BIOPHYSICAL BASES OF PULSED ULTRASOUND BIOEFFECTS

脉冲超声生物效应的生物物理基础

基本信息

批准号：
2414124
负责人：
Morton Miller
金额：
$ 35.77万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 2000-04-30
项目状态：
已结题

项目摘要

Two profound changes will soon modify medical ultrasound use: on-screen safety indexes (regulatory), and 2) the emergence of clinically-useful microbubbles for contrast enhancement. The safety indexes relate clinical ultrasound (US) fields to the potential for bioeffects. The Thermal Index concerns US-generated temperature increments in tissues. The Mechanical Index (MI) is defined in terms of peak negative acoustic pressure and concerns non-thermal bioeffects. Both indexes are based upon knowledge of the mechanisms of action of US fields on tissues/cells. The bioeffect and physical bases for the MI are limited; e.g., the MI does not acknowledge the importance of US pulse length for generating inertial cavitation (IC). Doppler US device output levels generally exceed those requisite for IC from micron-sized nuclei. The general aim of the project is to provide mechanistic insights on dynamic US-induced bubble interactions with in vitro and in vivo biological systems in relation to the MI. The overall hypothesis guiding the proposed project is that non-thermal US-induced cellular effects are due primarily to the action of bubbles. All projects involve the use of a stabilized microbubble echo contrast agent as a control on the presence of bubbles during insonation. SupportIng preliminary data or demonstrable expertise in the area of investigation exists for all projects. Ten hypotheses are proposed for testing, and deal with acoustic thresholds for: (1) pulsed US exposure conditions and hemolysis in vitro, (2) 'jet'-induced erosion of artificial and natural membranes, (3) increases in in vitro mammalian cell mutation and sister chromatid exchanges, (4) confirmation of US-induced potentiation of in vitro cell killing by an anti-cancer drug, (5) confirmation that a specific US exposure of cells in vitro inhibits adenylate cyclase activity, (6) discerning the mechanism for US-induced cell lysis in vitro, (7) ascertaining if species-specific differences in erythrocyte cell size and critical shear stress correspond to differences in sensitivity to US-induced hemolysis, and (8) verifying the detectability of US-induced bubbles in the guinea pig hind limb and ascertaining if injected, stabilized microbubbles enhance the frequency of detectable bubbles. Hypotheses (9) and (10) entail developing comprehensive analytic constructs of US-induced kinetics of bubble action under blood vessel confinement to determine if rigorous theory supports the current MI definition, and if cavitation microjets may occur in vivo. The proposed experiments are aimed at elucidating the physical mechanism(s) of action involved in US bioeffect induction, with particular emphasis on the relationships between the US exposure conditions associated with effect induction and the MI as proposed for use in clinical US applications.

两个深刻的变化将很快修改医疗超声使用：屏幕上安全指数（调节）和2）临床利用的出现微泡以增强对比度。安全指数将临床超声（US）领域与潜力联系起来用于生物效应。热指数涉及美国生成的温度组织的增加。机械指数（MI）是根据峰值负声压力和关注非热生物效应。两个都索引基于对美国领域作用机制的了解在组织/细胞上。 MI的生物效应和物理基础受到限制；例如，Mi确实不承认美国脉搏长度对产生惯性的重要性空化（IC）。多普勒美国设备输出级别通常超过来自微米大小核的IC所需。该项目的总体目标是为动态美国引起的气泡提供机械见解与体外和体内生物系统相互作用 mi。指导拟议项目的总体假设是非热的美国诱导的细胞作用主要是由于气泡的作用。所有项目都涉及使用稳定的微泡回声对比度代理作为控制气泡的控制。支持初步数据或在该领域的表明专业知识所有项目都存在调查。提出了十个假设测试，并处理：（1）脉冲美国暴露的声学阈值体外情况和溶血，（2）'jet诱导的人造侵蚀和天然膜，（3）增加体外哺乳动物细胞突变和姐妹染色单体交换，（4）确认美国诱导的通过抗癌药对体外细胞杀死的增强，（5）确认美国特定的细胞体外暴露会抑制腺苷酸环化酶活性，（6）辨别美国诱导的机制细胞裂解在体外，（7）确定物种特异性差异是否存在红细胞细胞大小和临界剪切应力对应于差异对美国诱导的溶血的敏感性，（8）验证豚鼠后肢中美国引起的气泡的可检测性和确定注射，稳定的微泡是否会提高可检测的气泡。假设（9）和（10）需要发展美国引起的气泡动作动力学的全面分析结构在血管限制下，确定严格的理论是否支持当前的MI定义，如果气腔微聚会可能在体内发生。提出的实验旨在阐明物理美国生物效应诱导涉及的作用机制，特别是强调美国暴露条件之间的关系与效应诱导和提议使用的MI相关美国临床应用。