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摘要:
深度学习可以有效提取图像隐含特征,在医学影像识别方面的应用快速发展. 由于糖尿病视网膜病变(Diabetic retinopathy, DR)诊断标准明确、分类体系成熟,应用深度学习诊断糖尿病视网膜病变近年来成为研究热点. 本文从深度学习方法在DR诊断中的最新研究进展、DR诊断的一般流程、公共数据集、医学影像标注方法、主要实现模型、面临的主要挑战几方面, 对深度学习方法在糖尿病视网膜病变诊断中的应用进行了详细综述, 便于更多机器视觉、尤其是深度学习医学影像的研究者们参照对比,加快该领域研究的成熟度和临床落地应用.
Abstract:Deep learning can effectively extract the hidden features of image and its application in medical image recognition is developing rapidly. Due to the clear diagnostic criteria for diabetic retinopathy (DR) and the mature classification system, the application of deep learning to diagnose diabetic retinopathy has become a research hotspot in recent years. Therefore, this paper reviews the application of deep learning methods in the diagnosis of diabetic retinopathy detailedly based on the latest research progress of deep learning for DR diagnosis, the general flow for DR diagnosis, public dataset, medical image annotation method, main models and major challenges. It brings convenience for more researchers of computer vision deepling learning, especially medical imaging deep learning, to speed up the research maturity and clinical application in this field.
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表 1 糖尿病视网膜病变国际分级标准
Table 1 International classification of diabetic retinopathy and diabetic macular edema
糖尿病视网膜病变 散瞳后眼镜所见 随访建议 无视网膜病变 (无DR) 无异常 1 ~ 2 年随访一次 轻度非增殖性糖尿病视网膜
病变 (轻度NPDR)仅有微动脉瘤 1 ~ 2 年随访一次 中度非增殖性糖尿病视网膜
病变 (中度NPDR)比仅有微动脉瘤重, 比重者轻 半年到一年随访一次或转
诊至眼科医师重度非增殖性糖尿病视网
膜病变 (重度NPDR)有以下任一症状之一:
4个象限每个都有20个以上的内出血病灶;
2个以上象限有确定的静脉珠状改变;
1个以上象限有明显的视网膜
内微血管异常并且无增殖性病变体征转诊至眼科医师 增殖性糖尿病视网膜
病变 (PDR)具有重度非增殖性症状且有以下一种或多种情形:
新生血管, 玻璃体积血/视网膜前出血转诊至眼科医师 表 2 糖尿病视网膜病变公共数据集
Table 2 Public data set on diabetic retinal
名称 数据类型 图像信息 图片尺寸 图片格式 数据量 (幅) 获取权限 链接 IDRID[24] CFP 图像按照国际标准进行糖网和黄斑水肿分级, 并对其中 81 幅有糖网征象的图像进行了病变的像素级标注. 4228 × 2848 JPEG 516 注册 IEEE
账号获取https://ieee-dataport.org/open-access/indian-diabetic-retinopathy-image-dataset-idrid E-Ophtha[25] CFP 由 e-ophtha-MA (微动脉瘤) 和E-Ophtha-EX (渗出) 两个子数据库组成. 标注了 EX 和 MA 的区域, 以掩模的方式给出. 2544 × 1696
1440 × 960
1504 × 1000 等JPEG 463 提交邮箱以
获取下载码https://ieee-dataport.org/open-access/indian-diabetic-retinopathy-image-dataset-idrid DRiDB[26] CFP 每幅图像由至少5名专家标注, 标注内容包含所有视网膜主要解剖结构和病理特征以及糖网分级. 720 × 676 BMP 50 发送邮件来请求
