Leukemia classification relies on a detailed cytomorphological examination of Bone Marrow (BM) smear. However, applying existing deep-learning methods to it is facing two significant limitations. Firstly, these methods require large-scale datasets with expert annotations at the cell level for good results and typically suffer from poor generalization. Secondly, they simply treat the BM cytomorphological examination as a multi-class cell classification task, thus failing to exploit the correlation among leukemia subtypes over different hierarchies. Therefore, BM cytomorphological estimation as a time-consuming and repetitive process still needs to be done manually by experienced cytologists. Recently, Multi-Instance Learning (MIL) has achieved much progress in data-efficient medical image processing, which only requires patient-level labels (which can be extracted from the clinical reports). In this paper, we propose a hierarchical MIL framework and equip it with Information Bottleneck (IB) to tackle the above limitations. First, to handle the patient-level label, our hierarchical MIL framework uses attention-based learning to identify cells with high diagnostic values for leukemia classification in different hierarchies. Then, following the information bottleneck principle, we propose a hierarchical IB to constrain and refine the representations of different hierarchies for better accuracy and generalization. By applying our framework to a large-scale childhood acute leukemia dataset with corresponding BM smear images and clinical reports, we show that it can identify diagnostic-related cells without the need for cell-level annotations and outperforms other comparison methods. Furthermore, the evaluation conducted on an independent test cohort demonstrates the high generalizability of our framework.

Computational Pathology (CPATH) offers the possibility for highly accurate and low-cost automated pathological diagnosis. However, the high time cost of model inference is one of the main issues limiting the application of CPATH methods. Due to the large size of Whole-Slide Image (WSI), commonly used CPATH methods divided a WSI into a large number of image patches at relatively high magnification, then predicted each image patch individually, which is time-consuming. In this paper, we propose a novel Uncertainty-based Model Acceleration (UMA) method for reducing the time cost of model inference, thereby relieving the deployment burden of CPATH applications. Enlightened by the slide-viewing process of pathologists, only a few high-uncertain regions are regarded as “suspicious” regions that need to be predicted at high magnification, and most of the regions in WSI are predicted at low magnification, thereby reducing the times of image patch extraction and prediction. Meanwhile, uncertainty estimation ensures prediction accuracy at low magnification. We take two fundamental CPATH classification tasks (i.e., cancer region detection and subtyping) as examples. Extensive experiments on two large-scale renal cell carcinoma classification datasets demonstrate that our UMA can significantly reduce the time cost of model inference while maintaining competitive classification performance.

Pathological diagnosis is the gold standard for cancer diagnosis, but it is labor-intensive, in which tasks such as cell detection, classification, a nd c ounting a re particularly prominent. A common solution for automating these tasks is using nucleus segmentation technology. However, it is hard to train a robust nucleus segmentation model, due to several challenging problems,i.e., the nucleus adhesion, stacking, and excessive fusion with the background. Recently, some researchers proposed a series of automatic nucleus segmentation methods based on point annotation, which can significant i mprove t he m odel performance. Nevertheless, the point annotation needs to be marked by experienced pathologists. In order to take advantage of segmentation methods based on point annotation, further alleviate the manual workload, and make cancer diagnosis more efficient and accurate, it is necessary to develop an automatic nucleus detection algorithm, which can automatically and efficiently l ocate the position of the nucleus in the pathological image and extract valuable information for pathologists. In this paper, we propose a W-shaped network for automatic nucleus detection. Different from the traditional U-Net based method, mapping the original pathology image to the target mask directly, our proposed method split the detection task into two sub-tasks. The first sub-task maps the original pathology image to the binary mask, then the binary mask is mapped to the density mask in the second subtask. After the task is split, the task's difficulty i s significantly reduced, and the network's overall performance is improved. Our proposed network can automatic identify the center of each nucleus. Combined with the NuClick, a semi-supervised recognition model based on point annotation, we implement a fully automatic nucleus annotation framework.

Digital pathology plays a crucial role in the development of artificial intelligence in the medical field. The digital pathology platform can make the pathological resources digital and networked, and realize the permanent storage of visual data and the synchronous browsing processing without the limitation of time and space. It has been widely used in various fields of pathology. However, there is still a lack of an open and universal digital pathology platform to assist doctors in the management and analysis of digital pathological sections, as well as the management and structured description of relevant patient information. Most platforms cannot integrate image viewing, annotation and analysis, and text information management. To solve the above problems, we propose a comprehensive and extensible platform, PIMIP (Pathology Information Management & Integration Platform). PIMIP has developed the image annotation functions based on the visualization of digital pathological sections. Our annotation functions support multi-user collaborative annotation and multi-device annotation, and realize the automation of some annotation tasks. In the annotation task, we invited a professional pathologist for guidance. We introduce a machine learning module for image analysis. The data we collected included public data from local hospitals and clinical examples. Our platform is more clinical and suitable for clinical use. In addition to image data, we also structured the management and display of text information. So our platform is comprehensive. The platform framework is built in a modular way to support users to add machine learning modules independently, which makes our platform extensible.