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Image-guided sonoporation in an ex vivo machine perfused porcine liver
© Keravnou et al; licensee BioMed Central Ltd. 2015
Published: 30 June 2015
Sonoporation is the transient and reversible cell membrane permeability change induced with ultrasound and microbubbles. It allows for the uptake of normally impermeable macromolecules and has been suggested for improving drug delivery. The exact sonoporation mechanism and the optimal ultrasound parameters are still under investigation. Ex vivo machine perfused porcine livers are an excellent platform for investigating the sonoporation parameters and specifically the interaction of ultrasound driven microbubbles with the capillaries. Our objective was to identify the ultrasound parameters that are capable of causing detectable perfusion changes in the sonoporation area. Three types of perfusion changes were considered: large mechanical damage void of perfusion, reduced perfusion due to capillary destruction, and unaltered perfusion.
Results and conclusions
Perfusion change caused by image-guided sonoporation [Fig. 1(c) baseline, (d) after sonoporation] was demonstrated in an ex vivo machine perfused liver with a combined therapy-imaging system. The use of unfocused therapy transducers led to a much larger treatment area and was easier to identify and measure perfusion changes with DCEUS. Focused therapy transducers produced higher acoustic pressures but at smaller areas that were difficult to identify with DCEUS unless the focused transducer was mechanically scanned to treat a larger area. Sonoporated areas with ultrasound pressure above 1 MPa showed a detectable perfusion change. Complete mechanical damage was present at much larger acoustic pressures (~10 MPa). Shorter acoustic pulses (50 cycles) produced less perfusion changes than longer pulses (500 cycles) for the same duty cycle.
This work was supported by the Didaktor/0311/78 Fellowship under the Framework Program for Research, Technological Development and Innovation 2009-2010; DESMI 2009-2010 is co-funded by the Republic of Cyprus and the European Regional Development Fund. We gratefully acknowledge Bracco Suisse SA for the BR38 contrast microbubbles used in this study.
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