STANDARDIZED CONTRAST AGENT FOR NEUROSONOGRAPHIC IMAGING

THE OVERALL OBJECTIVE OF THIS PROGRAM IS TO DEVELOP A TECHNIQUE FOR THE PRODUCTION OF VERY UNIFORM (LESS THAN 5 MICRONS) AND ULTRASTABLE GASEOUS MICROBUBBLES TO BE USED AS A STANDARDIZED ULTRASOUND CONTRAST AGENT IN NEUROSONOGRAPHY (ECHOENCEPHALOGRAPHY). THIS DEVELOPMENT WOULD ALLOW FURTHER PROGRESS IN THE NEWLY DEVELOPING FIELD OF CONTRAST-ENHANCED ULTRASONIC IMAGING OF INTRACRANIAL STRUCTURES. IN PARTICULAR, THE STANDARDIZED CONTRAST AGENT SHOULD SIGNIFICANTLY FACILITATE VENTRICULAR SHUNT PLACEMENT IN PEDIATRIC OBSTRUCTIVE HYDROCEPHALUS AND ASSESSMENT OF SHUNT PATENCY. THE SPECIFIC OBJECTIVE OF THE PHASE I PROGRAM IS TO PRODUCE IN A SIMPLE (BY HAND AGITATION, INSTEAD OF SONICATION) AND RAPID (IN 5 SECONDS) MANNER ARTIFICIAL MICROBUBBLES THAT ARE STABILIZED BY NONTOXIC SURFACE-ACTIVE COMPOUNDS. THE SURFACTANT MIXTURE EMPLOYS A COMBINATION OF SATURATED MONOGLYCERIDES AND CHOLESTEROL ESTERS. THE SIZE, DEGREE OF UNIFORMITY, AND DEGREE OF STABILITY IS A FUNCTION OF THE RATIO OF THE MONOGLYCERIDES AND CHOLESTEROL ESTERS PRESENT IN THE MIXTURE. THE EFFECT OF PHYSIOLOGICAL CONCENTRATIONS OF THE MAJOR COMPONENTS OF CEREBROSPINAL FLUID ON THE MICROBUBBLE PROPERTIES WILL BE ASSESSED EXPERIMENTALLY. THE PHASE II PROGRAM WILL ADDRESS ULTRASONIC IMAGING IN VIVO BY CONDUCTING ANIMAL AND CLINICAL VALIDATION STUDIES WITH THE PROPOSED STANDARDIZED CONTRAST AGENT FOR NEUROSONOGRAPHY.