Active induction of in vivo microbubbles by acoustic radiation force at the bifurcation of blood vessel and its evaluation

Abstract

Alhough the development of drug delivery system using microbubbles and ultrasound is expected, because microbubbles diffuse in bloodstream, we have so far reported our attempts for active control of the microbubbles in flow by acoustic radiation force in order to increase local concentration of the microbubbles. However, there was no evidence that in vivo microbubbles act as similar as in vitro experiments, because there were limitations for reproduction of in vivo conditions. In this study, we have elucidated the relationship between brightness variation and microbubbles concentration in the suspension to estimate the absolute concentration in an invisible condition considering in vivo experiment. Then we conducted an experiment of active induction of microbubbles in a Y-form bifurcation of artificial blood vessel, where experimental conditions were with focused ultrasound, the central frequency of 5 MHz, flow velocity of 30 mm/s, and maximum sound pressure of 300 kPa-pp, respectively. Then we applied the conditions for active induction of in vivo microbubbles to compare with in vitro experiments. We used a bifurcation of blood vessel in an ear of a rabbit because the bifurcation shape in its blood vessel is visible. As the results of the experiment, the microbubbles concentration in the induced path was almost two times higher than that in the other path, which agrees with the results from in vitro experiments.

Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery

“…Later on, Wang, et al also published preliminary data where ARF was used to induce the attachment of targeted microbubbles in large blood vessels [171]. A general concern is that it remains very complicated to determine the efficacy of ARF-induced microbubble attachment in vivo [183,200] as the main read-out for microbubble retainment in vivo is a gradual increase in contrast compared to the baseline, that is persistent while the ARF is turned off again [171,183]. Moreover, Gessner, et al state that, for molecular imaging, the microbubbles should remain intact to enable this increase in contrast [197].…”

Experimental analysis of behavior in nanobubbles using echograms under ultrasound exposure

“…The determination of absolute NB concentration in suspension is still ongoing in in vivo studies. [25][26][27][28][29][30][31] In this study, we observed the behavior of two types of NB, which were produced by the authors at Teikyo University and stabilized in water, in multiple shapes of paths, using brightness variation in echograms.…”