Ultrastructural biologic effects of sonography with pulse inversion and microbubble contrast in rabbit liver

Purpose. This prospective study was conducted to evaluate the biologic effects of microbubble destruction with pulse-inversion harmonic imaging on rabbit liver parenchyma. Methods. The livers of 6 albino rabbits were examined sonographically by a single investigator. Three rabbits underwent contrast-enhanced sonography, with scanning starting 5 seconds after injection by using pulseinversion harmonic imaging with a mechanical index of 1.2. Four time-triggered images were recorded at a rate of 1 frame every 2 seconds. For comparison, 3 control rabbits had pulse-inversion harmonic imaging with a mechanical index of 1.2 only, without contrast medium. Immediately after sonography, the animals were killed and uninterrupted, thin serial sections of the liver from both groups were analyzed by energy-filtered transmission electron microscopy. Results. The hepatic parenchyma of rabbits exposed to contrast agents had ultrastructural damage: mitochondria with fragmented crests; interrupted rough endoplasmic reticulum; enlarged intercellular spaces; highly vacuolized cytoplasmic areas; dilated sinusoids, sometimes with an irregular and interrupted endothelial wall; fragmented hepatocyte microvilli in dilated spaces of Disse; fragmented or missing microvilli in bile canaliculi; vacuolated and lysosome-deprived hepatic cytoplasm around the bile canaliculi; markedly injured or fragmented enclothelium in larger vessels; and damaged basal membrane. Control-group results indicated that exposure to ultrasound alone did not cause ultrastructural damage to hepatic cells. Conclusions. Simultaneous exposure to contrast administration and pulse-inversion harmonic imaging with a high mechanical index causes uitrastructural damage in the rabbit liver. (c) 2005 Wiley Periodicals, Inc. J Clin Ultrasound 33:106-111, 2005; Published online in Wiley InterScience (www.interscience.wiley. com).