眼底摄影作为一种方便的工具，研究微血管回应流行病学研究心血管疾病的风险因素
Summary
视网膜图像分析是一个不显眼的过程可视化微循环。心血管疾病危险因素的影响，可能会导致视网膜血管口径的变化。的程序，以取得眼底图像和步骤，用于计算口径是所述的容器中。
Abstract
微循环是由血管直径小于150微米。它构成了循环系统的很大一部分并在维持心血管健康具有重要作用。视网膜是一种组织的线眼的内部，这是允许的微血管的非侵入性分析的唯一组织。现在，高品质的眼底图像可以使用数码相机来获取。视网膜图像可以被收集在5分钟或更少，即使没有瞳孔的扩张。这不显眼的和快速的程序的可视化微循环是有吸引力的流行病学研究应用，并从幼年到老年监测心血管的健康。
影响循环全身性疾病可以导致在视网膜脉管渐进的形态学变化。例如，改变在视网膜动脉和静脉的血管口径已患有高血压，动脉粥样相关硬化和中风和心肌梗死的风险增加。容器的宽度是使用图像分析软件和六个最大的动脉的宽度衍生和静脉总结在中央视网膜小动脉当量（CRAE）和中央视网膜小静脉当量（CRVE）。后者的功能已经显示，研究可修改的生活方式和环境心血管疾病的危险因素的影响是有用的。
该程序以获取眼底图像和分析步骤，以获得CRAE和CRVE描述。的CRAE和CRVE重复测量的变异系数是小于2％，并在信度是非常高的。使用面板的研究中，视网膜血管口径在微粒空气污染的短期变化的快速反应，对心脑血管发病率和死亡率的一个已知危险因素，报道。总之，视网膜成像提议作为一种方便的工具的工具流行病学studies到学习微血管应对心血管疾病的危险因素。
Introduction
微循环是由血管直径小于150微米，并且包括最小的阻力动脉，小动脉，毛细血管和小静脉。这些血管弥补循环系统的很大一部分并在维持心血管健康具有重要作用。 150微米的血管直径是一种生理和物理限制。容器，直径小于150微米的流变学特性，从大动脉不同。此外，大多数的自动调节的电阻发生变化，从150微米的下游在血管床表现出血流自动调节1。微循环有两个重要的功能。其主要功能是提供细胞与氧和代谢底物以匹配组织需求和排出废物和二氧化碳。在交换血管和微血管血流模式的数目的改变降低了有效交换的表面积，并且可以LEAd，来次优的组织灌注，未能满足代谢需求2。此外，静压力降低的血管床内的微循环在调节整体外周阻力3的作用。
视网膜是层状组织衬眼睛内部。它的主要功能是将入射光转换成被进一步传播到视觉皮层用于处理视觉信息的神经信号。视网膜的功能是看外界和所有参与该过程的眼结构是光学透明的。这使得视网膜组织访问的微血管4的非侵入性的成像。视网膜成像被用来识别眼疾。例如，黄斑变性的一种高级形式可以导致由于异常的血管生长成黄斑视力丧失。这些血管往往更可渗透的，可能会流血克和内或下方的视网膜渗漏血液和蛋白质。后者的事件是负责向光感受器的不可逆损伤。青光眼的相关发展具有破坏性的神经节细胞及其轴突。这一过程的作用导致拔罐视盘，它可以在视网膜图像5可以观察到的。糖尿病视网膜病变是高血糖导致的视网膜血管壁损伤造成的。这可能导致局部缺血，新血管的生长和在血管几何网络的变化。此外，血-视网膜屏障可能会受到破坏，从而引起扩张hyperpermeable毛细血管和动脉瘤6的泄漏。
视网膜微血管显示同源性在心脏，肺和大脑7中发现的微血管床。经确定了影响大脑的微循环全身性疾病可引起视网膜平行的变化。动脉NArrowing和视网膜小动脉增强光的反射与血管发育异常，脑白质病变与腔隙是由脑小血管病变引起的8有关。 à显著关系较窄视网膜静脉，改变的视网膜微血管网络和早老性痴呆症的发生之间被发现。因此建议患者大脑具有改变的脑微血管那也是可观察到的视网膜中的9。
证据也越来越多关于视网膜血管的改变与冠状动脉心脏疾病10,11之间的相关性。视网膜动脉与视网膜静脉（A / V）的直径之间的比例已被证明是一个敏感的代理，以反映高血压和动脉粥样硬化12。变窄的动脉和静脉增宽，导致降低的A / V比，证实了中风和心肌梗死的风险13。高血压可以引起直接的视网膜缺血，视网膜梗塞的变得像棉絮斑和深层视网膜白斑14可见。塞尔和Sasongko最近总结了文献中，他们得出的结论是暴露在生活方式和环境危险因素（ 如饮食，体力活动，吸烟和空气污染），可诱导的视网膜微血管床15的形态变化。重要的是，这样的眼底改变与心血管危险因素有关，甚至在疾病的16个临床表现。
