Ultrasound-induced tissue damage assessment

拟议的研究计划是一项具有潜在重要意义的基础科学(非临床)研究 超声(US)诱导的生物效应，即是否应用超声造影剂 (UCAS)对人类的血管系统产生不利影响。医疗行业从这些研究中受益，如果它 通过向临床医生建议这种风险，诊断性US对患者是一个重大的医疗风险， 并建议临床医生如何监控风险程度。同样，医疗行业也是如此 如果证明诊断性US通过以下方式对患者不是重大的医疗风险，则从这些研究中受益 消除血管损伤是临床需要关注的问题。无论是哪种情况，都有明显的医学意义。数据 决定这一问题所需的信息目前不可用。今天，我们面临着一项重大挑战 关于UCA在人类身上的使用，也就是缺乏关于美国与 UCAS是人类的一个重大医学问题。FDA也不确定UCAS的安全性和/或 在批准新的UCA之前，正在等待更多关于这些代理的风险的了解， 从而否定了他们对患者众所周知的好处。 由一个跨学科小组设计的研究旨在直接解决这一“安全使用”问题 在美国诱导的组织损伤研究方面有相当经验的调查人员，以及 在美国生物物理学和相关物理领域有丰富的实验和理论经验。 使用我们持续主动的方法，我们建议利用我们广泛的美国生物效应/生物物理学 专业知识，以及我们的病理、营养、生物统计建模和动物模型专业知识， 确定US与UCAS的相互作用是否是人类的重大医学问题。这个 实验(基于动物)和理论(机制发展)研究计划有四个具体的 目的，即，1)确定正常、健康的新西兰白鼠动脉损伤的美国阈值 (2)超声对兔动脉损伤阈值的确定 暴露后喂饲致动脉粥样硬化饲料的新西兰兔，当US与UCAS在体内相互作用；3)确定 暴露前喂食致动脉粥样硬化饲料的新西兰兔在超声作用下动脉损伤的阈值 体内UCA检测；4)体外检测UCA阈值。我们计划进行7项活体研究和一系列 体外研究，以实现我们的实验和理论目标。

The proposed research program is a basic science (non-clinical) investigation of a potentially significant ultrasound (US)-induced biological effect, that is, whether the application of ultrasound contrast agents (UCAs) in humans adversely affects the vasculature. The medical profession benefits from these studies if it is shown that diagnostic US is a significant medical risk to the patient by advising clinicians about this risk, and by suggesting how the clinician can monitor the degree of risk. Likewise, the medical profession benefits from these studies if it is shown that diagnostic US is not a significant medical risk to the patient by eliminating vascular injury as a clinical concern. In either case, there is clear medical significance. The data necessary to decide this issue are not currently available. Today, we are faced with a significant challenge about the use of UCAs in humans, that is, the lack of knowledge as to whether the interaction of US with UCAs is a significant medical problem in humans. The FDA is also uncertain about UCAs' safety and/or effectiveness and is waiting until more is known about the risk of these agents before approving new UCAs, thus denying their well-known benefits to the patient. Studies have been designed to address directly this "safe-use" issue by an interdisciplinary group of investigators who have considerable experience with US-induced tissue damage studies, as well as considerable experimental and theoretical experience with US biophysics and related physics areas. Using our continued proactive approach, we propose to utilize our extensive US bioeffects/biophysics expertise, along with our pathological, nutritional, biostatistical modeling and animal model expertise, to determine whether the interaction of US with UCAs is a significant medical problem in humans. The experimental (animal-based) and theoretical (mechanism-development) research program has four specific aims, viz., 1) to determine the US thresholds for arterial damage in normal, healthy New Zealand white (NZW) rabbits when US interacts with UCAs in vivo; 2) to determine the US thresholds for arterial damage in post-exposure atherogenic diet-fed NZW rabbits when US interacts with UCAs in vivo; 3) to determine the US thresholds for arterial damage in pre-exposure atherogenic diet-fed NZW rabbits when US interacts with UCAs in vivo; and 4) to determine UCA thresholds in vitro. We are proposing 7 in vivo studies and a set of in vitro studies to accomplish our experimental and theoretical objectives.