Abstract

PurposeTo 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 methodsFor 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.ResultsIn 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.ConclusionOur results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.

Highlights

  • Various imaging techniques are widely used for the diagnosis and monitoring of the treatment response of cancer

  • Our results suggest that contrast-enhanced ultrasound (CEUS) is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility

  • Because of the need for standardization of CEUS findings and for defining inter-scanner and inter-operator reproducibility, there are some attempts to improve reproducibility and to standardize CEUS findings and protocols, such as the quantitative imaging biomarkers alliance (QIBA) which is a group of researchers, healthcare professionals, and industry personnel [4]

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Summary

Introduction

Various imaging techniques are widely used for the diagnosis and monitoring of the treatment response of cancer. CEUS has strong points for evaluating the treatment response using quantitative information for tumor perfusion, there are only a few studies regarding CEUS reproducibility. There is a need for better imaging features than tumor size in order to evaluate the efficacy of sorafenib therapy with successful reproducibility [10]. To date, there have been small number of studies focusing on the inter-scanner and inter-operator reproducibility using CEUS. The purpose of this study is to assess therapeutic responses monitoring after targeted therapy in an orthotopic rat model of HCC using CEUS while focusing on the inter-scanner and inter-operator reproducibility

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