显著增加心血管疾病发病率和死亡率的发生归因于长期和短期暴露于颗粒物质空气污染17,18。研究表明，颗粒物（PM），空气污染的一个重要部分，导致心血管病的发展和诱发心血管事件19,20。功能的损害微血管床认为在观察协会的作用。在这方面，暴露于空气污染和动脉变窄的视网膜之间的关联已经报道由亚达和同事21。视网膜动脉管径较窄和小静脉管径是4607参与者动脉粥样硬化（MESA）是生活在地区增加长期和短期暴露于PM 2.5（颗粒物的多种族研究之间更广泛≤2.5微米直径）21。引起的慢性空气污染暴露全身性炎症可导致较宽的小静脉的直径22。这证实了报道吸烟对视网膜微血管床23的影响研究。短期空气污染暴露与健康成人微血管的变化（22-63岁）与视网膜眼底照相24测量之间的关系最近出版的报告。一个increa本身在PM 10（粒子状物质≤10微米的直径）和BC（黑碳，燃烧副产物可以被用作用于与交通有关的柴油机废气的代理）用在小动脉口径24,25的减少相关联。
在这个科学视频协议，该程序的描述来收集眼睛的眼底图像，进行图像分析，以获得小动脉和小静脉血管的口径，并且计算中央视网膜小动脉当量（CRAE）和中央视网膜小静脉当量（CRVE）。视网膜成像是获得越来越多的关注，因为视网膜，使微血管和图像的一个不显眼的分析，可以从早期收集到老年26,27的唯一组织。 CRAE和CRVE似乎反映改变的生活方式和环境的心血管疾病危险因素对微血管的影响敏感的参数。在手稿中，可重复性容器的分析论证。此外，在流行病学研究视网膜微血管分析的应用如通过总结我们在重复测量设计，获得了专注于微粒空气污染暴露24的影响的研究结果。
Protocol
Representative Results
Discussion
视网膜图像分析，提出作为一个方便的工具，用于研究在流行病学研究微血管反应。当操作者经验丰富，只需不到5分钟取眼底照片。此外，可用于从幼年到老年参与者这个不显眼的过程可视化的微循环。
文献在增加相对于形态学变化之间的关联，在视网膜脉管系统（例如改变在容器口径，几何图案等）和可修改的生活方式和环境风险因素15,16。实验和流行病学的…
Offenlegungen
The authors have nothing to disclose.
Acknowledgements
关于微血管回应空气污染微粒的结果复制与环境与健康展望24权限。经证实，在气象和空气质量数据进行了亲切比利时皇家气象研究所和佛兰芒语环境局提供的。视网膜图像分析软件，从北费里尔博士（工程麦迪逊学院和眼底照相读片中心，眼科及视觉科学系，威斯康星大学麦迪逊分校）获得。 Tijs Louwies和埃利纳教务长与一个VITO奖学金支持。埃利纳教务长认为佛兰德科学基金的上进研究奖学金。蒂姆·S. Nawrot是一个欧洲研究委员会开始拨款持有人。
Materials
| Name of Material/ Equipment | Company | Catalog Number | Comments/Description |
| Canon CR-2 nonmydriatic retinal camera | Hospithera (Brussels, Belgium) | http://www.usa.canon.com/cusa/healthcare/products/eyecare/digital_non_mydriatic_retinal_cameras/cr_2. Any other retinal camera with comparable resolution and specifications can be used for the analysis of the retinal microvasculature. Compatibility should be checked before starting a study. | |
| IVAN: Vessel Measurement Software | This software can be used without charge for scientific purpose. It can be obtained by contacting Dr. Nicola Ferrier (Madison School of Engineering and the Fundus Photograph Reading Center, Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison). http://directory.engr.wisc.edu/me/faculty/ferrier_nicola. Phone: (608) 265-8793, Fax: (608) 265-2316 or e-mail: ferrier@engr.wisc.edu |
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