Recent advancements in computer vision, including convolutional neural networks, multilayer perceptrons, graph-based methods and transformer architectures, have significantly improved image classification. However, applying these techniques to digital pathology, particularly gigapixel whole-slide images (WSIs), presents unique challenges due to their vast size and heterogeneity. We introduce FourierMIL, a multiple instance learning framework that leverages the discrete Fourier transform to efficiently capture global and local dependencies in WSIs. Unlike conventional approaches, FourierMIL is adaptable to diverse digital stains and pathology tasks. To evaluate its versatility, we tested FourierMIL on three distinct challenges using public and private datasets. (1) Metastasis detection in hematoxylin and eosin (H&E)- stained lymph node WSIs from CAncer MEtastases in LYmph nOdes challeNge (CAMELYON16) dataset. (2) Lung cancer classification (adenocarcinoma versus squamous cell carcinoma) using The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets. (3) Alzheimer's disease pathology identification in phospho-tau monoclonal antibody (AT8)- stained WSIs from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE), the Framingham Heart Study (FHS), and the Boston University Alzheimer's Disease Research Center (ADC) cohorts. FourierMIL outperformed state-of-the-art methods across all tasks, demonstrating its robustness as an attention-free solution for diverse applications in digital pathology.

Set-to-set matching aims to identify correspondences between two sets of unordered items by minimizing a distance metric or maximizing a similarity measure. Traditional metrics, such as Chamfer Distance (CD) and Earth Mover’s Distance (EMD), are widely used for this purpose but often suffer from limitations like suboptimal performance in terms of accuracy and robustness, or high computational costs - or both. In this paper, we propose a novel, simple yet effective set-to-set matching similarity measure, GPS, based on Gumbel prior distributions. These distributions are typically used to model the extrema of samples drawn from various distributions. Our approach is motivated by the observation that the distributions of minimum distances from CD, as encountered in real world applications such as point cloud completion, can be accurately modeled using Gumbel distributions. We validate our method on tasks like few-shot image classification and 3D point cloud completion, demonstrating significant improvements over state of-the-art loss functions across several benchmark datasets. Our demo code is publicly available at https://github.com/Zhang-VISLab/ICLR2025-GPS

In many practical applications, including medicine, acquiring all relevant data for machine learning models is often infeasible due to constraints on time, cost, and resources. This makes it important to selectively acquire only the most informative features, yet traditional static feature selection methods fall short in scenarios where feature importance varies across instances. Here, we propose an active feature acquisition (AFA) framework, which dynamically selects features based on their importance to each individual case. Our method leverages local explanation techniques to generate instance-specific feature importance rankings. We then reframe the AFA problem as a feature prediction task, introducing a policy network grounded in a decision transformer architecture. This policy network is trained to select the next most informative feature by learning from the feature importance rankings. As a result, features are acquired sequentially, ordered by their predictive significance, leading to more efficient feature selection and acquisition. Extensive experiments on multiple datasets demonstrate that our approach outperforms current state-of-the-art AFA methods in both predictive accuracy and feature acquisition efficiency. These findings highlight the promise of an explainability-driven AFA strategy in scenarios where the cost of feature acquisition is a key concern.

Multimodal machine learning models are being developed to analyze pathology images and other modalities, such as gene expression, to gain clinical and biological insights. However, most frameworks for multimodal data fusion do not fully account for the interactions between different modalities. Here, we present an attention-based fusion architecture that integrates a graph representation of pathology images with gene expression data and concomitantly learns from the fused information to predict patient-specific survival. In our approach, pathology images are represented as undirected graphs, and their embeddings are combined with embeddings of gene expression signatures using an attention mechanism to stratify tumors by patient survival. We show that our framework improves the survival prediction of human non-small cell lung cancers, outperforming existing state-of-the-art approaches that leverage multimodal data. Our framework can facilitate spatial molecular profiling to identify tumor heterogeneity using pathology images and gene expression data, complementing results obtained from more expensive spatial transcriptomic and proteomic technologies.

A point cloud is a discrete set of data points sampled from a 3D geometric surface. Chamfer distance (CD) is a popular metric and training loss to measure the distances between point clouds, but also well known to be sensitive to outliers. To address this issue, in this paper we propose InfoCD, a novel contrastive Chamfer distance loss to learn to spread the matched points for better distribution alignments between point clouds as well as accounting for a surface similarity estimator. We show that minimizing InfoCD is equivalent to maximizing a lower bound of the mutual information between the underlying geometric surfaces represented by the point clouds, leading to a regularized CD metric which is robust and computationally efficient for deep learning. We conduct comprehensive experiments for point cloud completion using InfoCD and observe significant improvements consistently over all the popular baseline networks trained with CD-based losses, leading to new state-of-the-art results on several benchmark datasets. Demo code is available at https://github.com/Zhang-VISLab/NeurIPS2023-InfoCD.

Machine learning and artificial intelligence (AI)-driven technologies are contributing significantly to various facets of medicine and care management. It is likely that the next generation of healthcare professionals will be confronted with a series of innovations that are powered by AI, and they may not have sufficient time during their professional tenure to learn about the underlying machine learning frameworks that are driving these systems. Educating the aspiring clinicians and care providers with the right foundational courses in machine learning as part of postsecondary education will likely transform them as high-tech physicians and care providers of the future.

Deep learning is a powerful tool for whole slide image (WSI) analysis. Typically, when performing supervised deep learning, a WSI is divided into small patches, trained and the outcomes are aggregated to estimate disease grade. However, patch-based methods introduce label noise during training by assuming that each patch is independent with the same label as the WSI and neglect overall WSI-level information that is significant in disease grading. Here we present a Graph-Transformer (GT) that fuses a graph-based representation of an WSI and a vision transformer for processing pathology images, called GTP, to predict disease grade. We selected 4,818 WSIs from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), the National Lung Screening Trial (NLST), and The Cancer Genome Atlas (TCGA), and used GTP to distinguish adenocarcinoma (LUAD) and squamous cell carcinoma (LSCC) from adjacent non-cancerous tissue (normal). First, using NLST data, we developed a contrastive learning framework to generate a feature extractor. This allowed us to compute feature vectors of individual WSI patches, which were used to represent the nodes of the graph followed by construction of the GTP framework. Our model trained on the CPTAC data achieved consistently high performance on three-label classification (normal versus LUAD versus LSCC: mean accuracy = 91.2 ± 2.5%) based on five-fold cross-validation, and mean accuracy = 82.3 ± 1.0% on external test data (TCGA). We also introduced a graph-based saliency mapping technique, called GraphCAM, that can identify regions that are highly associated with the class label. Our findings demonstrate GTP as an interpretable and effective deep learning framework for WSI-level classification.