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Rethinking Transformer for Long Contextual Histopathology Whole Slide Image Analysis

Neural Information Processing Systems

Histopathology Whole Slide Image (WSI) analysis serves as the gold standard for clinical cancer diagnosis in the daily routines of doctors. To develop computer-aided diagnosis model for histopathology WSIs, previous methods typically employ Multi-Instance Learning to enable slide-level prediction given only slide-level labels.Among these models, vanilla attention mechanisms without pairwise interactions have traditionally been employed but are unable to model contextual information. More recently, self-attention models have been utilized to address this issue. To alleviate the computational complexity of long sequences in large WSIs, methods like HIPT use region-slicing, and TransMIL employs Nystr\{o}mformer as an approximation of full self-attention. Both approaches suffer from suboptimal performance due to the loss of key information.


Retrieval-Augmented Multiple Instance Learning

Neural Information Processing Systems

Multiple Instance Learning (MIL) is a crucial weakly supervised learning method applied across various domains, e.g., medical diagnosis based on whole slide images (WSIs). Recent advancements in MIL algorithms have yielded exceptional performance when the training and test data originate from the same domain, such as WSIs obtained from the same hospital. However, this paper reveals a performance deterioration of MIL models when tested on an out-of-domain test set, exemplified by WSIs sourced from a novel hospital. To address this challenge, this paper introduces the Retrieval-AugMented MIL (RAM-MIL) framework, which integrates Optimal Transport (OT) as the distance metric for nearest neighbor retrieval. The development of RAM-MIL is driven by two key insights. First, a theoretical discovery indicates that reducing the input's intrinsic dimension can minimize the approximation error in attention-based MIL. Second, previous studies highlight a link between input intrinsic dimension and the feature merging process with the retrieved data. Empirical evaluations conducted on WSI classification demonstrate that the proposed RAM-MIL framework achieves state-of-the-art performance in both in-domain scenarios, where the training and retrieval data are in the same domain, and more crucially, in out-of-domain scenarios, where the (unlabeled) retrieval data originates from a different domain. Furthermore, the use of the transportation matrix derived from OT renders the retrieval results interpretable at the instance level, in contrast to the vanilla $l_2$ distance, and allows for visualization for human experts.


Dual-Curriculum Contrastive Multi-Instance Learning for Cancer Prognosis Analysis with Whole Slide Images

Neural Information Processing Systems

The multi-instance learning (MIL) has advanced cancer prognosis analysis with whole slide images (WSIs). However, current MIL methods for WSI analysis still confront unique challenges. Previous methods typically generate instance representations via a pre-trained model or a model trained by the instances with bag-level annotations, which, however, may not generalize well to the downstream task due to the introduction of excessive label noises and the lack of fine-grained information across multi-magnification WSIs. Additionally, existing methods generally aggregate instance representations as bag ones for prognosis prediction and have no consideration of intra-bag redundancy and inter-bag discrimination. To address these issues, we propose a dual-curriculum contrastive MIL method for cancer prognosis analysis with WSIs. The proposed method consists of two curriculums, i.e., saliency-guided weakly-supervised instance encoding with cross-scale tiles and contrastive-enhanced soft-bag prognosis inference. Extensive experiments on three public datasets demonstrate that our method outperforms state-of-the-art methods in this field.


Domain-Specific Foundation Model Improves AI-Based Analysis of Neuropathology

Verma, Ruchika, Kandoi, Shrishtee, Afzal, Robina, Chen, Shengjia, Jegminat, Jannes, Karlovich, Michael W., Umphlett, Melissa, Richardson, Timothy E., Clare, Kevin, Hossain, Quazi, Samanamud, Jorge, Faust, Phyllis L., Louis, Elan D., McKee, Ann C., Stein, Thor D., Cherry, Jonathan D., Mez, Jesse, McGoldrick, Anya C., Mora, Dalilah D. Quintana, Nirenberg, Melissa J., Walker, Ruth H., Mendez, Yolfrankcis, Morgello, Susan, Dickson, Dennis W., Murray, Melissa E., Cordon-Cardo, Carlos, Tsankova, Nadejda M., Walker, Jamie M., Dangoor, Diana K., McQuillan, Stephanie, Thorn, Emma L., De Sanctis, Claudia, Li, Shuying, Fuchs, Thomas J., Farrell, Kurt, Crary, John F., Campanella, Gabriele

