Contrast Ultrasound and Diabetic Microvascular Disease

超声造影与糖尿病微血管疾病

• 批准号: 6576283
• 负责人: Jonathan R Lindner
• 金额: $ 33.15万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6576283
• 关键词: bioimaging /biomedical imaging; clinical research; diabetes mellitus; diabetic angiopathy; diagnosis design /evaluation; dogs; exercise; human subject; inflammation; insulin; insulin sensitivity /resistance; ischemia; laboratory rat; leukocytes; microcirculation; noninvasive diagnosis; oxygen consumption; patient oriented research; striated muscles; ultrasound blood flow measurement

DESCRIPTION (provided by applicant): A diagnostic technique capable of accurately assessing pathologic changes of the peripheral microcirculation in patients with diabetes could be used to detect early microvascular complications, to assess response to new and established therapies, and possibly to detect large-vessel vascular disease. The overall purpose of this proposal is to apply the recently developed non-invasive perfusion imaging technique of contrast-enhanced ultrasound, which is able to assess skeletal muscle perfusion at the capillary level, for the evaluation of microvascular alterations associated with diabetes and insulin-resistance. The first aim of this proposal is to determine whether contrast ultrasound can be used to detect abnormalities in the skeletal muscle capillary responses to increased muscle oxygen demand (exercise) and to insulin in patients and animal models of insulin-resistance and diabetes. Any association between abnormal capillary responses and diabetic microvascular complications will be characterized. The second aim is to develop a method for detecting peripheral vascular disease and for assessing its physiologic significance on limb perfusion using contrast ultrasound in a canine model and in patients with peripheral vascular disease. Data from these studies will be clinically important since information will be provided on the total impact of combined large-vessel and microvascular disease on distal perfusion. The final aim will be to use contrast ultrasound with novel site-targeted ultrasound contrast agents that bind to activated leukocytes in regions of injury/inflammation to assess tissue inflammatory responses that occur in response to peripheral vascular disease and demand ischemia. Data from these studies will be used to determine whether inflammatory responses are enhanced in animal models of diabetes. Successful completion of these studies will represent the first step in developing a reliable, widely available, and inexpensive method for ultrasound detection and characterization of diabetic vascular disease and microvascular complications.

描述（由申请人提供）：一种能够准确评估糖尿病患者外周血微循环的病理变化的诊断技术，可用于检测早期的微血管并发症，评估对新疗法的反应，并可能检测大型血管血管疾病。该提案的总体目的是应用最近开发的对比增强超声的非侵入性灌注成像技术，该技术能够评估毛细血管水平的骨骼肌灌注，以评估与糖尿病和胰岛素抵抗相关的微血管改变。该提案的第一个目的是确定是否可以使用对比度超声来检测骨骼肌毛细管反应的异常，以提高肌肉氧需求（运动）和胰岛素耐药性和糖尿病的动物模型的肌肉需求（运动）和胰岛素。毛细血管反应异常和糖尿病微血管并发症之间的任何关联都将被表征。第二个目的是开发一种检测周围血管疾病的方法，并在犬模型中使用对比度超声和外周血管疾病患者评估其在肢体灌注方面的生理意义。这些研究的数据将在临床上很重要，因为将提供有关大血管和微血管疾病对远端灌注的总影响的信息。最终目的是将对比度超声与靶向位点的超声对比剂与损伤/炎症区域中活化的白细胞结合的新型超声对比剂进行评估，以评估对周围血管疾病和需求缺血的响应发生的组织炎症反应。这些研究的数据将用于确定糖尿病动物模型中炎症反应是否增强。这些研究的成功完成将代表开发可靠，广泛且廉价的方法，用于超声检测和表征糖尿病血管疾病和微血管并发症。