fMRI Studies of Retinal Oxygenation in Diabetic Patients

描述(由申请人提供)： 获得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记物将极大地改善这一导致视力损害或失明的主要原因的诊断和治疗。本研究项目的目的是确定功能磁共振成像(FMRI)对高氧吸入挑战时视网膜氧合的测量是否可以用于预测风险，提高早期诊断，监测糖尿病视网膜病变的微血管并发症的进展，并评估有不同程度视网膜病变的I型糖尿病患者的治疗效果。之前在糖尿病动物模型上进行的功能磁共振研究，以及对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可用，所以还不可能在人类受试者身上测试这一假设。然而，有了一项创新的功能磁共振技术，现在可以准确地测量人类对高氧血症的视网膜氧合作用。因此，现在有理由认为，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。这项建议的主要目的是测试以下具体假设：i)I型糖尿病患者对高氧挑战的fMRI视网膜氧合反应显着降低，以及ii)随着糖尿病视网膜病变的严重程度增加，这种反应变得越来越不正常。为了实现这一目标，将使用功能磁共振成像来测量糖尿病患者视网膜病变程度的视网膜氧合反应，并将其与年龄相近的正常人类志愿者的反应进行对比。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。这项研究的结果可能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。

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.