Spatial Transcriptomics Expression Prediction from Histopathology Based on Cross-Modal Mask Reconstruction and Contrastive Learning

Spatial transcriptomics is a technology that captures gene expression levels at different spatial locations, widely used in tumor microenvironment analysis and molecular profiling of histopathology, providing valuable insights into resolving gene expression and clinical diagnosis of cancer. Due to the high cost of data acquisition, large-scale spatial transcriptomics data remain challenging to obtain. In this study, we develop a contrastive learning-based deep learning method to predict spatially resolved gene expression from whole-slide images. Evaluation across six different disease datasets demonstrates that, compared to existing studies, our method improves Pearson Correlation Coefficient (PCC) in the prediction of highly expressed genes, highly variable genes, and marker genes by 6.27%, 6.11%, and 11.26% respectively. Further analysis indicates that our method preserves gene-gene correlations and applies to datasets with limited samples. Additionally, our method exhibits potential in cancer tissue localization based on biomarker expression.

CENet: Context Enhancement Network for Medical Image Segmentation

Medical image segmentation, particularly in multi-domain scenarios, requires precise preservation of anatomical structures across diverse representations. While deep learning has advanced this field, existing models often struggle with accurate boundary representation, variability in organ morphology, and information loss during downsampling, limiting their accuracy and robustness. To address these challenges, we propose the Context Enhancement Network (CENet), a novel segmentation framework featuring two key innovations. First, the Dual Selective Enhancement Block (DSEB) integrated into skip connections enhances boundary details and improves the detection of smaller organs in a context-aware manner. Second, the Context Feature Attention Module (CFAM) in the decoder employs a multi-scale design to maintain spatial integrity, reduce feature redundancy, and mitigate overly enhanced representations. Extensive evaluations on both radiology and dermoscopic datasets demonstrate that CENet outperforms state-of-the-art (SOTA) methods in multi-organ segmentation and boundary detail preservation, offering a robust and accurate solution for complex medical image analysis tasks. The code is publicly available at https://github.com/xmindflow/cenet.

Attention-based Generative Latent Replay: A Continual Learning Approach for WSI Analysis

Whole slide image (WSI) classification has emerged as a powerful tool in computational pathology, but remains constrained by domain shifts, e.g., due to different organs, diseases, or institution-specific variations. To address this challenge, we propose an Attention-based Generative Latent Replay Continual Learning framework (AGLR-CL), in a multiple instance learning (MIL) setup for domain incremental WSI classification. Our method employs Gaussian Mixture Models (GMMs) to synthesize WSI representations and patch count distributions, preserving knowledge of past domains without explicitly storing original data. A novel attention-based filtering step focuses on the most salient patch embeddings, ensuring high-quality synthetic samples. This privacy-aware strategy obviates the need for replay buffers and outperforms other buffer-free counterparts while matching the performance of buffer-based solutions. We validate AGLR-CL on clinically relevant biomarker detection and molecular status prediction across multiple public datasets with diverse centers, organs, and patient cohorts. Experimental results confirm its ability to retain prior knowledge and adapt to new domains, offering an effective, privacy-preserving avenue for domain incremental continual learning in WSI classification.

Towards Robust and Generalizable Gerchberg Saxton based Physics Inspired Neural Networks for Computer Generated Holography: A Sensitivity Analysis Framework

