Early detection of steatohepatitis in fatty rat liver by using MR elastography.
OBJECTIVE
To assess the potential value of magnetic resonance (MR) elastographic imaging to help detect nonalcoholic steatohepatitis in the fatty rat liver.


METHODS
This study was approved by the regional ethics committee. Fifty-four rats were imaged after being fed either a standard diet, a choline-deficient diet for up to 8 weeks to induce steatohepatitis, or a 2-week orotic acid diet to induce steatosis; or were imaged 48 hours after carbon tetrachloride injection to model acute liver injury. MR elastography was performed at 7.0 T to assess viscoelastic liver parameters. Steatosis and fibrosis were quantified with morphometric and biochemical analysis. Myofibroblast activation was assessed with morphometric analysis of alpha-smooth muscle actin. Expression of transforming growth factor beta1 and procollagens 1 and 3 as markers of fibrogenesis was evaluated with real-time reverse transcription polymerase chain reaction. Inflammation was scored at histologic analysis.


RESULTS
In rats with steatohepatitis, mean elasticity (2.24 kPa +/- 0.19 [standard deviation] vs 1.82 kPa +/- 0.22) and mean viscosity (0.86 kPa +/- 0.10 vs 0.59 kPa +/- 0.12) increased significantly (P < .005) after the 2-week orotic acid diet, while steatosis, inflammation, myofibroblast activation, and increase of other fibrogenesis markers were observed. Fibrosis appeared only after 5 weeks. In rats with steatosis, viscosity increased (0.77 kPa +/- 0.11, P < .005), elasticity remained constant. In rats with acute liver injury, elasticity (2.96 kPa +/- 0.63) and viscosity (0.85 kPa +/- 0.22) increased (P < .005), while fibrogenesis and inflammation were observed without substantial fibrosis or steatosis. At multivariate analysis in all rats, liver elasticity correlated only with myofibroblast activation (P < .001, r > 0.6).


CONCLUSIONS
The results suggest that in nonalcoholic fatty rat liver, MR elastography may be useful in the early detection of steatohepatitis by showing increased elasticity and appearing before fibrosis development, which was linked to myofibroblast activation.


BACKGROUND
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2523081817/-/DC1.
Salameh
Najat
N
Diagnostic Radiology Unit, and Laboratory of Gastroenterology, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium. najat.salameh@u-psud.fr
Larrat
Benoît
B
Abarca-Quinones
Jorge
J
Pallu
Stéphane
S
Dorvillius
Mylène
M
Leclercq
Isabelle
I
Fink
Mathias
M
Sinkus
Ralph
R
Van Beers
Bernard E
BE
D000818:Animals; D002251:Carbon Tetrachloride; D002796:Choline Deficiency; D054459:Elasticity Imaging Techniques; D005234:Fatty Liver / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009963:Orotic Acid; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D011347:Procollagen; D053773:Transforming Growth Factor beta1; D009963:Orotic Acid; D002251:Carbon Tetrachloride