Combining Datasets with Different Label Sets for Improved Nucleus Segmentation and Classification

Segmentation and classification of cell nuclei in histopathology images using deep neural networks (DNNs) can save pathologists' time for diagnosing various diseases, including cancers, by automating cell counting and morphometric assessments. It is now well-known that the accuracy of DNNs increases with the sizes of annotated datasets available for training. Although multiple datasets of histopathology images with nuclear annotations and class labels have been made publicly available, the set of class labels differ across these datasets. We propose a method to train DNNs for instance segmentation and classification on multiple datasets where the set of classes across the datasets are related but not the same. Specifically, our method is designed to utilize a coarse-to-fine class hierarchy, where the set of classes labeled and annotated in a dataset can be at any level of the hierarchy, as long as the classes are mutually exclusive. Within a dataset, the set of classes need not even be at the same level of the class hierarchy tree. Our results demonstrate that segmentation and classification metrics for the class set used by the test split of a dataset can improve by pre-training on another dataset that may even have a different set of classes due to the expansion of the training set enabled by our method. Furthermore, generalization to previously unseen datasets also improves by combining multiple other datasets with different sets of classes for training. The improvement is both qualitative and quantitative. The proposed method can be adapted for various loss functions, DNN architectures, and application domains.

EGFR Mutation Prediction of Lung Biopsy Images using Deep Learning

The standard diagnostic procedures for targeted therapies in lung cancer treatment involve histological subtyping and subsequent detection of key driver mutations, such as EGFR. Even though molecular profiling can uncover the driver mutation, the process is often expensive and time-consuming. Deep learning-oriented image analysis offers a more economical alternative for discovering driver mutations directly from whole slide images (WSIs). In this work, we used customized deep learning pipelines with weak supervision to identify the morphological correlates of EGFR mutation from hematoxylin and eosin-stained WSIs, in addition to detecting tumor and histologically subtyping it. We demonstrate the effectiveness of our pipeline by conducting rigorous experiments and ablation studies on two lung cancer datasets - TCGA and a private dataset from India. With our pipeline, we achieved an average area under the curve (AUC) of 0.964 for tumor detection, and 0.942 for histological subtyping between adenocarcinoma and squamous cell carcinoma on the TCGA dataset. For EGFR detection, we achieved an average AUC of 0.864 on the TCGA dataset and 0.783 on the dataset from India. Our key learning points include the following. Firstly, there is no particular advantage of using a feature extractor layers trained on histology, if one is going to fine-tune the feature extractor on the target dataset. Secondly, selecting patches with high cellularity, presumably capturing tumor regions, is not always helpful, as the sign of a disease class may be present in the tumor-adjacent stroma.

Deep Multi-Scale U-Net Architecture and Noise-Robust Training Strategies for Histopathological Image Segmentation

Although the U-Net architecture has been extensively used for segmentation of medical images, we address two of its shortcomings in this work. Firstly, the accuracy of vanilla U-Net degrades when the target regions for segmentation exhibit significant variations in shape and size. Even though the U-Net already possesses some capability to analyze features at various scales, we propose to explicitly add multi-scale feature maps in each convolutional module of the U-Net encoder to improve segmentation of histology images. Secondly, the accuracy of a U-Net model also suffers when the annotations for supervised learning are noisy or incomplete. This can happen due to the inherent difficulty for a human expert to identify and delineate all instances of specific pathology very precisely and accurately. We address this challenge by introducing auxiliary confidence maps that emphasize less on the boundaries of the given target regions. Further, we utilize the bootstrapping properties of the deep network to address the missing annotation problem intelligently. In our experiments on a private dataset of breast cancer lymph nodes, where the primary task was to segment germinal centres and sinus histiocytosis, we observed substantial improvement over a U-Net baseline based on the two proposed augmentations.