Ultrasound-induced tissue damage assessment

拟议的研究计划是一项基础科学（非临床）研究， 超声（US）引起的生物效应，即是否应用超声造影剂 （UCA）在人类中对脉管系统产生不利影响。医学界受益于这些研究，如果它 显示诊断性超声对患者是一个重大的医疗风险，通过告知临床医生这种风险， 并建议临床医生如何监测风险程度。同样，医学界 如果通过以下方式证明诊断性超声对患者没有重大医疗风险， 从而消除了临床关注的血管损伤。无论哪种情况，都有明显的医学意义。数据 目前没有必要决定这个问题。今天，我们面临着一个重大挑战， 关于UCA在人类中的使用，也就是说，缺乏关于US与 UCA是人类的一个重要医学问题。FDA也不确定UCA的安全性和/或 有效性，并等待更多的是了解这些代理的风险之前，批准新的UCA， 从而否定了它们对患者的众所周知的益处。 一个跨学科小组设计了一些研究来直接解决这个“安全使用”问题， 在超声诱导组织损伤研究方面具有丰富经验的研究者，以及 在美国生物物理学和相关物理领域具有丰富的实验和理论经验。 使用我们持续的主动方法，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，沿着我们的病理，营养，生物统计建模和动物模型的专业知识， 确定US与UCA的相互作用是否是人类的重大医学问题。的 实验（基于动物）和理论（机制开发）研究计划有四个具体的 目的，即，1)确定正常健康新西兰白色人动脉损伤的US阈值 (NZW)2）确定超声在兔体内与UCA相互作用时的动脉损伤阈值; 当US与UCA在体内相互作用时，暴露后致动脉粥样硬化饮食喂养的NZW兔; 3）确定 当US与暴露前致动脉粥样硬化饮食喂养的NZW兔相互作用时，US动脉损伤阈值 体内UCA;和4）体外确定UCA阈值。我们提出了7项体内研究和一组体内研究。 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.