Computer-generated holography (CGH) enables applications in holographic augmented reality (AR), 3D displays, systems neuroscience, and optical trapping. The fundamental challenge in CGH is solving the inverse problem of phase retrieval from intensity measurements. Physics-inspired neural networks (PINNs), especially Gerchberg-Saxton-based PINNs (GS-PINNs), have advanced phase retrieval capabilities. However, their performance strongly depends on forward models (FMs) and their hyperparameters (FMHs), limiting generalization, complicating benchmarking, and hindering hardware optimization. We present a systematic sensitivity analysis framework based on Saltelli's extension of Sobol's method to quantify FMH impacts on GS-PINN performance. Our analysis demonstrates that SLM pixel-resolution is the primary factor affecting neural network sensitivity, followed by pixel-pitch, propagation distance, and wavelength. Free space propagation forward models demonstrate superior neural network performance compared to Fourier holography, providing enhanced parameterization and generalization. We introduce a composite evaluation metric combining performance consistency, generalization capability, and hyperparameter perturbation resilience, establishing a unified benchmarking standard across CGH configurations. Our research connects physics-inspired deep learning theory with practical CGH implementations through concrete guidelines for forward model selection, neural network architecture, and performance evaluation. Our contributions advance the development of robust, interpretable, and generalizable neural networks for diverse holographic applications, supporting evidence-based decisions in CGH research and implementation.

Modality-Independent Brain Lesion Segmentation with Privacy-aware Continual Learning

Traditional brain lesion segmentation models for multi-modal MRI are typically tailored to specific pathologies, relying on datasets with predefined modalities. Adapting to new MRI modalities or pathologies often requires training separate models, which contrasts with how medical professionals incrementally expand their expertise by learning from diverse datasets over time. Inspired by this human learning process, we propose a unified segmentation model capable of sequentially learning from multiple datasets with varying modalities and pathologies. Our approach leverages a privacy-aware continual learning framework that integrates a mixture-of-experts mechanism and dual knowledge distillation to mitigate catastrophic forgetting while not compromising performance on newly encountered datasets. Extensive experiments across five diverse brain MRI datasets and four dataset sequences demonstrate the effectiveness of our framework in maintaining a single adaptable model, capable of handling varying hospital protocols, imaging modalities, and disease types. Compared to widely used privacy-aware continual learning methods such as LwF, SI, EWC, and MiB, our method achieves an average Dice score improvement of approximately 11%. Our framework represents a significant step toward more versatile and practical brain lesion segmentation models, with implementation available at \href{https://github.com/xmindflow/BrainCL}{GitHub}.

Domain-incremental White Blood Cell Classification with Privacy-aware Continual Learning

White blood cell (WBC) classification plays a vital role in hematology for diagnosing various medical conditions. However, it faces significant challenges due to domain shifts caused by variations in sample sources (e.g., blood or bone marrow) and differing imaging conditions across hospitals. Traditional deep learning models often suffer from catastrophic forgetting in such dynamic environments, while foundation models, though generally robust, experience performance degradation when the distribution of inference data differs from that of the training data. To address these challenges, we propose a generative replay-based Continual Learning (CL) strategy designed to prevent forgetting in foundation models for WBC classification. Our method employs lightweight generators to mimic past data with a synthetic latent representation to enable privacy-preserving replay. To showcase the effectiveness, we carry out extensive experiments with a total of four datasets with different task ordering and four backbone models including ResNet50, RetCCL, CTransPath, and UNI. Experimental results demonstrate that conventional fine-tuning methods degrade performance on previously learned tasks and struggle with domain shifts. In contrast, our continual learning strategy effectively mitigates catastrophic forgetting, preserving model performance across varying domains. This work presents a practical solution for maintaining reliable WBC classification in real-world clinical settings, where data distributions frequently evolve.

Touchstone Benchmark: Are We on the Right Way for Evaluating AI Algorithms for Medical Segmentation?

