Biomedical Foundation Model: A Survey

Foundation models, first introduced in 2021, are large-scale pre-trained models (e.g., large language models (LLMs) and vision-language models (VLMs)) that learn from extensive unlabeled datasets through unsupervised methods, enabling them to excel in diverse downstream tasks. These models, like GPT, can be adapted to various applications such as question answering and visual understanding, outperforming task-specific AI models and earning their name due to broad applicability across fields. The development of biomedical foundation models marks a significant milestone in leveraging artificial intelligence (AI) to understand complex biological phenomena and advance medical research and practice. This survey explores the potential of foundation models across diverse domains within biomedical fields, including computational biology, drug discovery and development, clinical informatics, medical imaging, and public health. The purpose of this survey is to inspire ongoing research in the application of foundation models to health science.

Poststroke rehabilitative mechanisms in individualized fatigue level-controlled treadmill training -- a Rat Model Study

Individualized training improved post-stroke motor function rehabilitation efficiency. However, the mechanisms of how individualized training facilitates recovery is not clear. This study explored the cortical and corticomuscular rehabilitative effects in post-stroke motor function recovery during individualized training. Sprague-Dawley rats with intracerebral hemorrhage (ICH) were randomly distributed into two groups: forced training (FOR-T, n=13) and individualized fatigue-controlled training (FAT-C, n=13) to receive training respectively from day 2 to day 14 post-stroke. The FAT-C group exhibited superior motor function recovery and less central fatigue compared to the FOR-T group. EEG PSD slope analysis demonstrated a better inter-hemispheric balance in FAT-C group compare to the FOR-T group. The dCMC analysis indicated that training-induced fatigue led to a short-term down-regulation of descending corticomuscular coherence (dCMC) and an up-regulation of ascending dCMC. In the long term, excessive fatigue hindered the recovery of descending control in the affected hemisphere. The individualized strategy of peripheral fatigue-controlled training achieved better motor function recovery, which could be attributed to the mitigation of central fatigue, optimization of inter-hemispheric balance and enhancement of descending control in the affected hemisphere.

Movable Antenna Array Aided Ultra Reliable Covert Communications

In this paper, we construct a framework of the movable antenna (MA) aided covert communication shielded by the general noise uncertainty for the first time. According to the analysis performance on the derived closed-form expressions of the sum of the probabilities of the detection errors and the communication outage probability, the perfect covertness and the ultra reliability can be achieved by adjusting the antenna position in the MA array. Then, we formulate the communication covertness maximization problem with the constraints of the ultra reliability and the independent discrete movable position to optimize the transmitter's parameter. With the maximal ratio transmitting (MRT) design for the beamforming, we solve the closed-form optimal information transmit power and design a lightweight discrete projected gradient descent (DPGD) algorithm to determine the optimal antenna position. The numerical results show that the optimal achievable covertness and the feasible region of the steering angle with the MA array is significant larger than the one with the fixed-position antenna (FPA) array.

TopoCellGen: Generating Histopathology Cell Topology with a Diffusion Model

Accurately modeling multi-class cell topology is crucial in digital pathology, as it provides critical insights into tissue structure and pathology. The synthetic generation of cell topology enables realistic simulations of complex tissue environments, enhances downstream tasks by augmenting training data, aligns more closely with pathologists' domain knowledge, and offers new opportunities for controlling and generalizing the tumor microenvironment. In this paper, we propose a novel approach that integrates topological constraints into a diffusion model to improve the generation of realistic, contextually accurate cell topologies. Our method refines the simulation of cell distributions and interactions, increasing the precision and interpretability of results in downstream tasks such as cell detection and classification. To assess the topological fidelity of generated layouts, we introduce a new metric, Topological Frechet Distance (TopoFD), which overcomes the limitations of traditional metrics like FID in evaluating topological structure. Experimental results demonstrate the effectiveness of our approach in generating multi-class cell layouts that capture intricate topological relationships.

Learn2Synth: Learning Optimal Data Synthesis Using Hypergradients

Domain randomization through synthesis is a powerful strategy to train networks that are unbiased with respect to the domain of the input images. Randomization allows networks to see a virtually infinite range of intensities and artifacts during training, thereby minimizing overfitting to appearance and maximizing generalization to unseen data. While powerful, this approach relies on the accurate tuning of a large set of hyper-parameters governing the probabilistic distribution of the synthesized images. Instead of manually tuning these parameters, we introduce Learn2Synth, a novel procedure in which synthesis parameters are learned using a small set of real labeled data. Unlike methods that impose constraints to align synthetic data with real data (e.g., contrastive or adversarial techniques), which risk misaligning the image and its label map, we tune an augmentation engine such that a segmentation network trained on synthetic data has optimal accuracy when applied to real data. This approach allows the training procedure to benefit from real labeled examples, without ever using these real examples to train the segmentation network, which avoids biasing the network towards the properties of the training set. Specifically, we develop both parametric and nonparametric strategies to augment the synthetic images, enhancing the segmentation network's performance. Experimental results on both synthetic and real-world datasets demonstrate the effectiveness of this learning strategy. Code is available at: https://github.com/HuXiaoling/Learn2Synth.

