Self-Contrastive Weakly Supervised Learning Framework for Prognostic Prediction Using Whole Slide Images

We present a pioneering investigation into the application of deep learning techniques to analyze histopathological images for addressing the substantial challenge of automated prognostic prediction. Prognostic prediction poses a unique challenge as the ground truth labels are inherently weak, and the model must anticipate future events that are not directly observable in the image. To address this challenge, we propose a novel three-part framework comprising of a convolutional network based tissue segmentation algorithm for region of interest delineation, a contrastive learning module for feature extraction, and a nested multiple instance learning classification module. Our study explores the significance of various regions of interest within the histopathological slides and exploits diverse learning scenarios. The pipeline is initially validated on artificially generated data and a simpler diagnostic task. Transitioning to prognostic prediction, tasks become more challenging. Employing bladder cancer as use case, our best models yield an AUC of 0.721 and 0.678 for recurrence and treatment outcome prediction respectively.

NMGrad: Advancing Histopathological Bladder Cancer Grading with Weakly Supervised Deep Learning

The most prevalent form of bladder cancer is urothelial carcinoma, characterized by a high recurrence rate and substantial lifetime treatment costs for patients. Grading is a prime factor for patient risk stratification, although it suffers from inconsistencies and variations among pathologists. Moreover, absence of annotations in medical imaging difficults training deep learning models. To address these challenges, we introduce a pipeline designed for bladder cancer grading using histological slides. First, it extracts urothelium tissue tiles at different magnification levels, employing a convolutional neural network for processing for feature extraction. Then, it engages in the slide-level prediction process. It employs a nested multiple instance learning approach with attention to predict the grade. To distinguish different levels of malignancy within specific regions of the slide, we include the origins of the tiles in our analysis. The attention scores at region level is shown to correlate with verified high-grade regions, giving some explainability to the model. Clinical evaluations demonstrate that our model consistently outperforms previous state-of-the-art methods.

Equipping Computational Pathology Systems with Artifact Processing Pipelines: A Showcase for Computation and Performance Trade-offs

Histopathology is a gold standard for cancer diagnosis under a microscopic examination. However, histological tissue processing procedures result in artifacts, which are ultimately transferred to the digitized version of glass slides, known as whole slide images (WSIs). Artifacts are diagnostically irrelevant areas and may result in wrong deep learning (DL) algorithms predictions. Therefore, detecting and excluding artifacts in the computational pathology (CPATH) system is essential for reliable automated diagnosis. In this paper, we propose a mixture of experts (MoE) scheme for detecting five notable artifacts, including damaged tissue, blur, folded tissue, air bubbles, and histologically irrelevant blood from WSIs. First, we train independent binary DL models as experts to capture particular artifact morphology. Then, we ensemble their predictions using a fusion mechanism. We apply probabilistic thresholding over the final probability distribution to improve the sensitivity of the MoE. We developed DL pipelines using two MoEs and two multiclass models of state-of-the-art deep convolutional neural networks (DCNNs) and vision transformers (ViTs). DCNNs-based MoE and ViTs-based MoE schemes outperformed simpler multiclass models and were tested on datasets from different hospitals and cancer types, where MoE using DCNNs yielded the best results. The proposed MoE yields 86.15% F1 and 97.93% sensitivity scores on unseen data, retaining less computational cost for inference than MoE using ViTs. This best performance of MoEs comes with relatively higher computational trade-offs than multiclass models. The proposed artifact detection pipeline will not only ensure reliable CPATH predictions but may also provide quality control.

A Dual Convolutional Neural Network Pipeline for Melanoma Diagnostics and Prognostics

Melanoma is a type of cancer that begins in the cells controlling the pigment of the skin, and it is often referred to as the most dangerous skin cancer. Diagnosing melanoma can be time-consuming, and a recent increase in melanoma incidents indicates a growing demand for a more efficient diagnostic process. This paper presents a pipeline for melanoma diagnostics, leveraging two convolutional neural networks, a diagnosis, and a prognosis model. The diagnostic model is responsible for localizing malignant patches across whole slide images and delivering a patient-level diagnosis as malignant or benign. Further, the prognosis model utilizes the diagnostic model's output to provide a patient-level prognosis as good or bad. The full pipeline has an F1 score of 0.79 when tested on data from the same distribution as it was trained on.

Balancing Privacy and Progress in Artificial Intelligence: Anonymization in Histopathology for Biomedical Research and Education

The advancement of biomedical research heavily relies on access to large amounts of medical data. In the case of histopathology, Whole Slide Images (WSI) and clinicopathological information are valuable for developing Artificial Intelligence (AI) algorithms for Digital Pathology (DP). Transferring medical data "as open as possible" enhances the usability of the data for secondary purposes but poses a risk to patient privacy. At the same time, existing regulations push towards keeping medical data "as closed as necessary" to avoid re-identification risks. Generally, these legal regulations require the removal of sensitive data but do not consider the possibility of data linkage attacks due to modern image-matching algorithms. In addition, the lack of standardization in DP makes it harder to establish a single solution for all formats of WSIs. These challenges raise problems for bio-informatics researchers in balancing privacy and progress while developing AI algorithms. This paper explores the legal regulations and terminologies for medical data-sharing. We review existing approaches and highlight challenges from the histopathological perspective. We also present a data-sharing guideline for histological data to foster multidisciplinary research and education.

Deep Learning for Predicting Metastasis on Melanoma WSIs

Northern Europe has the second highest mortality rate of melanoma globally. In 2020, the mortality rate of melanoma rose to 1.9 per 100 000 habitants. Melanoma prognosis is based on a pathologist's subjective visual analysis of the patient's tumor. This methodology is heavily time-consuming, and the prognosis variability among experts is notable, drastically jeopardizing its reproducibility. Thus, the need for faster and more reproducible methods arises. Machine learning has paved its way into digital pathology, but so far, most contributions are on localization, segmentation, and diagnostics, with little emphasis on prognostics. This paper presents a convolutional neural network (CNN) method based on VGG16 to predict melanoma prognosis as the presence of metastasis within five years. Patches are extracted from regions of interest from Whole Slide Images (WSIs) at different magnification levels used in model training and validation. Results infer that utilizing WSI patches at 20x magnification level has the best performance, with an F1 score of 0.7667 and an AUC of 0.81.

Detection and Localization of Melanoma Skin Cancer in Histopathological Whole Slide Images

Melanoma diagnosed and treated in its early stages can increase the survival rate. A projected increase in skin cancer incidents and a dearth of dermatopathologists have emphasized the need for computational pathology (CPATH) systems. CPATH systems with deep learning (DL) models have the potential to identify the presence of melanoma by exploiting underlying morphological and cellular features. This paper proposes a DL method to detect melanoma and distinguish between normal skin and benign/malignant melanocytic lesions in Whole Slide Images (WSI). Our method detects lesions with high accuracy and localizes them on a WSI to identify potential regions of interest for pathologists. Interestingly, our DL method relies on using a single CNN network to create localization maps first and use them to perform slide-level predictions to determine patients who have melanoma. Our best model provides favorable patch-wise classification results with a 0.992 F1 score and 0.99 sensitivity on unseen data. The source code is https://github.com/RogerAmundsen/Melanoma-Diagnosis-and-Localization-from-Whole-Slide-Images-using-Convolutional-Neural-Networks.