Use of novel MRI technology to study pathophysiology diabetic gastroparesis

利用新型 MRI 技术研究糖尿病性胃轻瘫的病理生理学

• 批准号: 10363841
• 负责人: Jiande Chen
• 金额: $ 37.94万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10363841
• 关键词: Address; Anatomy; Animals; Antral; Back; Bilateral; Clinical; Complex; Complication; Complications of Diabetes Mellitus; Computer Models; Computer-Assisted Image Processing; Development; Diabetes Mellitus; Disease; Duodenum; Event; Functional disorder; Fundus; Gastric Emptying; Gastroparesis; Health; Human; Hydrostatic Pressure; Image; Imaging technology; Impairment; Individual; Intestines; Investigation; Liquid substance; Magnetic Resonance Imaging; Modeling; Motor; Nerve; Patients; Play; Prevalence; Process; Pylorus; Rattus; Regulation; Relaxation; Rodent; Rodent Model; Role; Solid; Stomach; Streptozocin; Symptoms; Technology; Testing; Vagotomy; Vagus nerve structure; base; cell motility; contrast enhanced; diabetic; diabetic gastroparesis; diabetic patient; diabetic rat; effective therapy; image processing; imaging study; improved; in vivo; models and simulation; new technology; novel; novel strategies; pressure; responders and non-responders; side effect; success; symptomatic improvement

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.

项目摘要 胃排空延迟是长期站立且身体状况不佳的患者常见且严重的并发症。 控制糖尿病。目前的促运动疗法是有限的并且会引起严重的副作用。一个改进的 了解糖尿病性胃轻瘫的病理生理学对于开发新的药物至关重要 治疗这种困难疾病的方法。胃排空是一个复杂的过程， 协调。胃底调节、胃窦蠕动和强直收缩以及胃窦-幽门​​协调 在调节胃排空方面发挥重要作用。由于技术限制，我们还不知道 这些胃运动组件中的每一个产生的胃排空程度是多少。为了解决这些 针对缺陷，我们开发了一种强大的策略来成像和表征大鼠胃动力和排空 基于对比增强磁共振成像 (MRI) 和计算机辅助图像的人类 加工。这项新技术不仅显示了胃的解剖结构，还捕获并量化了胃 通过全自动图像处理进行排空、肠道充盈、胃窦收缩和幽门打开。 基于我们从胃的计算模型和模拟中得出的试点调查和研究 流量，我们假设胃运动功能的适当协调是最佳排空所必需的。芬迪克 运动事件、胃窦收缩和幽门打开密切协调。这些方面出现异常 事件可能导致胃排空延迟。为了验证这一假设，我们计划进行胃 MRI 研究 在健康和糖尿病大鼠和人类中。我们有 3 个具体目标： 目标 1：开发并执行胃 MRI 检查大鼠和健康受试者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影响 排空健康。目标2：应用MRI技术研究STZ诱导的糖尿病大鼠胃轻瘫和 研究迷走神经刺激如何改善十二指肠窦协调并增强胃排空。 目标3：利用MRI技术研究糖尿病胃轻瘫患者的胃动力和排空情况。 我们将研究胃运动功能不同部分的异常如何导致延迟 胃排空。在单独的研究中，我们将研究普卡必利改善的机制 胃动力和排空。将比较普卡必利应答者和非应答者之间的胃 MRI 轮廓 应答者阐明胃运动功能的哪些组成部分被普卡必利所改变 改善排空。这些胃 MRI 研究可能提供新的信息来确定新的策略 改善糖尿病胃轻瘫的胃排空。