Watanabe Rira, Matsumura Manabu, Chen Chun-Jen, Kaneda Yuki, Fujimaki Masayoshi
New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Biol Pharm Bull. 2005 Jun;28(6):972-7. doi: 10.1248/bpb.28.972.
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.
为了研究使用相位反转成像的声诺维对肝肿瘤检测能力的改善情况，通过视频密度测定法和视觉评估对转移性癌模型兔肝脏的造影效果进行了评估。使用相同的动物研究了声诺维的造影增强与组织病理学之间的相关性。对另一只健康兔的肝组织进行电子显微镜检查，以确定声诺维微泡的分布。结果，所有肿瘤直径均小于12毫米，静脉注射声诺维后，在早期阶段（至30秒）肿瘤周围出现增强信号环，随后在延迟期（10分钟后）出现明显的造影剂缺损。组织病理学观察显示，环状增强是由肿瘤中的新生血管引起的，造影剂缺损对应于缺乏库普弗细胞的肿瘤存活和坏死部分。在延迟期，肿瘤与健康组织之间的视频密度测定差异显著增加，使用声诺维时肿瘤的视觉可检测性得到改善。超微结构分析显示库普弗细胞中有微泡样结构，这表明声诺维微泡被这些细胞摄取。总之，声诺维与相位反转成像结合使用时，通过在早期突出新生血管并在延迟期由于摄取声诺维微泡的库普弗细胞缺失而提供清晰的造影剂缺损，大大提高了小肝肿瘤的可检测性。
