Molecular MR imaging of liver fibrosis: A feasibility study using rat and mouse models

Miloslav Polasek, Bryan C. Fuchs, Ritika Uppal, Daniel T. Schühle, Jamu K. Alford, Galen S. Loving, Suguru Yamada, Lan Wei, Gregory Y. Lauwers, Alexander R. Guimaraes, Kenneth K. Tanabe, Peter Caravan

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Background & Aims: Liver biopsy, the current clinical gold standard for fibrosis assessment, is invasive and has sampling errors, and is not optimal for screening, monitoring, or clinical decision-making. Fibrosis is characterized by excessive accumulation of extracellular matrix proteins including type I collagen. We hypothesize that molecular magnetic resonance imaging (MRI) with a probe targeted to type I collagen could provide a direct and non-invasive method of fibrosis assessment. Methods: Liver fibrosis was induced in rats with diethylnitrosamine and in mice with carbon tetrachloride. Animals were imaged prior to and immediately following i.v. administration of either collagen-targeted probe EP-3533 or non-targeted control Gd-DTPA. Magnetic resonance (MR) signal washout characteristics were evaluated from T1 maps and T1-weighted images. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline. Results: EP-3533-enhanced MR showed greater signal intensity on delayed imaging (normalized signal enhancement mice: control = 0.39 ± 0.04, fibrotic = 0.55 ± 0.03, p <0.01) and slower signal washout in the fibrotic liver compared to controls (liver t1/2 = 51.3 ± 3.6 vs. 42.0 ± 2.5 min, p <0.05 and 54.5 ± 1.9 vs. 44.1 ± 2.9 min, p <0.01 for fibrotic vs. controls in rat and mouse models, respectively). Gd-DTPA-enhanced MR could not distinguish fibrotic from control animals. EP-3533 gadolinium concentration in the liver showed strong positive correlations with hydroxyproline levels (r = 0.74 (rats), r = 0.77 (mice)) and with Ishak scoring (r = 0.84 (rats), r = 0.79 (mice)). Conclusions: Molecular MRI of liver fibrosis with a collagen-specific probe identifies fibrotic tissue in two rodent models of disease.

Original languageEnglish (US)
Pages (from-to)549-555
Number of pages7
JournalJournal of Hepatology
Volume57
Issue number3
DOIs
StatePublished - Sep 1 2012

Keywords

  • Carbon tetrachloride
  • Diethylnitrosamine
  • Gadolinium
  • Molecular imaging
  • Type I collagen

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Molecular MR imaging of liver fibrosis: A feasibility study using rat and mouse models'. Together they form a unique fingerprint.

  • Cite this

    Polasek, M., Fuchs, B. C., Uppal, R., Schühle, D. T., Alford, J. K., Loving, G. S., Yamada, S., Wei, L., Lauwers, G. Y., Guimaraes, A. R., Tanabe, K. K., & Caravan, P. (2012). Molecular MR imaging of liver fibrosis: A feasibility study using rat and mouse models. Journal of Hepatology, 57(3), 549-555. https://doi.org/10.1016/j.jhep.2012.04.035