Use of novel MRI technology to study pathophysiology diabetic gastroparesis

项目摘要 胃排空延迟是长期站立和不良反应患者常见的严重并发症， 控制糖尿病。目前的促动力疗法是有限的，并引起严重的副作用。一种改进 了解糖尿病胃轻瘫的病理生理学对于开发新药物至关重要 治疗这种困难的疾病的方法。胃排空是一个复杂的过程， 协调一致。胃底调节，蠕动和紧张性胃窦收缩，胃窦幽门协调， 在调节胃排空中起重要作用。由于技术的限制，我们还不知道 这些胃运动成分中的每一个产生胃排空的程度。解决这些 不足之处，我们开发了一个强大的战略，图像和表征胃运动和排空大鼠 和人类的对比增强磁共振成像（MRI）和计算机辅助图像 处理.这项新技术不仅显示了胃的解剖结构，而且还捕获和量化了胃 排空、肠道充盈、胃窦收缩和幽门打开，全自动图像处理。 基于我们的初步调查和研究来自计算建模和模拟胃 流动，我们假设胃运动功能的适当协调是最佳排空所必需的。胃底 运动事件、胃窦收缩和幽门的打开是密切协调的。在这些abandon 事件可导致胃排空延迟。为了验证这一假设，我们计划进行胃MRI研究 健康和糖尿病大鼠和人类。我们有3个具体目标：目标1：开发和执行胃MRI， 检查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轮廓，并阐明胃运动事件的每个组成部分如何有助于 在健康中放空。目的2：应用MRI技术研究糖尿病大鼠胃轻瘫， 研究迷走神经刺激如何改善胃窦十二指肠协调和增强胃排空。 目的3：应用MRI技术研究糖尿病胃轻瘫患者的胃运动和排空功能。 我们将研究胃运动功能的不同组成部分的异常如何有助于延迟 胃排空在单独的研究中，我们将研究普卢卡必利改善 胃运动和排空。将比较普卢卡必利应答者和非应答者的胃MRI特征。 应答者，以阐明哪些胃运动功能的组成部分被普卢卡必利改变， 更好的排空。这些胃MRI研究可能提供新的信息，以确定新的策略， 改善糖尿病胃轻瘫胃排空。

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.