In vivo ultrasound thermal ablation control using echo decorrelation imaging in rabbit liver and VX2 tumor

Autoři: Mohamed A. Abbass aff001;  Syed A. Ahmad aff002;  Neeraja Mahalingam aff001;  K. Sameer Krothapalli aff001;  Jack A. Masterson aff001;  Marepalli B. Rao aff001;  Peter G. Barthe aff004;  T. Douglas Mast aff001
Působiště autorů: Dept of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, United States of America aff001;  Dept of Surgery, University of Cincinnati, Cincinnati, Ohio, United States of America aff002;  Dept of Environmental Health, University of Cincinnati, Cincinnati, Ohio, United States of America aff003;  Guided Therapy Systems/Ardent Sound, Mesa, Arizona, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


The utility of echo decorrelation imaging feedback for real-time control of in vivo ultrasound thermal ablation was assessed in rabbit liver with VX2 tumor. High-intensity focused ultrasound (HIFU) and unfocused (bulk) ablation were performed using 5 MHz linear image-ablate arrays. Treatments comprised up to nine lower-power sonications, followed by up to nine higher-power sonications, ceasing when the average cumulative echo decorrelation within a control region of interest exceeded a predefined threshold (− 2.3, log10-scaled echo decorrelation per millisecond, corresponding to 90% specificity for tumor ablation prediction in previous in vivo experiments). This threshold was exceeded in all cases for both HIFU (N = 12) and bulk (N = 8) ablation. Controlled HIFU trials achieved a significantly higher average ablation rate compared to comparable ablation trials without image-based control, reported previously. Both controlled HIFU and bulk ablation trials required significantly less treatment time than these previous uncontrolled trials. Prediction of local liver and VX2 tumor ablation using echo decorrelation was tested using receiver operator characteristic curve analysis, showing prediction capability statistically equivalent to uncontrolled trials. Compared to uncontrolled trials, controlled trials resulted in smaller thermal ablation regions and higher contrast between echo decorrelation in treated vs. untreated regions. These results indicate that control using echo decorrelation imaging may reduce treatment duration and increase treatment reliability for in vivo thermal ablation.

Klíčová slova:

Acoustics – Cancer treatment – Echoes – Histology – In vivo imaging – Liver and spleen scan – Rabbits – Sonication


1. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. The Lancet. 2018;391(10127):1301–1314. doi: 10.1016/S0140-6736(18)30010-2

2. Sherman M. Hepatocellular carcinoma: epidemiology, surveillance, and diagnosis. Semin Liver Dis. 2010;30(01):3–16. doi: 10.1055/s-0030-1247128 20175029

3. Ardito F, Vellone M, Cassano A, De Rose AM, Pozzo C, Coppola A, et al. Chance of cure following liver resection for initially unresectable colorectal metastases: analysis of actual 5-year survival. J Gastrointest Surg. 2013;17(2):352–359. doi: 10.1007/s11605-012-2103-3 23225196

4. Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol. 2014;11:525–535. doi: 10.1038/nrclinonc.2014.122 25091611

5. Delis SG, Dervenis C. Selection criteria for liver resection in patients with hepatocellular carcinoma and chronic liver disease. World J Gastroenterol. 2008;14(22):3452–3460. doi: 10.3748/wjg.14.3452 18567070

6. Dhar V, Thomas RM, Ahmad SA. In: Bentrem D, Benson AB, editors. Repeat Hepatectomy for Colorectal Liver Metastases. Cham: Springer International Publishing; 2016. p. 203–220.

7. Morris EJA, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L, et al. Surgical management and outcomes of colorectal cancer liver metastases. BJS. 2010;97(7):1110–1118.

8. Lee MW, Raman SS, Asvadi NH, Siripongsakun S, Hicks RM, Chen J, et al. Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis. Hepatology. 2017;65(6):1979–1990 28170115

9. Hoffmann R, Rempp H, Kessler DE, Weiss J, Pereira PL, Nikolaou K, et al. MR-guided microwave ablation in hepatic tumours: initial results in clinical routine. Eur Radiol. 2017;27(4):1467–1476. doi: 10.1007/s00330-016-4517-x 27553935

10. Chartier T, Carpentier O, Genestie B, Hornez JC, Monchau F. Numerical and ex vivo studies of a bioprobe developed for laser-induced thermotherapy (LITT) in contact with liver tissue. Med Eng Physics. 2016;38(8):733–740.

