ULTRASOUND CONTRAST AGENTS FOR DETECTION OF LIVER TUMORS

本提案的目的是制定和评估若干 颗粒超声造影剂，其选择性地 在正常肝实质中积累，但在大多数肿瘤中不积累。 超声经常用于肝脏评估， 由于其可用性，分期和随访治疗， 成本低，患者容易接受。 然而，肝脏肿瘤 病变具有不同的超声特征， 通过这种方式进行检测。 即使是轻微的改善， 使用对比度增强的灵敏度将提高效用 超声用于初级筛查和随访， 显示有肝转移 我们建议全面评价碘帕胺乙酯（IDE） 颗粒悬浮液开发模型超声颗粒 和超声波-粒子-组织相互作用。 初步 使用悬浮在琼脂中的IDE颗粒的实验证实了 IDE增加了超声背向散射和衰减 随着颗粒直径和浓度的增加系数。 兔肝脏（体内）和大鼠肝脏（体外）的B扫描图像 含有IDE颗粒的显示出更大的对比增强 与对照肝脏相比， 琼脂。 在肝脏中起作用的其他机制需要 进一步调查 其他微粒的附加研究 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性能 用于优化超声对比度增强的特性。 新的颗粒超声造影剂将使用 技术已经为IDE开发。 的超声评价 这些新的代理人，使用仪器开发， 机构以及商业成像设备，将开始 用简单的琼脂悬浮液， 涉及用于安全性评价的小鼠和正常大鼠的实验， 正常兔和肝肿瘤植入兔的疗效 评价 每种新造影剂的筛选将终止 用最简单的研究来证明这种药物 上级于IDE。 调查人员对所有的 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， 精确测量正常和 治疗的组织应该产生定量的了解， 超声-粒子-组织相互作用，以及可能的临床 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.