Whole Slide Image (WSI) analysis, with its ability to reveal detailed tissue structures in magnified views, plays a crucial role in cancer diagnosis and prognosis. Due to their giga-sized nature, WSIs require substantial storage and computational resources for processing and training predictive models. With the rapid increase in WSIs used in clinics and hospitals, there is a growing need for a continual learning system that can efficiently process and adapt existing models to new tasks without retraining or fine-tuning on previous tasks. Such a system must balance resource efficiency with high performance. In this study, we introduce COSFormer, a Transformer-based continual learning framework tailored for multi-task WSI analysis. COSFormer is designed to learn sequentially from new tasks wile avoiding the need to revisit full historical datasets. We evaluate COSFormer on a sequence of seven WSI datasets covering seven organs and six WSI-related tasks under both class-incremental and task-incremental settings. The results demonstrate COSFormer's superior generalizability and effectiveness compared to existing continual learning frameworks, establishing it as a robust solution for continual WSI analysis in clinical applications. The code is released at https://github.com/QuIIL/COSFormer.

In computational pathology, cancer grading has been mainly studied as a categorical classification problem, which does not utilize the ordering nature of cancer grades such as the higher the grade is, the worse the cancer is. To incorporate the ordering relationship among cancer grades, we introduce a differential ordinal learning problem in which we define and learn the degree of difference in the categorical class labels between pairs of samples by using their differences in the feature space. To this end, we propose a transformer-based neural network that simultaneously conducts both categorical classification and differential ordinal classification for cancer grading. We also propose a tailored loss function for differential ordinal learning. Evaluating the proposed method on three different types of cancer datasets, we demonstrate that the adoption of differential ordinal learning can improve the accuracy and reliability of cancer grading, outperforming conventional cancer grading approaches. The proposed approach should be applicable to other diseases and problems as they involve ordinal relationship among class labels.

In computational pathology, graphs have shown to be promising for pathology image analysis. There exist various graph structures that can discover differing features of pathology images. However, the combination and interaction between differing graph structures have not been fully studied and utilized for pathology image analysis. In this study, we propose a parallel, bi-graph neural network, designated as SCUBa-Net, equipped with both graph convolutional networks and Transformers, that processes a pathology image as two distinct graphs, including a spatially-constrained graph and a spatially-unconstrained graph. For efficient and effective graph learning, we introduce two inter-graph interaction blocks and an intra-graph interaction block. The inter-graph interaction blocks learn the node-to-node interactions within each graph. The intra-graph interaction block learns the graph-to-graph interactions at both global- and local-levels with the help of the virtual nodes that collect and summarize the information from the entire graphs. SCUBa-Net is systematically evaluated on four multi-organ datasets, including colorectal, prostate, gastric, and bladder cancers. The experimental results demonstrate the effectiveness of SCUBa-Net in comparison to the state-of-the-art convolutional neural networks, Transformer, and graph neural networks.

In pathology, cancer grading is crucial for patient management and treatment. Recent deep learning methods, based upon convolutional neural networks (CNNs), have shown great potential for automated and accurate cancer diagnosis. However, these do not explicitly utilize tissue/cellular composition, and thus difficult to incorporate the existing knowledge of cancer pathology. In this study, we propose a multi-cell type and multi-level graph aggregation network (MMGA-Net) for cancer grading. Given a pathology image, MMGA-Net constructs multiple cell graphs at multiple levels to represent intra- and inter-cell type relationships and to incorporate global and local cell-to-cell interactions. In addition, it extracts tissue contextual information using a CNN. Then, the tissue and cellular information are fused to predict a cancer grade. The experimental results on two types of cancer datasets demonstrate the effectiveness of MMGA-Net, outperforming other competing models. The results also suggest that the information fusion of multiple cell types and multiple levels via graphs is critical for improved pathology image analysis.

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.

Automated nuclei segmentation and classification are the keys to analyze and understand the cellular characteristics and functionality, supporting computer-aided digital pathology in disease diagnosis. However, the task still remains challenging due to the intrinsic variations in size, intensity, and morphology of different types of nuclei. Herein, we propose a self-guided ordinal regression neural network for simultaneous nuclear segmentation and classification that can exploit the intrinsic characteristics of nuclei and focus on highly uncertain areas during training. The proposed network formulates nuclei segmentation as an ordinal regression learning by introducing a distance decreasing discretization strategy, which stratifies nuclei in a way that inner regions forming a regular shape of nuclei are separated from outer regions forming an irregular shape. It also adopts a self-guided training strategy to adaptively adjust the weights associated with nuclear pixels, depending on the difficulty of the pixels that is assessed by the network itself. To evaluate the performance of the proposed network, we employ large-scale multi-tissue datasets with 276349 exhaustively annotated nuclei. We show that the proposed network achieves the state-of-the-art performance in both nuclei segmentation and classification in comparison to several methods that are recently developed for segmentation and/or classification.

