Acoustic Radiation Force Imaging(ARFI) and Transient Elastography(TE) for liver fibrosis assessment in chronic viral hepatitis

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1 Acoustic Radiation Force Imaging(ARFI) and Transient Elastography(TE) for liver fibrosis assessment in chronic viral hepatitis Poster No.: C-2115 Congress: ECR 2013 Type: Scientific Exhibit Authors: A. Corazza, G. Turtulici, A. Arcidiacono, G. Ferrero, S. Perugin Bernardi, E. Silvestri ; Genova/IT, Genova (GE)/IT, Genoa 4 (GE)/IT, Genoa/IT Keywords: Inflammation, Infection, Comparative studies, Ultrasound, Liver, Abdomen DOI: /ecr2013/C-2115 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 27

2 Purpose Liver fibrosis evaluation is an important step in clinical management of patients with chronic viral hepatitis. Prognosis assessment and treatment of these patients mostly rely on the staging of liver fibrosis. Liver biopsy (LB) is still considered the gold standard for hepatological evaluation, but in the recent years many non-invasive methods have been proposed to replace this invasive procedure in order to make liver fibrosis evaluation easier and safer for patient. The aim of our study is to assess the effectiveness of combining two non-invasive ultrasound-based elastographic methods in staging liver fibrosis in patients with chronic viral hepatitis: acoustic radiation force impulse (ARFI) and transient elastography (TE). Page 2 of 27

3 Methods and Materials Transient elastography (TE) and Acoustic Radiation Force Impulse (ARFI) elastography are non-invasive methods for the evaluation of liver fibrosis using ultrasound waves. Basically they use respectively a mechanical pulse and a ultrasonic pulse to generate shear waves into liver tissue in order to measure its elasticity. TE uses a single ultrasonic transducer that is both used as an ultrasonic emitter and receiver and as a low-frequency piston-like vibrator to generate a transient vibration. A low-frequency elastic wave is sent through the medium under investigation by the vibrator. Elasticity is derived from the velocity of the low-frequency elastic wave. The principle of ARFI elastography is that compression of the liver parenchyma induces a smaller strain in hard tissues than in softer ones. The compression is provided by an acoustic pulse, automatically generated by the ultrasound transducer, that propagates deep into the tissue generating orthogonal shearwaves. Their speed, can be quantified (in meters/ second) by a proprietary implementation of ARFI technology in a precise liver segment, focusing on a region-of-interest (ROI), and is displayed on the screen. The propagation speed increases with fibrosis severity. Fig. 1: ARFI imaging technology. red line: high energy acoustic pulse; green box: sampling ROI for measurements; yellow arrows: shear waves generated by the Page 3 of 27

4 acoustic pulse and propagating orthogonally into liver parenchyma; blue lines: transducer receiving pulses. References: - Genova/IT PATIENTS Our study includes 18 patients (8 males, 10 females; mean age:61±15) with diagnosis of chronic viral hepatitis (11 HBsAg positive and 7 HCV-RNA positive). All of them underwent liver biopsy (LB) within last 6 months and TE in the last month. Fibrosis was staged on a 0-4 scale according to METAVIR score (F0: no fibrosis# F1: portal fibrosis without septa# F2: portal fibrosis and few septa extending into lobules; F3: numerous septa extending to adjacent portal tracts or terminal hepatic venules; F4: cirrhosis). Exclusion criteria were history of hepatic nodules or masses, hepatobiliary surgery, complications like ascites, pregnancy, and any other co-existing liver disease. TE was performed in all patients with a FibroScan TM device (Echosens - Paris, France) by 2 experienced physicians (more than 200 examinations each). For the 18 patients a median value of the liver stiffness (LS) was obtained, measured in kpa. Only patients with measurements obtained with a success rate of at least 60%, with an IQR<30%, were included. Table 1: Main patients characteristics.(xuln: times the upper limit of normal) Page 4 of 27

5 References: - Genova/IT ARFI Arfi was performed in all the patients with a Siemens Acuson S2000 TM ultrasound system provided with Virtual Touch Tissue Imaging and Quantification software. The physician selected the depth at which the liver elasticity has to be evaluated, by placing a measuring box (10 mm long and 5 mm wide) in the desired ROI. The patients were examined supine and in left decubitus in order to investigate the whole liver parenchyma and were asked to stop breathing for a moment during the shear wave velocity (SWV) measurement. ARFI measurement were performed for every liver segment and a median value expressed in meters/second (m/s) was calculated for all of them in order to have a quantitative reproducible measure of the whole liver stiffness. The most discriminating cut-off values were determined from the distribution of SWV according to METAVIR fibrosis stage and were established at 1.18(F#1), 1.28(F#2), 1.60(F#3), 2.0(F#4). The procedure was performed during normal liver examinations and took about 5 minutes per patient. No complications occurred. Fig. 2: Example of measurement into liver segment n.2 References: Ospedale Evangelico Internazionale di Genova Page 5 of 27

