Ultrasound and microbubbles induced extravasation in a machine-perfused pig liver

Abstract

Ultrasound driven microbubbles interact with capillaries and cells and have been proposed to be beneficial for localized drug delivery and uptake. Some of the mechanisms involved is transient cell membrane permeability alteration and vessel poration which increase particle extravasation. Ex vivo machine perfusion of human-sized organs is a technique that provides an ideal environment for preclinical investigations with high physiological relevance not possible with in vitro experiments. In this work, ex vivo machine-perfused pig livers combined with an image-guided therapy system were used to investigate extravasation induced by ultrasound driven microbubbles. Local microvascular flow changes (measured by contrast enhanced ultrasound) and leakage of Evans blue dye in liver parenchyma were used to assess the degree of extravasation. 1—4 MPa peak negative pressure and 20—1000 cycles were considered. Liver areas that were exposed to long pulses (1000 cycles) and peak negative pressure >2.5 MPa showed a detec...