MRI METHODS FOR ANALYSIS OF BLADDER AND GI TRACT IN MICE

DESCRIPTION (provided by applicant): The availability of well-defined mouse models that develop gastrointestional tract and urinary bladder pathologies make noninvasive studies of mice particularly attractive. In vivo noninvasive magnetic resonance imaging (MRI) methods have been employed in numerous studies of experimental animals and in humans; however the applications to the urinary bladder and gastrointestinal tract, particularly in animal models of chronic infection, have been limited. In this exploratory project we aim to evaluate in vivo MRI methods for the assessment of gastrointestinal tract and urinary bladder morphology and function. We will study mouse models of Chagas' disease generated to investigate the role of chronic infection in development of gastrointestinal tract and urinary bladder pathology. Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and affects nearly 20 million people in Mexico and Central and South America. It results in approx. 50,000 deaths each year. There are many individuals in the United States who have emigrated from the endemic areas and are chronically infected. In addition, Chagas' disease is now appreciated as an opportunistic infection in immune compromised individuals, including those with AIDS. After infection, a short acute phase is followed by a lifelong chronic phase characterized by scarce parasitemia. Ten to thirty percent of infected individuals develop chronic Chagas' disease with progressive inflammatory destruction of heart, muscles, nerves, and gastrointestinal tract tissue. In endemic areas, chronic Chagas' disease is the leading cause of cardiovascular death among patients aged 30-50 years. The digestive disease leads to megaesophagus and/or megacolon in 1/3 of chronic cases. Mega-organ syndrome in chronic Chagas' disease has been shown to also affect the urinary bladder in experimental animals. In this project we aim to develop and apply 1H and 19F MRI methods to study changes in the gastrointestinal tract and urinary bladder of mice chronically infected with T. cruzi. The methods will be developed and employed to provide detailed morphological information that can be correlated with function. The methods will have application to other chronic diseases, such as diabetes, that are known to result in urinary bladder dysfunction and gastrointestinal dysfunction.