6 Fig. 3: Example of measurement into liver segment n.3 References: Ospedale Evangelico Internazionale di Genova Page 6 of 27

7 Fig. 4: Example of measurement into liver segment n.4 References: Ospedale Evangelico Internazionale di Genova STATISTICAL ANALYSIS The statistical analysis was performed collecting data in a Microsoft Excel file and using Med-Calc Software (MedCalc program, Belgium). For numerical variables, mean value and standard deviation were calculated. Spearman's rank correlation coefficient was used to assess the correlation between elastographic methods and with histologic findings(metavir scoring system, ordinal scale). Cut-off values were chosen so that sensitivity and specificity would be the highest. A p-value less than 0.05 was regarded as significant for each statistic test. Page 7 of 27

8 Fig. 5: Example of measurement into liver segment n.5 References: Ospedale Evangelico Internazionale di Genova Page 8 of 27

9 Fig. 6: Example of measurement into liver segment n.6 References: Ospedale Evangelico Internazionale di Genova Page 9 of 27

10 Fig. 7: Example of measurement into liver segment n.7 References: Ospedale Evangelico Internazionale di Genova Page 10 of 27

11 Fig. 8: Example of measurement into liver segment n.8 References: Ospedale Evangelico Internazionale di Genova Page 11 of 27

12 Images for this section: Fig. 1: ARFI imaging technology. red line: high energy acoustic pulse; green box: sampling ROI for measurements; yellow arrows: shear waves generated by the acoustic pulse and propagating orthogonally into liver parenchyma; blue lines: transducer receiving pulses. - Genova/IT Page 12 of 27

13 Fig. 2: Example of measurement into liver segment n.2 Ospedale Evangelico Internazionale di Genova Page 13 of 27

14 Fig. 3: Example of measurement into liver segment n.3 Ospedale Evangelico Internazionale di Genova Page 14 of 27

15 Fig. 4: Example of measurement into liver segment n.4 Ospedale Evangelico Internazionale di Genova Page 15 of 27

16 Fig. 5: Example of measurement into liver segment n.5 Ospedale Evangelico Internazionale di Genova Page 16 of 27

17 Fig. 6: Example of measurement into liver segment n.6 Ospedale Evangelico Internazionale di Genova Page 17 of 27

18 Fig. 7: Example of measurement into liver segment n.7 Ospedale Evangelico Internazionale di Genova Page 18 of 27

19 Fig. 8: Example of measurement into liver segment n.8 Ospedale Evangelico Internazionale di Genova Page 19 of 27

20 Table 1: Main patients characteristics.(xuln: times the upper limit of normal) - Genova/IT Page 20 of 27

21 Results In our preliminary study, valid ARFI measurements were performed in 100% of cases and ranged from 1.19 to 1.91 m/sec. Previous TE measurements resulted valid in 94.4% of cases and ranged from 4.3 to 9.8 kpa. On LB 3 patients had F1, 8 patients were F2, 7 patients resulted F3, no patients were F0 or F4. With our mentioned cut-offs ARFI and TE measurements presented a high correlation between the two techniques(r=0.693)(p<0.0001); a strong correlation was also found between ARFI and the grade of fibrosis(r=0.889)(p<0.0001). Page 21 of 27

22 Conclusion Our preliminary study showed that ARFI in association with TE is a highly predictive method in evaluating liver fibrosis in patients with chronic viral hepatitis. ARFI showed a high correlation with the grade of fibrosis and also with TE with the established cut-offs. The combination of the two techniques could be very useful in clinical management of these patients avoiding LB. Unlike TE, ARFI is a faster examination (about 5 minutes), can be performed also from less-experienced operators (optimal knowledge of liver segmentation is required), and in patients with ascites; it allows a more comprehensive evaluation of the whole liver tissue (right and left lobe) and grants almost zero percentage of failure. The main advantage of ARFI elastography is that this technology is integrated into an ultrasound machine that can also perform real time b-mode liver evaluation and, eventually, Doppler examination and contrast enhanced ultrasonography in the same session(fig. 9 on page 23, Fig. 10 on page 23, Fig. 11 on page 24 ). The weak point of our study is the limited number of patients; anyway our preliminary results correlates with more comprehensive studies from other Authors and are encouraging for further work. Page 22 of 27

23 Images for this section: Fig. 9: Example of portal vein Doppler imaging conducted during a normal US liver evaluation; in the same session it's possible performing ARFI measurement. Ospedale Evangelico Internazionale di Genova Page 23 of 27

