Lowering the Cost of Imaging for Retinal Microvasculature in Diabetic Patients

 描述（由申请人提供）：最近，我们发现视网膜微血管的广泛重塑，发生在一些糖尿病患者中，比预期早得多。这提供了新的生物标志物的潜力。然而，该设备对于大多数诊所和小诊所来说太昂贵了。这些早期视网膜微血管改变不能用常规临床检查或传统成像设备看到。我们建议降低成本，提高这项技术的易用性，以允许广泛检测视网膜微血管变化作为生物标志物。这些设备的高成本的一部分是自适应光学（AO）子系统，其是为人眼的光学器件的像差提供补偿所需的可变形反射镜。通过规划高分辨率，但小于衍射极限分辨率，可以实现更宽的视场和不太极端的可变形反射镜性能。重要的毛细血管变化在视网膜中仍然可见。我们提出三个目标。 在目标1中，我们将优化低成本视网膜成像仪，数字光检眼镜（DLO），用于高放大率和高对比度成像，足以可视化中央凹外的视网膜毛细血管和视锥。Aeon将建立一个具有中等尺寸视野的DLO，它提供了一个足够大的图像，可以在单个图像中显示毛细血管网络，毛细血管和锥体在图像处理后可以更好地可视化。这也更容易允许为该第一阶段提案连续拍摄的AO图像的剪辑。 在目标2中，我们将开发用于AO-DLO的AO子系统，以校正人眼的像差，从而使高分辨率图像具有高对比度。我们将使用市售的可见波长可变形镜，并从现有的定制软件中调整定制AO传感器和控制技术。这些Hartman Shack控制算法和软件已出版并与其他机构共享。一个关键特征是能够在年龄较大的受试者中使用瞳孔的较小区域。 目的三：将AO与DLO结合，研制出一种AO-DLO，并对10例正常人视网膜微循环进行了标测。我们将比较毛细血管灌注图与用于发现视网膜微血管变化的AO扫描激光检眼镜（AO-SLO）的相应图。对于AO-DLO和AO-SLO，我们将通过从AO-DLO收集一系列图像，对齐它们，并绘制缩放图像的方差来生成毛细血管图。这是可能的，因为随着时间的推移，移动的血液颗粒导致不同的反射率，而剩余的视网膜反射率在我们使用的波长范围内相对不变。然后，我们将比较每种器械的毛细管图的重测与两种器械的比较。

 DESCRIPTION (provided by applicant): Recently, we found extensive remodeling of the microvasculature of the retina, occurring in some diabetic patients much earlier than expected. This provides the potential for novel biomarkers. However, the equipment is too expensive for most clinics and small practices. These early retinal microvascular changes cannot be seen with routine clinical examination or traditional imaging devices. We propose to reduce the cost and improve ease of use of this technology to allow widespread detection of retinal microvascular changes as biomarkers. Part of the high cost of these devices is the adaptive optics (AO) subsystem, which is deformable mirrors needed to provide compensation for the aberrations of the optics of the human eye. By planning for high resolution, but less than diffraction limited resolution, a wider field of view and less extreme deformable mirror performance can be realized. The important capillary changes will be nevertheless visualized in the retina. We propose 3 Aims. In Aim 1, we will optimize a lower cost retinal imager, the Digital Light Ophthalmoscope (DLO), for high magnification and high contrast imaging that is sufficient to visualize retinal capillaries and cones outside the central fovea. Aeon will build a DLO with a mid- size for the field of view, which provides an image sufficiently large to show capillary networks in a single image, with the capillaries and cones being better visualized following image processing. This also more readily allows the montaging of AO images taken sequentially for this Phase I proposal. In Aim 2, we will develop the AO subsystem for the AO-DLO to correct aberrations of the human eye, so that the high resolution images are high contrast. We will use a commercially available, visible wavelength deformable mirror and adapt the custom AO sensor and control techniques from existing, custom software. These Hartman Shack control algorithms and software are published and have been shared with other institutions. One key feature is the ability to use a smaller region of the pupil in older subjects. In Aim 3, we wil develop an AO-DLO by integrating AO with the DLO, and map the microcirculation of the retina in 10 normal subjects. We will compare the capillary perfusion maps to corresponding maps from the AO Scanning Laser Ophthalmoscope (AO-SLO), that was used discover the retinal microvascular changes. For both AO-DLO and AO-SLO, we will produce capillary maps by collecting a series of images from the AO-DLO, aligning them, and plotting the variance of scaled images. This is possible because the moving blood particles lead to differing amounts of reflectivity over time, whereas the remaining retinal reflectivity is relatively unchanged in the wavelength range that we use. Then we will compare the test-retest of the capillary maps for each device vs. the comparison of the two devices.