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.
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-3533gadolinium 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.
Authors: Paul R Hutson; Mark E Crawford; Ronald L Sorkness Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2003-07-05 Impact factor: 3.205
Authors: Laurent Huwart; Christine Sempoux; Eric Vicaut; Najat Salameh; Laurence Annet; Etienne Danse; Frank Peeters; Leon C ter Beek; Jacques Rahier; Ralph Sinkus; Yves Horsmans; Bernard E Van Beers Journal: Gastroenterology Date: 2008-04-04 Impact factor: 22.682
Authors: Jason M Hui; James G Kench; Shivakumar Chitturi; Archana Sud; Geoffrey C Farrell; Karen Byth; Pauline Hall; Mahbub Khan; Jacob George Journal: Hepatology Date: 2003-08 Impact factor: 17.425
Authors: Pauline Désogère; Luis F Tapias; Tyson A Rietz; Nicholas Rotile; Francesco Blasi; Helen Day; Justin Elliott; Bryan C Fuchs; Michael Lanuti; Peter Caravan Journal: J Nucl Med Date: 2017-06-13 Impact factor: 10.057
Authors: David P Basile; Joseph V Bonventre; Ravindra Mehta; Masaomi Nangaku; Robert Unwin; Mitchell H Rosner; John A Kellum; Claudio Ronco Journal: J Am Soc Nephrol Date: 2015-10-30 Impact factor: 10.121
Authors: Howard H Chen; Philip A Waghorn; Lan Wei; Luis F Tapias; Daniel T Schühle; Nicholas J Rotile; Chloe M Jones; Richard J Looby; Gaofeng Zhao; Justin M Elliott; Clemens K Probst; Mari Mino-Kenudson; Gregory Y Lauwers; Andrew M Tager; Kenneth K Tanabe; Michael Lanuti; Bryan C Fuchs; Peter Caravan Journal: JCI Insight Date: 2017-06-02
Authors: Iris Y Zhou; Veronica Clavijo Jordan; Nicholas J Rotile; Eman Akam; Smitha Krishnan; Gunisha Arora; Hema Krishnan; Hannah Slattery; Noah Warner; Nathaniel Mercaldo; Christian T Farrar; Jeremy Wellen; Robert Martinez; Franklin Schlerman; Kenneth K Tanabe; Bryan C Fuchs; Peter Caravan Journal: Radiology Date: 2020-04-28 Impact factor: 11.105
Authors: Bryan C Fuchs; Huifang Wang; Yan Yang; Lan Wei; Miloslav Polasek; Daniel T Schühle; Gregory Y Lauwers; Ashfaq Parkar; Anthony J Sinskey; Kenneth K Tanabe; Peter Caravan Journal: J Hepatol Date: 2013-07-06 Impact factor: 25.083