ULTRASOUND CONTRAST AGENTS FOR DETECTION OF LIVER TUMORS

用于检测肝脏肿瘤的超声造影剂

• 批准号: 3187494
• 负责人: KEVIN J PARKER
• 金额: $ 26.26万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187494
• 关键词: Kupffer's cell; clinical biomedical equipment; contrast media; early diagnosis; image enhancement; laboratory rabbit; liver disorder diagnosis; liver neoplasms; metastasis; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; technology /technique; ultrasonography

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.

超声波扫描的优点包括成本低、范围广 可用性和患者接受度高，使得超声成为一种有吸引力的 CA 筛查和分期的方式。 然而，可检测性 部分肝转移超声 B 扫描成像不太理想 由于肿瘤回声相对于肝脏的变化性 薄壁组织。 增强实质的造影剂 回声，但不是肿瘤回声，会显着改善 超声检测肝转移并监测其转移的能力 反应，对治疗。 在我们的第一个资助期内，我们评估了肝脏的对比增强 由碘二酰乙酯 (IDE) 的微米级固体颗粒组成。 这些 颗粒具有生物相容性，在库普弗细胞中积累 肝脏，并在一到两天内被消除。 因为这些颗粒 密度大（2.4 g/cm3），它们充当散射体并增加 肝脏的回声，但缺乏肿瘤的回声 枯否细胞。由于 IDE 中含有碘，颗粒还起到以下作用： 作为X射线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 正常兔肝脏回声增强3dB，这是一个有用且有意义的 后向散射增加。 这使得能够检测小型（7 毫米）VX2 肿瘤，否则在兔肝脏中是等回声且无法检测到的 使用超声 B 扫描成像。 此外，我们发现库普弗 门脉三联附近的细胞获得了大部分 IDE，形成了小叶 沉积的带状图案增强了超声反向散射。 在下一个资助期内，我们将量化小叶区域模式 IDE 被库普弗细胞获取并尝试修改区域模式， 使用涂有旨在激活不同物质的 DDE 颗粒 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。 这个新的 配方可稳定疏水缝隙中的气体，从而 持续回声，对环境压力不敏感，这是一个特征 缺乏商业开发的起泡剂。 新配方 首次提供了引入高度 产生回声的气体进入肝脏的库普弗细胞，产生肝脏 以优雅而有效的方式进行对比。 这项研究应该有助于更好地了解超声波 反向散射增强和可能的肝脏造影剂 对超声和 CT 都有临床用途。