WSI-INR: Implicit Neural Representations for Lesion Segmentation in Whole-Slide Images
Authors: Yunheng Wu, Wenqi Huang, Liangyi Wang, Masahiro Oda, Yuichiro Hayashi, Daniel Rueckert, Kensaku Mori
Organizations: Graduate School of Informatics, Nagoya University, Nagoya, Japan · Chair for AI in Healthcare and Medicine, Technical University of Munich (TUM) and TUM University Hospital, Munich, Germany · School of Computation and Information Technology, Technical University of Munich, Munich, Germany · Information Technology Center, Nagoya University, Nagoya, Japan · Munich Center for Machine Learning, Technical University of Munich, Munich, Germany · Department of Computing, Imperial College London, London, United Kingdom · Research Center for Medical Bigdata, National Institute of Informatics, Tokyo, Japan
Whole-slide images (WSIs) are fundamental for computational pathology, where accurate lesion segmentation is critical for clinical decision making. Existing methods partition WSIs into discrete patches, disrupting spatial continuity and treating multi-resolution views as independent samples, which leads to spatially fragmented segmentation and reduced robustness to resolution variations. To address the issues, we propose WSI-INR, a novel patch-free framework based on Implicit Neural Representations (INRs). WSI-INR models the WSI as a continuous implicit function mapping spatial coordinates directly to tissue semantics features, outputting segmentation results while preserving intrinsic spatial information across the entire slide. In the WSI-INR, we incorporate multi-resolution hash grid encoding to regard different resolution levels as varying sampling densities of the same continuous tissue, achieving a consistent feature representation across resolutions. In addition, by jointly training a shared INR decoder, WSI-INR can capture general priors across different cases. Experimental results showed that WSI-INR maintains robust segmentation performance across resolutions; at Base/4, our resolution-specific optimization improves Dice score by +26.11%, while U-Net and TransUNet decrease by 54.28% and 36.18%, respectively. Crucially, this work enables INRs to segment highly heterogeneous pathological lesions beyond structurally consistent anatomical tissues, offering a fresh perspective for pathological analysis.
Figures & tables
Figure 1: (a) Patch-based methods. (b) Our WSI-INR. (c) WSI resolution pyramid and multi-resolution hash encoding. (d) Patches across resolutions exhibit inconsistent representations. Visualization of U-Net bottleneck features trained on a WSI dataset.
Figure 2: Workflow of our WSI-INR. Training: We first optimize the decoder, reconstruction head and hash encoding by minimizing the reconstruction loss. These modules are frozen, and only the segmentation head is trained. Inference: For each unseen WSI, network parameters remain fixed, while the hash encoding is optimized via the reconstruction loss. The final segmentation is obtained from the optimized representation.
Figure 3: We compare our WSI-INR with U-Net and TransUNet across multi resolutions, while all models are trained at a single base resolution. For WSI-INR, we adopt base-resolution optimization. U-Net performs well at training resolution, but U-Net and TransUNet degrade at lower resolutions, with fragmented predictions (black arrows).
Method
Resolution: Base
Resolution: Base/2
Resolution: Base/4
U-Net [ 18 ]
0.4858
0.2418 (-50.23%)
0.2221 (-54.28%)
TransUNet [ 3 ]
0.1534
0.1146 (-25.29%)
0.0979 (-36.18%)
Ours (Base-resolution opt)
0.2417
0.1664 (-31.15%)
0.1683 (-30.37%)
Ours (Resolution-specific opt)
0.2417
0.2333 (-3.48%)
0.3048 (+26.11%)
Table 1: Segmentation performance on CAMELYON16 across resolutions evaluated by Dice score. Models are trained at the base resolution (Base) and evaluated at the same resolution as well as two other unseen resolutions in training (Base/2 and /4). Values in red denote the performance change relative to the results at the base resolution.
Method
Resolution: Base
Resolution: Base/2
Resolution: Base/4
w/o encoding
0.0000
0.0000
0.0000
w/ NeRF positional encoding [ 13 ]
0.0901
0.0901
0.0901
w/ hash grid encoding
0.2417
0.1664
0.1683
Table 2: Ablation study for coordinate encoding on CAMELYON16. Models are trained at base resolution and evaluated at the same resolution and other resolutions.
Figure 4: We visualize the reconstruction and segmentation results under three settings: high-level only (dense sampling), low-level only, and the full hash grid. Columns: (a) global reconstruction, (b) zoomed-in local patch, (c) frequency spectrum (FFT) of local patch, (d) global segmentation prediction, and (e) local segmentation mask.
