Can early hepatic fibrosis stages be discriminated by combining ultrasonic parameters? Razika Bouzitoune a , Mahmoud Meziri a,⇑ , Christiano Bittencourt Machado b , Frédéric Padilla c , Wagner Coelho de Albuquerque Pereira d a Laboratoire de Magnétisme et de Spectroscopie des Solides (LM2S), Université Badji Mokhtar, Annaba 23000, Algeria b Biomedical Ultrasound Laboratory, Estácio de Sá University, Rio de Janeiro, Brazil c LabTau, Unité Inserm1032, 141 Cours Albert Thomas, Lyon 69003, France d Biomedical Engineering Program, COPPE/Federal University of Rio de Janeiro, RJ, Brazil article info Article history: Received 5 August 2015 Received in revised form 31 January 2016 Accepted 22 February 2016 Available online 27 February 2016 Keywords: Discriminant analysis Liver fibrosis Ultrasound abstract In this study, we put forward a new approach to classify early stages of fibrosis based on a multiparamet- ric characterization using backscatter ultrasonic signals. Ultrasonic parameters, such as backscatter coefficient (Bc), speed of sound (SoS), attenuation coefficient (Ac), mean scatterer spacing (MSS), and spectral slope (SS), have shown their potential to differentiate between healthy and pathologic samples in different organs (eye, breast, prostate, liver). Recently, our group looked into the characterization of stages of hepatic fibrosis using the parameters cited above. The results showed that none of them could individually distinguish between the different stages. Therefore, we explored a multiparametric approach by combining these parameters in two and three, to test their potential to discriminate between the stages of liver fibrosis: F0 (normal), F1, F3, and/without F4 (cirrhosis), according to METAVIR Score. Discriminant analysis showed that the most relevant individual parameter was Bc, followed by SoS, SS, MSS, and Ac. The combination of (Bc, SoS) along with the four stages was the best in differentiating between the stages of fibrosis and correctly classified 85% of the liver samples with a high level of signif- icance (p < 0.0001). Nevertheless, when taking into account only stages F0, F1, and F3, the discriminant analysis showed that the parameters (Bc, SoS) and (Bc, Ac) had a better classification (93%) with a high level of significance (p < 0.0001). The combination of the three parameters (Bc, SoS, and Ac) led to a 100% correct classification. In conclusion, the current findings show that the multiparametric approach has great potential in differentiating between the stages of fibrosis, and thus could play an important role in the diagnosis and follow-up of hepatic fibrosis. Ó 2016 Elsevier B.V. All rights reserved. 1. Introduction It is known that the initiation of the hepatic fibrosis process alters the acoustical properties of the tissues. Therefore, techniques for biological tissue characterization with ultrasound (US) have been proposed in the last decades. Ultrasonic tissue characteriza- tion using radio frequency (RF) signals has shown the potential in supplying the data required for the assessment of tissue microstructures. In this context, different investigations have indi- cated that parameters such as Speed of Sound (SoS), Backscatter coefficient (Bc), Spectral Slope (SS), Attenuation coefficient (Ac) and Mean Scatterer Spacing (MSS) could differentiate normal from pathological tissues. For example, several studies have utilized these parameters for characterizing different organs, such as breast, kidney, skin, spleen, bone [1–6], and hepatic tissue [4,7–11]. So far, however, investigations of the differences between extreme liver structures (e.g., normal vs. cirrhosis or cancerous) [12–14] have neglected the detection of initial stages of fibrosis. Chronic viral hepatic infections lead to progressive fibrosis. They may eventually lead to severe complications like cirrhosis, a state that may lead to serious problems like oesophageal varices and hepatocellular carcinoma. To obviate this, it would be interest- ing to quantify the stages of hepatic fibrosis. The methods for the diagnosis of fibrosis have made headway during the last decade (FibroTest, Elastography, and Ultrasound). However, liver biopsy remains the ‘‘gold standard” to assess the degree of liver fibrosis [15] despite certain limitations (i.e., high level of morbidity and http://dx.doi.org/10.1016/j.ultras.2016.02.014 0041-624X/Ó 2016 Elsevier B.V. All rights reserved. ⇑ Corresponding author at: BP 790 RP, Annaba 23000, Algeria. Tel.: +213 551 91 85 17; fax: +213 38 87 53 59. E-mail addresses: mirazika75@yahoo.fr (R. Bouzitoune), mahmoud.meziri@ gmail.com (M. Meziri), cbmfisio@gmail.com (C.B. Machado), frederic.pad@gmail. com (F. Padilla), wagner.coelho@ufrj.br (W.C.A. Pereira). Ultrasonics 68 (2016) 120–126 Contents lists available at ScienceDirect Ultrasonics journal homepage: www.elsevier.com/locate/ultras