Neda Zamanitajeddin

Mostafa Jahanifar, Manahil Raza, Kesi Xu et al.

Deep learning models have exhibited exceptional effectiveness in Computational Pathology (CPath) by tackling intricate tasks across an array of histology image analysis applications. Nevertheless, the presence of out-of-distribution data (stemming from a multitude of sources such as disparate imaging devices and diverse tissue preparation methods) can cause \emph{domain shift} (DS). DS decreases the generalization of trained models to unseen datasets with slightly different data distributions, prompting the need for innovative \emph{domain generalization} (DG) solutions. Recognizing the potential of DG methods to significantly influence diagnostic and prognostic models in cancer studies and clinical practice, we present this survey along with guidelines on achieving DG in CPath. We rigorously define various DS types, systematically review and categorize existing DG approaches and resources in CPath, and provide insights into their advantages, limitations, and applicability. We also conduct thorough benchmarking experiments with 28 cutting-edge DG algorithms to address a complex DG problem. Our findings suggest that careful experiment design and CPath-specific Stain Augmentation technique can be very effective. However, there is no one-size-fits-all solution for DG in CPath. Therefore, we establish clear guidelines for detecting and managing DS depending on different scenarios. While most of the concepts, guidelines, and recommendations are given for applications in CPath, we believe that they are applicable to most medical image analysis tasks as well.

Mostafa Jahanifar, Adam Shephard, Neda Zamanitajeddin et al.

Counting of mitotic figures is a fundamental step in grading and prognostication of several cancers. However, manual mitosis counting is tedious and time-consuming. In addition, variation in the appearance of mitotic figures causes a high degree of discordance among pathologists. With advances in deep learning models, several automatic mitosis detection algorithms have been proposed but they are sensitive to {\em domain shift} often seen in histology images. We propose a robust and efficient two-stage mitosis detection framework, which comprises mitosis candidate segmentation ({\em Detecting Fast}) and candidate refinement ({\em Detecting Slow}) stages. The proposed candidate segmentation model, termed \textit{EUNet}, is fast and accurate due to its architectural design. EUNet can precisely segment candidates at a lower resolution to considerably speed up candidate detection. Candidates are then refined using a deeper classifier network, EfficientNet-B7, in the second stage. We make sure both stages are robust against domain shift by incorporating domain generalization methods. We demonstrate state-of-the-art performance and generalizability of the proposed model on the three largest publicly available mitosis datasets, winning the two mitosis domain generalization challenge contests (MIDOG21 and MIDOG22). Finally, we showcase the utility of the proposed algorithm by processing the TCGA breast cancer cohort (1,125 whole-slide images) to generate and release a repository of more than 620K mitotic figures.

Neda Zamanitajeddin, Mostafa Jahanifar, Kesi Xu et al.

Deep learning models have shown immense promise in computational pathology (CPath) tasks, but their performance often suffers when applied to unseen data due to domain shifts. Addressing this requires domain generalization (DG) algorithms. However, a systematic evaluation of DG algorithms in the CPath context is lacking. This study aims to benchmark the effectiveness of 30 DG algorithms on 3 CPath tasks of varying difficulty through 7,560 cross-validation runs. We evaluate these algorithms using a unified and robust platform, incorporating modality-specific techniques and recent advances like pretrained foundation models. Our extensive cross-validation experiments provide insights into the relative performance of various DG strategies. We observe that self-supervised learning and stain augmentation consistently outperform other methods, highlighting the potential of pretrained models and data augmentation. Furthermore, we introduce a new pan-cancer tumor detection dataset (HISTOPANTUM) as a benchmark for future research. This study offers valuable guidance to researchers in selecting appropriate DG approaches for CPath tasks.

Neda Zamanitajeddin, Mostafa Jahanifar, Nasir Rajpoot

Digitization of histology images and the advent of new computational methods, like deep learning, have helped the automatic grading of colorectal adenocarcinoma cancer (CRA). Present automated CRA grading methods, however, usually use tiny image patches and thus fail to integrate the entire tissue micro-architecture for grading purposes. To tackle these challenges, we propose to use a statistical network analysis method to describe the complex structure of the tissue micro-environment by modelling nuclei and their connections as a network. We show that by analyzing only the interactions between the cells in a network, we can extract highly discriminative statistical features for CRA grading. Unlike other deep learning or convolutional graph-based approaches, our method is highly scalable (can be used for cell networks consist of millions of nodes), completely explainable, and computationally inexpensive. We create cell networks on a broad CRC histology image dataset, experiment with our method, and report state-of-the-art performance for the prediction of three-class CRA grading.