing MJG (1994) Noninvasive assessment of diffuse liver disease by in vivo measurement of proton nuclear magnetic resonance relaxation times at 0.08 T. Br J Radiol 67:1083–1087

    Article  PubMed  CAS  Google Scholar 

  15. Ohno A, Ohta Y, Ohtomo K, Hirata K, Takatsuki K, Mochida S, Ogata I, Itai Y, Iio M, Fujiwara K (1990) Magnetic resonance imaging in chronic liver disease evaluated in relation to hepatic fibrosis—clinical and experimental results. Radiat Med 8:159–163

    PubMed  CAS  Google Scholar 

  16. Thomsen C, Christoffersen P, Henriksen O, Juhl E (1990) Prolonged T1 in patients with liver cirrhosis: An in vivo MRI study. MRI 8:599–604

    Article  CAS  Google Scholar 

  17. Thomsen C (1996) Quantitative magnetic resonance methods for in vivo investigation of the human liver and spleen. Acta Radiol 401(Suppl):1–34

    CAS  Google Scholar 

  18. Marti-Bonmati L, Talens A, del Olmo J, de Val A, Serra MA, Rodrigo JM, Ferrandez A, Torres V, Rayon M, Vilar JS (1993) Chronic hepatitis and cirrhosis: Evaluation by means of MR imaging with histologic correlation. Radiology 188:37–43

    PubMed  CAS  Google Scholar 

  19. Chen JH, Chai JW, Shen WC (1999) Magnetization transfer contrast imaging of liver cirrhosis. Hepato–gastroenterology 46:2872–2877

    PubMed  CAS  Google Scholar 

  20. Hannesson PH, Wallegren NO, Lyttkens K, Melin T, Brockstedt S, Stahlberg F (1995) Magnetic resonance imaging with signal-intensity measurements in diffuse liver disease. Eur Radiol 5:626–629

    Google Scholar 

  21. Oberti F, Vuillemin E, Fort J, Calès P (2000) Experimental models of portal hypertension. Gastroenterol Clin Biol [in French] 24:896–901

    CAS  Google Scholar 

  22. Abdel-Aziz G, Lebeau G, Rescan PY, Clement B, Rissel M, Deugnier Y, Campion JP, Guillouzo A (1990) Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. Am J Pathol 137:1333–1342

    PubMed  CAS  Google Scholar 

  23. Kinnman N, Housset C (2002) Peribiliary myofibroblast in biliary type liver fibrosis. Front Biosci 7:496–503

    Article  Google Scholar 

  24. Gall JA, Bhathal PS (1990) A quantitative analysis of the liver following ligation of the common bile duct. Liver 10:116–125

    PubMed  CAS  Google Scholar 

  25. Beck PL, Lee SS (1995) Vitamin K1 improves survival in bile-duct-ligated rats with cirrhosis. J Hepatol 23:235

    Article  PubMed  CAS  Google Scholar 

  26. Jamall IS, Finelli VN, Hee SS (1981) A simple method to determine nanogram levels of 4 hydroxyproline in biological tissues. Anal Biochem 112:70–75

    Article  PubMed  CAS  Google Scholar 

  27. Pilette C, Rousselet MC, Bedossa P, Chappard D, Oberti F, Rifflet H, Maiga MY, Gallois Y, Cales P (1998) Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores. Comparison with serum markers. J Hepatol 28:439–436

    CAS  Google Scholar 

  28. Oberti F, Valsesia E, Pilette C, Rousselet MC, Bedossa P, Aube C, Gallois Y, Rifflet H, Maiga MY, Penneau-Fontbonne D, Calès P (1997) Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology 113:1609–1616

    Article  PubMed  CAS  Google Scholar 

  29. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T (2001) Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: A prospective study. Lancet 357:1069–1075

    Article  PubMed  CAS  Google Scholar 

  30. Aubé C, Oberti F, Nouri K, Namour MA, Loisel D, Tanguy JY, Valsesia E, Pilette C, Rousselet MC, Bedossa P, Riflet H, Penneau D, Caron C, Calès P (1999) Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis. J Hepatol 30:472–478

    Article  PubMed  Google Scholar 

  31. James J, Bosh KS, Aronson DC, Houtkooper JM (1990) Sirius red histophotometry and spectrophometry of sections in the assessment of the collagen content of liver tissue and its application in growing rat liver. Liver 10:1–5

    PubMed  CAS  Google Scholar 

  32. Dashti H, Jeppsson B, Hagerstrand I, Hultberg B, Srinivas U, Abdulla M, Bengmark S (1989) Thioacetamide and carbon tetrachloride-induced liver cirrhosis. Eur Surg Res 21:83–91

    PubMed  CAS  Google Scholar 

  33. Kountouras J, Billing BH, Scheuer PJ (1984) Prolonged bile duct obstruction: A new experimental model for cirrhosis in the rat. Br J Exp Path 65:305–311

    CAS  Google Scholar 

  34. Parés A, Deulofeu R, Giménez A, et al. (1996) Serum hyaluronate reflects hepatic fibrogenesis in alcoholic liver disease and is useful as a marker of fibrosis. Hepatology 24:1399–1403

    Article  PubMed  Google Scholar 

  35. Zimmermann H, Blasez H, Zimmermann A, Reichen J (1994) Effect of development on the functional and histological changes induced by bile-duct ligation in the rat. J Hepatol 20:231–239

    Article  PubMed  CAS  Google Scholar 

  36. Chen J, Lin J, Shen W (2003) Noninvasive diagnosis of liver fibrosis: Explore the potential role of magnetisation transfer contrast imaging. Eur Radiol 13(Suppl):C0018

    Google Scholar 

  37. Kim T, Murakami T, Takahashi S, Tsuda K, Nakamura H (1999) Diffusion-weighted single-shot echoplanar MR imaging for liver disease. Am J Roentgenol 173:93–98

    Google Scholar 

  38. Amano Y, Kumazaki T, Ishirhara M (1998) Single-shot diffusion-weighted echo-planar imaging of normal and cirrhotic livers using a phased-array multicoil. Acta Radiol 39:440–442

    Article  PubMed  CAS  Google Scholar 

  39. Taouli B, Vilgrain V, Dumont E, Daire JL, Fan B, Menu Y (2003) Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: Prospective study in 66 patients. Radiology 226:71–78

    Article  PubMed  Google Scholar 

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Correspondence to Christophe Aubé.

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Aubé, C., Moal, F., Oberti, F. et al. Diagnosis and Measurement of Liver Fibrosis by MRI in Bile Duct Ligated Rats. Dig Dis Sci 52, 2601–2609 (2007). https://doi.org/10.1007/s10620-006-9143-z

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  • DOI: https://doi.org/10.1007/s10620-006-9143-z

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