Passive cavitation imaging with nucleic acid-loaded microbubbles in mouse tumors

Abstract

Ultrasound-targeted microbubble (MB) destruction has been used to deliver nucleic acids to cancer cells for therapeutic effect. Identifying both the location and cavitation activities of the MBs is needed for efficient and effective treatment. In this study, we implemented passive cavitation imaging into a commercially available ultrasound open platform (Verasonics) for a 128-element linear array transducer, centered at 5 MHz, and applied it to an in-vivo mouse tumor model. Cationic lipid MBs were loaded with a transcription factor decoy that suppresses STAT3 signaling and inhibits tumor growth in murine squamous cell carcinomas. During systemic MB infusion, ultrasound pulses (4 or 20 cycles) were delivered with a 1-MHz single-element transducer (0.4–1.4MPa peak pressures). Channel data were offline beamformed, band-pass filtered, subtracted from reference images acquired without MBs, and co-registered with B-mode images. During MB infusion, harmonics and broadband emissions were detected in the tumor with both frequency spectra and cavitation images. For 4-cycle 0.4 MPa pulses, harmonic signals at 5 MHz and broadband signals 3–7 MHz were 23 dB and at least 5 dB greater with MBs than without MBs, respectively. These preliminary results demonstrate the feasibility of in-vivo passive cavitation imaging and could lead to further studies for optimizing US/MB-mediated delivery of nucleic acids to tumors.