Contrast-enhanced ultrasound evaluation of pancreatic cancer xenografts in nude mice after irradiation with sub-threshold focused ultrasound for tumor ablation.

Yi Hui Gao,Qian Guo,Li Xin Jiang,Yi Ni Chen,Bing Hu,Rui Wang,Lei Wu

doi:10.18632/oncotarget.16621

Abstract

We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors after irradiation with sub-threshold focused ultrasound (FUS) ablation in pancreatic cancer xenografts in nude mice. Thirty tumor-bearing nude mice were divided into three groups: Group A received sham irradiation, Group B received a moderate-acoustic energy dose (sub-threshold), and Group C received a high-acoustic energy dose. In Group B, B-mode ultrasound (US), color Doppler US, and dynamic contrast-enhanced ultrasound (DCE-US) studies were conducted before and after irradiation. After irradiation, tumor growth was inhibited in Group B, and the tumors shrank in Group C. In Group A, the tumor sizes were unchanged. In Group B, contrast-enhanced ultrasound (CEUS) images showed a rapid rush of contrast agent into and out of tumors before irradiation. After irradiation, CEUS revealed contrast agent perfusion only at the tumor periphery and irregular, un-perfused volumes of contrast agent within the tumors. DCE-US perfusion parameters, including peak intensity (PI) and area under the curve (AUC), had decreased 24 hours after irradiation. PI and AUC were increased 48 hours and 2weeks after irradiation. Time to peak (TP) and sharpness were increased 24 hours after irradiation. TP decreased at 48 hours and 2 weeks after irradiation. CEUS is thus an effective method for early evaluation after irradiation with sub-threshold FUS.

Highlights

High-intensity focused ultrasound (HIFU) irradiation is a non-invasive tumor treatment method
We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors after irradiation with sub-threshold focused ultrasound (FUS) ablation in pancreatic cancer xenografts in nude mice
We evaluated the efficacy of dynamic contrastenhanced ultrasound (DCE-US) in assessing lesions after irradiation of pancreatic cancer xenografts in nude mice with sub-threshold focused ultrasound (FUS), as well as the role of DCE-US for predicting the early treatment response compared with the pathology results

Summary

Introduction

High-intensity focused ultrasound (HIFU) irradiation is a non-invasive tumor treatment method. Animal experiments and clinical studies have confirmed that during HIFU irradiation, an excessive acoustic energy dose can cause serious side effects, such as damage to normal tissues outside of the target area [2, 3]. Reducing the acoustic energy dose of HIFU can prevent adverse reactions but can cause tissue damage by inducing apoptosis [4]. No appropriate methods to detect tumor cell apoptosis, necrosis, and cellular function changes in the early phase after HIFU irradiation (within 1 week) were available [5, 6]. Because of the edema and inflammatory cell infiltration of tissues surrounding the ablation lesions during the early phase after HIFU, B-mode ultrasound (US) and color Doppler US cannot accurately determine the extent www.impactjournals.com/oncotarget

Methods

Results

Conclusion