Value of quantitative contrast-enhanced ultrasound in differential diagnosis of focal liver lesions

Contrast-enhanced ultrasound (bolus intravenous injection of 1.2 ml of SonoVue (Bracco Swiss SA, Switzerland) followed with 5 ml saline flush) was performed in 57patients aged 25-72 years old with focal liver lesions (34 benign lesions and 23 malignant). All patients underwent contrast-enhanced liver computed tomography. In 34 (11 + 23) of 57 cases, a morphological evaluation was performed after a targeted biopsy or autopsy. The studies utilized DC-8 scanner (Mindray, China) with a 3-5 MHz convex transducer, in specialized Contrast mode with a low mechanical index (0.08-0.12). The quantitative analysis was performed in post-processing mode with built in ContrastQA software. Cine-loop from the moment of the introduction of the ultrasound contrast agent up to complete washout of ultrasound contrast agent from the lesion or up 300 s in the cases of absence of wash out was analysed. Quantitative parameters of CEUS (1) arrival time (AT), 2) ascending slope (AS) or slope of wash in (SWI), 3) time to the peak intensity (TPI) or time to peak (TTP), 4) peak intensity (PI), 5) half of descending time (DT/2), 6) descending slope (DS)) were analysed. The following parameters were proposed for the differential diagnosis of malignant lesions: DT/2 ≤ 147.970 s (sensitivity - 100.0%, specificity - 93.1%, AUC - 0.997), DS ≤ -0.060 dB/s (sensitivity - 95.7%, specificity - 96.6%, AUC - 0.996). For the differential diagnosis of liver metastases were proposed DT/2 ≤ 82.340 s (sensitivity - 100.0%, specificity - 100.0%, AUC - 1.000), DS < -0.090 dB/s (sensitivity - 94.7%, specificity - 100.0%, AUC - 0.992). For haemangiomas in the group of benign lesions TPI ≥ 32.620 s (sensitivity - 97.5%, specificity - 100.0%, AUC - 0.998), AS ≤ 0.670 dB/s (sensitivity - 77.5%, specificity - 100.0%, AUC - 0.934). For focal nodular hyperplasia in the group of benign lesions PI ≥ 36.280 dB (sensitivity - 81.80%, specificity - 87.50%, AUC - 0.895). Quantitative analysis of contrast-enhanced ultrasound based diagnostic algorithm was suggested for differential diagnosis of different types focal liver lesions.

ультразвуковое исследование с контрастным усилением (КУУЗИ), количественный анализ КУУЗИ, Соновью, очаговые образования печени, гемангиома, очаговая узловая гиперплазия, метастаз, contrast-enhanced ultrasound (CEUS), quantitative CEUS, SonoVue, focal liver lesion, haemangioma, focal nodular hyperplasia, metastasis

1. Зубарев А.В. Методы медицинской визуализации - УЗИ, КТ, МРТ - в диагностике опухолей и кист печени. М.: Видар, 1995. С. 10-14.

2. Вишневский В.А., Корняк Б.С., Щеголев А.И., Калиниченко А.Ю., Колганова И.П., Тинькова И.О., Яковлева О.В., Кармазановский Г.Г. Кистозные опухоли печени // Медицинская визуа лизация. 2004. № 4. С. 35-42.

3. Аскерова Н.Н., Кармазановский Г.Г. Контрастное усиление изображения препаратом SonoVue: пути усовершенствования ультразвуковой диагностики очаговой патологии органов брюшной полости и забрюшинного пространства // Медицинская визуализация. 2015. № 1. С. 115-125.

4. Сенча А.Н., Могутов М.С., Патрунов Ю.Н., Пеняева Э.И., Кашманова А.В., Сенча Е.А. Ультразвуковое исследование с использованием контрастных препаратов. М.: Видар-М, 2015. 144 p.

5. Агева З.А., Авхадов Т.С., Горбов Л.В., Каранадзе Е.Н. Опыт применения контрастной сонографии в дифференциальной диагностике опухолевых образований печени // Медицинская визуализация. 2017. № 1. С. 13-19.

6. Пеняева Э.И., Камалов Ю.Р., Сенча А.Н., Патрунов Ю.Н., Сенча Е.А. Ультразвуковое исследование с контрастным усилением в дифференциальной диагностике опухолевых образований печени // Медицинская визуа лизация. 2017. № 2. С. 36-52.

