Clustered Patch Embeddings for Permutation-Invariant Classification of Whole Slide Images

Whole Slide Imaging (WSI) is a cornerstone of digital pathology, offering detailed insights critical for diagnosis and research. Yet, the gigapixel size of WSIs imposes significant computational challenges, limiting their practical utility. Our novel approach addresses these challenges by leveraging various encoders for intelligent data reduction and employing a different classification model to ensure robust, permutation-invariant representations of WSIs. A key innovation of our method is the ability to distill the complex information of an entire WSI into a single vector, effectively capturing the essential features needed for accurate analysis. This approach significantly enhances the computational efficiency of WSI analysis, enabling more accurate pathological assessments without the need for extensive computational resources. This breakthrough equips us with the capability to effectively address the challenges posed by large image resolutions in whole-slide imaging, paving the way for more scalable and effective utilization of WSIs in medical diagnostics and research, marking a significant advancement in the field.

Classification and Morphological Analysis of DLBCL Subtypes in H\&E-Stained Slides

We address the challenge of automated classification of diffuse large B-cell lymphoma (DLBCL) into its two primary subtypes: activated B-cell-like (ABC) and germinal center B-cell-like (GCB). Accurate classification between these subtypes is essential for determining the appropriate therapeutic strategy, given their distinct molecular profiles and treatment responses. Our proposed deep learning model demonstrates robust performance, achieving an average area under the curve (AUC) of (87.4 pm 5.7)\% during cross-validation. It shows a high positive predictive value (PPV), highlighting its potential for clinical application, such as triaging for molecular testing. To gain biological insights, we performed an analysis of morphological features of ABC and GCB subtypes. We segmented cell nuclei using a pre-trained deep neural network and compared the statistics of geometric and color features for ABC and GCB. We found that the distributions of these features were not very different for the two subtypes, which suggests that the visual differences between them are more subtle. These results underscore the potential of our method to assist in more precise subtype classification and can contribute to improved treatment management and outcomes for patients of DLBCL.

Efficient Whole Slide Image Classification through Fisher Vector Representation

The advancement of digital pathology, particularly through computational analysis of whole slide images (WSI), is poised to significantly enhance diagnostic precision and efficiency. However, the large size and complexity of WSIs make it difficult to analyze and classify them using computers. This study introduces a novel method for WSI classification by automating the identification and examination of the most informative patches, thus eliminating the need to process the entire slide. Our method involves two-stages: firstly, it extracts only a few patches from the WSIs based on their pathological significance; and secondly, it employs Fisher vectors (FVs) for representing features extracted from these patches, which is known for its robustness in capturing fine-grained details. This approach not only accentuates key pathological features within the WSI representation but also significantly reduces computational overhead, thus making the process more efficient and scalable. We have rigorously evaluated the proposed method across multiple datasets to benchmark its performance against comprehensive WSI analysis and contemporary weakly-supervised learning methodologies. The empirical results indicate that our focused analysis of select patches, combined with Fisher vector representation, not only aligns with, but at times surpasses, the classification accuracy of standard practices. Moreover, this strategy notably diminishes computational load and resource expenditure, thereby establishing an efficient and precise framework for WSI analysis in the realm of digital pathology.

Evaluation Metric for Quality Control and Generative Models in Histopathology Images

Our study introduces ResNet-L2 (RL2), a novel metric for evaluating generative models and image quality in histopathology, addressing limitations of traditional metrics, such as Frechet inception distance (FID), when the data is scarce. RL2 leverages ResNet features with a normalizing flow to calculate RMSE distance in the latent space, providing reliable assessments across diverse histopathology datasets. We evaluated the performance of RL2 on degradation types, such as blur, Gaussian noise, salt-and-pepper noise, and rectangular patches, as well as diffusion processes. RL2's monotonic response to increasing degradation makes it well-suited for models that assess image quality, proving a valuable advancement for evaluating image generation techniques in histopathology. It can also be used to discard low-quality patches while sampling from a whole slide image. It is also significantly lighter and faster compared to traditional metrics and requires fewer images to give stable metric value.

PathoGen-X: A Cross-Modal Genomic Feature Trans-Align Network for Enhanced Survival Prediction from Histopathology Images

Accurate survival prediction is essential for personalized cancer treatment. However, genomic data - often a more powerful predictor than pathology data - is costly and inaccessible. We present the cross-modal genomic feature translation and alignment network for enhanced survival prediction from histopathology images (PathoGen-X). It is a deep learning framework that leverages both genomic and imaging data during training, relying solely on imaging data at testing. PathoGen-X employs transformer-based networks to align and translate image features into the genomic feature space, enhancing weaker imaging signals with stronger genomic signals. Unlike other methods, PathoGen-X translates and aligns features without projecting them to a shared latent space and requires fewer paired samples. Evaluated on TCGA-BRCA, TCGA-LUAD, and TCGA-GBM datasets, PathoGen-X demonstrates strong survival prediction performance, emphasizing the potential of enriched imaging models for accessible cancer prognosis.

