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.