Antivascular effects of pulsed low intensity ultrasound and microbubbles in mouse tumors

In this study we investigate the feasibility of inducing transient and sustained blood flow changes in murine tumors with pulsed low intensity ultrasound. Subcutaneous xenograft melanoma tumors were situated in the hind limbs of mice and exposed to 1 MHz (740 kPa) pulsed ultrasound following a bolus injection of Definitytrade microbubbles. Flow within the tumors was monitored using a 9 MHz array probe in contrast imaging mode following the bolus injection of agent during treatment, and at 2 and 24 hours post treatment. The contrast enhancement was quantified in ROIs encompassing either the periphery or center of the tumors. The results demonstrate the feasibility of producing transient reductions of flow in tumors lasting for less than 15 minutes and, with repeated exposures, the ability to induce sustained reductions in contrast enhancement in lasting for at least 24 hours. Both short and long term flow modifications have implications for the guidance and enhancement of microbubble potentiated local drug enhancement.