利用无注释全切片图像深度学习识别结直肠癌的微转移淋巴结。
Identification of nodal micrometastasis in colorectal cancer using deep learning on annotation-free whole-slide images.
机构信息
Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
aetherAI Co., Ltd., Taipei, Taiwan.
出版信息
Mod Pathol. 2021 Oct;34(10):1901-1911. doi: 10.1038/s41379-021-00838-2. Epub 2021 Jun 8.
Detection of nodal micrometastasis (tumor size: 0.2-2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.
检测淋巴结微转移(肿瘤大小:0.2-2.0 毫米)对病理学家来说具有挑战性,因为转移灶的体积较小。由于带有微转移的淋巴结被视为阳性淋巴结,因此检测微转移对于准确的结直肠癌病理分期至关重要。此前,使用人工标注图像开发的深度学习算法在识别前哨淋巴结中乳腺癌的微转移方面表现良好。然而,人工标注的过程既费力又耗时。后来使用多实例学习来识别无人工标注的转移性乳腺癌,但它在检测微转移方面的表现似乎较差。在这里,我们使用仅具有幻灯片级标签(阳性或阴性幻灯片)的结直肠癌区域淋巴结的全幻灯片图像开发了一种深度学习模型。训练、验证和测试集分别包含 1963、219 和 1000 张幻灯片。使用超级计算机 TAIWANIA 2 来训练深度学习模型以识别转移。在幻灯片级别,我们的算法在识别大转移(肿瘤大小>2.0 毫米)和微转移方面表现良好,其接收者操作特征曲线下面积(AUC)分别为 0.9993 和 0.9956。由于我们的大多数幻灯片包含一个以上的淋巴结,因此我们随后在从测试集中随机裁剪的 538 张单个淋巴结图像上测试了我们算法的性能。在单个淋巴结级别,我们的算法在识别大转移和微转移方面保持良好的性能,AUC 分别为 0.9944 和 0.9476。使用类激活映射的可视化证实了我们的模型是根据肿瘤细胞区域来识别淋巴结转移的。我们的结果首次证明,无需人工标注,深度学习就可以在全幻灯片图像上检测微转移。