How can we test AI performance? This question seems trivial, but it isn't. Standard benchmarks often have problems such as in-distribution and small-size test sets, oversimplified metrics, unfair comparisons, and short-term outcome pressure. As a consequence, good performance on standard benchmarks does not guarantee success in real-world scenarios. To address these problems, we present Touchstone, a large-scale collaborative segmentation benchmark of 9 types of abdominal organs. This benchmark is based on 5,195 training CT scans from 76 hospitals around the world and 5,903 testing CT scans from 11 additional hospitals. This diverse test set enhances the statistical significance of benchmark results and rigorously evaluates AI algorithms across various out-of-distribution scenarios. We invited 14 inventors of 19 AI algorithms to train their algorithms, while our team, as a third party, independently evaluated these algorithms on three test sets. In addition, we also evaluated pre-existing AI frameworks--which, differing from algorithms, are more flexible and can support different algorithms--including MONAI from NVIDIA, nnU-Net from DKFZ, and numerous other open-source frameworks. We are committed to expanding this benchmark to encourage more innovation of AI algorithms for the medical domain.

Single-Layer Learnable Activation for Implicit Neural Representation (SL$^{2}$A-INR)

Implicit Neural Representation (INR), leveraging a neural network to transform coordinate input into corresponding attributes, has recently driven significant advances in several vision-related domains. However, the performance of INR is heavily influenced by the choice of the nonlinear activation function used in its multilayer perceptron (MLP) architecture. Multiple nonlinearities have been investigated; yet, current INRs face limitations in capturing high-frequency components, diverse signal types, and handling inverse problems. We have identified that these problems can be greatly alleviated by introducing a paradigm shift in INRs. We find that an architecture with learnable activations in initial layers can represent fine details in the underlying signals. Specifically, we propose SL$^{2}$A-INR, a hybrid network for INR with a single-layer learnable activation function, prompting the effectiveness of traditional ReLU-based MLPs. Our method performs superior across diverse tasks, including image representation, 3D shape reconstructions, inpainting, single image super-resolution, CT reconstruction, and novel view synthesis. Through comprehensive experiments, SL$^{2}$A-INR sets new benchmarks in accuracy, quality, and convergence rates for INR.

Continual Domain Incremental Learning for Privacy-aware Digital Pathology

In recent years, there has been remarkable progress in the field of digital pathology, driven by the ability to model complex tissue patterns using advanced deep-learning algorithms. However, the robustness of these models is often severely compromised in the presence of data shifts (e.g., different stains, organs, centers, etc.). Alternatively, continual learning (CL) techniques aim to reduce the forgetting of past data when learning new data with distributional shift conditions. Specifically, rehearsal-based CL techniques, which store some past data in a buffer and then replay it with new data, have proven effective in medical image analysis tasks. However, privacy concerns arise as these approaches store past data, prompting the development of our novel Generative Latent Replay-based CL (GLRCL) approach. GLRCL captures the previous distribution through Gaussian Mixture Models instead of storing past samples, which are then utilized to generate features and perform latent replay with new data. We systematically evaluate our proposed framework under different shift conditions in histopathology data, including stain and organ shift. Our approach significantly outperforms popular buffer-free CL approaches and performs similarly to rehearsal-based CL approaches that require large buffers causing serious privacy violations.

Tissue Concepts: supervised foundation models in computational pathology

Due to the increasing workload of pathologists, the need for automation to support diagnostic tasks and quantitative biomarker evaluation is becoming more and more apparent. Foundation models have the potential to improve generalizability within and across centers and serve as starting points for data efficient development of specialized yet robust AI models. However, the training foundation models themselves is usually very expensive in terms of data, computation, and time. This paper proposes a supervised training method that drastically reduces these expenses. The proposed method is based on multi-task learning to train a joint encoder, by combining 16 different classification, segmentation, and detection tasks on a total of 912,000 patches. Since the encoder is capable of capturing the properties of the samples, we term it the Tissue Concepts encoder. To evaluate the performance and generalizability of the Tissue Concepts encoder across centers, classification of whole slide images from four of the most prevalent solid cancers - breast, colon, lung, and prostate - was used. The experiments show that the Tissue Concepts model achieve comparable performance to models trained with self-supervision, while requiring only 6% of the amount of training patches. Furthermore, the Tissue Concepts encoder outperforms an ImageNet pre-trained encoder on both in-domain and out-of-domain data.