Adaptive Optics Imaging of Human Retinal Vascular Structure and Function

描述(申请人提供)：糖尿病和其他视网膜血管疾病是不可避免的视力丧失的主要原因。视网膜血管系统在帮助理解糖尿病和高血压等系统性疾病如何损害体内其他血管系统方面也具有独特的作用，这些血管系统可能不像视网膜那样容易获得非侵入性措施。最近，我们已经证明，视网膜血管的自适应光学成像可以精确地量化血流和血管结构。我们能够成像视网膜血管系统壁内的单个细胞，测量小至10微米的血管中血管管腔和血管壁之间的关系，并能够测量对小于2度视觉范围的视觉刺激的血流变化。目前的建议将结合测量微血管的整体结构(包括管壁与管腔的比率)和精细结构(细胞成分)，以及血流速度的测量，这是基于我们对单个红细胞在血管中移动的成像能力)。通过提供视觉刺激，我们将观察神经血管偶联，并开发技术来观察局部区域如何调节血流，以及神经血管偶联的损害是局部的还是全局的。通过对空间测量的梳理，我们将测量血管树中的网络变化，以及结构如何与血流速度相关。我们还将进行一项有限的纵向研究，以检查毛细血管脱落和异常血管结构是如何扩散的，以及在局部缺血和血管改变存在的情况下，局部血流是如何改变的。我们还将扩展我们的能力，使用可编程孔径显微镜(PAM)识别毛细管壁组件。这将扩展我们基于自适应光学的视网膜暗视野成像技术，使我们能够成像和量化体内最小的视网膜毛细血管的细胞。这种测量的组合将使我们能够查看 衰老、糖尿病和高血压如何导致局部血管系统的变化，进而血管变化如何改变局部向视网膜的血液输送。这种用于人类血管疾病的细胞成像方法的独特优势在于，它填补了当前临床措施和动物研究之间亟需的联系。长期目标是更深入地了解为什么一些患者的病情比其他患者更好，并根据个人的血管系统对严重血管并发症的预后提供量化估计。这种能力将允许进行更具体的治疗，最终降低医疗保健成本。由于视网膜的血管系统有可能成为身体其他部位晚期微血管疾病的生物标记物，这些工具也将有助于管理糖尿病和高血压的系统性并发症。

DESCRIPTION (provided by applicant): Diabetes and other retinal vascular diseases are a major cause of unavoidable vision loss. The retinal vasculature also has a unique role in helping to understand how systemic diseases such as diabetes and hypertension are damaging other vasculature in the body which may not be as readily accessible to noninvasive measures as the retina. Recently we have shown that adaptive optics imaging of the retinal vessels allows precise quantification of blood flow and vascular structure. We are able to image individual cells within the walls of the retinal vasculature, measure the relation between vascular lumens and vascular walls in vessels as small as 10 microns, and can measure blood flow changes in response to visual stimuli smaller than 2 degrees of visual extent. The current proposal will combine measures of both the overall structure of the microvasculature (including the wall to lumen ratio) and fine structure (cellular composition), with measurements of blood velocity, based on our ability to image individual erythrocytes as they move through the blood vessels). By providing visual stimuli we will look at the neurovascular coupling and develop techniques to look at how local regions regulate flow as well as whether impairment of neurovascular coupling is local or global. By combing measurements over space we will measure network changes in the vascular tree and how structure is related to blood velocity. We will also perform a limited longitudinal study to examine how capillary dropout and anomalous vascular structures spread, as well as how local blood flow is altered in the presence of local ischemia and vascular alterations. We will also extend our capabilities to identify capillary wall components using programmable aperture microscopy (PAM). This will extend our adaptive optics based techniques for darkfield imaging of the retina to allow us to image and quantify the cells of even the smallest retinal capillaries in vivo. This combination of measurements will allow us to look at how aging, diabetes and hypertension cause local changes to the vasculature, and in turn how vascular changes alter the delivery of blood to the retina locally. The unique advantage of this cellular imaging approach to vascular disease in humans is that it fills a much needed link between current clinical measures and animal studies. The long term goal is to provide a deeper understanding of why some patients do better than others and to provide a quantitative estimate of the prognosis for severe vascular complications based on an individual's own vasculature. Such ability would allow more specific treatments, ultimately decreasing the cost of health care. Since the vasculature of the retina has the potential to act as a biomarker for advanced microvascular disease in other parts of the body such tools would also be of help in managing the systemic complications of diabetes and hypertension.