ULTRASOUND CONTRAST AGENTS FOR DETECTION OF LIVER TUMORS

该提案目标是制定和评估以下几项 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。 在这两种情况下，经常使用超声进行肝脏评估 由于可获得性低，治疗的分期和随访 成本，以及容易接受的病人。然而，肿瘤性肝脏 病变有不同的超声特征，可能会阻碍 通过这种方式进行检测。即使在以下方面略有改进 使用对比度增强的敏感度将增强实用性 用于初步筛查和随访的超声检查 发现有肝转移。 我们建议彻底评估碘化二胺乙酯(IDE) 颗粒悬浮液开发超声颗粒模型 以及超声波-颗粒-组织相互作用。初步 用悬浮在琼脂中的IDE颗粒进行的实验证明 IDE增加了超声后向散射和衰减 随着颗粒直径和浓度的增加而增加的系数。 兔肝(活体)和大鼠肝(体外)的B超图像 包含IDE颗粒的对比度增强效果更好 与对照肝脏相比，比从研究中预期的要好 琼脂。作用于肝脏的其他机制需要 进一步调查。对其他颗粒物的其他研究 覆盖一系列机械性能(可压缩性)的试剂 和密度)应指示所需的化学机械 超声对比度增强的优化特性。 新的颗粒超声造影剂将使用 已经为IDE开发的技术。超声心动图评价的研究 这些新的代理，使用在这个地方开发的仪器 机构以及商业成像设备，将开始 用简单的琼脂悬浮液，然后进行更复杂的 用小鼠和正常大鼠进行安全性评估的实验， 正常兔和兔肝肿瘤移植瘤的疗效观察 评估。每种新造影剂的筛选将终止 用最简单的研究证明该试剂不是 优于IDE。调查人员对所有 本申请中提出的方法。 拟议的研究结合了一种独特的技术 颗粒悬浮液配方和独特的仪器设备 正常和非正常组织超声特性的精确测量 治疗后的组织应该产生对 超声-颗粒-组织相互作用，并可能在临床上 有用的超声造影剂。

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.