MRI METHODS FOR ANALYSIS OF BLADDER AND GI TRACT IN MICE

描述(由申请人提供)： 发展胃肠道和膀胱病理的明确的小鼠模型的可用性使得对小鼠的非侵入性研究特别吸引人。体内无创磁共振成像(MRI)方法已被用于大量实验动物和人类的研究，但在膀胱和胃肠道，特别是在慢性感染的动物模型中的应用一直受到限制。在这个探索性的项目中，我们旨在评估活体MRI方法在评估胃肠道和膀胱的形态和功能方面的作用。我们将研究查加斯病小鼠模型的产生，以探讨慢性感染在胃肠道发育和膀胱病理中的作用。查加斯病是由原生动物寄生虫克氏锥虫引起的，在墨西哥和中南美洲有近2000万人患病。其结果是大约。每年有5万人死亡。在美国，有许多人是从疫区移民过来的，他们是慢性感染者。此外，恰加斯病现在被认为是免疫受损个人的一种机会性感染，包括艾滋病患者。感染后，一个短暂的急性期之后是一个终生的慢性期，其特征是罕见的寄生虫血症。10%至30%的感染者发展为慢性恰加斯病，心脏、肌肉、神经和胃肠道组织逐渐受到炎性破坏。在流行地区，慢性恰加斯病是30-50岁患者心血管死亡的主要原因。在三分之一的慢性病例中，消化系统疾病会导致巨食症和/或巨结肠。慢性恰加斯病的巨器官综合征也被证明会影响实验动物的膀胱。在本项目中，我们旨在建立和应用1H和19F磁共振方法来研究慢性感染克氏毛滴虫小鼠的胃肠道和膀胱的变化。这些方法将被开发和应用，以提供与功能相关的详细形态信息。这些方法将适用于其他慢性疾病，如糖尿病，这些疾病已知会导致膀胱功能障碍和胃肠功能障碍。

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.