ULTRASOUND-INDUCED LUNG DAMAGE ASSESSMENT

超出所提供的空间。拟议的研究计划是一项潜在的重大超声（US）诱导的生物效应的基础科学（非临床）研究，即超声造影剂（UCAs）在人类中的应用是否对血管系统产生不利影响。如果通过向临床医生建议这种风险，并建议临床医生如何监测风险程度，这些研究表明诊断性美国对患者是一种重大的医疗风险，那么医疗行业将受益于这些研究。同样，如果这些研究表明，通过消除血管损伤作为临床问题，诊断性US对患者没有重大的医疗风险，那么医学界将受益于这些研究。无论哪种情况，都有明确的医学意义。目前还没有决定这个问题所需的数据。今天，我们面临着在人类中使用uca的重大挑战，即缺乏关于US与uca的相互作用是否对人类构成重大医学问题的知识。FDA也不确定uca的安全性和/或有效性，并且在批准新的uca之前等待更多关于这些药物的风险的信息，从而否认它们对患者的众所周知的益处。研究的目的是直接解决这一“安全使用”问题，研究人员是一个跨学科的研究小组，他们在美国诱导的组织损伤研究方面有丰富的经验，在美国生物物理学和相关物理领域也有丰富的实验和理论经验。通过我们持续积极的方法，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，来确定美国与UCAs的相互作用是否对人类构成重大的医学问题。实验（以动物为基础）和理论（机制开发）研究计划有四个具体目标，即：1)确定US与体内UCAs相互作用时正常健康新西兰白兔（NZW）动脉损伤的US阈值；2)确定US与UCAs在体内相互作用时，暴露后致动脉粥样硬化膳食喂养的NZW家兔动脉损伤的US阈值；3)当US与体内UCAs相互作用时，确定暴露前致动脉粥样硬化膳食喂养的NZW家兔动脉损伤的US阈值；4)确定体外UCA阈值。我们提议进行7项体内研究和一系列体外研究，以实现我们的实验和理论目标。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================