访问数据库https://ipg.fer.hr/ipg/resources/image_database Messidor[27] CFP 图像标注了糖尿病性视网膜病变分级及黄斑水肿分级. 1400 × 960
2 240 × 1488
2304 × 1536TIFF 1200 提交邮箱以
获取下载码http://www.adcis.net/en/Download-Third-Party/Messidor.html Messidor-2[28] CFP 每幅图像标注了糖尿病性视网膜病变分级及黄斑水肿分级. 1400 × 960
2240 × 1488
2304 × 1536TIFF 1784 提交邮箱以
获取下载码http://latim.univ-brest.fr/indexfce0.html DIARETDB0[29] CFP 该数据集是用于糖尿病视网膜病变检测的基准的公开数据集, 每幅图像标注了病变信息. 1500 × 1152 PNG 130 直接下载 http://www.it.lut.fi/project/imageret/diaretdb0/index.html DIARETDB1[30] CFP 该数据集可用做基准糖尿病视网膜病变检测数据集, 由 4 名医学专家对糖网相关病变区域进行
标注.1500 × 1152 PNG 89 直接下载 http://www.it.lut.fi/project/imageret/diaretdb1/ Large dataset of OCT on Mendeley[15] OCT 图像分为训练集和测试集, 每个集合含有 4 种标签的数据: CNV, DME, DR-USEN 和 NORMAL. 不统一约为
400 × 500JPEG > 50000 直接下载 https://data.mendeley.com/archiver/rscbjbr9sj?version=3 Dataset for OCT classification[31] OCT 由 50 个正常、48 个干性 AMD 和 50 个 DME 组成. 765 × 765 TIFF 3700 直接下载 https://sites.google.com/site/hosseinrabbanikhorasgani/datasets-1 表 3 病变区域检测相关研究
Table 3 Related works on lesion detection
相关研究 方法 数据集 提取特征 性能 Shan 等[51] Patches + 堆叠稀疏自动编码(SSAE) + 迁移学习 DIARETDB MA 敏感性: 91.6%, F-score: 91.3%, 准确性: 91.38% Budak 等[55] 深度卷积神经网络 (DCNN) 在线挑战数据集 (ROC) MA 比赛分数为 0.221, 高于其他方法 Dai 等[54] Alex-Net 框架为基础的 MS-
CNN模型当地医院收集数据, DIARETDB1 MA 准确率: 96.1% Orlando 等[56] CNN + 手工工程特征 + 随机
森林 (Random forest) 分类器MESSIDOR E-Ophtha MA, HE AUC: CNN: 0.7912, 手工工程: 0.7325, CNN+手工工程: 0.8932 AUC: CNN: 0.8374, 手工工程: 0.8812, CNN+手工工程: 0.9031 van Grinsven 等[53] 动态选择抽样策略 (SeS,
NSeS) + 10 层 CNNKaggle MESSIDOR HE 敏感性: 84.8%, 特异性: 90.4%, AUC: 91.7%, 敏感性: 93.1%,
特异性: 91.5%, AUC: 97.9%Prentasic 等[57] DNN DRiDB EX, SE 敏感性: 78%, F-score: 78% Otálora 等[58] 基于LeNet网络 + EGL的主
动学习策略 + 迁移学习E-Ophtha EX, SE 敏感性: 99.8%, 特异性: 99.6%,
准确性: 99.6%Abbasi-Sureshjani 等[52] ResNet DIARETDB1, DR2, E-Ophtha EX, SE AUC 分别为: 96.5%, 97.2 %, 99.4% Badar 等[40] SegNet 模型为基础的 Auto-encoder 网络 Messidor MA, HE, EX 精确度: 99.24% (EX),
97.86% (HM), 88.65% (MA)ISBI 韩国 VRT 团队 DeepLab + U-Net DRiDB MA, HE, SE, EX F-score 分别为: 0.4951, 0.6804, 0.6995, 0.7127 ISBI 中国平安科技
Patech 团队DenseNet + DeepLab V3 DRiDB MA, HE, EX F-score 分别为: 0.474, 0.649, 0.885 ISBI 中国科大讯飞 U-Net + 注意力机制 + DeepLabV3 + DRiDB MA, HE, SE, EX F-score 分别为: 0.5017, 0.5588, 0.6588, 0.8741 Tan 等[59] DCNN CLEOPATRA MA, HM, HE, SE 敏感性: 87.58%, 特异性: 98.73% 表 4 病变等级分类相关研究
