ULTRASOUND CONTRAST AGENTS FOR DETECTION OF LIVER TUMORS

超声扫描的优点包括成本低、范围广、 可用性和高患者接受度，使超声成为一种有吸引力的 用于CA筛查和分期的模式。 然而， 超声B扫描成像的肝转移不太理想，部分 由于肿瘤回声相对于肝脏的可变性 薄壁组织 一种造影剂， 回声，而不是肿瘤回声，将显着改善 超声检测肝转移并监测其 对治疗的反应 在我们的第一个资助期，我们评估了肝脏的对比增强， 通过碘帕胺乙酯（IDE）的固体、微米尺寸颗粒。 这些 颗粒是生物相容的，积聚在枯否细胞中， 肝脏，并在一到两天内消除。 因为这些颗粒 是致密的，（2.4 g/cm 3），它们作为散射体，并增加了 肝脏的回声，但不是肿瘤的回声， 枯否细胞。由于IDE中的碘，颗粒也起作用， 作为X射线CT造影剂。 在我们最近的实验中，我们发现IDE在安全剂量下可以提高 正常兔肝回声强度降低3dB， 反向散射增加。 这使得能够检测小（7 mm）VX 2 肿瘤，否则在兔肝中是等回声的并且检测不到 使用超声波B扫描成像。 此外，我们发现库普弗 靠近门静脉三联体的细胞获得了大部分IDE，形成了一个小叶 增强超声背向散射的带状沉积模式。 在下一个资助期，我们将量化 通过枯否细胞获得IDE并试图修改带状模式， 使用DDE颗粒，该颗粒被设计用于激活不同的 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-气泡剂。 这个新 配方稳定了疏水缝隙中的气体， 持续的回声反射性，对环境压力不敏感， 缺乏商业开发的起泡剂。 新制剂 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对比。 这项研究将使人们更好地了解超声 反向散射增强和可能的肝脏造影剂， 在临床上对超声和CT都有用。

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.