Peijing Li1, Mei Zhu2, Yali Xu3, Yang Zhao3, Shunji Gao3, Zheng Liu4, Yun-Hua Gao3. 1. Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; Department of Ultrasound, General Hospital of Jinan Military Area, Jinan, Shandong 250000, China. 2. Department of Ultrasound, First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650032, China. 3. Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. 4. Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Email: liuzhengs@hotmail.com.
Abstract
BACKGROUND: Intravascular microbubble-enhanced acoustic cavitation is capable of disrupting the vascular walls of capillaries and small vessels. This study was designed to investigate the impact of microbubble-enhanced, pulsed and focused ultrasound (MEUS) on the blood perfusion of subcutaneous VX2 tumors in rabbits. METHODS: Subcutaneous VX2 cancers in twenty New Zealand rabbits were treated by combining high-pressure amplitude, pulsed and focused therapeutic ultrasound (TUS) and intravenous microbubble injections. The TUS transducer was operated with a peak negative pressure of 4.6 MPa and a duty cycle of 0.41%. Controls were subcutaneous VX2 cancers treated with TUS or microbubbles only. Contrast-enhanced ultrasound (CEUS) and intravenous Evans Blue (EB) perfusion were performed to assess the tumor circulation. The tumor microvascular disruption was assessed by histological examination. RESULTS: CEUS showed that the tumor circulation almost vanished after MEUS treatment. The average peak grayscale value (GSV) of tumor CEUS dropped significantly from 84.1±22.4 to 15.8±10.8 in the MEUS-treated tumors but no significant GSV changes were found in tumors in the two control groups. The mean tumor EB content of the MEUS-treated tumors was significantly lower than that of the controls. Histological examination found scattered tumor microvascular disruption with intercellular edema after MEUS treatment. CONCLUSION: The tumor circulation of VX2 cancers can be arrested or significantly reduced by MEUS due to microvascular disruption.
BACKGROUND: Intravascular microbubble-enhanced acoustic cavitation is capable of disrupting the vascular walls of capillaries and small vessels. This study was designed to investigate the impact of microbubble-enhanced, pulsed and focused ultrasound (MEUS) on the blood perfusion of subcutaneous VX2 tumors in rabbits. METHODS: Subcutaneous VX2 cancers in twenty New Zealand rabbits were treated by combining high-pressure amplitude, pulsed and focused therapeutic ultrasound (TUS) and intravenous microbubble injections. The TUS transducer was operated with a peak negative pressure of 4.6 MPa and a duty cycle of 0.41%. Controls were subcutaneous VX2 cancers treated with TUS or microbubbles only. Contrast-enhanced ultrasound (CEUS) and intravenous Evans Blue (EB) perfusion were performed to assess the tumor circulation. The tumor microvascular disruption was assessed by histological examination. RESULTS: CEUS showed that the tumor circulation almost vanished after MEUS treatment. The average peak grayscale value (GSV) of tumor CEUS dropped significantly from 84.1±22.4 to 15.8±10.8 in the MEUS-treated tumors but no significant GSV changes were found in tumors in the two control groups. The mean tumorEB content of the MEUS-treated tumors was significantly lower than that of the controls. Histological examination found scattered tumor microvascular disruption with intercellular edema after MEUS treatment. CONCLUSION: The tumor circulation of VX2 cancers can be arrested or significantly reduced by MEUS due to microvascular disruption.