Bioeffects of Gas Body Activation in Medical Ultrasound

描述（由申请人提供）：气体体造影剂首次为诊断超声带来了可证实的生物效应风险。我们的研究（以及世界各地的其他研究）已经确定了造影剂辅助诊断超声的微尺度损伤的发生。我们的实验室已经开发了敏感的动物模型和特定的新的测试在心脏和肾脏的微尺度生物效应。USFDA批准的造影剂和普通诊断超声扫描仪与仔细校准的暴露方法一起使用，不仅可以复制市售气体体造影剂的推荐剂量和给药方法，还可以复制人体暴露中遇到的衰减和延长路径长度。因此，几乎可以肯定的是，全世界的临床医生在使用这些方法获得诊断图像时会在不知不觉中造成类似的微尺度损伤。在我们对大鼠肾脏的初步研究中，诊断超声激活的造影剂气体体使高压肾小球毛细血管破裂，导致血液流失到鲍曼氏囊中，阻塞了整个肾单位并破坏了近端小管的吸收上皮。我们的四个具体目标是：（1）在微观水平上检查生物效应的基本生物物理学，（2）开发新的剂量测定参数和指数，以帮助临床医生理解和避免这些生物效应，（3）测试造影超声生物效应可能导致医学显著损伤的常见患者情况，以及（4）证明超声成像方法，最大限度地减少生物效应的可能性。对比辅助诊断超声似乎是诊断的一个突破，但不幸的是，进展已被生物效应问题所阻碍，这可以说是当今医学超声最迫切的研究需求。在这项拟议的研究中，经验丰富的独立研究人员将全面检查这个问题，并解决it.The建立的原则和成像程序，以确保安全使用造影剂辅助诊断超声是迫切需要和实现的。通俗语言：造影剂的发明是为了通过向血液中注入小气泡来增强超声图像。在获得批准后，动物研究显示，诊断超声与气泡的相互作用会对心脏和肾脏造成微观损伤。该项目将研究细胞和组织中的生物效应，并展示如何安全地使用超声造影剂进行诊断成像。

DESCRIPTION (provided by applicant): Gas body contrast agents bring a demonstrable risk of bioeffects to diagnostic ultrasound for the first time. Our research (and others throughout the world) has established the occurrence of micro-scale damage from contrast aided diagnostic ultrasound. Our laboratory has developed sensitive animal models and specific new tests for microscale bioeffects in heart and kidney. USFDA approved contrast agents and common diagnostic ultrasound scanners are used with carefully calibrated exposure methods to replicate not only the recommended doses and methods of administration of commercially available gas body contrast agents but also the attenuation and extended path lengths encountered in human exposures. It is therefore virtually certain that clinicians worldwide unknowingly cause similar microscale damage while obtaining diagnostic images with these methods. In our preliminary research on rat kidney, contrast gas bodies activated by diagnostic ultrasound ruptured the high pressure glomerular capillaries, and the resulting blood loss into the Bowman's capsule blocked entire nephrons and destroyed the resorptive epithelium of the proximal tubules. Our four specific aims will (1) examine the fundamental biophysics of the bioeffects at the microscopic level, (2) develop new dosimetric parameters and indices to aid clinicians in understanding and avoiding these bioeffects, (3) test common patient situations in which contrast ultrasound bioeffects potentially could result in medically significant injury, and (4) demonstrate ultrasound imaging methods which minimize bioeffects potential. Contrast aided diagnostic ultrasound appears to be a breakthrough for diagnosis but unfortunately progress has been stalled by the bioeffects problem, which is arguably the most pressing research need in medical ultrasound today. In this proposed research, experienced independent researchers will examine comprehensively this problem and resolve it. The establishment of principles and imaging procedures to insure safe use of contrast aided diagnostic ultrasound is urgently needed and achievable. Lay language: Contrast media have been invented to enhance ultrasound images by injecting small gas bubbles into the blood. After approval, research in animals has revealed microscopic damage in heart and kidney caused by the interaction of diagnostic ultrasound with the bubbles. This project will examine bioeffects in cells and tissues and show how to safely use ultrasound contrast agents in diagnostic imaging.