fMRI Studies of Retinal Oxygenation in Diabetic Patients

糖尿病患者视网膜氧合的功能磁共振成像研究

• 批准号: 6561268
• 负责人: GARY L TRICK
• 金额: $ 15.97万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6561268
• 关键词: biomarker; blood vessel disorder; clinical research; diabetic retinopathy; early diagnosis; eye circulation; eye disorder diagnosis; eye fundus photography; fluorescein angiography; functional magnetic resonance imaging; human subject; hyperoxia; image processing; insulin dependent diabetes mellitus; medical complication; oxygen transport; pathologic process

DESCRIPTION (provided by applicant): The availability of an accurate and objective surrogate biomarker of the vascular complications associated with the development and progression of diabetic retinopathy would substantially improve the diagnosis and management of this major cause of visual impairment or blindness. The purpose of this research project is to determine whether the functional MRI (fMRI) measurement of the retinal oxygenation to a hyperoxic inhalation challenge can be used to predict risk, improve early diagnosis, monitor the progression of the microvascular complications of diabetic retinopathy and assess treatment efficacy in patients with Type I diabetes mellitus with varying degrees of retinopathy. Previous fMRI studies in animal models of diabetes, as well of studies of retinal blood flow in diabetic patients, suggest that the retinal oxygenation response to a hyperoxic challenge will be subnormal in patients with diabetes. However, it has not been possible to test this hypothesis in human subjects because adequate technologies were not available until recently. However, with an innovative fMRI technique it is now possible to accurately measure the retinal oxygenation to a hyperoxic challenge in humans. Consequently, it is now plausible to suggest that an fMRI measure of the retinal oxygenation response will provide a physiological surrogate endpoint that can be used to predict risk, improve early diagnosis, assess treatment efficacy and monitor the progression of the microvascular complications of diabetic retinopathy. The principal objective of this proposal is to test the specific hypotheses that i) the fMRI retinal oxygenation response to a hyperoxic challenge is significantly reduced in patients with Type I diabetes and ii) this response becomes increasingly subnormal as the degree of diabetic retinopathy increases in severity. To accomplish this objective fMRI will be used to measure the retinal oxygenation response as a function of the degree of retinopathy in patients with diabetes and contrast it with the response obtained from normal human volunteers of similar age. This will provide, for the first-time, direct information about oxygenation of the retina in human diabetics. The results of this proposed study may aid in the early diagnosis and staging of diabetic retinopathy as well as in the development and application of rational prevention and treatment strategies.

描述（由申请人提供）： 与糖尿病视网膜病变的发展和进展相关的血管并发症的准确和客观的替代生物标志物的可用性将大大改善视力损害或失明的这一主要原因的诊断和管理。本研究项目的目的是确定功能性MRI（fMRI）测量高氧吸入挑战的视网膜氧合是否可用于预测风险，改善早期诊断，监测糖尿病视网膜病变微血管并发症的进展，并评估不同程度视网膜病变的I型糖尿病患者的治疗效果。先前在糖尿病动物模型中的fMRI研究以及糖尿病患者视网膜血流的研究表明，糖尿病患者对高氧挑战的视网膜氧合反应将低于正常。然而，由于直到最近才有足够的技术，因此不可能在人类受试者中测试这一假设。 然而，通过创新的功能磁共振成像技术，现在可以准确地测量人类高氧挑战的视网膜氧合。因此，现在似乎可以认为，视网膜氧合反应的fMRI测量将提供一个生理替代终点，可用于预测风险，提高早期诊断，评估治疗效果和监测糖尿病视网膜病变的微血管并发症的进展。本提案的主要目的是检验以下特定假设：i）I型糖尿病患者对高氧激发的fMRI视网膜氧合反应显著降低，ii）随着糖尿病视网膜病变严重程度的增加，该反应变得越来越低于正常。为了实现这一目标，fMRI将被用来测量视网膜氧合反应作为糖尿病患者视网膜病变程度的函数，并将其与从相似年龄的正常人类志愿者获得的反应进行对比。这将首次提供有关人类糖尿病患者视网膜氧合的直接信息。本研究的结果有助于糖尿病视网膜病变的早期诊断和分期，以及制定和应用合理的预防和治疗策略。