Image-guided focused ultrasound-mediated drug delivery andcomparison between 2-D and 3-D therapeutic strategies

Abstract

The objective of this research was to test a new US image-guided FUS (USgFUS) system for stimulating microvascular permeabilization and enhancing intratumoral drug delivery in volume space. 3-D USgFUS therapy functionality was implemented on a programmable US system with a dual transducer for interleaved imaging and 3-D therapy. 3-D therapy consisted of focal zones distributed over a user-defined volume whereas 2-D treatment had the same focal zones but about a single plane. Using breast cancer-bearing mice (N = 4), US therapy was conducted with a mechanical index of 0.5, pulse repetition frequency of 10 Hz, and duty cycle of 10%. Therapy was performed immediately after a 100 μl bolus injection of microbubbles and IR-780 dye. In-vivo optical imaging was performed at 0, 24, and 48 h. Tumors were then excised for ex-vivo analysis. 3-D USgFUS treatment increased dye extravasation within the tumor space at 24 (245.5%) and 48 h (297.5%) when compared to 2-D US therapy (p = 0.01). Ex vivo optical images revealed a similar trend with 3-D US treatment producing a higher fluorescent signal than the 2-D approach. Preliminary results suggest that 3-D USgFUS-mediated drug delivery is an exciting prospect for treatment of the entire cancer burden.