School of Engineering Medicine, Beihang University, Beijing 100191, China; School of Biological Science, Beihang University and Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing 100191, China.
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
Med Image Anal. 2023 Oct;89:102931. doi: 10.1016/j.media.2023.102931. Epub 2023 Aug 12.
Accurate and quick binuclear cell (BC) detection plays a significant role in predicting the risk of leukemia and other malignant tumors. However, manual counting of BCs using microscope images is time consuming and subjective. Moreover, traditional image processing approaches perform poorly due to the limitations in staining quality and the diversity of morphological features in binuclear cell (BC) microscopy whole-slide images (WSIs). To overcome this challenge, we propose a multi-task method inspired by the structure prior of BCs based on deep learning, which cascades to implement BC coarse detection at the WSI level and fine-grained classification at the patch level. The coarse detection network is a multitask detection framework based on circular bounding boxes for cell detection and central key points for nucleus detection. Circle representation reduces the degrees of freedom, mitigates the effect of surrounding impurities compared to usual rectangular boxes and can be rotation invariant in WSIs. Detecting key points in the nucleus can assist in network perception and be used for unsupervised color layer segmentation in later fine-grained classification. The fine classification network consists of a background region suppression module based on color layer mask supervision and a key region selection module based on a transformer due to its global modeling capability. Additionally, an unsupervised and unpaired cytoplasm generator network is first proposed to expand the long-tailed distribution dataset. Finally, experiments are performed on BC multicenter datasets. The proposed BC fine detection method outperforms other benchmarks in almost all evaluation criteria, providing clarification and support for tasks such as cancer screenings.
准确快速的双核细胞 (BC) 检测在预测白血病和其他恶性肿瘤的风险方面起着重要作用。然而,使用显微镜图像手动计数 BC 既耗时又主观。此外,由于染色质量的限制和双核细胞 (BC) 显微镜全切片图像 (WSI) 中形态特征的多样性,传统的图像处理方法表现不佳。为了克服这一挑战,我们提出了一种基于深度学习的受 BC 结构先验启发的多任务方法,该方法级联实现了 WSI 级别的 BC 粗检测和斑块级别的细粒度分类。粗检测网络是一种基于圆形边界框的多任务检测框架,用于细胞检测和核中心关键点检测。圆形表示减少了自由度,与通常的矩形框相比减轻了周围杂质的影响,并且在 WSI 中可以旋转不变。检测核中的关键点可以辅助网络感知,并可用于后期细粒度分类中的无监督颜色层分割。细分类网络由基于颜色层掩模监督的背景区域抑制模块和基于转换器的关键区域选择模块组成,由于其具有全局建模能力。此外,我们首次提出了一种无监督和无配对细胞质生成网络,以扩展长尾分布数据集。最后,在 BC 多中心数据集上进行了实验。所提出的 BC 精细检测方法在几乎所有评估标准中都优于其他基准,为癌症筛查等任务提供了明确和支持。