7. Trillaud M., Bruel J.M., Valette P.J., Vilgrain V., Schmutz G., Oyen R., Jakubowski W., Danes J., Valek V., Greis C. Characterization of focal liver lesions with SonoVue-enhanced sonography: international multicenter-study in comparison to CT and MRI // World J. Gastroenterol. 2009. V. 15. No. 30. P. 3748-3756.

8. Wang W., Liu J.Y., Yang Z., Wang Y.F., Shen S.L., Yi F.L., Huang Y., Xu E.J., Xie X.Y., Lu M.D., Wang Z., Chen L.D. Hepatocellular adenoma: compa rison between real-time contrast-enhanced ultrasound and dynamic computed tomography // Springerplus. 2016. V. 5. No. 1. P. 951. Doi: 10.1186/s40064-016-2406-z.

9. Ophir J., Parker K.J. Contrast agents in diagnostic ultrasound // Ultrasound Med. Biol. 1990. V. 16. No. 2. P. 209.

10. Solbiati L., Martegani A., Leen E., Correas J.M., Burns P.N., Becker D. Contrast-Enhanced Ultrasound of Liver Diseases. Milan: Springer-Verlag, 2003. 131 p.

11. Albrecht T., Blomley M., Bolondi L., Claudon M., Correas J.M., Cosgrove D., Greiner L., Jager K., Jong N.D., Leen E., Lencioni R., Lindsell D., Martegani A., Solbiati L., Thorelius L., Tranquart F., Weskott H.P., Whittingham T., EFSUMB Study Group. Guidelines for the use of contrast agents in ultrasound. January 2004 // Ultraschall Med. 2004. V. 25. No. 4. P. 249-256. Doi: 10.1055/s-2004-813245.

12. Claudon M., Cosgrove D., Albrecht T., Bolondi L., Bosio M., Calliada F., Correas J.M., Darge K., Dietrich C., D’Onofrio M., Evans D.H., Filice C., Greiner L., Jager K., Jong N., Leen E., Lencioni R., Lindsell D., Martegani A., Meairs S., Nolsoe C., Piscaglia F., Ricci P., Seidel G., Skjoldbye B., Solbiati L., Thorelius L., Tranquart F., Weskott H.P., Whittingham T. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) - update 2008 // Ultraschall Med. 2008. V. 29. No. 1. P. 28-44. Doi: 10.1055/s-2007-963785.

13. Claudon M., Dietrich C.F., Choi B.I., Cosgrove D.O., Kudo M., Nolsoe C.P., Piscaglia F., Wilson S.R., Barr R.G., Chammas M.C., Chaubal N.G., Chen M.H., Clevert D.A., Correas J.M., Ding H., Forsberg F., Fowlkes J.B., Gibson R.N., Goldberg B.B., Lassau N., Leen E.L., Mattrey R.F., Moriyasu F., Solbiati L., Weskott H.P., Xu H.X. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver - update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS // Ultraschall Med. 2013. V. 34. No. 1. P. 11-29. Doi: 10.1055/s-0032-1325499.

14. Weskott H.-P. Contrast Sonography. 2nd ed. Bremen: UNI-MED Science, 2013. 240 p.

15. Cantisani V., David E., Meloni F.M., Dietrich C.F., Badea R., Messineo D., D’Ambrosio F., Pisgalia F. Recall strategies for patients found to have a nodule in cirrhosis: is there still a role for CEUS? // Med. Ultrason. 2015. V. 17. No. 4. P. 515-520. Doi: 10.11152/mu.2013.2066.174.rsp.

16. Quaia E., Palumbo A., Rossi S., Degobbis F., Cernic S., Tona G., Cova M. Comparison of visual and quantitative analysis for characterization of insonated liver tumors after microbubble contrast injection // Am. J. Roentgenol. 2006. V. 186. No. 6. P. 1560-1570. Doi: 10.2214/AJR.05.0527.

17. Huang-Wei C., Bleuzen A., Bourlier P., Roumy J., Bouakaz A., Pourcelot L., Tranquart F. Differential diagnosis of focal nodular hyperplasia with quantitative parametric analysis in contrastenhanced sonography // Invest. Radiol. 2006. V. 41. No. 3. P. 363-368. Doi: 10.1097/01.rli.0000195835.56589.55.

18. Pei X.Q., Liu L.Z., Zheng W., Cai M.Y., Han F., He J.H., Li A.H., Chen M.S. Contrast-enhanced ultrasonography of hepatocellular carcinoma: corre lation between quantitative parameters and arteries in neoangiogenesis or sinusoidal capillarization // Eur. J. Radiol. 2012. V. 81. No. 3. P. e182-e188. Doi: 10.1016/j.ejrad.2011.01.083.