arXiv.org Artificial Intelligence

Foundation models have transformed computational pathology by providing generalizable representations from large-scale histology datasets. However, existing models are predominantly trained on surgical pathology data, which is enriched for non-nervous tissue and overrepresents neoplastic, inflammatory, metabolic, and other non-neurological diseases. Neuropathology represents a markedly different domain of histopathology, characterized by unique cell types (neurons, glia, etc.), distinct cytoarchitecture, and disease-specific pathological features including neurofibrillary tangles, amyloid plaques, Lewy bodies, and pattern-specific neurodegeneration. This domain mismatch may limit the ability of general-purpose foundation models to capture the morphological patterns critical for interpreting neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and cerebellar ataxias. To address this gap, we developed NeuroFM, a foundation model trained specifically on whole-slide images of brain tissue spanning diverse neurodegenerative pathologies. NeuroFM demonstrates superior performance compared to general-purpose models across multiple neuropathology-specific downstream tasks, including mixed dementia disease classification, hippocampal region segmentation, and neurodegenerative ataxia identification encompassing cerebellar essential tremor and spinocerebellar ataxia subtypes. This work establishes that domain-specialized foundation models trained on brain tissue can better capture neuropathology-specific features than models trained on general surgical pathology datasets. By tailoring foundation models to the unique morphological landscape of neurodegenerative diseases, NeuroFM enables more accurate and reliable AI-based analysis for brain disease diagnosis and research, setting a precedent for domain-specific model development in specialized areas of digital pathology.


Autonomous labeling of surgical resection margins using a foundation model

Yang, Xilin, Aydin, Musa, Lu, Yuhong, Selcuk, Sahan Yoruc, Bai, Bijie, Zhang, Yijie, Birkeland, Andrew, Ehrlich, Katjana, Bec, Julien, Marcu, Laura, Pillar, Nir, Ozcan, Aydogan

arXiv.org Artificial Intelligence

Assessing resection margins is central to pathological specimen evaluation and has profound implications for patient outcomes. Current practice employs physical inking, which is applied variably, and cautery artifacts can obscure the true margin on histological sections. We present a virtual inking network (VIN) that autonomously localizes the surgical cut surface on whole-slide images, reducing reliance on inks and standardizing margin-focused review. VIN uses a frozen foundation model as the feature extractor and a compact two-layer multilayer perceptron trained for patch-level classification of cautery-consistent features. The dataset comprised 120 hematoxylin and eosin (H&E) stained slides from 12 human tonsil tissue blocks, resulting in ~2 TB of uncompressed raw image data, where a board-certified pathologist provided boundary annotations. In blind testing with 20 slides from previously unseen blocks, VIN produced coherent margin overlays that qualitatively aligned with expert annotations across serial sections. Quantitatively, region-level accuracy was ~73.3% across the test set, with errors largely confined to limited areas that did not disrupt continuity of the whole-slide margin map. These results indicate that VIN captures cautery-related histomorphology and can provide a reproducible, ink-free margin delineation suitable for integration into routine digital pathology workflows and for downstream measurement of margin distances.


CORE -- A Cell-Level Coarse-to-Fine Image Registration Engine for Multi-stain Image Alignment

Nasir, Esha Sadia, Elhaminia, Behnaz, Eastwood, Mark, King, Catherine, Cain, Owen, Harper, Lorraine, Moss, Paul, Chanouzas, Dimitrios, Snead, David, Rajpoot, Nasir, Shephard, Adam, Raza, Shan E Ahmed

arXiv.org Artificial Intelligence

Accurate and efficient registration of whole slide images (WSIs) is essential for high-resolution, nuclei-level analysis in multi-stained tissue slides. We propose a novel coarse-to-fine framework CORE for accurate nuclei-level registration across diverse multimodal whole-slide image (WSI) datasets. The coarse registration stage leverages prompt-based tissue mask extraction to effectively filter out artefacts and non-tissue regions, followed by global alignment using tissue morphology and ac- celerated dense feature matching with a pre-trained feature extractor. From the coarsely aligned slides, nuclei centroids are detected and subjected to fine-grained rigid registration using a custom, shape-aware point-set registration model. Finally, non-rigid alignment at the cellular level is achieved by estimating a non-linear dis- placement field using Coherent Point Drift (CPD). Our approach benefits from automatically generated nuclei that enhance the accuracy of deformable registra- tion and ensure precise nuclei-level correspondence across modalities. The pro- posed model is evaluated on three publicly available WSI registration datasets, and two private datasets. We show that CORE outperforms current state-of-the-art methods in terms of generalisability, precision, and robustness in bright-field and immunofluorescence microscopy WSIs



Wage Sentiment Indices Derived from Survey Comments via Large Language Models

Sone, Taihei

arXiv.org Artificial Intelligence

The emergence of generative Artificial Intelligence (AI) has created new opportunities for economic text analysis. This study proposes a Wage Sentiment Index (WSI) constructed with Large Language Models (LLMs) to forecast wage dynamics in Japan. The analysis is based on the Economy Watchers Survey (EWS), a monthly survey conducted by the Cabinet Office of Japan that captures real-time economic assessments from workers in industries highly sensitive to business conditions. The WSI extends the framework of the Price Sentiment Index (PSI) used in prior studies, adapting it specifically to wage related sentiment. To ensure scalability and adaptability, a data architecture is also developed that enables integration of additional sources such as newspapers and social media. Experimental results demonstrate that WSI models based on LLMs significantly outperform both baseline approaches and pretrained models. These findings highlight the potential of LLM-driven sentiment indices to enhance the timeliness and effectiveness of economic policy design by governments and central banks.