Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co., Biberach an der Riß, Germany.
Cardiometabolic-Diseases Research, 417986Boehringer Ingelheim Pharma GmbH & Co., Biberach an der Riß, Germany.
Toxicol Pathol. 2021 Jun;49(4):862-871. doi: 10.1177/0192623320972964. Epub 2020 Dec 2.
Proliferative retinopathies, such as diabetic retinopathy and retinopathy of prematurity, are leading causes of vision impairment. A common feature is a loss of retinal capillary vessels resulting in hypoxia and neuronal damage. The oxygen-induced retinopathy model is widely used to study revascularization of an ischemic area in the mouse retina. The presence of endothelial tip cells indicates vascular recovery; however, their quantification relies on manual counting in microscopy images of retinal flat mount preparations. Recent advances in deep neural networks (DNNs) allow the automation of such tasks. We demonstrate a workflow for detection of tip cells in retinal images using the DNN-based Single Shot Detector (SSD). The SSD was designed for detection of objects in natural images. We adapt the SSD architecture and training procedure to the tip cell detection task and retrain the DNN using labeled tip cells in images of fluorescently stained retina flat mounts. Transferring knowledge from the pretrained DNN and extensive data augmentation reduced the amount of required labeled data. Our system shows a performance comparable to the human level, while providing highly consistent results. Therefore, such a system can automate counting of tip cells, a readout frequently used in retinopathy research, thereby reducing routine work for biomedical experts.
增生性视网膜病变,如糖尿病性视网膜病变和早产儿视网膜病变,是导致视力损害的主要原因。一个共同的特征是视网膜毛细血管的丧失导致缺氧和神经元损伤。氧诱导的视网膜病变模型被广泛用于研究小鼠视网膜缺血区的血管再生。内皮细胞尖端细胞的存在表明血管恢复;然而,它们的定量依赖于视网膜平片制备的显微镜图像的手动计数。深度学习网络 (DNN) 的最新进展允许此类任务的自动化。我们使用基于 DNN 的单镜头检测器 (SSD) 展示了一种在视网膜图像中检测尖端细胞的工作流程。SSD 是专为自然图像中的物体检测而设计的。我们将 SSD 架构和训练过程适用于尖端细胞检测任务,并使用荧光染色的视网膜平片图像中的标记尖端细胞重新训练 DNN。从预先训练的 DNN 转移知识和广泛的数据扩充减少了所需标记数据的数量。我们的系统显示出与人类水平相当的性能,同时提供高度一致的结果。因此,这样的系统可以自动计数尖端细胞,这是视网膜病变研究中常用的一种检测方法,从而减少了生物医学专家的日常工作。