Histopathological image segmentation is a laborious and time-intensive task, often requiring analysis from experienced pathologists for accurate examinations. To reduce this burden, supervised machine-learning approaches have been adopted using large-scale annotated datasets for histopathological image analysis. However, in several scenarios, the availability of large-scale annotated data is a bottleneck while training such models. Self-supervised learning (SSL) is an alternative paradigm that provides some respite by constructing models utilizing only the unannotated data which is often abundant. The basic idea of SSL is to train a network to perform one or many pseudo or pretext tasks on unannotated data and use it subsequently as the basis for a variety of downstream tasks. It is seen that the success of SSL depends critically on the considered pretext task. While there have been many efforts in designing pretext tasks for classification problems, there haven't been many attempts on SSL for histopathological segmentation. Motivated by this, we propose an SSL approach for segmenting histopathological images via generative diffusion models in this paper. Our method is based on the observation that diffusion models effectively solve an image-to-image translation task akin to a segmentation task. Hence, we propose generative diffusion as the pretext task for histopathological image segmentation. We also propose a multi-loss function-based fine-tuning for the downstream task. We validate our method using several metrics on two publically available datasets along with a newly proposed head and neck (HN) cancer dataset containing hematoxylin and eosin (H\&E) stained images along with annotations. Codes will be made public at https://github.com/suhas-srinath/GenSelfDiff-HIS.
Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40X magnification in 2.5 seconds per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.
In this paper, we present a new neural architectural block for the vision domain, named Mixing Regionally and Locally (MRL), developed with the aim of effectively and efficiently mixing the provided input features. We bifurcate the input feature mixing task as mixing at a regional and local scale. To achieve an efficient mix, we exploit the domain-wide receptive field provided by self-attention for regional-scale mixing and convolutional kernels restricted to local scale for local-scale mixing. More specifically, our proposed method mixes regional features associated with local features within a defined region, followed by a local-scale features mix augmented by regional features. Experiments show that this hybridization of self-attention and convolution brings improved capacity, generalization (right inductive bias), and efficiency. Under similar network settings, MRL outperforms or is at par with its counterparts in classification, object detection, and segmentation tasks. We also show that our MRL-based network architecture achieves state-of-the-art performance for H&E histology datasets. We achieved DICE of 0.843, 0.855, and 0.892 for Kumar, CoNSep, and CPM-17 datasets, respectively, while highlighting the versatility offered by the MRL framework by incorporating layers like group convolutions to improve dataset-specific generalization.
Histopathological image segmentation is a challenging and important topic in medical imaging with tremendous potential impact in clinical practice. State of the art methods rely on hand-crafted annotations which hinder clinical translation since histology suffers from significant variations between cancer phenotypes. In this paper, we propose a weakly supervised framework for whole slide imaging segmentation that relies on standard clinical annotations, available in most medical systems. In particular, we exploit a multiple instance learning scheme for training models. The proposed framework has been evaluated on multi-locations and multi-centric public data from The Cancer Genome Atlas and the PatchCamelyon dataset. Promising results when compared with experts' annotations demonstrate the potentials of the presented approach. The complete framework, including $6481$ generated tumor maps and data processing, is available at https://github.com/marvinler/tcga_segmentation.