MRI of the Human Retina

描述(申请人提供)：糖尿病视网膜病变(DR)是糖尿病的一种并发症，也是劳动年龄成年人失明的主要原因，是一种视网膜疾病，其长期病程通常在确诊前数年开始。目前，糖尿病视网膜病变的诊断依据是临床检查结果；当这些症状可见时，大多数患者的视网膜已经发生了重大的不可逆转的损伤。与耗能的光感受器相关的氧气输送不足和低氧与疾病的早期阶段有关。这种氧供应和利用的错配最终导致晚期新生血管和视力丧失。我们假设视网膜氧输送和利用的不匹配导致视网膜在视力丧失之前的早期阶段出现异常的血流和组织氧合。目前，还没有现有的非侵入性成像技术来检测这些早期变化，此时干预可能是最有效的。可以检测血流和氧合早期变化的成像技术可以加快DR的早期检测，提供对高危人群的重点筛查，并实现纵向治疗监测。早期发现有可能预防失明，改善治疗结果，包括生活质量。大多数现有的视网膜成像技术缺乏深度分辨信息(除了用于解剖成像的光学相干断层扫描)，并且依赖于光学透明度，而光学透明度经常受到介质不透明(例如，白内障和玻璃体出血)的阻碍。相反，MRI可以提供具有椎板特定深度分辨率的解剖、生理和功能数据。然而，它在薄视网膜上的应用一直是具有挑战性的。我们小组率先在动物身上进行了多参数、层特异性视网膜磁共振成像，并展示了一些独特的优势。这项提议旨在迈出第一步，将这种创新的方法转化为研究人类视网膜的方法。我们的中心假设是：i)高分辨率MRI可以提供具有层状分辨率的人类视网膜的解剖、生理和功能图像，ii)DR患者的功能和生理变化将在结构异常被检测到之前发生。

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR), a complication of diabetes and the leading cause of blindness in working-age adults, is a retinal disease whose prolonged course typically begins years prior to diagnosis. DR is presently diagnosed by clinical findings on examination; by the time these are visible, significant irreversible damage to the retina has already occurred for most patients. Insufficient oxygen delivery and hypoxia associated with the energy-demanding photoreceptors has been implicated in the early stage of the disease. Such oxygen delivery-utilization mismatch ultimately precipitates late stage neovascularization and vision loss. We hypothesize that the mismatch in oxygen delivery-utilization in the retina results in abnormal blood flow and tissue oxygenation in the early stage of DR before vision loss. Currently, there are no existing non- invasive imaging technologies available to detect these early changes, when intervention could be most effective. Imaging technologies that can detect early changes in blood flow and oxygenation could accelerate early detection of DR, offer focused screening of population at risk, and enable longitudinal treatment monitoring. Early detection has the potential to prevent blindness and improve treatment outcomes, including quality of life. Most existing retinal imaging techniques lack depth-resolved information (except optical coherence tomography for anatomical imaging) and rely on optical transparency which is frequently hampered by media opacity (e.g., cataracts and vitreous hemorrhages). In contrast, MRI can provide anatomical, physiological, and functional data with lamina-specific depth resolution. Its application to the thin retina, however, has been challenging. Our group pioneered multi-parametric, layer-specific retinal MRI in animals and has demonstrated some unique advantages. This proposal aims to take the first step to translate this innovative approach to study the human retina. Our central hypothesis is that: i) high-resolution MRI can provide anatomical, physiological, and functional images of the human retina with laminar resolution, and ii) functional and physiological changes in DR patients will occur before structural abnormalities can be detected.