EXCEED THE SPACE PROVIDED. . Ultrasound contrast agents have a unique safety concern caused by the interaction of ultrasound pulses with the echogenic gas bodies in the agents. The hypothesis of our research is that contrast aided diagnostic ultrasound (CADU) can cause medically significant harm under clinical conditions. Our research has revealed CADU biological effects in vitro and in vivo, such as petechial hemorrhage, cardiomyocyte injury and tissue fibrosis. The three specific aims are designed to examine the CADU bioeffects problem: 1. Explore basic biophysics and dosimetry of CADU bioeffects to resolve questions about (i) pathways of cell injury and death (ii) the relation of gas body destabilization to bioeffects (iii) why thresholds are so disparate for cell suspensions and monolayers, and (iv) how in vitro and in vivo cellular effects are related. 2. Resolve risk issues for myocardial contrast echocardiography (MCE). Research has pointed to several safety issues including (i) how MCE leads to the loss of cardiomyocytes, (ii) whether the frequency dependence of injury relates to the Mechanical Index, (iii) the relative risks of different sonography methods, and (iv) the possible interaction between MCE and ischemia-reperfusion injury in heart disease. 3. Examine tissues with sensitivity to CADU in radiological diagnosis. These include (i) a potential for metastasis enhancement from tumors, (ii) bioeffects of CADU on liver, (iii) ranges of parameters for kidney nephron injury, (iv) the consequences of nephron injury and (v) the effects of CADU in kidney function. The rationale for the proposed research is that full understanding of the potential bioeffects from CADU will lead to clinical safety guidance and avoidance of medically significant harm. Achieving the specific aims will create a comprehensive knowledge base for risk analysis in echocardiography and radiological applications of CADU helping assure an optimum safety profile for the patient. 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 a range of subtle bioeffects caused by the ultrasound interaction with the bubbles when making images, including small hemorrhages and cellular injury in the heart and kidneys. This project will examine bioeffects in cells and tissues to provide data and guidance for safe use of ultrasound contrast agents in diagnostic imaging. PERFORMANCE SITE ========================================Section End===========================================
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