11. Makin IRS, Mast TD, Faidi W, Runk MM, Barthe PG, Slayton MH. Miniaturized ultrasound arrays for interstitial ablation and imaging. Ultrasound Med Biol. 2005;31(11):1539–1550. doi: 10.1016/j.ultrasmedbio.2005.07.008 16286031

12. Delabrousse E, Salomir R, Birer A, Paquet C, Mithieux F, Chapelon JY, et al. Automatic temperature control for MR-guided interstitial ultrasound ablation in liver using a percutaneous applicator: Ex vivo and in vivo initial studies. Magn Reson Med. 2010;63(3):667–679 20187177

13. Vincenot J, Melodelima D, Chavrier F, Vignot A, Kocot A, Chapelon JY. Electronic beam steering used with a toroidal HIFU transducer substantially increases the coagulated volume. Ultrasound Med Biol. 2013;39(7):1241–1254. doi: 10.1016/j.ultrasmedbio.2013.01.019 23643055

14. Forner A, Reig ME, Rodriguez de Lope C, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30(01):061–074. doi: 10.1055/s-0030-1247133

15. Kim KH, Yoon YS, Yu CS, Kim TW, Kim HJ, Kim PN, et al. Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases. J Korean Surg Soc. 2011;81(1):25–34. doi: 10.4174/jkss.2011.81.1.25 22066097

16. Ng KKC, Lam CM, Poon RTP, Shek TWH, Fan ST, Wong J. Delayed portal vein thrombosis after experimental radiofrequency ablation near the main portal vein. Br J Surg. 2004;91:632–639 15122617

17. Hynynen K, McDannold N. MRI guided and monitored focused ultrasound thermal ablation methods: A review of progress. Int J Hyperthermia. 2004;20(7):725–737. doi: 10.1080/02656730410001716597 15675668

18. Lepetit-Coiffé M, Laumonier H, Seror O, Quesson B, Sesay MB, Moonen CTW, et al. Real-time monitoring of radiofrequency ablation of liver tumors using thermal-dose calculation by MR temperature imaging: Initial results in nine patients, including follow-up. Eur Radiol. 2010;20(1):193–201. doi: 10.1007/s00330-009-1532-1 19657650

19. Napoli A, Anzidei M, Ciolina F, Marotta E, Cavallo Marincola B, Brachetti G, et al. MR-guided high-intensity focused ultrasound: Current status of an emerging technology. Cardiovasc Intervent Radiol. 2013;36(5):1190–1203. doi: 10.1007/s00270-013-0592-4 23474917

20. Vigen KK, Jarrard J, Rieke V, Frisoli J, Daniel BL, Pauly KB. In vivo porcine liver radiofrequency ablation with simultaneous MR temperature imaging. J Magn Reson Imaging. 2006;23(4):578–584 16508928

21. Kim YS, Lim HK, Rhim H, Lee MW, Choi D, Lee WJ, et al. Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: Analysis of prognostic factors. J Hepatol. 2013;58(1):89–97. doi: 10.1016/j.jhep.2012.09.020 23023009

22. Liu R, Li K, Luo H, Zhang W, Zhang T, Gao M, et al. Ultrasound-guided percutaneous microwave ablation for small liver cancers adjacent to large vessels: long-term outcomes and strategies. Oncol Transl Med. 2017;3:P57–P64.

23. Engstrand J, Toporek G, Harbut P, Jonas E, Nilsson H, Freedman J. Stereotactic CT-guided percutaneous microwave ablation of liver tumors with the use of high-frequency jet ventilation: an accuracy and procedural safety study. Am J Roentgenol. 2017;208(1):193–200. doi: 10.2214/AJR.15.15803

24. Raman SS, Lu DSK, Vodopich DJ, Sayre J, Lassman C. Creation of radiofrequency lesions in a porcine model: correlation with sonography, CT, and histopathology. Am J Roentgenol. 2000;175(5):1253–1258. doi: 10.2214/ajr.175.5.1751253

25. Wiggermann P, Brünn K, Rennert J, Loss M, Wobser H, Schreyer A, et al. Monitoring during hepatic radiofrequency ablation (RFA): comparison of real-time ultrasound elastography (RTE) and contrast-enhanced ultrasound (CEUS): first clinical results of 25 patients. Eur J Ultrasound. 2013;34(6):590–594.