Multi-scale approaches have been widely studied in pathology image analysis. These offer an ability to characterize tissues in an image at various scales, in which the tissues may appear differently. Many of such methods have focused on extracting multi-scale hand-crafted features and applied them to various tasks in pathology image analysis. Even, several deep learning methods explicitly adopt the multi-scale approaches. However, most of these methods simply merge the multi-scale features together or adopt the coarse-to-fine/fine-to-coarse strategy, which uses the features one at a time in a sequential manner. Utilizing the multi-scale features in a cooperative and discriminative fashion, the learning capabilities could be further improved. Herein, we propose a multi-scale approach that can identify and leverage the patterns of the multiple scales within a deep neural network and provide the superior capability of cancer classification. The patterns of the features across multiple scales are encoded as a binary pattern code and further converted to a decimal number, which can be easily embedded in the current framework of the deep neural networks. To evaluate the proposed method, multiple sets of pathology images are employed. Under the various experimental settings, the proposed method is systematically assessed and shows an improved classification performance in comparison to other competing methods.

Grading for cancer, based upon the degree of cancer differentiation, plays a major role in describing the characteristics and behavior of the cancer and determining treatment plan for patients. The grade is determined by a subjective and qualitative assessment of tissues under microscope, which suffers from high inter- and intra-observer variability among pathologists. Digital pathology offers an alternative means to automate the procedure as well as to improve the accuracy and robustness of cancer grading. However, most of such methods tend to mimic or reproduce cancer grade determined by human experts. Herein, we propose an alternative, quantitative means of assessing and characterizing cancers in an unsupervised manner. The proposed method utilizes conditional generative adversarial networks to characterize tissues. The proposed method is evaluated using whole slide images (WSIs) and tissue microarrays (TMAs) of colorectal cancer specimens. The results suggest that the proposed method holds a potential for quantifying cancer characteristics and improving cancer pathology.

Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated. Contestants were given a training set with 30 images from seven organs with annotations of 21,623 individual nuclei. A test dataset with 14 images taken from seven organs, including two organs that did not appear in the training set was released without annotations. Entries were evaluated based on average aggregated Jaccard index (AJI) on the test set to prioritize accurate instance segmentation as opposed to mere semantic segmentation. More than half the teams that completed the challenge outperformed a previous baseline. Among the trends observed that contributed to increased accuracy were the use of color normalization as well as heavy data augmentation. Additionally, fully convolutional networks inspired by variants of U-Net, FCN, and Mask-RCNN were popularly used, typically based on ResNet or VGG base architectures. Watershed segmentation on predicted semantic segmentation maps was a popular post-processing strategy. Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics.

Temporal enhanced ultrasound (TeUS), comprising the analysis of variations in backscattered signals from a tissue over a sequence of ultrasound frames, has been previously proposed as a new paradigm for tissue characterization. In this paper, we propose to use deep recurrent neural networks (RNN) to explicitly model the temporal information in TeUS. By investigating several RNN models, we demonstrate that long short-term memory (LSTM) networks achieve the highest accuracy in separating cancer from benign tissue in the prostate. We also present algorithms for in-depth analysis of LSTM networks. Our in vivo study includes data from 255 prostate biopsy cores of 157 patients. We achieve area under the curve, sensitivity, specificity, and accuracy of 0.96, 0.76, 0.98, and 0.93, respectively. Our result suggests that temporal modeling of TeUS using RNN can significantly improve cancer detection accuracy over previously presented works.

BACKGROUND: The current practice of histopathology review is limited in speed and accuracy. The current diagnostic paradigm does not fully describe the complex and complicated patterns of cancer. To address these needs, we develop an automated and objective system that facilitates a comprehensive and easy information management and decision-making. We also develop a tissue similarity measure scheme to broaden our understanding of tissue characteristics. RESULTS: The system includes a database of previously evaluated prostate tissue images, clinical information and a tissue retrieval process. In the system, a tissue is characterized by its morphology. The retrieval process seeks to find the closest matching cases with the tissue of interest. Moreover, we define 9 morphologic criteria by which a pathologist arrives at a histomorphologic diagnosis. Based on the 9 criteria, true tissue similarity is determined and serves as the gold standard of tissue retrieval. Here, we found a minimum of 4 and 3 matching cases, out of 5, for ~80 % and ~60 % of the queries when a match was defined as the tissue similarity score ≥5 and ≥6, respectively. We were also able to examine the relationship between tissues beyond the Gleason grading system due to the tissue similarity scoring system. CONCLUSIONS: Providing the closest matching cases and their clinical information with pathologists will help to conduct consistent and reliable diagnoses. Thus, we expect the system to facilitate quality maintenance and quality improvement of cancer pathology.