Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 May;4(3):035039.
doi: 10.1088/2057-1976/aabb14. Epub 2018 Apr 18.

Evaluation of Hepatocellular Carcinoma Transarterial Chemoembolization using Quantitative Analysis of 2D and 3D Real-time Contrast Enhanced Ultrasound

Kibo Nam  1 , Maria Stanczak  1 , Andrej Lyshchik  1 , Priscilla Machado  1 , Yuko Kono  2 , Flemming Forsberg  1 , Colette M Shaw  1 , John R Eisenbrey  1
Affiliations

Evaluation of Hepatocellular Carcinoma Transarterial Chemoembolization using Quantitative Analysis of 2D and 3D Real-time Contrast Enhanced Ultrasound

Kibo Nam et al. Biomed Phys Eng Express. 2018 May.

Abstract

Quantitative 2D and 3D contrast-enhanced ultrasound (CEUS) was assessed to evaluate early transarterial chemoembolization (TACE) treatment response. Seventeen patients scheduled for TACE for the treatment of hepatocellular carcinoma participated in the study. 2D and 3D CEUS were performed for each patient at three time points: prior to TACE, 1-2 weeks post TACE, and 1 month post TACE. Peak-intensities of the tumor and surrounding liver tissue were calculated from 2D and 3D data before and after TACE and used to evaluate tumor treatment response. Residual tumor percentages were calculated from 2D and 3D CEUS acquired 1-2 weeks and 1 month post TACE and compared with results from MRI 1 month post TACE. Nine subjects had complete response while 8 had incomplete response. Peak-intensities of the tumor from 3D CEUS prior to TACE were similar between the complete and incomplete treatment groups (p=0.70), while 1-2 weeks (p<0.01) and 1 month post treatment (p<0.01) were significantly lower in the complete treatment group than in the incomplete treatment group. For 2D CEUS, only the peak-intensity values of the tumor from1 month post TACE were significantly different (p<0.01). The correlation coefficients between 2D and 3D residual tumor estimates 1-2 weeks post TACE and the estimates from MRI were 0.73 and 0.94, respectively, while those from 2D and 3D CEUS 1 month post TACE were 0.66 and 0.91, respectively. Quantitative analysis on 2D and 3D CEUS shows potential to differentiate patients with complete vs. incomplete response to TACE as early as 1-2 weeks post treatment.

Keywords: 3D contrast enhanced ultrasound; hepatocellular carcinoma; quantitative analysis; therapy response; transarterial chemoembolization.

PubMed Disclaimer

Figures

Figure 1
Figure 1
An example of region of interest selections on 8 equidistant 2D slices extracted from 3D contrast-enhanced ultrasound imaging is shown. The yellow circle includes surrounding liver tissue and the red circle includes the tumor on each 2D slice.
Figure 2
Figure 2
Flowchart of study participants
Figure 3
Figure 3
(A) The contrast-enhanced ultrasound imaging 2 week post transarterial chemotherapy with drug-eluting beads showed the hyperechoic artifacts (arrowheads) within the tumor (arrows) and (B) these artifacts disappeared on contrast-enhanced ultrasound imaging 1 month post treatment.
Figure 4
Figure 4
These examples of time-intensity curves were acquired from a subject with complete response prior to TACE (A),1-2 weeks post TACE (B), and approximately 1 month post TACE (C) as well as from a subject with incomplete response prior to TACE (D),1-2 weeks post TACE (E), and approximately 1 month post TACE (F) using 3D CEUS (A.U: Arbitrary Unit). The peak-intensity was obtained directly from each curve.
Figure 5
Figure 5
The peak-intensities from 2D and 3D contrast-enhanced ultrasound 2 weeks and 1 month post transarterial chemotherapy were compared between the complete and incomplete response groups. (A) The peak-intensities in the tumor and (B) the ratios of the tumor peak-intensity to surrounding liver tissue peak-intensity showed similar performance to predict transarterial chemotherapy response in 3D contrast-enhanced ultrasound. (The central mark on each box is the median, the edges of the box are the 25th and 75th percentiles, the whiskers extended to approximately ±2.7 standard deviation, and outliers are plotted individually).
Figure 6
Figure 6
An example of residual tumor estimation – (A) 2D residual tumor estimate was calculated using the difference in tumor area on B-mode and non-enhanced intratumoral area on contrast-enhanced ultrasound, each outlined in red dashed line. 3D residual tumor estimate was calculated using the differences in tumor and non-enhancing intratumoral volumes, by adding 15 equidistant 2D areas across the tumor as outlined in red dashed lines, extracted from (B) B-mode volume and (C) contrast-enhanced ultrasound volume, respectively. (D) The residual tumor (arrow) was confirmed in magnetic resonance imaging 1 month post transarterial chemotherapy.
Figure 7
Figure 7
The residual tumor estimates from 2D and 3D contrast-enhanced ultrasound acquired 1-2 week and 1 month post transarterial chemotherapy (TACE) were correlated with the residual tumor estimate from magnetic resonance imaging 1 month post TACE. The correlation coefficients between 2D and 3D residual tumor estimates 1-2 weeks post TACE and the estimates from magnetic resonance imaging were 0.73 and 0.94, respectively, while those from 2D and 3D contrast-enhanced ultrasound 1 month post TACE were 0.66 and 0.91, respectively.
Figure 8
Figure 8
The Bland-Altman plots with repeatability coefficients (RPCs) were obtained between the residual tumor estimate from magnetic resonance imaging 1 month post TACE and (A) 2D and (B) 3D residual tumor estimates 1-2 weeks post TACE as well as those from (C) 2D and (D) 3D contrast-enhanced ultrasound 1 month post TACE (KS: Kolmogorov-Smirnov test, SD: Standard deviation).
See this image and copyright information in PMC

References

    1. Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109:542–53. - PMC - PubMed
    1. Bargellini I, Bozzi E, Campani D, Carrai P, De Simone P, Pollina L, Cioni R, Filipponi F, Bartolozzi C. Modified RECIST to assess tumor response after transarterial chemoembolization of hepatocellular carcinoma: CT-pathologic correlation in 178 liver explants. Eur J Radiol. 2013;82:e212–8. - PubMed
    1. Brown DB, Nikolic B, Covey AM, Nutting CW, Saad WE, Salem R, Sofocleous CT, Sze DY, Society of Interventional Radiology Standards of Practice Committee Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol. 2012;23:287–94. - PubMed
    1. Burrel M, Reig M, Forner A, Barrufet M, de Lope C R, Tremosini S, Ayuso C, Llovet J M, Real M I, Bruix J. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design. J Hepatol. 2012;56:1330–5. - PubMed
    1. Cho YZ, Park SY, Choi EH, Baik SK, Kwon SO, Kim YJ, Cha SH, Kim MY. The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study. Clin Mol Hepatol. 2015;21:165–74. - PMC - PubMed

LinkOut - more resources