Accurate analysis of histopathological images is critical for disease diagnosis and treatment planning. Whole-slide images (WSIs), which digitize tissue specimens at gigapixel resolution, are fundamental to this process but require aggregating thousands of patches for slide-level predictions. Multiple Instance Learning (MIL) tackles this challenge with a two-stage paradigm, decoupling tile-level embedding and slide-level prediction. However, most existing methods implicitly embed patch representations in homogeneous Euclidean spaces, overlooking the hierarchical organization and regional heterogeneity of pathological tissues. This limits current models' ability to capture global tissue architecture and fine-grained cellular morphology. To address this limitation, we introduce a hybrid hyperbolic-Euclidean representation that embeds WSI features in dual geometric spaces, enabling complementary modeling of hierarchical tissue structures and local morphological details. Building on this formulation, we develop BatMIL, an MIL method that leverages both geometric spaces. To model long-range dependencies among thousands of patches, we employ a structured state space sequence model backbone that encodes patch sequences with linear computational complexity. Furthermore, to account for regional heterogeneity, we introduce a mixture-of-experts module that dynamically routes each patch to specialized expert sub-networks based on its features, improving representational capacity while reducing redundant computation. Experiments on seven datasets spanning six cancer types demonstrate that BatMIL achieves outstanding performance against fifteen state-of-the-art MIL approaches, demonstrating that geometry-embedding representation learning offers a promising direction for computational pathology.
Enhui Chai, Sicheng Chen, Tianyi Zhang +4
PuzzleLogic Pte Ltd, Singapore 229594, Singapore · Nhu Department of Electrical Engineering and Computer Science, University of California, Irvine · Department of Electrical & Computer Engineering, National University of Singapore
Multiple instance learning (MIL) has become a standard paradigm for whole slide image (WSI) analysis in digital pathology, as it enables slide-level prediction without dense annotations. Existing MIL methods typically rely on exhaustive extraction and encoding of high-resolution patches. However, this practice suffers from two critical limitations in real-world clinical settings: it struggles to capture global visual cues at lower magnifications, and incurs substantial computational overhead due to the massive number of high-resolution patches per slide. To address these limitations, we propose an efficient low-resolution multiple instance learning (LRMIL) framework that transfers high-resolution knowledge to low-resolution representations. LRMIL adopts a two-stage distillation strategy. First, patch-level cross-resolution distillation aligns low-resolution patch embeddings with high-resolution representations. Second, slide-level knowledge distillation trains a low-resolution student MIL model under both slide-level supervision and teacher guidance. At inference time, LRMIL operates exclusively on low-resolution patches, substantially reducing data preprocessing and computational cost. Extensive experiments on multiple WSI benchmarks demonstrate that LRMIL consistently outperforms state-of-the-art MIL methods while achieving more efficient inference. These results highlight LRMIL as a practical and scalable solution for WSI analysis in clinical pathology.
Yonghan Shin, Won-Ki Jeong
Department of Computer Science and Engineering, Korea University, Seoul, Korea
Whole-slide image (WSI) analysis remains computationally challenging due to the extremely large spatial resolution of slides and the sparse distribution of tumour regions. We propose an end-to-end reinforcement learning framework for sequential tumour segmentation directly on WSIs. Instead of treating the slide as a predefined collection of candidate patches, we formulate the WSI itself as a hierarchical multi-resolution environment through which an agent navigates using movement, zooming, and tumour selection actions. The agent jointly processes local observations and a global thumbnail representation within an actor-critic architecture trained using proximal policy optimization (PPO). Experiments on pulmonary adenocarcinoma WSIs demonstrate the feasibility of direct sequential tumour segmentation on full slides, achieving comparable coarse segmentation quality relative to patch-based approaches operating at similar magnification levels, while reducing inference time to a few seconds per slide. We further analyse the impact of environment design and action-space granularity. Our results suggest that modelling WSIs as interactive environments provides a promising direction for RL-based computational pathology
Mohamad Mohamad, Francesco Ponzio, Maxime Gassier +2
Universit´e Cˆote d’Azur, Inria, CNRS, I3S, INSERM, IBV, Sophia Antipolis, France · Department of Control and Computer Engineering, Politecnico di Torino, Turin, Italy · Department of Pathology, Bichat Hospital, Assistance Publique–Hˆopitaux de Paris, Paris, France