Yu Wenjin, Liu Yangyang, Zhao Yunsong, Huang Haofan, Liu Jiahao, Yao Xiaofeng, Li Jingwen, Xie Zhen, Jiang Luyue, Wu Heping, Cao Xinhao, Zhou Jiaming, Guo Yuting, Li Gaoyang, Ren Matthew Xinhu, Quan Yi, Mu Tingmin, Izquierdo Guillermo Ayuso, Zhang Guoxun, Zhao Runze, Zhao Di, Yan Jiangyun, Zhang Haijun, Lv Junchao, Yao Qian, Duan Yan, Zhou Huimin, Liu Tingting, He Ying, Bian Ting, Dai Wen, Huai Jiahui, Wang Xiyuan, He Qian, Gao Yi, Ren Wei, Niu Gang, Zhao Gang
Department of Neurology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Department of Neurology, Yan'an University Medical College No. 3 Affiliated Hospital, Xianyang, China.
Front Oncol. 2022 Feb 22;12:821594. doi: 10.3389/fonc.2022.821594. eCollection 2022.
It is a critical challenge to diagnose leptomeningeal metastasis (LM), given its technical difficulty and the lack of typical symptoms. The existing gold standard of diagnosing LM is to use positive cerebrospinal fluid (CSF) cytology, which consumes significantly more time to classify cells under a microscope.
This study aims to establish a deep learning model to classify cancer cells in CSF, thus facilitating doctors to achieve an accurate and fast diagnosis of LM in an early stage.
The cerebrospinal fluid laboratory of Xijing Hospital provides 53,255 cells from 90 LM patients in the research. We used two deep convolutional neural networks (CNN) models to classify cells in the CSF. A five-way cell classification model (CNN1) consists of lymphocytes, monocytes, neutrophils, erythrocytes, and cancer cells. A four-way cancer cell classification model (CNN2) consists of lung cancer cells, gastric cancer cells, breast cancer cells, and pancreatic cancer cells. Here, the CNN models were constructed by Resnet-inception-V2. We evaluated the performance of the proposed models on two external datasets and compared them with the results from 42 doctors of various levels of experience in the human-machine tests. Furthermore, we develop a computer-aided diagnosis (CAD) software to generate cytology diagnosis reports in the research rapidly.
With respect to the validation set, the mean average precision (mAP) of CNN1 is over 95% and that of CNN2 is close to 80%. Hence, the proposed deep learning model effectively classifies cells in CSF to facilitate the screening of cancer cells. In the human-machine tests, the accuracy of CNN1 is similar to the results from experts, with higher accuracy than doctors in other levels. Moreover, the overall accuracy of CNN2 is 10% higher than that of experts, with a time consumption of only one-third of that consumed by an expert. Using the CAD software saves 90% working time of cytologists.
A deep learning method has been developed to assist the LM diagnosis with high accuracy and low time consumption effectively. Thanks to labeled data and step-by-step training, our proposed method can successfully classify cancer cells in the CSF to assist LM diagnosis early. In addition, this unique research can predict cancer's primary source of LM, which relies on cytomorphologic features without immunohistochemistry. Our results show that deep learning can be widely used in medical images to classify cerebrospinal fluid cells. For complex cancer classification tasks, the accuracy of the proposed method is significantly higher than that of specialist doctors, and its performance is better than that of junior doctors and interns. The application of CNNs and CAD software may ultimately aid in expediting the diagnosis and overcoming the shortage of experienced cytologists, thereby facilitating earlier treatment and improving the prognosis of LM.
鉴于软脑膜转移(LM)的诊断技术难度大且缺乏典型症状,这是一项严峻的挑战。现有的诊断LM的金标准是使用脑脊液(CSF)细胞学检查呈阳性,但在显微镜下对细胞进行分类需要耗费大量时间。
本研究旨在建立一种深度学习模型,用于对CSF中的癌细胞进行分类,从而帮助医生在早期实现对LM的准确快速诊断。
西京医院脑脊液实验室提供了研究中90例LM患者的53255个细胞。我们使用两个深度卷积神经网络(CNN)模型对CSF中的细胞进行分类。一个五路细胞分类模型(CNN1)由淋巴细胞、单核细胞、中性粒细胞、红细胞和癌细胞组成。一个四路癌细胞分类模型(CNN2)由肺癌细胞、胃癌细胞、乳腺癌细胞和胰腺癌细胞组成。在此,CNN模型由Resnet-inception-V2构建。我们在两个外部数据集上评估了所提出模型的性能,并在人机测试中将其与42位不同经验水平的医生的结果进行了比较。此外,我们在研究中开发了一种计算机辅助诊断(CAD)软件,以快速生成细胞学诊断报告。
在验证集方面,CNN1的平均平均精度(mAP)超过95%,CNN2的平均平均精度接近80%。因此,所提出的深度学习模型有效地对CSF中的细胞进行了分类,便于癌细胞的筛查。在人机测试中,CNN1的准确率与专家的结果相似,比其他水平的医生准确率更高。此外,CNN2的总体准确率比专家高10%,且时间消耗仅为专家的三分之一。使用CAD软件可节省细胞学家90%的工作时间。
已开发出一种深度学习方法,可有效协助LM诊断,具有高准确性和低时间消耗。由于有标记数据和逐步训练,我们提出的方法能够成功对CSF中的癌细胞进行分类,以早期协助LM诊断。此外,这项独特的研究可以预测LM癌症的原发部位,这依赖于细胞形态学特征而无需免疫组织化学。我们的结果表明,深度学习可广泛应用于医学图像中,以对脑脊液细胞进行分类。对于复杂的癌症分类任务,所提出方法的准确率显著高于专科医生,其性能优于初级医生和实习生。CNNs和CAD软件的应用最终可能有助于加快诊断并克服经验丰富的细胞学家短缺的问题,从而促进早期治疗并改善LM的预后。