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全景病理切片神经母细胞瘤分化类型的交叉伪监督识别方法

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评估神经母细胞瘤的分化类型对肿瘤预后至关重要.虽然计算机辅助诊断能有效减轻医生的负担,但细胞级结构的精细标注较为耗时.为优化细胞级数据标注问题,采用一种基于交叉伪监督的深度学习方法,充分利用无标签数据的分布特性,结合少量标注数据,通过两个分支相互监督,提升模型的泛化能力.针对神经母细胞瘤复杂的细胞环境和异质性,提出一种新型网络CSA-U-Net,用于全景病理图像中细胞的分割和分类.该网络在U-Net网络的瓶颈层加入通道和空间注意力模块.将CSA-U-Net作为交叉伪监督模型的基础网络,通过结合不同比例的有标签和无标签数据进行训练,当有标签数据和无标签数据比例为1∶4时,模型在分化差和分化细胞上的F1分数和准确度分别达到81.02%、65.48%、98.02%,优于其他分割算法,从而验证半监督学习的有效性.最后,使用K-means算法对不同类型细胞进行计数,并与医生的诊断金标准进行对比,结果显示分化差和分化的神经母细胞计数结果的准确率分别为94.00%和89.89%.通过计数结果中分化的神经母细胞占比,可以判断出神经母细胞瘤的分化类型,辅助病理医生进行诊断.
Cross Pseudo Supervision Algorithm for Identifying Neuroblastoma Differentiation Type in Whole Slide Pathology Image
Objective Neuroblastoma(NB)is a type of peripheral neuroblastic tumor commonly found in children and characterized by obvious heterogeneity in biological behavior and rapid development.Determining the differentiation type is helpful in assessing the prognosis of neuroblastoma for making early judgments regarding postoperative treatment options.Whole-slide images(WSIs)of the NB have ultrahigh resolution and contain rich information,facilitating clinical interpretation.However,early diagnosis is time-consuming and poses significant challenges.Considering the complex cellular environment and heterogeneity of NB,this study proposes a novel network,CSA-U-Net,for cell segmentation and classification of NB WSI.Additionally,a cross-pseudo-supervised(CPS)approach,combining different proportions of labeled and unlabeled data,is used for training,which improves the robustness and generalization ability of the model,thereby assisting pathologists in clinical diagnosis,reducing their workload,and decreasing the misdiagnosis rate.Methods To address the cell-level data labeling problem,this study adopt a deep learning method based on CPS,fully utilizing the distributional characteristics of unlabeled data and combining a small amount of labeled data,to improve the model's generalization ability by having the two branches supervise each other.To address the complex cellular environment and heterogeneity of NB,channel and spatial attention modules are added to the bottleneck layer of U-Net network.The proposed novel network,CSA-U-Net,is served as the base network for the CPS model,effectively improving model accuracy.Finally,the K-means algorithm is used to classify and count poorly differentiated and differentiated NB cells in the pathology slide images.The percentage of differentiated NB to the total number of tumor cells is calculated,to assist pathologists in determining histopathological typing.Results and Discussions The CPS approach for NB WSI segmentation is shown in Fig.1,with CSA-U-Net as the underlying network for the two branches(Fig.5).The CSA-U-Net network was compared with U-Net,DeepLabv3+,PSPNet,HrNet,SA-U-Net,HoVer-Net,and MEDIAR.The results showed that the CSA-U-Net outperforms the other methods in all indicators.The F1 score was 79.05%in poorly differentiated cells and 62.21%in differentiated cells,and the accuracy was 96.78%,which is an improvement compared with that of the traditional U-Net(Table 1).In the prediction result graph,the prediction results of CSA-U-Net exhibit more accuracy,clearer boundaries,and less noise in the image,relative to other networks.A lower error rate is observed in the regions prone to erroneous segmentation(Fig.8).Next,the performance difference of the CPS method with CSA-U-Net as the base network,was explored for labeled to unlabeled data ratios of 1∶1,1∶2,1∶3,and 1∶4.The results show that the segmentation accuracy of the model gradually increases with an increase in the amount of unlabeled data,and the F1 score of the model improves faster before the ratio of labeled to unlabeled data reaches 1∶3.After the ratio reaches 1∶4,the model enhancement is slower,and the speed of accuracy enhancement decreases significantly(Table 2).Subsequently,the CPS method was compared with other semi-supervised methods,at a 1:3 ratio of labeled to unlabeled data.The CPS method showed the best detection performance,with F1 score of 80.99%in poorly differentiated cells,65.40%in differentiated cells,and 97.99%accuracy(Table 3).Finally,the different types of cells in the prediction results were counted using the k-means method and compared with the gold standard of physicians(Fig.9).The average accuracy of the counting results of poorly differentiated and differentiated NB cells was 94.00%and 89.89%,respectively(Table 4).This result indicates that the method in this study excels in the counting accuracy of poorly differentiated and differentiated cells and operates stably in images of any size,further validating the reliability of the method.Conclusions To address the problem of large amounts of cellular data and heavy labeling in NB images,this study adopted a CPS approach for model training.By introducing unlabeled data during training,the model can better capture the features of poorly differentiated and differentiated cells,thereby more accurately extracting and categorizing these cells from tissue backgrounds and displaying better adaptation to the variability and complexity of different samples.The CPS approach ensures the consistency of the two branches in terms of network structure while making them differ in parameter space through different initializations and independent training,which drives the model to learn a more robust and comprehensive feature representation.Meanwhile,for the features of NB pathology slide images,this study proposes a CSA-U-Net network model,incorporating an attention mechanism based on the original U-Net network,which further improves the accuracies of the segmentation and classification results.This study is based on the CSA-U-Net network and effectively integrates labeled and unlabeled data using a CPS semi-supervised model.The experimental results show that the CSA-U-Net network exhibits better performance on the NB dataset than existing control methods,with the segmentation accuracy of the model gradually improving as the amount of unlabeled data increases,which further validates the effectiveness of the CPS method.Finally,the K-means method was used to count the different types of cells in the model prediction results for pathological staging.The method proposed in this study effectively reduced the workload of pathologists,improved diagnostic efficiency,and is of great significance in determining the prognosis of NB.

whole slide pathology imagesneuroblastomacross pseudo supervisionattention mechanismimage segmentationcell counting

万真真、刘雨薇、施宁、李昊成、刘芳

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河北大学电子信息工程学院河北省数字医疗工程重点实验室,河北保定 071002

首都医科大学附属北京儿童医院保定医院病理科,河北保定 071002

全景病理切片 神经母细胞瘤 交叉伪监督 注意力机制 图像分割 细胞计数

国家自然科学基金区域创新发展联合基金河北省自然科学基金

U20A20224F20222010371

2024

中国激光
中国光学学会 中科院上海光机所

中国激光

CSTPCD北大核心
影响因子:2.204
ISSN:0258-7025
年,卷(期):2024.51(15)