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Bioeffects of Gas Body Activation in Medical Ultrasound

医学超声中气体激活的生物效应

基本信息

批准号：
7648026
负责人：
DOUGLAS LAWRENCE MILLER
金额：
$ 45.73万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-01-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7648026
关键词：
Age Animal Model Animals Biological Models Biophysics Blood Blood Circulation Blood capillaries Cardiac Myocytes Cardiomyopathies Cell Death Cells Cessation of life Complex Confusion Contrast Media Contrast echocardiography procedure Dependence Development Diagnosis Diagnostic Imaging Disease Dose Ensure Epithelium Fibrosis Frequencies Gases Glomerular Capillary Glomerular capsule structure Heart Hemorrhage Image Imaging Techniques In Vitro Injury Interdisciplinary Study Kidney Knowledge Laboratories Language Lead Length Life Light Mechanics Methods Microbubbles Microscopic Modeling Myocardial Nephrons Pathway interactions Patients Perfusion Pharmaceutical Preparations Pharmacotherapy Physiologic pulse Property Rattus Reperfusion Injury Research Research Personnel Risk Rupture Safety Suspension substance Suspensions Testing Therapeutic Time Tissues Translating Ultrasonics Ultrasonography Uncertainty United States Food and Drug Administration attenuation capillary clinically relevant design diabetic rat experience exposed human population functional disability imaging modality in vivo in vivo Model indexing interstitial monolayer podocyte pressure programs theories

项目摘要

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.

描述（由申请人提供）：气体造影剂首次给超声诊断带来了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）已经确定了超声造影辅助诊断会造成微尺度损伤。我们的实验室开发了敏感的动物模型和针对心脏和肾脏微观生物效应的特定新测试。美国食品和药物管理局批准的造影剂和常见的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中遇到的衰减和延长的路径长度。因此，几乎可以肯定，世界各地的临床医生在使用这些方法获取诊断图像时，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，诊断超声激活的对比气体体使高压肾小球毛细血管破裂，由此导致的鲍曼囊失血阻塞了整个肾单位并破坏了近端肾小管的再吸收上皮。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）测试超声造影生物效应可能导致医学上重大损伤的常见患者情况，以及（4）演示超声成像方法，最大限度地减少潜在的生物效应。超声造影似乎是诊断的一项突破，但不幸的是，生物效应问题使进展陷入停滞，而生物效应问题可以说是当今医学超声领域最紧迫的研究需求。在这项拟议的研究中，经验丰富的独立研究人员将全面研究这个问题并解决它。迫切需要建立确保安全使用超声造影辅助诊断的原则和成像程序，并且是可以实现的。外行语言：已经发明了造影剂，通过将小气泡注入血液来增强超声图像。获得批准后，对动物的研究表明，诊断超声波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使用超声造影剂。