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: 3187496
• 负责人: KEVIN J PARKER
• 金额: $ 15.71万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187496
• 关键词: clinical biomedical equipment; image enhancement; laboratory mouse; laboratory rabbit; laboratory rat; liver neoplasms; particle; ultrasonography

The objective of this proposal is to develop and evaluate several particulate ultrasonic contrast agents which selectively accumulate in normal liver parenchyma but not in most tumors. Ultrasound is frequently employed for liver evaluation in both staging and followup of therapy because of its availability, low cost, and easy patient acceptance. However, neoplastic liver lesions have variable ultrasonographic features which can hinder detection by this modality. Even modest improvements in sensitivity using contrast enhancement would enhance the utility of ultrasound for primary screening and for followup of already demonstrated liver metastases. We propose to thoroughly evaluate iodipamide ethyl ester (IDE) particulate suspensions to develop models for ultrasound-particle and ultrasound-particle-tissue interactions. Preliminary experiments using IDE particles suspended in agar demonstrated that IDE increased ultrasonic backscatter and attenuation coefficients with increased particle diameter and concentration. B-scan images of rabbit livers (in vivo) and rat livers (ex vivo) containing IDE particles showed greater contrast enhancement compared to control livers than was anticipated from studies of agar. The additional mechanisms which act in liver require further investigation. Additional studies of other particulate agents covering a range of mechanical properties (compressibility and density) should indicate the desirable chemical-mechanical properties for optimization of ultrasound contrast enhancement. New particulate ultrasonic contrast agents will be produced using technology already developed for IDE. Ultrasonic evaluation of these new agents, using instrumentation developed at this institution as well as commercial imaging equipment, will start with simple agar suspensions and proceed to more complex experiments involving mice for safety evaluation and normal rats, normal rabbits, and rabbits with liver tumor implants for efficacy evaluation. Screening of each new contrast agent will terminate with the least complex study which demonstrates the agent is not superior to IDE. The investigators have experience with all of the methodology proposed in this application. The proposed studies, combining a unique technology for particulate suspension formulation and unique instrumentation for precise measurement of ultrasonic properties of normal and treated tissues should produce quantitative understanding of ultrasound-particle-tissue interactions and, possibly, a clinically useful ultrasound contrast agent.

该提案的目的是开发和评估几个 颗粒超声造影剂选择性地 在正常肝实质中积聚，但在大多数肿瘤中不积聚。 超声经常用于肝脏评估 治疗的分期和随访由于其可用性、低 成本低，患者容易接受。 然而，肿瘤性肝 病变具有可变的超声检查特征，这可能会阻碍 通过这种方式进行检测。 即使是适度的改进 使用对比度增强的灵敏度将提高实用性 超声用于初步筛查和随访 证实有肝转移。 我们建议彻底评估碘二酰胺乙酯（IDE） 颗粒悬浮液开发超声颗粒模型 和超声-颗粒-组织相互作用。 初步的 使用悬浮在琼脂中的 IDE 颗粒进行的实验表明 IDE 增加了超声波反向散射和衰减 系数随颗粒直径和浓度的增加而变化。 兔肝脏（体内）和大鼠肝脏（离体）的 B 扫描图像 含有 IDE 颗粒的对比度增强效果更强 与对照肝脏相比，超出了研究的预期 琼脂。 在肝脏中起作用的其他机制需要 进一步调查。 对其他颗粒物的进一步研究 涵盖一系列机械性能（压缩性 和密度）应表明理想的化学机械 用于优化超声对比度增强的特性。 新型颗粒超声造影剂将使用 已经为 IDE 开发的技术。 超声波评估 这些新药剂，使用在此开发的仪器 机构以及商业成像设备，将启动 使用简单的琼脂悬浮液，然后进行更复杂的琼脂悬浮液 涉及用于安全性评估的小鼠和正常大鼠的实验， 正常兔和肝肿瘤植入兔的疗效 评估。 每个新造影剂的筛查将终止 用最简单的研究证明该药物不是 优于IDE。 调查人员对所有问题都有经验 本申请中提出的方法。 拟议的研究结合了独特的技术 颗粒悬浮液配方和独特的仪器 精确测量正常和正常的超声波特性 处理过的组织应该产生定量的理解 超声-颗粒-组织相互作用，以及可能的临床 有用的超声造影剂。