Original Article
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World J Gastroenterol. Feb 28, 2011; 17(8): 968-975
Published online Feb 28, 2011. doi: 10.3748/wjg.v17.i8.968
Transient micro-elastography: A novel non-invasive approach to measure liver stiffness in mice
Cécile Bastard, Matteo R Bosisio, Michèle Chabert, Athina D Kalopissis, Meriem Mahrouf-Yorgov, Hélène Gilgenkrantz, Sebastian Mueller, Laurent Sandrin
Cécile Bastard, Matteo R Bosisio, Laurent Sandrin, Echosens, Research and Development Department, Paris, F-75013, France
Cécile Bastard, INSERM, U930, Tours, F-37000, France
Cécile Bastard, CNRS, ERL3106, Tours, F-37000, France
Cécile Bastard, Univ François Rabelais, Tours, F-37000, France
Matteo R Bosisio, UPMC Univ Paris 06, UMR 7623, LIP, Paris, F-75005, France
Matteo R Bosisio, CNRS, UMR 7623, Laboratoire d’Imagerie Paramétrique, Paris, F-75005, France
Michèle Chabert, Athina D Kalopissis, INSERM, U872, Centre de Recherche des Cordeliers, Equipe 4, Paris, F-75006, France
Michèle Chabert, Athina D Kalopissis, UPMC Univ Paris 06, UMR S 872, Equipe 4, Paris, F-75006, France
Michèle Chabert, Athina D Kalopissis, Univ Paris Descartes, UMR S 872, Equipe 4, Paris, F-75006, France
Michèle Chabert, EPHE, Laboratoire de Pharmacologie Cellulaire Et Moléculaire, Paris, F-75006, France
Meriem Mahrouf-Yorgov, Hélène Gilgenkrantz, INSERM, U1016, Institut Cochin, Paris, F-75014, France
Meriem Mahrouf-Yorgov, Hélène Gilgenkrantz, CNRS, UMR8104, Paris, F-75014, France
Meriem Mahrouf-Yorgov, Hélène Gilgenkrantz, Univ Paris Descartes, Paris, F-75014, France
Sebastian Mueller, Department of Medicine and Center for Alcohol Research, Liver Disease and Nutrition, Salem Medical Center, University of Heidelberg, 69121 Heidelberg, Germany
Author contributions: Bastard C, Bosisio MR and Sandrin L designed the research; Chabert M, Gilgenkrantz H and Kalopissis AD provided the animal models; Bastard C, Bosisio MR, Chabert M, Gilgenkrantz H and Kalopissis AD performed the study; Chabert M, Kalopissis AD and Mahrouf-Yorgov M analyzed the histological sections; Bastard C, Bosisio MR, Chabert M, Kalopissis AD and Gilgenkrantz H analyzed the data; Bastard C, Bosisio MR, Mueller S and Sandrin L wrote the paper.
Supported by Echosens, Research and Development Department, 153 avenue d’Italie, 75013, Paris, France
Correspondence to: Cécile Bastard, Echosens, Research and Development Department, 153 avenue d’Italie, 75013, Paris, France. cecile.bastard@echosens.com
Telephone: +33-1-44827850 Fax: +33-1-44827860
Received: July 21, 2010
Revised: September 13, 2010
Accepted: September 20, 2010
Published online: February 28, 2011
Abstract

AIM: To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice.

METHODS: A novel transient micro-elastography (TME) device, dedicated to LS measurements in mice with a range of measurement from 1-170 kPa, was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston. The novel probe was validated in a classical fibrosis model (CCl4) and in a transgenic murine model of systemic amyloidosis.

RESULTS: TME could be successfully performed in control mice below the xiphoid cartilage, with a mean LS of 4.4 ± 1.3 kPa, a mean success rate of 88%, and an excellent intra-observer agreement (0.98). Treatment with CCl4 over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa). Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88, P < 0.01). In the amyloidosis model, much higher LS values were obtained, reaching maximum values of > 150 kPa. LS significantly correlated with the amyloidosis index (0.93, P < 0.0001) and the plasma concentration of mutant hapoA-II (0.62, P < 0.005).

CONCLUSION: Here, we have established the first non-invasive approach to measure LS in mice, and have successfully validated it in two murine models of high LS.

Keywords: Transient elastography; Micro-elastography; Liver stiffness; Liver; Mice; Amyloidosis; Fibrosis; Ultrasound