Localized ex-vivo microbubble-based model drug delivery using an ultrasound catheter

Abstract

Focal drug delivery using ultrasound applied to microbubbles in the vascular system relies on the microbubbles being in close proximity to the vessel wall. In-vitro microbubble translation to a vessel wall under primary radiation force using an intravascular ultrasound (IVUS) catheter was tested using a wall-less flow phantom. Experiments were performed in 40% hematocrit blood to optimize the Pulse Repetition Frequency (PRF) for translating microbubbles to the edge of a channel under flow. An optimal PRF of 10 kHz in blood was selected for the IVUS catheter based on the results of the wall-less flow phantom experiments. Ex-vivo delivery of Dil, a hydrophobic fluorescent dye used as a model drug, was performed on excised porcine arteries under flow conditions of 30 ml/min with microbubbles incorporating Dil and both a 30 μs, 80 kPa PNP, 1.5 MHz Gaussian ramped sinusoid at 10kHz PRF for microbubble translation and 20% fractional bandwidth, 120 kPa PNP, Gaussian at 1kHz PRF for microbubble destruction. The results of Dil delivery were imaged with a fluorescent microscope and indicated a 665% greater intensity (in arbitrary units derived from fluorescence intensity) in the treated region versus the untreated region. This demonstrates that the IVUS catheter successfully provided localized delivery of the Dil marker to a porcine carotid artery.