Bioeffects of Gas Body Activation in Medical Ultrasound

描述（由申请人提供）：气体体造影剂首次给超声诊断带来明显的生物效应风险。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。我们的实验室开发了敏感的动物模型和特定的新测试，用于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造影剂的推荐剂量和给药方法，还可以复制人体暴露时遇到的衰减和延长路径长度。因此，几乎可以肯定的是，世界各地的临床医生在使用这些方法获得诊断图像时，在不知不觉中造成了类似的微尺度损伤。在我们对大鼠肾脏的初步研究中，超声诊断激活造影剂小体使高压肾小球毛细血管破裂，导致血流进入Bowman’s被囊，阻断整个肾单位，破坏近端小管的吸收上皮。我们的四个具体目标将：(1)在微观水平上检查生物效应的基本生物物理学，(2)开发新的剂量学参数和指标，以帮助临床医生理解和避免这些生物效应，(3)测试常见的患者情况，对比超声生物效应可能导致医学上重大的伤害，(4)演示超声成像方法，以最大限度地减少生物效应的潜力。造影剂辅助诊断超声似乎是诊断的一个突破，但不幸的是，生物效应问题阻碍了进展，而生物效应问题可以说是当今医学超声最迫切的研究需求。在这个建议的研究中，有经验的独立研究人员将全面检查这个问题并解决它。建立原则和成像程序，以确保安全使用造影剂辅助诊断超声是迫切需要和可实现的。造影剂已经被发明出来，通过向血液中注入小气泡来增强超声图像。经批准后，在动物身上进行的研究显示，诊断超声与气泡的相互作用会对心脏和肾脏造成微观损害。该项目将检查细胞和组织中的生物效应，并展示如何在诊断成像中安全地使用超声造影剂。

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.