Network Inversion for Training-Like Data Reconstruction

Machine Learning models are often trained on proprietary and private data that cannot be shared, though the trained models themselves are distributed openly assuming that sharing model weights is privacy preserving, as training data is not expected to be inferred from the model weights. In this paper, we present Training-Like Data Reconstruction (TLDR), a network inversion-based approach to reconstruct training-like data from trained models. To begin with, we introduce a comprehensive network inversion technique that learns the input space corresponding to different classes in the classifier using a single conditioned generator. While inversion may typically return random and arbitrary input images for a given output label, we modify the inversion process to incentivize the generator to reconstruct training-like data by exploiting key properties of the classifier with respect to the training data along with some prior knowledge about the images. To validate our approach, we conduct empirical evaluations on multiple standard vision classification datasets, thereby highlighting the potential privacy risks involved in sharing machine learning models.

Cross-Domain Evaluation of Few-Shot Classification Models: Natural Images vs. Histopathological Images

In this study, we investigate the performance of few-shot classification models across different domains, specifically natural images and histopathological images. We first train several few-shot classification models on natural images and evaluate their performance on histopathological images. Subsequently, we train the same models on histopathological images and compare their performance. We incorporated four histopathology datasets and one natural images dataset and assessed performance across 5-way 1-shot, 5-way 5-shot, and 5-way 10-shot scenarios using a selection of state-of-the-art classification techniques. Our experimental results reveal insights into the transferability and generalization capabilities of few-shot classification models between diverse image domains. We analyze the strengths and limitations of these models in adapting to new domains and provide recommendations for optimizing their performance in cross-domain scenarios. This research contributes to advancing our understanding of few-shot learning in the context of image classification across diverse domains.

Semantic Segmentation Based Quality Control of Histopathology Whole Slide Images

We developed a software pipeline for quality control (QC) of histopathology whole slide images (WSIs) that segments various regions, such as blurs of different levels, tissue regions, tissue folds, and pen marks. Given the necessity and increasing availability of GPUs for processing WSIs, the proposed pipeline comprises multiple lightweight deep learning models to strike a balance between accuracy and speed. The pipeline was evaluated in all TCGAs, which is the largest publicly available WSI dataset containing more than 11,000 histopathological images from 28 organs. It was compared to a previous work, which was not based on deep learning, and it showed consistent improvement in segmentation results across organs. To minimize annotation effort for tissue and blur segmentation, annotated images were automatically prepared by mosaicking patches (sub-images) from various WSIs whose labels were identified using a patch classification tool HistoROI. Due to the generality of our trained QC pipeline and its extensive testing the potential impact of this work is broad. It can be used for automated pre-processing any WSI cohort to enhance the accuracy and reliability of large-scale histopathology image analysis for both research and clinical use. We have made the trained models, training scripts, training data, and inference results publicly available at https://github.com/abhijeetptl5/wsisegqc, which should enable the research community to use the pipeline right out of the box or further customize it to new datasets and applications in the future.

FedStein: Enhancing Multi-Domain Federated Learning Through James-Stein Estimator

Federated Learning (FL) facilitates data privacy by enabling collaborative in-situ training across decentralized clients. Despite its inherent advantages, FL faces significant challenges of performance and convergence when dealing with data that is not independently and identically distributed (non-i.i.d.). While previous research has primarily addressed the issue of skewed label distribution across clients, this study focuses on the less explored challenge of multi-domain FL, where client data originates from distinct domains with varying feature distributions. We introduce a novel method designed to address these challenges FedStein: Enhancing Multi-Domain Federated Learning Through the James-Stein Estimator. FedStein uniquely shares only the James-Stein (JS) estimates of batch normalization (BN) statistics across clients, while maintaining local BN parameters. The non-BN layer parameters are exchanged via standard FL techniques. Extensive experiments conducted across three datasets and multiple models demonstrate that FedStein surpasses existing methods such as FedAvg and FedBN, with accuracy improvements exceeding 14% in certain domains leading to enhanced domain generalization. The code is available at https://github.com/sunnyinAI/FedStein

Normalizing Flow Based Metric for Image Generation

We propose two new evaluation metrics to assess realness of generated images based on normalizing flows: a simpler and efficient flow-based likelihood distance (FLD) and a more exact dual-flow based likelihood distance (D-FLD). Because normalizing flows can be used to compute the exact likelihood, the proposed metrics assess how closely generated images align with the distribution of real images from a given domain. This property gives the proposed metrics a few advantages over the widely used Fr\'echet inception distance (FID) and other recent metrics. Firstly, the proposed metrics need only a few hundred images to stabilize (converge in mean), as opposed to tens of thousands needed for FID, and at least a few thousand for the other metrics. This allows confident evaluation of even small sets of generated images, such as validation batches inside training loops. Secondly, the network used to compute the proposed metric has over an order of magnitude fewer parameters compared to Inception-V3 used to compute FID, making it computationally more efficient. For assessing the realness of generated images in new domains (e.g., x-ray images), ideally these networks should be retrained on real images to model their distinct distributions. Thus, our smaller network will be even more advantageous for new domains. Extensive experiments show that the proposed metrics have the desired monotonic relationships with the extent of image degradation of various kinds.