title: In vivo quantification of liver stiffness in a rat model of hepatic fibrosis with acoustic radiation force.
abstract: Liver fibrosis is currently staged using needle biopsy, a highly invasive procedure with a number of disadvantages. Measurement of liver stiffness changes that accompany progression of the disease may provide a quantitative and noninvasive method to assess the health of the liver. The purpose of this study is to investigate the correlation between liver stiffness measured by radiation force induced shear waves and disease related changes in the liver. An additional aim is to present initial findings on the effects of liver viscosity on radiation force induced shear wave morphology. Liver fibrosis was induced in 10 rats using carbon tetrachloride (CCl(4)), while five rats acted as controls. Liver stiffness was measured in vivo in all rats after a treatment period of 8 weeks using a modified Siemens SONOLINE Antares scanner (Siemens Medical Solutions USA, Ultrasound Division, Issaquah, WA, USA). The spatial coherence of radiation force induced shear waves propagating in the viscoelastic rat liver decreased significantly with propagation distance, compared with shear waves in an elastic phantom and a finite element model of a purely elastic medium. Animals were sacrificed after imaging and liver samples were taken for histopathologic analysis and collagen quantification using picrosirius red staining and hydroxyproline assay. At the end of the treatment period, five rats had healthy livers (stage F0), while six had severe fibrosis (F3) and the rest had light to moderate fibrosis (F1 and F2). The measured liver stiffness for the F0 group was 1.5+/-0.1 kPa (mean+/-95% confidence interval) and for F3 livers was 1.8+/-0.2 kPa. In this study, liver stiffness was found to be linearly correlated with the amount of collagen in the liver measured by picrosirius red staining (r(2)=0.43, p=0.008). In addition, stiffness spatial heterogeneity was also linearly correlated with liver collagen content (r(2)=0.58, p=0.001) by picrosirius red staining. These results are consistent with those obtained by Salameh et al. (2007) and Yin et al. (2007b) using animal models of liver fibrosis and MR elastography. This suggests that stiffness measurement using acoustic radiation force can provide a quantitative assessment of the extent of fibrosis in the liver and can be potentially used for the diagnosis, management and study of liver fibrosis.
authors.affiliation: Department of Biomedical Engineering, Duke University, Duke University Medical Center, Durham, NC 27708-0281, USA. michael.h.wang@duke.edu
authors.forename: Michael H
authors.initials: MH
authors.lastname: Wang
authors.forename: Mark L
authors.initials: ML
authors.lastname: Palmeri
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Guy
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Laurence W
authors.initials: LW
authors.lastname: Hedlund
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Nightingale
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D003094:Collagen / Q000032:analysis; D004548:Elasticity; D054459:Elasticity Imaging Techniques / Q000379:methods*; D005240:Feasibility Studies; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014783:Viscosity
chemical_list: D003094:Collagen; D002251:Carbon Tetrachloride
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