Therapeutic Response Monitoring After Targeted Therapy in an Orthotopic Rat Model of Hepatocellular Carcinoma Using Contrast-enhanced Ultrasound: Focusing on Inter-scanner, and Inter-operator Reproducibility

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Dec 28

PMID 33362203

Citations 1

Authors

Hwaseong Ryu

Jung Hoon Kim

Seunghyun Lee

Joon Koo Han

Affiliations

Soon will be listed here.

Abstract

Purpose: To assess therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) using CEUS with focusing on inter-scanner and inter-operator reproducibility.

Materials And Methods: For reproducibility, CEUS was performed using two different US scanners by two operators in sixteen rat models of HCC. Using perfusion analysis software (VueBox ®), eleven parameters were collected, and intra-class correlation coefficient (ICC) was used to analyze reproducibility. Then seventeen rat models of HCC were divided into treatment group (n = 8, 30 mg/kg/day sorafenib for five days) and control group (n = 9). CEUS was performed at baseline and 14 days after first treatment, and changes of perfusion parameters were analyzed.

Results: In treatment group, CEUS perfusion parameters showed a significant change. The peak enhancement (PE, 2.50 x103±1.68 x103 vs 5.55x102±4.65x102, p = 0.010) and wash-in and wash out AUC (WiWoAUC, 1.07x105±6.48 x104 vs 2.65x104±2.25x104, p = 0.009) had significantly decreased two weeks after treatment. On the contrary, control group did not show a significant change, including PE (1.15 x103±7.53x102 vs 9.43x102± 7.81 x102, p = 0.632) and WiWoAUC (5.09 x104±3.25x104 vs 5.92 x104±3.20x104, p = 0.646). For reproducibility, the various degrees of inter-scanner reproducibility were from poor to good (ICC: <0.01-0.63). However, inter-operator reproducibility of important perfusion parameters, including WiAUC, WoAUC, and WiWoAUC, ranged from fair to excellent (ICC: 0.59-0.93) in a different scanner.

Conclusion: Our results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.

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References

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

Zhou J, Zheng W, Cao L, Liu M, Han F, Li A . Antiangiogenic tumor treatment: noninvasive monitoring with contrast pulse sequence imaging for contrast-enhanced grayscale ultrasound. Acad Radiol. 2010; 17(5):646-51. DOI: 10.1016/j.acra.2010.01.008. View

Lamuraglia M, Bridal S, Santin M, Izzi G, Rixe O, Angelo Paradiso . Clinical relevance of contrast-enhanced ultrasound in monitoring anti-angiogenic therapy of cancer: current status and perspectives. Crit Rev Oncol Hematol. 2009; 73(3):202-12. DOI: 10.1016/j.critrevonc.2009.06.001. View

Lee S, Kim J, Lee J, Lee J, Han J . Non-invasive monitoring of the therapeutic response in sorafenib-treated hepatocellular carcinoma based on photoacoustic imaging. Eur Radiol. 2017; 28(1):372-381. DOI: 10.1007/s00330-017-4960-3. View

Lamby P, Prantl L, Fellner C, Geis S, Jung E . Post-operative monitoring of tissue transfers: advantages using contrast enhanced ultrasound (CEUS) and contrast enhanced MRI (ceMRI) with dynamic perfusion analysis?. Clin Hemorheol Microcirc. 2011; 48(1):105-17. DOI: 10.3233/CH-2011-1405. View

Arditi M, Frinking P, Zhou X, Rognin N . A new formalism for the quantification of tissue perfusion by the destruction-replenishment method in contrast ultrasound imaging. IEEE Trans Ultrason Ferroelectr Freq Control. 2006; 53(6):1118-29. DOI: 10.1109/tuffc.2006.1642510. View

Quaia E, Sozzi M, Angileri R, Gennari A, Cova M . Time-Intensity Curves Obtained after Microbubble Injection Can Be Used to Differentiate Responders from Nonresponders among Patients with Clinically Active Crohn Disease after 6 Weeks of Pharmacologic Treatment. Radiology. 2016; 281(2):606-616. DOI: 10.1148/radiol.2016152461. View

