In order to investigate improvement of hepatic
tumor detectability by
Sonazoid with phase inversion imaging, the contrast effects on the liver of metastatic
carcinoma-model rabbits were evaluated by videodensitometry and visual assessment. Correlation between the contrast enhancement of
Sonazoid and histopathology was examined using the same animals. Electron microscopy was performed on hepatic tissue from another healthy rabbits to identify the distribution of
Sonazoid microbubbles. As a result, all
tumors were smaller than 12 mm in diameter, and after
intravenous injection of
Sonazoid, they were surrounded with a ring of enhanced signal during the early phase (up to 30 s), followed by a clear contrast defect during the delayed phase (after 10 min). Histopathologic observation revealed that the ring-enhancement was caused by neovasculature in the
tumor, and the contrast defects corresponded to living and dead parts of
tumors, which lack Kupffer cells. Videodensitometric differences between
tumor and healthy tissue markedly increased at delayed phase, and visual detectability of
tumors was improved when
Sonazoid was used. Ultrastructural analysis showed
microbubble-like structures in Kupffer cells, which indicated that
Sonazoid microbubbles were taken up with these cells. In conclusion,
Sonazoid, used with phase inversion imaging, greatly increases the detectability of small hepatic
tumors by highlighting neovascularity at early phase and providing clear contrast defects due to absence of Kupffer cells, which take up
Sonazoid microbubbles, at delayed phase.