Use of novel MRI technology to study pathophysiology diabetic gastroparesis

项目摘要 胃排空延迟是慢性胃病患者常见且严重的并发症。 控制住了糖尿病。目前的促运动疗法是有限的，并且会引起严重的副作用。一种改进的 了解糖尿病胃轻瘫的病理生理机制对开发新的 治疗这种难治性疾病的方法。胃排空是一个复杂的过程， 协调一致。胃底调节、胃窦蠕动和紧张性收缩、胃窦-幽门协调 在调节胃排空方面发挥重要作用。由于技术上的限制，我们还不知道 这些胃运动成分中的每一个能产生多大程度的胃排空。要解决这些问题 ，我们开发了一种强有力的策略来成像和表征大鼠的胃运动和排空 基于对比度增强磁共振成像(MRI)和计算机辅助图像的人体 正在处理。这项新技术不仅显示了胃的解剖结构，而且还捕捉和量化了胃 排空、肠道充盈、胃窦收缩和幽门打开，采用全自动图像处理。 基于我们从计算建模和模拟中得出的初步调查和研究 我们假设胃运动功能的适当协调是最佳排空所必需的。滑稽 运动事件、胃窦收缩和幽门开放是密切协调的。它们中的异常 这些事件可能会导致胃排空延迟。为了验证这一假设，我们计划进行胃部核磁共振研究。 在健康和糖尿病大鼠和人类身上。我们有三个具体目标：目标1：开发和执行胃MRI以 检测大鼠和健康受试者在餐后条件下的胃运动事件。这将定义 正常的胃MRI表现，并阐明胃运动事件的每个组成部分是如何参与 在健康中排空。目的：应用MRI技术研究链脲佐菌素(STZ)诱导的糖尿病大鼠的胃轻瘫及 研究迷走神经刺激如何改善胃窦十二指肠的协调性和增强胃排空。 目的：应用磁共振成像技术研究糖尿病胃轻瘫患者的胃动力和胃排空功能。 我们将研究胃运动功能的不同组成部分的异常如何导致延迟 胃排空。在单独的研究中，我们将调查普鲁比利改善的机制 胃动力和胃排空。普鲁卡必利应答者和非应答者的胃部MRI资料将进行比较 应答者澄清普鲁卡必利导致的胃运动功能的哪些成分被改变 在改进的排空方面。这些胃部MRI研究可能提供新的信息，以确定新的治疗策略 改善糖尿病胃轻瘫患者的胃排空功能。

PROJECT ABSTRACT Delayed gastric emptying is a common and serious complication among patients with long standing and poorly controlled diabetes. Current prokinetic therapies are limited and elicit serious side effects. An improved understanding of the pathophysiology of diabetic gastroparesis is critical to the development of new approaches in the treatment of this difficult disorder. Gastric emptying is a complex process that is tightly coordinated. Fundic accommodation, peristaltic and tonic antral contractions, and antral-pyloric coordination all play important roles in regulating gastric emptying. Because of technical limitations, we still do not know to what extent gastric emptying is produced by each of these gastric motor components. To address these deficiencies, we developed a robust strategy to image and characterize gastric motility and emptying in rats and humans based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing. This novel technology not only shows gastric anatomy, but also captures and quantifies stomach emptying, intestinal filling, antral contractions and pylorus opening with fully automated image processing. Based on our pilot investigations and studies derived from computational modeling and simulations of gastric flow, we hypothesize that proper coordination of gastric motor function is required for optimal emptying. Fundic motor events, antral contractions, and opening of the pylorus are closely coordinated. Abnormalities in these events can result in delayed gastric emptying. To test this hypothesis, we plan to perform gastric MRI studies in healthy and diabetic rats and humans. We have 3 Specific Aims: Aim 1: Develop and perform gastric MRI to examine gastric motor events under postprandial conditions in rats and healthy subjects. This will define normal gastric MRI profiles and elucidate how each component of the gastric motor events contribute to emptying in health. Aim 2: Apply MRI technology to study gastroparesis in STZ-induced diabetes in rats and investigate how vagal stimulation might improve antral duodenal coordination and enhance gastric emptying. Aim 3: Employ MRI technology to study gastric motility and emptying in diabetic patients with gastroparesis. We will examine how abnormalities of different components of gastric motor function contribute to delayed gastric emptying. In separate studies, we will investigate the mechanisms by which prucalopride improves gastric motility and emptying. Gastric MRI profiles will be compared between prucalopride responders and non- responders to elucidate which components of the gastric motor function are modified by prucalopride resulting in improved emptying. These gastric MRI studies may provide novel information to identify new strategies to improve gastric emptying in diabetic gastroparesis.