24 Fig. 10: Example of middle hepatic vein Doppler imaging conducted during a normal US liver evaluation; in the same session it's possible performing ARFI measurement. Ospedale Evangelico Internazionale di Genova Page 24 of 27

25 Fig. 11: Example of contrast enhanced ultrasonography (CEUS) of an hepatic nodular lesion conducted during a normal US liver evaluation; in the same session it's possible performing ARFI measurement. Ospedale Evangelico Internazionale di Genova Page 25 of 27

26 References 1. Sporea I, Sirli R, Bota S, Popescu A, Sendroiu M, Jurchis A. Comparative study concerning the value of acoustic radiation force impulse elastography (ARFI) in comparison with transient elastography (TE) for the assessment of liver fibrosis in patients with chronic hepatitis B and C. Ultrasound Med Biol Aug;38(8): Colombo S, Buonocore M, Del Poggio A, Jamoletti C, Elia S, Mattiello M, Zabbialini D, Del Poggio P. Head-to-head comparison of transient elastography (TE), real-time tissue elastography (RTE), and acoustic radiation force impulse (ARFI) imaging in the diagnosis of liver fibrosis. J Gastroenterol Apr;47(4): Sporea I, Badea R, Sirli R, Lupsor M, Popescu A, Danila M, Focsa M, Deleanu A. How efficient is acoustic radiation force impulse elastography for the evaluation of liver stiffness? Hepat Mon Jul;11(7): Sporea I, Bota S, Peck-Radosavljevic M, Sirli R, Tanaka H, Iijima H, Badea R, Lupsor M, Fierbinteanu-Braticevici C, Petrisor A, Saito H, Ebinuma H, Friedrich-Rust M, Sarrazin C, Takahashi H, Ono N, Piscaglia F, Borghi A, D'Onofrio M, Gallotti A, Ferlitsch A, Popescu A, Danila M. Acoustic Radiation Force Impulse elastography for fibrosis evaluation in patients with chronic hepatitis C: an international multicenter study. Eur J Radiol Dec;81(12): Forestier N, Gaus A, Herrmann E, Sarrazin C, Bojunga J, Poynard T, Albert J, Gerber L, Schneider MD, Dultz G, Zeuzem S, Friedrich-Rust M. Acoustic radiation force impulse imaging for evaluation of antiviral treatment response in chronic hepatitis C. J Gastrointestin Liver Dis Dec;21(4): Piscaglia F, Salvatore V, Di Donato R, et al. Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography. Ultraschall in der Medizin 2011;32(2): Friedrich-Rust M, Wunder K, Kriener S, et al. Liver fibrosis in viral hepatitis. Noninvasive assessment with acoustic radiation force impulse imaging versus transient elastogra- phy.radiology 2009; 252: Rizzo L, Calvaruso V, Cacopardo B, Alessi N, Attanasio M, Petta S, Fatuzzo F, Montineri A, Mazzola A, L'abbate L, Nunnari G, Bronte F, Di Marco V, Craxì A, Cammà C. Comparison of transient elastography and acoustic radiation force impulse for non-invasive staging of liver fibrosis in patients with chronic hepatitis C. Am J Gastroenterol Dec;106(12): Sporea I, S#irli R, Deleanu A, et al. Comparison of the liver stiffness measurement by transient elastography with the liver biopsy. World J Gastroenterol 2008; 14: Chon YE, Choi EH, Song KJ, Park JY, Kim do Y, Han KH, Chon CY, Ahn SH, Kim SU. Performance of transient elastography for the staging of liver Page 26 of 27

27 fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS One. 2012;7(9):e Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008; 134: Sporea I, S#irli R, Popescu A, et al. Transient elastography (FibroScan) as compared to real time-elastography (Siemens) in patients with chronic hepatopathies. Gastroenterology 2009; 136: A-327. Lupsor M, Badea R, Stefanescu H, et al. Performance of a new elastographic method (ARFI technology) compared to unidimensional transient elastography in the noninvasive assessment of chronic hepatitis C. Preliminary results. J Gastrointestin Liver Dis 2009; 18): Gebo KA, Herlong HF, Torbenson MS, et al. Role of liver biopsy in management of chronic hepatitis C: a systematic review. Hepatology 2002; 36 (5 Suppl 1): S161-S172. Sandrin L, Tanter M, Gennisson JL, Catheline S, Fink M. Shear elasticity probe for soft tissues with 1D transient elastography.ieee Trans Ultrason Ferroelec Freq Control 2002b;49: Sporea I, Sirli R, Popescu A, et al. How relevant is real time elastography (Siemens) for the evaluation of liver stiffness? Ultrasound Med Biol 2009; 35 (Suppl): S53. Page 27 of 27

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