19. Dill-Macky M., Burns P., Khalili K., Wilson S.R. Focal hepatic masses: enhancement patterns with SH U 508A and pulse-inversion US // Radiology. 2002. V. 222. No. 1. P. 95-102. Doi: 10.1148/radiol.2221010092.

20. Wen Y.L., Kudo M., Zheng R.Q., Ding H., Zhou P., Minami Y., Chung H., Kitano M., Kawasaki T., Maekawa K. Characterization of hepatic tumors: value of contrast-enhanced coded phase-inversion harmonic angio // AJR. 2004. V. 182. No. 4. P. 1019-1026. Doi: 10.2214/ajr.182.4.1821019.

21. Dietrich C.F., Mertens J.C., Braden B., Schuessler G., Ott M., Ignee A. Contrast-enhanced ultrasound of histologically proven liver hemangiomas // Hepatology. 2007. V. 45. No. 5. P. 1139-1145. Doi: 10.1002/hep.21615.

22. Matsui O. Detection and characterization of hepatocellular carcinoma by imaging // Clin. Gastroenterol. Hepatol. 2005. V. 3. No. 10. Suppl. 2. P. S136-S140.

23. Xu H.X., Lu M.D. The current status of contrastenhanced ultrasound in China // J. Med. Ultrason. (2001). 2010. V. 37. No. 3. P. 97-106. Doi: 10.1007/s10396-010-0264-9.

24. Klein D., Jenett M., Gassel H.J., Sandstede J., Hahn D. Quantitative dynamic contrast-enhanced sonography of hepatic tumors // Eur. Radiol. 2004. V. 14. No. 6. P. 1082-1091.

25. Koda M., Matsunaga Y., Ueki M., Maeda Y., Mimura K., Okamoto K., Hosho K., Murawaki Y. Qualitative assessment of tumor vascularity in hepatocellular carcinoma by contrast-enhanced coded ultrasound: comparison with arterial phase of dynamic CT and conventional color/power Doppler ultrasound // Eur. Radiol. 2004. V. 14. No. 6. P. 1100-1108.

26. Quaia E., Calliada F., Bertolotto M., Rossi S., Garioni L., Rosa L., Pozzi-Mucelli R. Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride-filled microbubble contrast agent: diagnostic performance and confidence // Radiology. 2004. V. 232. No. 2. P. 420-430. Doi: 10.1148/radiol.2322031401.

27. Von Herbay A., Westendorff J., Gregor M. Contrast-enhanced ultrasound with SonoVue: differentiation between benign and malignant focal liver lesions in 317 patients // J. Clin. Ultrasound. 2010. V. 38. No. 1. P. 1-9. Doi: 10.1002/jcu.20626.

28. Fan Z.H., Chen M.H., Dai Y., Wang Y.B., Yan K., Wu W., Yang W., Yin S.S. Evaluation of primary malignancies of the liver using contrast-enhanced sonography: correlation with pathology // AJR. 2006. V. 186. No. 6. P. 1512-1519. Doi: 10.2214/AJR.05.0943.

29. Wilson S.R., Lyshchik A., Piscaglia F., Cosgrove D., Jang H.J., Sirlin C., Dietrich C.F., Kim T.K., Willmann J.K., Kono Y. CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI // Abdom. Radiol. (NY). 2018. V. 43. No. 1. P. 127-142. Doi: 10.1007/s00261-017-1250-0.

30. Shan Q.Y., Chen L.D., Zhou L.Y., Wang Z., Liu G.J., Huang Y., Li W., Liu J.Y., Xie X.Y., Lu M.D., Liu J., Wang W. Focal lesions in fatty liver: if quantitative analysis facilitates the differentiation of atypical benign from malignant lesions // Sci. Rep. 2016. V. 6. P. 18640. Doi: 10.1038/srep18640.

31. Beyer L.P., Pregler B., Wiesinger I., Stroszczynski C., Wiggermann P., Jung E.M. Continuous dynamic registration of microvascularization of liver tumors with contrast-enhanced ultrasound // Radiol. Res. Pract. 2014. 2015: 347416. Doi: 10.1155/2014/347416.

32. Pei X.Q., Liu L.Z., Xiong Y.H., Zou R.H., Chen M.S., Li A.N., Cai M.Y. Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma // Br. J. Radiol. 2013. V. 86. No. 1023. P. 20120536. Doi: 10.1259/bjr.20120536.