26. Han Y, Hou GY, Wang S, Konofagou E. High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI). Phys Med Biol. 2015;60(15):5911. doi: 10.1088/0031-9155/60/15/5911 26184846

27. Yang W, Alexander M, Rubert N, Ingle A, Lubner M, Ziemlewicz T, et al. Monitoring microwave ablation for liver tumors with electrode displacement strain imaging. In: Proc. IEEE Int. Ultrason. Symp.; 2014. p. 1128–1131.

28. Kumon RE, Gudur MSR, Zhou Y, Deng CX. High-frequency ultrasound M-mode imaging for identifying lesion and bubble activity during high-intensity focused ultrasound ablation. Ultrasound Med Biol. 2012;38(4):626–641. doi: 10.1016/j.ultrasmedbio.2012.01.004 22341055

29. Yan SY, Zhang Y, Sun C, Cao HX, Li GM, Wang YQ, et al. Comparison of real-time contrast-enhanced ultrasonography and standard ultrasonography in liver cancer microwave ablation. Exp Ther Med. 2016;12(3):1345–1348. doi: 10.3892/etm.2016.3448 27602065

30. Toshikuni N, Matsue Y, Ozaki K, Yamada K, Hayashi N, Tsuchishima M, et al. An image fusion system for estimating the therapeutic effects of radiofrequency ablation on hepatocellular carcinoma. Radiol Oncol. 2017;51(3):263–269. doi: 10.1515/raon-2017-0028 28959162

31. Seip R, Tavakkoli J, Carlson R, Wunderlich A, Sanghvi N, Dines K, et al. High-intensity focused ultrasound (HIFU) multiple lesion imaging: Comparison of detection algorithms for real-time treatment control. In: IEEE Int Ultrason Symp. vol. 2; 2002. p. 1427–1430.

32. Chen W, Sanghvi NT, Carlson R, Uchida T. Real-time tissue change monitoring on the Sonablate 500 during high intensity focused ultrasound (HIFU) treatment of prostate cancer. AIP Conf Proc. 2011;1359(1):391–396. doi: 10.1063/1.3607939

33. Curiel L, Huang Y, Vykhodtseva N, Hynynen K. Focused ultrasound treatment of VX2 tumors controlled by local harmonic motion. Phys Med Biol. 2009;54(11):3405. doi: 10.1088/0031-9155/54/11/009 19436103

34. Varghese T, Techavipoo U, Zagzebski JA, Lee J F T. Impact of gas bubbles generated during interstitial ablation on elastographic depiction of in vitro thermal lesions. J Ultrasound Med. 2004;23(4):535–544 15098873

35. Mast TD, Pucke D, Subramanian S, Bowlus W, Rudich S, Buell J. Ultrasound monitoring of in vitro radio frequency ablation by echo decorrelation. J Ultrasound Med. 2008;27(12):1685–1697 19022994

36. Subramanian S, Rudich SM, Alqadah A, Karunakaran CP, Rao MB, Mast TD. In vivo thermal ablation monitoring using ultrasound echo decorrelation imaging. Ultrasound Med Biol. 2014;40(1):102–114. doi: 10.1016/j.ultrasmedbio.2013.09.007 24239361

37. Fosnight TR, Hooi FM, Keil RD, Ross AP, Subramanian S, Akinyi TG, et al. Echo decorrelation imaging of rabbit liver and VX2 tumor during in vivo ultrasound ablation. Ultrasound Med Biol. 2017;43(1):176–186. doi: 10.1016/j.ultrasmedbio.2016.08.025 27712923

38. Hooi FM, Nagle A, Subramanian S, Mast TD. Analysis of tissue changes, measurement system effects, and motion artifacts in echo decorrelation imaging. J Acoust Soc Am. 2015;137(2):585–597. doi: 10.1121/1.4906580 25697993

39. Matsuzawa R, Shishitani T, Yoshizawa S, Umemura SI. Monitoring of lesion induced by high-intensity focused ultrasound using correlation method based on block matching. Jpn J Appl Phys. 2012;51: 07GF26. doi: 10.1143/JJAP.51.07GF26

40. Subramanian S, Schmidt DT, Rao MB, Mast TD. Dependence of ultrasound echo decorrelation on local tissue temperature during ex vivo radiofrequency ablation. Phys Med Biol. 2016;61:2356. doi: 10.1088/0031-9155/61/6/2356 26943026

