Adaptive Optics Imaging of Human Retinal Vascular Structure and Function

人视网膜血管结构和功能的自适应光学成像

• 批准号: 8975208
• 负责人: Stephen A Burns
• 金额: $ 39万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8975208
• 关键词: Address; Adult; Affect; Age; Aging; Animal Model; Animals; Back; Background Diabetic Retinopathy; Biological Markers; Blindness; Blood; Blood Flow Velocity; Blood Vessels; Blood capillaries; Blood flow; Body part; Cell Wall; Cells; Cellular Structures; Cessation of life; Characteristics; Clinical; Clinical Treatment; Comb animal structure; Complications of Diabetes Mellitus; Data Set; Diabetes Mellitus; Diabetic Retinopathy; Disease; Dropout; Endothelial Cells; Erythrocytes; Essential Hypertension; Evaluation; Event; Fill-It; Future; Goals; Health; Health Care Costs; Human; Hypertension; Image; Imaging Techniques; Impairment; Individual; Ischemia; Link; Location; Longitudinal Studies; Maps; Measurement; Measures; Microscopic; Microscopy; Microvascular Dysfunction; Modification; Monitor; Motion; Nutrient; Optics; Oxygen; Patients; Pericytes; Play; Regulation; Research; Resolution; Retina; Retinal; Risk; Role; Smooth Muscle Myocytes; Staging; Stream; Structure; Systemic disease; Techniques; Time; Trees; Triplet Multiple Birth; Vascular Diseases; Vision; Visit; Visual; Work; adaptive optics; base; capillary; cellular imaging; constriction; contrast imaging; design; follow-up; imaging modality; imaging system; improved; in vivo; instrument; neurovascular coupling; novel strategies; optical imaging; outcome forecast; response; retina blood vessel structure; temporal measurement; tool; visual stimulus

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.

描述（由申请人提供）：糖尿病和其他视网膜血管疾病是视力丧失的主要原因。视网膜脉管系统在帮助了解诸如糖尿病和高血压等系统性疾病如何损害体内其他脉管系统方面也具有独特的作用，而无创措施可能与视网膜那样容易获得的其他脉管系统。最近，我们已经表明，视网膜血管的自适应光学成像可以精确定量血流和血管结构。我们能够在视网膜血管系统的壁中成像单个细胞，测量血管中的血管流明和血管壁之间的关系，小至10微米，并且可以测量小于2度视觉范围的视觉刺激的血流变化。目前的建议将结合微脉管系统的总体结构（包括壁与管腔比率）和精细结构（细胞组成），以及血液速度的测量，这是我们根据我们在血管中移动的单个红细胞的能力而进行的。通过提供视觉刺激，我们将研究神经血管耦合并开发技术，以研究当地区域如何调节流以及神经血管耦合的损害是局部还是全球。通过在空间上进行测量，我们将测量血管树中的网络变化以及结构与血液速度的关系。我们还将进行有限的纵向研究，以研究毛细血管辍学和异常血管结构如何扩散，以及在存在局部缺血和血管改变的情况下如何改变局部血液。我们还将扩展使用可编程的孔径显微镜（PAM）识别毛细管壁组件的能力。这将扩展我们基于自适应光学的技术，用于视网膜的黑场成像，使我们能够在体内形象和量化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引起局部变化对脉管系统的变化，进而导致血管变化如何改变血液向局部视网膜的递送。这种细胞成像方法对人类血管疾病的独特优势是，它填补了当前临床措施和动物研究之间急需的联系。长期目标是对某些患者的行为比其他人更好，并为基于个人自身的血管的严重血管并发症的预后进行定量估计，以提供更深入的了解。这种能力将允许更具体的治疗，最终降低医疗保健成本。由于视网膜的脉管系统有可能充当人体其他部位晚期微血管疾病的生物标志物，因此，这种工具也有助于管理糖尿病和高血压的系统性并发症。