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. 2020 Dec 23;15(12):e0244304.
doi: 10.1371/journal.pone.0244304. eCollection 2020.

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

Hwaseong Ryu  1 , Jung Hoon Kim  2   3   4 , Seunghyun Lee  2   3 , Joon Koo Han  2   3   4
Affiliations

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

Hwaseong Ryu et al. PLoS One. .

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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Outline of the experimental design.
Note–CEUS: contrast enhanced ultrasound examination. f/u: follow up.
Fig 2
Fig 2. Representative cases of CEUS examination of US scanner A (A, B, C) and US scanner B (D, E, F), demonstrating B-mode imaging (A, D), arterial phase (B, E), and delayed phase (C, F).
Note–CEUS: contrast enhanced ultrasound examination. Numbers in figure indicates time from contrast injection.
Fig 3
Fig 3. Representative case of CEUS image analysis using perfusion analysis software (VueBox ®), ROI manually drawn over tumor (A), and corresponding time-intensity curve profile (B).
Note–CEUS: contrast enhanced ultrasound examination. ROI: region of interest.
Fig 4
Fig 4. Representative cases of pathologic analysis, H&E (x40) (A and D), TUNEL (x400) (B and E), CD31 assay (x200) (C and F) of control group and sorafenib treated group.
Note–H&E: hematoxylin and eosin stain. TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling staining.
See this image and copyright information in PMC

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