41. Zhou Z, Wang Y, Song S, Wu W, Wu S, Tsui PH. Monitoring microwave ablation using ultrasound echo decorrelation imaging: an ex vivo study. Sensors. 2019;19(4):977. doi: 10.3390/s19040977

42. Abbass MA, Killin JK, Mahalingam N, Hooi FM, Barthe PG, Mast TD. Real-time spatiotemporal control of high-intensity focused ultrasound thermal ablation using echo decorrelation imaging in ex vivo bovine liver. Ultrasound Med Biol. 2018;44(1):199–213. doi: 10.1016/j.ultrasmedbio.2017.09.007 29074273

43. Abbass MA, Garbo A, Mahalingam N, Killin JK, Mast TD. Optimized echo decorrelation imaging feedback for bulk ultrasound ablation control. IEEE Trans Ultrason Ferroelectr Freq Control. 2018;65(10):1743–1755. doi: 10.1109/TUFFC.2018.2847599 29994657

44. Takagi R, Jimbo H, Iwasaki R, Tomiyasu K, Yoshizawa S, Umemura SI. Feasibility of real-time treatment feedback using novel filter for eliminating therapeutic ultrasound noise with high-speed ultrasonic imaging in ultrasound-guided high-intensity focused ultrasound treatment. Jpn J Appl Phys. 2016;55(7S1):07KC10.

45. Abbass MA. Real-time Control of Ultrasound Thermal Ablation using Echo Decorrelation Imaging Feedback [Ph.D. Dissertation]. Cincinnati (OH): University of Cincinnati; 2018.

46. Wu Hanping, Exner AA, Hong Shi, Bear Joshua, Haaga JR. Dynamic evolutionary changes in blood flow measured by MDCT in a hepatic VX2 tumor implant over an extended 28-day growth period: Time-density curve analysis. Acad Radiol. 2009;16(12):1483–1492. doi: 10.1016/j.acra.2009.09.009 19896066

47. Barthe PG, Slayton MH, Jaeger PM, Makin IRS, Gallagher LA, Mast TD, et al. Ultrasound therapy system and ablation results utilizing miniature imaging/therapy arrays. In: IEEE Int Ultrason Symp. vol. 3; 2004. p. 1792–1795.

48. Scheffer HJ, Nielsen K, van Tilborg AAJM, Vieveen JM, Bouwman RA, Kazemier G, et al. Ablation of colorectal liver metastases by irreversible electroporation: Results of the COLDFIRE-I ablate-and-resect study. Eur Radiol. 2014;24(10):2467–2475. doi: 10.1007/s00330-014-3259-x 24939670

49. Abbass MA, Garbo AJ, Mahalingam N, Killin JK, Mast TD. Real-time control of bulk ultrasound thermal ablation using echo decorrelation imaging feedback. In: Proc IEEE Int Ultrason Symp; 2017.

50. Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika. 1965;52(3/4):591–611. doi: 10.1093/biomet/52.3-4.591

51. Bauer DF. Constructing confidence sets using rank statistics. J Am Stat Assoc. 1972;67(339):687–690. doi: 10.1080/01621459.1972.10481279

52. Conover WJ. Practical Nonparametric Statistics, 2nd ed. New York Chichester Wiley; 1980.

53. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):64–71. doi: 10.1148/radiology.143.1.7063747

54. Krzanowski WJ, Hand DJ. ROC curves for continuous data. 1st ed. Chapman and Hall/CRC; 2009.

55. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics. 1988;44(3):837–845. doi: 10.2307/2531595 3203132

56. Kim KR, Thomas S. Complications of image-guided thermal ablation of liver and kidney neoplasms. Semin Intervent Radiol. 2014; 31(2):138–148. doi: 10.1055/s-0034-1373789 25049443

57. Chen WS, Lafon C, Matula TJ, Vaezy S, Crum LA. Mechanisms of lesion formation in high intensity focused ultrasound therapy. Acoust Res Lett Online. 2003;4(2):41–46. doi: 10.1121/1.1559911

58. Hänsler J, Neureiter D, Wasserburger M, Janka R, Bernatik T, Schneider T, et al. Percutaneous US-guided radiofrequency ablation with perfused needle applicators: Improved survival with the VX2 tumor model in rabbits. Radiology. 2004;230(1):169–174. doi: 10.1148/radiol.2301021136 14645878

59. Goel MK, Khanna P, Kishore J. Understanding survival analysis: Kaplan-Meier estimate. Int J Ayurveda Res. 2010;1(4):274–278 21455458

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