MR T1ρ as an imaging biomarker for monitoring liver injury progression and regression: an experimental study in rats with carbon tetrachloride intoxication
Recently it was shown that the magnetic resonance imaging (MRI) T1ρ value increased with the severity of liver fibrosis in rats with bile duct ligation. Using a rat carbon tetrachloride (CCl4) liver injury model, this study further investigated the merit of T1ρ relaxation for liver fibrosis evaluation.
Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl4 twice weekly for up to 6 weeks. Then CCl4 was withdrawn and the animals were allowed to recover. Liver T1ρ MRI and conventional T2-weighted images were acquired. Animals underwent MRI at baseline and at 2 days, 2 weeks, 4 weeks and 6 weeks post CCl4 injection, and they were also examined at 1 week and 4 weeks post CCl4 withdrawal. Liver histology was also sampled at these time points.
Liver T1ρ values increased slightly, though significantly, on day 2, and then increased further and were highest at week 6 post CCl4 insults. The relative liver signal intensity change on T2-weighted images followed a different time course compared with that of T1ρ. Liver T1ρ values decreased upon the withdrawal of the CCl4 insult. Histology confirmed the animals had typical CCl4 liver injury and fibrosis progression and regression processes.
MR T1ρ imaging can monitor CCl4-induced liver injury and fibrosis.
• MR T1ρ is a valuable imaging biomarker for liver injury/fibrosis.
• Liver T1ρ was only mildly affected by oedema and acute inflammation.
• Liver MR T1ρ decreased when liver fibrosis and injury regressed.
KeywordsT1ρ Liver fibrosis Liver cirrhosis CCl4 Imaging biomarker
This study was supported by a direct grant for research of The Chinese University of Hong Kong (2041607), by Hong Kong RGC General Research Fund 475911, by Hong Kong ITF grant ITS/021/10, and by a grant from the Research Grants Council of the Hong Kong SAR (Project No.SEG_CUHK02).
Yi-Xiang J. Wang, Jing Yuan and Jun Yu applied for a patent related to T1ρ MR imaging for detection and assignment of grade to liver fibrosis.
- 8.Leung NW, Lai CL, Chang TT, Guan R, Lee CM, Ng KY, Lim SG, Wu PC, Dent JC, Edmundson S, Condreay LD, Chien RN, Asia Hepatitis Lamivudine Study Group (2001) Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 33:1527–1532PubMedCrossRefGoogle Scholar
- 9.Hammel P, Couvelard A, O’Toole D, Ratouis A, Sauvanet A, Fléjou JF, Degott C, Belghiti J, Bernades P, Valla D, Ruszniewski P, Lévy P (2001) Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med 344:418–423PubMedCrossRefGoogle Scholar
- 25.Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ (1998) Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 102:538–549PubMedCrossRefGoogle Scholar
- 35.Knispel RR, Thompson RT, Pintar MM (1974) Dispersion of proton spin-lattice relaxation in tissues. J Magn Reson 14:44–51Google Scholar
- 36.Duvvuri U, Goldberg AD, Kranz JK, Hoang L, Reddy R, Wehrli FW, Wand AJ, Englander SW, Leigh JS (2001) Water magnetic relaxation dispersion in biological systems: the contribution of proton exchange and implications for the noninvasive detection of cartilage degradation. Proc Natl Acad Sci USA 98:12479–12484PubMedCrossRefGoogle Scholar
- 40.Fleiss JL (1986) Reliability of measurement. The design and analysis of clinical experiments. Wiley, New YorkGoogle Scholar
- 41.Deng M, Zhao F, Yuan J, Ahuja AT, Wang YX (2012) Liver MR T1ρ measurement in healthy human subjects at 3 T: a preliminary study with a two-dimensional fast-field echo sequence. Br J Radiol. doi: 10.1259/bjr/98745548
- 45.Wang YX (2010) In vivo biomedical imaging and spectroscopy in toxicogenomics and toxicoproteomics. Mol Cell Toxicol 6(Suppl):28Google Scholar