Ultrasonic visualization of perfluorochemicals (PFC) marks the first time that tissue echogenicity has been persistently altered following the intravenous administration of a contrast agent. PFC's are organic compounds where each hydrogen has been replaced by fluorine. PFC's are administered intravenously in an emulsion form. Preliminary studies have shown that two PFC's, perfluoroctylbromide (PFOB) and Fluosol DA (20% Fluosol), serve as echogenic contrast agents for the selective marked enhancement of the normal liver and produce an intense echogenic rim around VX2 tumor nodules allowing their recognition from normal intrahepatic structures. In pilot studies PFOB accumulated in significant quantity in abscess walls in both hepatic and peritoneal abscesses allowing differentiation of peritoneal abscess collection from bowel by CT. PFOB also accumulated in myocardial infarcts producing dense enhancement at the periphery of the infarct by CT. The proposed projects will be conducted utilizing laboratory animals to define the applications of these new contrast agents in clinical ultrasound. They will answer or give insight into the following: 1) The reasons for the ultrasonic visualization of PFC by assessing the acoustic property of the liver with and without PFOB; 2) Assess the increase in sensitivity in detecting hepatic tumors by comparing rabbits with diffuse liver tumors with and without PFC; 3) Determine the ideal dose and scanning time following PFC administration by timed repetitive CT and ultrasound scanning and correlating the two modalities in pigs; 4) Assess the ultrasonic appearance and the increase in detectability of hepatic and renal abscesses following PFC administration in rabbits with diffuse micro abscesses in both organs; 5) Assess whether the presence of PFC improves the ultrasonic diagnosis of acute hepatitis, induced by an injection of D-galactosamine; and 6) Assess the ultrasonic visualization of the enhanced rim of myocardial infarcts in pigs following the occlusion of the distal LAD, since to date all PFOB collections detected by CT have been also imaged by ultrasound. Fluosol, a PFC, is presently being tested clinically as an oxygen carrying blood expander. Extensive toxicity studies are already available, indicating its relative safety in human subjects. The proposed research project, will establish the basis for future clinical trials and give insight into pertinent clinical applications.
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