Abstract

Hepatic fibrosis and cirrhosis are a growing global health problem with increasing mortality rates. Early diagnosis and staging of hepatic fibrosis represent a major challenge. Currently liver biopsy is the gold standard for fibrosis assessment; however, biopsy requires an invasive procedure and is prone to sampling error and reader variability. In the current study we investigate using quantitative analysis of computer-extracted features of B-mode ultrasound as a non-invasive tool to characterize hepatic fibrosis. Twenty-two rats were administered diethylnitrosamine (DEN) orally for 12 weeks to induce hepatic fibrosis. Four control rats did not receive DEN. B-mode ultrasound scans sampling throughout the liver were acquired at baseline, 10, and 13 weeks. Computer extracted quantitative parameters representing brightness (echointensity, hepatorenal index) and variance (heterogeneity, anisotropy) of the liver were studied. DEN rats showed an increase in echointensity from 37.1 ± SD 7.8 to 53.5 ± 5.7 (10 w) to 57.5 ± 6.1 (13 w), while the control group remained unchanged at an average of 34.5 ± 4.5. The three other features studied increased similarly over time in the DEN group. Histologic analysis showed METAVIR fibrosis grades of F2-F4 in DEN rats and F0-F1 in controls. Increasing imaging parameters correlated with increasing METAVIR grades, and anisotropy showed the strongest correlation (ρ = 0.58). Sonographic parameters combined using multiparametric logistic regression were able to differentiate between clinically significant and insignificant fibrosis. Quantitative B-mode ultrasound imaging can be implemented in clinical settings as an accurate non-invasive tool for fibrosis assessment.

Highlights

  • Hepatic fibrosis and cirrhosis are a growing global health problem with increasing mortality rates

  • The effect of diethylnitrosamine is demonstrated by changes in weight over time and confirmed by histopathologic analysis

  • Advancement in current methods of assessing and monitoring changes hepatic fibrosis will be important for patient management as well as for studies developing antifibrotic drugs[24]

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Summary

Introduction

Hepatic fibrosis and cirrhosis are a growing global health problem with increasing mortality rates. In the current study we investigate using quantitative analysis of computer-extracted features of B-mode ultrasound as a non-invasive tool to characterize hepatic fibrosis. There are limitations to hepatic biopsy, including complications of the invasive procedure, sampling error, and intra- and interobserver variability[6,7] These limitations highlight the need for alternative methods of assessing fibrosis that are noninvasive, minimize sampling www.nature.com/scientificreports/. Improvement of tools assessing hepatic fibrosis can be especially helpful to monitor fibrosis early its course Toward this goal, the computerized analysis of liver features on B-mode ultrasound (US), which is widely available and used commonly in the clinic, could help to noninvasively characterize the progression of fibrosis. Applying computerized analysis to the liver may allow for measurement of fibrosis from common, standard B-mode abdominal examinations using quantitative continuous measures

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