ULTRASOUND CONTRAST AGENTS FOR DETECTION OF LIVER TUMORS

超声扫描的优点包括成本低、范围广 可用性和患者接受度高，使超声波成为一种有吸引力的 CA筛查和分期的方法。然而，病毒的可检测性 超声B超成像的肝转移瘤在一定程度上并不理想 因为相对于肝脏，肿瘤回声的差异性 薄壁组织。一种增强实质的造影剂 回声，而不是肿瘤回声，将显著改善 超声检测肝转移瘤并监测其转移的能力 对治疗的反应。 在我们的第一个赠款期间，我们评估了肝脏的对比度增强。 由固体、微米大小的碘乙酸乙酯(IDE)颗粒组成。这些 颗粒是生物相容的，积聚在库普弗细胞中 肝脏，并在一到两天内被消除。因为这些粒子 密度高，(2.4克/厘米~3)，它们充当散射体，增加了 肝脏的回声，而不是缺乏的肿瘤的回声 库普弗细胞。由于IDE中的碘，这些颗粒还可以， 作为X光CT造影剂。 在我们最近的实验中，我们发现安全剂量的IDE可以提高 正常兔肝的回声强度为3dB，具有实用和显著意义 后向散射增加。这使得能够检测到小的(7 Mm)VX2 肿瘤，否则等回声和在兔肝中检测不到 使用超声B超成像。此外，我们发现库普弗 门脉三联体附近的细胞获得了IDE的大部分，形成了小叶 增强超声背向散射的沉积带状图案。 在下一个授权期，我们将量化小叶带状模式 通过Kupffer单元获取IDE并尝试修改带状图案， 使用DDE颗粒包裹物质，旨在激活不同的 库普弗细胞上的受体。此外，我们将评估一个新的， 最近发明的混合颗粒泡沫剂。这是一项新的 配方稳定疏水缝隙中的气体，导致 持续回声，对环境压力不敏感，这是一种特征 缺乏商业化开发的起泡剂。新配方 第一次提供了引入高度 回声气体进入肝脏的枯否细胞，产生肝脏 以优雅而有效的方式进行对比。 这项研究应该会让我们更好地理解超声波 背向散射增强和可能的肝脏造影剂 对超声和CT都有临床应用价值。

The advantages of ultrasound scanning, including low cost, wide availability and high patient-acceptance, makes ultrasound an attractive modality for CA screening and staging. However, the detectability of liver metastases by ultrasound B-scan imaging is less than ideal, in part because of the variability in tumor echogenicity relative to liver parenchyma. A contrast agent which increases the parenchymal echogenicity, but not tumor echogenicity, would significantly improve the ability of ultrasound to detect liver metastases and to monitor their response, to therapy. In our first grant period, we evaluated the contrast enhancement of liver by solid, micron size particles of iodipamide ethyl ester (IDE). These particles are biocompatible, are accumulated in Kupffer cells in the liver, and are eliminated in one to two days. Because these particles are dense, (2.4 g/cm3), they act as scatterers and increase the echogenicity of liver, but not the echogenicity of tumors which lack Kupffer cells . Because of the iodine in IDE, the particles also serve, as an x-ray CT contrast agent. In our recent experiments, we found that IDE at safe doses could raise the echogenicity of normal rabbit liver by 3dB, a useful and significant increase in backscatter. This enabled the detection of small (7 mm) VX2 tumors, which were otherwise isoechoic and undetectable in rabbit livers using ultrasound B-scan imaging. Furthermore, we found that the Kupffer cells near the portal triads acquired much of the IDE, creating a lobular zonal pattern of deposition which enhanced the ultrasound backscatter. In the next grant period, we will quantify the lobular zonal pattern of IDE acquisition by Kupffer cells and attempt to modify the zonal pattern, using DDE particles coated with substances designed to activate different receptors on the Kupffer cells. Furthermore, we will evaluate a new, hybrid particle-bubble agent that was recently invented. This new formulation stabilizes gas in hydrophobic crevices, resulting in sustained echogenicity which is insensitive to ambient pressures, a trait lacking in commercially developed bubble agents. The new formulations offer, for the first time, the possibility of introducing highly echogenic gas into the Kupffer cells of the liver, producing liver contrast in an elegant and efficacious manner. This research should lead to a better understanding of ultrasound backscatter enhancement and possibly a liver contrast agent which could be clinically useful for both ultrasound and CT.