Table 4 Related works on classification of diabetic retinopathy
相关研究 应用 方法 数据集 性能 谷歌 Gulshan 等[69] 诊断 RDR InceptionV3 框架,
端到端分类EyePACS-1
Messidor-2特异性: 93.4 %, 敏感性: 97.5 %
特异性: 93.9 %, 敏感性: 96.1%Li 等[72] 诊断有无 DR VggNet, GoogLeNet, Vgg-s 等进行迁移学习 DR1
MESSIDORVgg-s 性能最好:
敏感性: 97.11 %, 特异性: 86.03 %,
准确度: 92.01 %, AUC: 0.9834ElTanboly 等[73] 诊断 RDR Stacked non-negativityconstraint autoencoder (SNCAE) 医院获取 OCT 图像 准确度: 96 % Gargeya 等[74] 诊断 RDR Data-driven DNN ResNet, Second-level gradientboosting
classifierEyePACS
MESSIDORAUC: 0.97
AUC: 0.94Abràmoff 等[75] 诊断 RDR, VTDR DCNN Messidor-2 RDR 敏感性: 96.8 %, 特异性: 87.0 %,
AUC: 0.980
从 RDR 分类出 VTDR: 敏感性: 100 %,
特异性: 91 %, AUC: 0.989Ting 等[76] 诊断 RDR, VTDR VGG-19 6 个不同国家招募了 10
组数据集RDR 敏感性: 90.5 %, 特异性: 91.6 %,
AUC: 0.936
从 RDR 分类出 VTDR: 敏感性: 100 %,
特异性: 91.1 %, AUC: 0.958中山大学[16] 诊断 RDR, VTDR InceptionV3 中国人彩色眼底图片
多种族彩色眼底图像敏感性: 97.0 %, 特异性: 91.4 %
敏感性: 92.5 %, 特异性: 98.5 %Abràmoff 等[77] 在初级保健诊所诊断
DR, 进行实际应用CNN 在初级保健诊所招收了 900
名受试者, 男性占 47.5 %; 其
中包括: 西班牙裔 16.1 %, 非
裔美国人 28.6%敏感性: 87.2 %, 特异性: 90.7 %,
显像率: 96.1 %Wang等[78] 划分五类等级 DenseNet, Boosting
tree algorithmKaggle 精确度: R0: 0.92, R1: 0.70,
R2: 0.64, R3: 0.67, R4: 0.69Zhou 等[79] 划分五类等级 Multi-Cell Multi-Task CNN Kaggle Kappa: 0.841 Doshi 等[80] 划分五类等级 5层 CNN 网络 EyePACs Kappa: 0.386 IBM 划分五类等级 DCNN EyePAC 准确度: 86 % 表 5 基于视网膜OCT影像的眼部疾病诊断相关研究
Table 5 Studies on diagnosis of ocular diseases based on retinal OCT images
相关研究 应用 方法 数据集 性能 Sandhu 等[84] 对 DR 患者早期诊断 基于融合形状, 强度和空间信息的联合模型, 两阶段深度融合分类网络 路易斯维尔大学 (University of Louisville) 接受常规筛查和 (或) 监测检查的 II 型糖尿病患者 OCT 数据 准确率平均为94% Hassan等[81] 从 OCT 扫描中分割出
8 个视网膜层深度卷积神经网络, 基于结构张力的分割框架(CNN-STSF) 取自不同公共可用数据集和当地武装部队眼科研究所 (AFIO) 数据集的超过 3.9 万幅视网膜 OCT 影像 准确性: 93.75% Vahadane等[82] 分割硬渗出物和囊肿
区域检测 DME图像处理, 深度学习,
基于规则方法1827 幅 OCT 影像 Precision: 96.43%, Recall:
89.45%, F1-score: 92.81%Kermany 等[15] 疾病分类转诊 InceptionV3+ 迁移
学习, 分类网络108312 幅 OCT 训练影像 (37206幅脉络膜新生血管, 11349 幅糖尿病黄斑水肿,
8617 幅玻璃膜疣, 51140 幅正常),
1000 幅 OCT 测试影像 (每个类别 250 幅)准确率: 96.6 %, 敏感性: 97.8 %,
特异性: 97.4 %, AUC: 99.9 %Li 等[83] 疾病分类转诊 VGG-16 + 迁移学习,
分类网络医院获取 109312 幅 OCT 影像 (37456 幅脉络膜新生血管, 11599 幅糖尿病黄斑水肿, 8867 幅玻璃膜疣, 51390 幅正常) 准确率: 98.6%, 敏感性: 97.8%,
特异性: 99.4%, AUC: 100%DeepMind
团队[18]分割疾病特征
分类转诊3DU-NET 分割网络, CNN 分类网络 摩尔菲尔兹眼科医院提供 14 884 幅 OCT 影像 准确度: 94%, AUC: 99.21% -
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