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: 3187497
• 负责人: KEVIN J PARKER
• 金额: $ 27.19万
• 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/3187497
• 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.

超声扫描的优点，包括低成本，宽 可用性和较高的患者感受，使超声波变得有吸引力 CA筛选和分期的方式。 但是，可检测性 超声B扫描成像的肝转移措施不理想，部分 由于肿瘤回声相对于肝脏的变化 实质。 一种增加实质的对比剂 回声性，但没有肿瘤的回声性，将显着改善 超声检测肝转移并监测其的能力 对治疗的反应。 在我们的第一个赠款期内，我们评估了肝脏的对比度增强 通过固体，碘氨基胺乙酯的微米尺寸颗粒（IDE）。 这些 颗粒是生物相容性的，积累在库普弗细胞中 肝脏，并在一到两天内被消除。 因为这些颗粒 是致密的（2.4 g/cm3），它们充当散射器并增加 肝脏的回声性，但没有缺乏肿瘤的回声性 kupffer细胞。由于IDE中的碘，颗粒也服务， 作为X射线CT对比剂。 在最近的实验中，我们发现安全剂量的IDE可能会增加 3DB的正常兔肝脏的回声，有用且显着的 增加反向散射。 这使得检测小（7毫米）VX2 肿瘤，肿瘤是等异，在兔肝中无法检测到的肿瘤 使用超声B扫描成像。 此外，我们发现Kupffer 门户三合会附近的细胞获得了大部分IDE，形成了一个小叶 地位沉积模式，增强了超声反向散射。 在下一个赠款期内，我们将量化 Kupffer细胞采集IDE，并试图修改区域模式， 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 最近发明的杂交粒子剂。 这个新 配方稳定疏水缝隙中的气体，导致 持续的回声性对环境压力不敏感，特征 缺乏商业开发的泡泡剂。 新配方 提供高度引入的可能性 回声气体进入肝脏的Kupffer细胞，产生肝脏 以优雅而有效的方式对比。 这项研究应导致对超声的更好理解 反向散射增强和可能是肝脏对比剂 对于超声和CT都有临床有用。