In this study, we propose the Ductal Instance-Oriented Pipeline (DIOP) that contains a duct-level instance segmentation model, a tissue-level semantic segmentation model, and three-levels of features for diagnostic classification. Based on recent advancements in instance segmentation and the Mask R-CNN model, our duct-level segmenter tries to identify each ductal individual inside a microscopic image; then, it extracts tissue-level information from the identified ductal instances. Leveraging three levels of information obtained from these ductal instances and also the histopathology image, the proposed DIOP outperforms previous approaches (both feature-based and CNN-based) in all diagnostic tasks; for the four-way classification task, the DIOP achieves comparable performance to general pathologists in this unique dataset. The proposed DIOP only takes a few seconds to run in the inference time, which could be used interactively on most modern computers. More clinical explorations are needed to study the robustness and generalizability of this system in the future.
Analysis of histopathology slides is a critical step for many diagnoses, and in particular in oncology where it defines the gold standard. In the case of digital histopathological analysis, highly trained pathologists must review vast whole-slide-images of extreme digital resolution ($100,000^2$ pixels) across multiple zoom levels in order to locate abnormal regions of cells, or in some cases single cells, out of millions. The application of deep learning to this problem is hampered not only by small sample sizes, as typical datasets contain only a few hundred samples, but also by the generation of ground-truth localized annotations for training interpretable classification and segmentation models. We propose a method for disease localization in the context of weakly supervised learning, where only image-level labels are available during training. Even without pixel-level annotations, we are able to demonstrate performance comparable with models trained with strong annotations on the Camelyon-16 lymph node metastases detection challenge. We accomplish this through the use of pre-trained deep convolutional networks, feature embedding, as well as learning via top instances and negative evidence, a multiple instance learning technique from the field of semantic segmentation and object detection.
Mitotic count is a commonly used method to assess the level of progression of breast cancer, which is now the fourth most prevalent cancer. Unfortunately, counting mitosis is a tedious and subjective task with poor reproducibility, especially for non-experts. Luckily, since the machine can read and compare more data with greater efficiency this could be the next modern technique to count mitosis. Furthermore, technological advancements in medicine have led to the increase in image data available for use in training. In this work, we propose a network constructed using a similar approach to one that has been used for image fraud detection with the segmented image map as the second stream input to Faster RCNN. This region-based detection model combines a fully convolutional Region Proposal Network to generate proposals and a classification network to classify each of these proposals as containing mitosis or not. Features from both streams are fused in the bilinear pooling layer to maintain the spatial concurrence of each. After training this model on the ICPR 2014 MITOSIS contest dataset, we received an F-measure score of 0.507, higher than both the winners score and scores from recent tests on the same data. Our method is clinically applicable, taking only around five min per ten full High Power Field slides when tested on a Quadro P6000 cloud GPU.
Empirical evaluation of breast tissue biopsies for mitotic nuclei detection is considered an important prognostic biomarker in tumor grading and cancer progression. However, automated mitotic nuclei detection poses several challenges because of the unavailability of pixel-level annotations, different morphological configurations of mitotic nuclei, their sparse representation, and close resemblance with non-mitotic nuclei. These challenges undermine the precision of the automated detection model and thus make detection difficult in a single phase. This work proposes an end-to-end detection system for mitotic nuclei identification in breast cancer histopathological images. Deep object detection-based Mask R-CNN is adapted for mitotic nuclei detection that initially selects the candidate mitotic region with maximum recall. However, in the second phase, these candidate regions are refined by multi-object loss function to improve the precision. The performance of the proposed detection model shows improved discrimination ability (F-score of 0.86) for mitotic nuclei with significant precision (0.86) as compared to the two-stage detection models (F-score of 0.701) on TUPAC16 dataset. Promising results suggest that the deep object detection-based model has the potential to learn the characteristic features of mitotic nuclei from weakly annotated data and suggests that it can be adapted for the identification of other nuclear bodies in histopathological images.
Digital histology images are amenable to the application of convolutional neural network (CNN) for analysis due to the sheer size of pixel data present in them. CNNs are generally used for representation learning from small image patches (e.g. 224x224) extracted from digital histology images due to computational and memory constraints. However, this approach does not incorporate high-resolution contextual information in histology images. We propose a novel way to incorporate larger context by a context-aware neural network based on images with a dimension of 1,792x1,792 pixels. The proposed framework first encodes the local representation of a histology image into high dimensional features then aggregates the features by considering their spatial organization to make a final prediction. The proposed method is evaluated for colorectal cancer grading and breast cancer classification. A comprehensive analysis of some variants of the proposed method is presented. Our method outperformed the traditional patch-based approaches, problem-specific methods, and existing context-based methods quantitatively by a margin of 3.61%. Code and dataset related information is available at this link: https://tia-lab.github.io/Context-Aware-CNN