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World J Gastroenterol. Nov 21, 2008; 14(43): 6743-6747
Published online Nov 21, 2008. doi: 10.3748/wjg.14.6743
Non-thermal ablation of rabbit liver VX2 tumor by pulsed high intensity focused ultrasound with ultrasound contrast agent: Pathological characteristics
Cheng-Wen Zhou, Fa-Qi Li, Yan Qin, Chun-Mei Liu, Xiao-Lin Zheng, Zhi-Biao Wang
Cheng-Wen Zhou, Xiao-Lin Zheng, Bioengineering College, Chongqing University, Chongqing 400044, China
Fa-Qi Li, Yan Qin, Chun-Mei Liu, Zhi-Biao Wang, Department of Biomedical Engineering, Chongqing Medical University; State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and MOST, Chongqing 400016, China
Author contributions: Zhou CW and Li FQ contributed equally to this work; Zhou CW, Li FQ and Wang ZB designed the research; Zhou CW, Li FQ, Qin Y and Liu CM performed the research; Zhou CW, Zheng XL and Qin Y analyzed data; Zhou CW, Liu CM and Qin Y wrote the paper.
Supported by Key Project of National Natural Science Foundation of China, No. 30830040; Outstanding Youth Funding Project of China, No. 30325027; Key Project of Natural Science Foundation of CQ CSTS, No. CSTC2006BA5020
Correspondence to: Cheng-Wen Zhou, Bioengineering College, Chongqing University, 174 Shazhengjie St, Shapingba District, Chongqing 400044, China. lifaqi70@163.com
Telephone: + 81-23-68485021 Fax: + 81-23-68485021
Received: January 3, 2008
Revised: September 18, 2008
Accepted: September 25, 2008
Published online: November 21, 2008
Abstract

AIM: To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound (PHIFU) combined with ultrasound contrast agent (UCA), SonoVue (Bracco SpA, Milan, Italy) in rabbit liver VX2 tumor.

METHODS: Liver VX2 tumor models were established in 20 rabbits, which were divided randomly into PHIFU combined with ultrasound contrast agent group (PHIFU + UCA group) and sham group. In the PHIFU + UCA group, 0.2 mL of SonoVue was injected intravenously into the tumor, followed by ultrasound exposure of ISP 5900 W/cm2. The rabbits were sacrificed one day after ultrasound exposure. Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope. The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride (TTC) staining.

RESULTS: Before TTC staining, tumor tissues in both the sham and the PHIFU + UCA groups resembled gray fish meat. After TTC staining, the tumor tissues were uniformly stained red, with a clear boundary between tumor tissue and normal tissue. Histological examination showed signs of tumor cell injury in PHIFU + UCA group, with cytoplasmic vacuoles of various sizes, chromatin margination and karyopyknosis. Electron microscopic examination revealed tumor cell volume reduction, karyopyknosis, chromatin margination, intercellular space widening, the presence of high electron-density apoptotic bodies and vacuoles in cytoplasm.

CONCLUSION: The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.

Keywords: Pulsed high intensity focused ultrasound; Ultrasound contrast agent; Non-thermal effects; Rabbit liver VX2 tumors; Histopathology