Effects of diagnostic ultrasound-targeted microbubble destruction on permeability of normal liver in rats

This work investigated the effect of diagnostic ultrasound-targeted microbubble destruction (UTMD) on the permeability of normal liver tissue and the safety of this technique. One hundred and four rats were divided into four groups: the control group, the microbubble-only (MB) group, the ultrasound-only (US) group, and the ultrasound-targeted microbubble destruction group (UTMD). The permeabilities of capillaries and cell membranes were determined using Evans blue and lanthanum nitrate as tracers, respectively. The amount of Evans blue was approximately fourfold higher in the UTMD group than in the control, MB-only, and US-only groups (all P<0.01). Evans blue extravasation, visualized as red fluorescence, was detectable by laser confocal scanning microscopy in the parenchyma only in the UTMD group. Lanthanum nitrate-tracing transmission electron microscopy examination indicated that intracellular lanthanum was detectable in the cytoplasm only in the UTMD group. Blood chemical analysis indicated that the effect of diagnostic ultrasound-targeted microbubble destruction on the rats' serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was transient and recoverable and that this technique had no obvious effect on renal function. Cellular swelling was observed in liver cells in the UTMD group at 0.5 h, but this swelling was no longer apparent after 1 week. These results suggest that diagnostic ultrasound-targeted microbubble destruction can increase the capillary and cell membrane permeabilities in normal liver tissue without a significant increase in hepatic and renal toxicity.