Characterization of Bioeffects on Endothelial Cells Under Acoustic Droplet Vaporization.

Abstract

An ultrasound-mediated cancer treatment called gas embolotherapy has the potential for providing selective occlusion of blood vessels for therapy. Vessel occlusion is achieved by locally vaporizing micron-sized droplets through acoustic droplet vaporization (ADV), which results in bubbles that are large enough to occlude blood flow directed to tumors. Endothelial cells, lining of our blood vessels, will be directly affected by these vaporization events and as such are the subject of this study. Damage to the endothelium could lead to a number of pathological states that, if left untreated could be harmful. However, if under control, these bioeffects could provide benefits that would be synergistic with bubble occlusion like increased endothelial permeability or occlusion by thrombosis. We investigate bioeffects caused by ADV under worst-case scenario cases by using a static endothelial culture model. Two insonation frequencies (3.5 MHz and 7.5 MHz) were chosen to characterize the effects of ADV and aid in the exploration of frequency dependent effects. Damage was observed through changes in peak-negative (rarefactional) pressure and pulse length, and described by the absence of cells after treatment. Damage was dependent in bubble cloud area and highly localized. Additional data was obtained to elucidate the role of ADV in open or confined environments, which simulate relatively large and small vessels, respectively. Through these experiments we try to provide the reader with some of the tools necessary to make an assessment on the repercussions of performing ADV in situations that allow the droplets and ultimately the bubbles, to be in direct contact with the endothelium. Knowing when significant damage is expected in gas embolotherapy could help in the development of preventive measures as well as additional therapeutic aids during treatment.