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

JOURNAL OF HEPATOLOGY

卷:57

Article

Polasek, Miloslav^1,2  Fuchs, Bryan C.^3,4  Uppal, Ritika^1,2  Schuehle, Daniel T.^1,2  Alford, Jamu K.^1,2  Loving, Galen S.^1,2  Yamada, Suguru^3,4  Wei, Lan^3,4  Lauwers, Gregory Y.⁴  Guimaraes, Alexander R.^1,2  Tanabe, Kenneth K.^3,4  Caravan, Peter^1,2 

[1] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA

[2] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

[3] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Boston, MA 02114 USA

关键词: Molecular imaging;    Gadolinium;    Type I collagen;    Carbon tetrachloride;    Diethylnitrosamine;   

DOI  :  10.1016/j.jhep.2012.04.035

来源: Elsevier

【 摘 要 】

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 t(1/2) = 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. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.

【 授权许可】

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