Whole Slide Image (WSI) representation is critical for cancer subtyping, cancer recognition and mutation prediction.Training an end-to-end WSI representation model poses significant challenges, as a standard gigapixel slide can contain tens of thousands of image tiles, making it difficult to compute gradients of all tiles in a single mini-batch due to current GPU limitations. To address this challenge, we propose a method of dynamic residual encoding with slide-level contrastive learning (DRE-SLCL) for end-to-end WSI representation. Our approach utilizes a memory bank to store the features of tiles across all WSIs in the dataset. During training, a mini-batch usually contains multiple WSIs. For each WSI in the batch, a subset of tiles is randomly sampled and their features are computed using a tile encoder. Then, additional tile features from the same WSI are selected from the memory bank. The representation of each individual WSI is generated using a residual encoding technique that incorporates both the sampled features and those retrieved from the memory bank. Finally, the slide-level contrastive loss is computed based on the representations and histopathology reports ofthe WSIs within the mini-batch. Experiments conducted over cancer subtyping, cancer recognition, and mutation prediction tasks proved the effectiveness of the proposed DRE-SLCL method.

Healthcare applications are inherently multimodal, benefiting greatly from the integration of diverse data sources. However, the modalities available in clinical settings can vary across different locations and patients. A key area that stands to gain from multimodal integration is breast cancer molecular subtyping, an important clinical task that can facilitate personalized treatment and improve patient prognosis. In this work, we propose a scalable and loosely-coupled multimodal framework that seamlessly integrates data from various modalities, including copy number variation (CNV), clinical records, and histopathology images, to enhance breast cancer subtyping. While our primary focus is on breast cancer, our framework is designed to easily accommodate additional modalities, offering the flexibility to scale up or down with minimal overhead without requiring re-training of existing modalities, making it applicable to other types of cancers as well. We introduce a dual-based representation for whole slide images (WSIs), combining traditional image-based and graph-based WSI representations. This novel dual approach results in significant performance improvements. Moreover, we present a new multimodal fusion strategy, demonstrating its ability to enhance performance across a range of multimodal conditions. Our comprehensive results show that integrating our dual-based WSI representation with CNV and clinical health records, along with our pipeline and fusion strategy, outperforms state-of-the-art methods in breast cancer subtyping.

A crucial step to efficiently integrate Whole Slide Images (WSIs) in computational pathology is assigning a single high-quality feature vector, i.e., one embedding, to each WSI. With the existence of many pre-trained deep neural networks and the emergence of foundation models, extracting embeddings for sub-images (i.e., tiles or patches) is straightforward. However, for WSIs, given their high resolution and gigapixel nature, inputting them into existing GPUs as a single image is not feasible. As a result, WSIs are usually split into many patches. Feeding each patch to a pre-trained model, each WSI can then be represented by a set of patches, hence, a set of embeddings. Hence, in such a setup, WSI representation learning reduces to set representation learning where for each WSI we have access to a set of patch embeddings. To obtain a single embedding from a set of patch embeddings for each WSI, multiple set-based learning schemes have been proposed in the literature. In this paper, we evaluate the WSI search performance of multiple recently developed aggregation techniques (mainly set representation learning techniques) including simple average or max pooling operations, Deep Sets, Memory networks, Focal attention, Gaussian Mixture Model (GMM) Fisher Vector, and deep sparse and binary Fisher Vector on four different primary sites including bladder, breast, kidney, and Colon from TCGA. Further, we benchmark the search performance of these methods against the median of minimum distances of patch embeddings, a non-aggregating approach used for WSI retrieval.

Digital pathology is revolutionizing the field of pathology by enabling the digitization, storage, and analysis of tissue samples as whole slide images (WSIs). WSIs are gigapixel files that capture the intricate details of tissue samples, providing a rich source of information for diagnostic and research purposes. However, due to their enormous size, representing these images as one compact vector is essential for many computational pathology tasks, such as search and retrieval, to ensure efficiency and scalability. Most current methods are "patch-oriented," meaning they divide WSIs into smaller patches for processing, which prevents a holistic analysis of the entire slide. Additionally, the necessity for compact representation is driven by the expensive high-performance storage required for WSIs. Not all hospitals have access to such extensive storage solutions, leading to potential disparities in healthcare quality and accessibility. This paper provides an overview of existing set-based approaches to single-vector WSI representation, highlighting the innovations that allow for more efficient and effective use of these complex images in digital pathology, thus addressing both computational challenges and storage limitations.

Whole slide images (WSI) are microscopy images of stained tissue slides routinely prepared for diagnosis and treatment selection in medical practice. WSI are very large (gigapixel size) and complex (made of up to millions of cells). The current state-of-the-art (SoTA) approach to classify WSI subdivides them into tiles, encodes them by pre-trained networks and applies Multiple Instance Learning (MIL) to train for specific downstream tasks. However, annotated datasets are often small, typically a few hundred to a few thousand WSI, which may cause overfitting and underperforming models. Conversely, the number of unannotated WSI is ever increasing, with datasets of tens of thousands (soon to be millions) of images available. While it has been previously proposed to use these unannotated data to identify suitable tile representations by self-supervised learning (SSL), downstream classification tasks still require full supervision because parts of the MIL architecture is not trained during tile level SSL pre-training. Here, we propose a strategy of slide level SSL to leverage the large number of WSI without annotations to infer powerful slide representations. Applying our method to The Cancer-Genome Atlas, one of the most widely used data resources in cancer research (16 TB image data), we are able to downsize the dataset to 23 MB without any loss in predictive power: we show that a linear classifier trained on top of these embeddings maintains or improves previous SoTA performances on various benchmark WSI classification tasks. Finally, we observe that training a classifier on these representations with tiny datasets (e.g. 50 slides) improved performances over SoTA by an average of +6.3 AUC points over all downstream tasks.