Lassau N, Lamuraglia M, Leclere J, Rouffiac V . [Functional and early evaluation of treatments in oncology: interest of ultrasonographic contrast agents]. J Radiol. 2004; 85(5 Pt 2):704-12. DOI: 10.1016/s0221-0363(04)97651-2. View

Zoppellaro G, Venneri L, Khattar R, Li W, Senior R . Simultaneous Assessment of Myocardial Perfusion, Wall Motion, and Deformation during Myocardial Contrast Echocardiography: A Feasibility Study. Echocardiography. 2016; 33(6):889-95. DOI: 10.1111/echo.13190. View

10.

Averkiou M, Juang E, Gallagher M, Cuevas M, Wilson S, Barr R . Evaluation of the Reproducibility of Bolus Transit Quantification With Contrast-Enhanced Ultrasound Across Multiple Scanners and Analysis Software Packages-A Quantitative Imaging Biomarker Alliance Study. Invest Radiol. 2020; 55(10):643-656. DOI: 10.1097/RLI.0000000000000702. View

11.

Kuzuya T, Ishigami M, Ishizu Y, Honda T, Hayashi K, Katano Y . Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma. PLoS One. 2015; 10(9):e0138776. PMC: 4589320. DOI: 10.1371/journal.pone.0138776. View

12.

Wang H, Hristov D, Qin J, Tian L, Willmann J . Three-dimensional Dynamic Contrast-enhanced US Imaging for Early Antiangiogenic Treatment Assessment in a Mouse Colon Cancer Model. Radiology. 2015; 277(2):424-34. PMC: 4627439. DOI: 10.1148/radiol.2015142824. View

13.

Tang M, Mulvana H, Gauthier T, Lim A, Cosgrove D, Eckersley R . Quantitative contrast-enhanced ultrasound imaging: a review of sources of variability. Interface Focus. 2012; 1(4):520-39. PMC: 3262271. DOI: 10.1098/rsfs.2011.0026. View

14.

Weidner N . Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 1995; 147(1):9-19. PMC: 1869874. View

15.

Sullivan D, Obuchowski N, Kessler L, Raunig D, Gatsonis C, Huang E . Metrology Standards for Quantitative Imaging Biomarkers. Radiology. 2015; 277(3):813-25. PMC: 4666097. DOI: 10.1148/radiol.2015142202. View

16.

Willmann J, Kimura R, Deshpande N, Lutz A, Cochran J, Gambhir S . Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast microbubbles conjugated to integrin-binding knottin peptides. J Nucl Med. 2010; 51(3):433-40. PMC: 4111897. DOI: 10.2967/jnumed.109.068007. View

17.

Chen M, Bechtold R, Savage P . Cystic changes in hepatic metastases from gastrointestinal stromal tumors (GISTs) treated with Gleevec (imatinib mesylate). AJR Am J Roentgenol. 2002; 179(4):1059-62. DOI: 10.2214/ajr.179.4.1791059. View

18.

Rubenthaler J, Reiser M, Cantisani V, Rjosk-Dendorfer D, Clevert D . The value of contrast-enhanced ultrasound (CEUS) using a high-end ultrasound system in the characterization of endoleaks after endovascular aortic repair (EVAR). Clin Hemorheol Microcirc. 2017; 66(4):283-292. DOI: 10.3233/CH-179102. View

19.

Leen E, Averkiou M, Arditi M, Burns P, Bokor D, Gauthier T . Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials. Eur Radiol. 2012; 22(7):1442-50. DOI: 10.1007/s00330-011-2373-2. View

20.

Yamashita Y, Shimada M, Hasegawa H, Minagawa R, Rikimaru T, Hamatsu T . Electroporation-mediated interleukin-12 gene therapy for hepatocellular carcinoma in the mice model. Cancer Res. 2001; 61(3):1005-12. View