Correlation Between Contrast-Enhanced Ultrasound and Immune Response of Distant Hepatocellular Carcinoma After Radiofrequency Ablation in a Murine Model

J Ultrasound Med. 2022 Mar;41(3):713-723. doi: 10.1002/jum.15753. Epub 2021 May 21.

Abstract

Objectives: To investigate the relationships between contrast-enhanced ultrasound (CEUS) and the immune status of a distant tumor after radiofrequency ablation (RFA) in a mouse model of hepatocellular carcinoma (HCC).

Methods: Twenty-four mice with two liver tumors were randomized into two groups. RFA was performed on the left tumor in the RFA group. Growth of the right tumors in both groups was monitored after RFA. According to tumor growth, two time points at which tumor growth was halted and restored were selected for study. Then, another 24 mice were randomized into RFA and non-RFA groups. The CEUS parameters, apoptosis, CD8+ T cell, and vasculogenic mimicry (VM) of the right tumors were analyzed on the two aforementioned time points in each group.

Results: Days 3 and 6 were selected as the time points of tumor retardation and progressive growth, respectively. The different immune status of the distant tumors at the two time points after RFA was confirmed by CD8+ T cell and apoptosis (both P < 0.001). Peak intensity, time to peak, area wash-in, and area wash-out of the CEUS parameters increased significantly in the day-6 RFA group versus the day-3 RFA group (P < .001, P = .017, P = .005, P = .002, respectively). VM of the day-6 RFA group was higher than that of the day-3 RFA group (P = .003).

Conclusions: CEUS maybe a good method to follow the immune response after RFA in an advanced HCC mouse model.

Keywords: adaptive immunity; contrast agent; hepatocellular carcinoma; microbubble; radiofrequency ablation; ultrasound.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / diagnostic imaging
  • Catheter Ablation*
  • Contrast Media
  • Disease Models, Animal
  • Immunity
  • Liver Neoplasms* / diagnostic imaging
  • Liver Neoplasms* / surgery
  • Mice
  • Radiofrequency Ablation*
  • Treatment Outcome

Substances

  • Contrast Media