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变的明确定义的小鼠模型的可用性使得小鼠的非侵入性研究特别有吸引力。体内非侵入性磁共振成像（MRI）方法已被用于许多实验动物和人类的研究中，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受到限制。在这个探索性的项目中，我们的目的是评估在体内的胃肠道和膀胱的形态和功能的评估MRI方法。我们将研究Chagas病的小鼠模型，以研究慢性感染在胃肠道和膀胱病理学发展中的作用。查加斯病是由原生动物寄生虫克氏锥虫引起的，影响了墨西哥和中美洲和南美洲的近2000万人。它导致近似。每年有5万人死亡。在美国有许多人从流行地区移居国外，并受到慢性感染。此外，南美锥虫病现在被认为是免疫受损个体（包括艾滋病患者）的机会性感染。感染后，一个短暂的急性期之后是一个终身的慢性期，其特征是罕见的寄生虫血症。10%至30%的受感染个体发展成慢性恰加斯病，伴随心脏、肌肉、神经和胃肠道组织的进行性炎性破坏。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。消化系统疾病导致1/3的慢性病例发生巨食管和/或巨结肠。慢性恰加斯病中的巨器官综合征已被证明也会影响实验动物的膀胱。本课题旨在发展和应用1H和19 F磁共振成像技术，研究小鼠慢性感染弓形虫后胃肠道和膀胱的变化。克鲁兹这些方法将被开发和使用，以提供详细的形态信息，可以与功能。所述方法将应用于已知导致膀胱功能障碍和胃肠功能障碍的其它慢性疾病，例如糖尿病。

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.