RankByGene: Gene-Guided Histopathology Representation Learning Through Cross-Modal Ranking Consistency

Spatial transcriptomics (ST) provides essential spatial context by mapping gene expression within tissue, enabling detailed study of cellular heterogeneity and tissue organization. However, aligning ST data with histology images poses challenges due to inherent spatial distortions and modality-specific variations. Existing methods largely rely on direct alignment, which often fails to capture complex cross-modal relationships. To address these limitations, we propose a novel framework that aligns gene and image features using a ranking-based alignment loss, preserving relative similarity across modalities and enabling robust multi-scale alignment. To further enhance the alignment's stability, we employ self-supervised knowledge distillation with a teacher-student network architecture, effectively mitigating disruptions from high dimensionality, sparsity, and noise in gene expression data. Extensive experiments on gene expression prediction and survival analysis demonstrate our framework's effectiveness, showing improved alignment and predictive performance over existing methods and establishing a robust tool for gene-guided image representation learning in digital pathology.

A Multimodal Approach Combining Structural and Cross-domain Textual Guidance for Weakly Supervised OCT Segmentation

Accurate segmentation of Optical Coherence Tomography (OCT) images is crucial for diagnosing and monitoring retinal diseases. However, the labor-intensive nature of pixel-level annotation limits the scalability of supervised learning with large datasets. Weakly Supervised Semantic Segmentation (WSSS) provides a promising alternative by leveraging image-level labels. In this study, we propose a novel WSSS approach that integrates structural guidance with text-driven strategies to generate high-quality pseudo labels, significantly improving segmentation performance. In terms of visual information, our method employs two processing modules that exchange raw image features and structural features from OCT images, guiding the model to identify where lesions are likely to occur. In terms of textual information, we utilize large-scale pretrained models from cross-domain sources to implement label-informed textual guidance and synthetic descriptive integration with two textual processing modules that combine local semantic features with consistent synthetic descriptions. By fusing these visual and textual components within a multimodal framework, our approach enhances lesion localization accuracy. Experimental results on three OCT datasets demonstrate that our method achieves state-of-the-art performance, highlighting its potential to improve diagnostic accuracy and efficiency in medical imaging.

Adversarial Vessel-Unveiling Semi-Supervised Segmentation for Retinopathy of Prematurity Diagnosis

Accurate segmentation of retinal images plays a crucial role in aiding ophthalmologists in diagnosing retinopathy of prematurity (ROP) and assessing its severity. However, due to their underdeveloped, thinner vessels, manual annotation in infant fundus images is very complex, and this presents challenges for fully supervised learning. To address the scarcity of annotations, we propose a semi supervised segmentation framework designed to advance ROP studies without the need for extensive manual vessel annotation. Unlike previous methods that rely solely on limited labeled data, our approach leverages teacher student learning by integrating two powerful components: an uncertainty weighted vessel unveiling module and domain adversarial learning. The vessel unveiling module helps the model effectively reveal obscured and hard to detect vessel structures, while adversarial training aligns feature representations across different domains, ensuring robust and generalizable vessel segmentations. We validate our approach on public datasets (CHASEDB, STARE) and an in-house ROP dataset, demonstrating its superior performance across multiple evaluation metrics. Additionally, we extend the model's utility to a downstream task of ROP multi-stage classification, where vessel masks extracted by our segmentation model improve diagnostic accuracy. The promising results in classification underscore the model's potential for clinical application, particularly in early-stage ROP diagnosis and intervention. Overall, our work offers a scalable solution for leveraging unlabeled data in pediatric ophthalmology, opening new avenues for biomarker discovery and clinical research.

Hard Negative Sample Mining for Whole Slide Image Classification

Weakly supervised whole slide image (WSI) classification is challenging due to the lack of patch-level labels and high computational costs. State-of-the-art methods use self-supervised patch-wise feature representations for multiple instance learning (MIL). Recently, methods have been proposed to fine-tune the feature representation on the downstream task using pseudo labeling, but mostly focusing on selecting high-quality positive patches. In this paper, we propose to mine hard negative samples during fine-tuning. This allows us to obtain better feature representations and reduce the training cost. Furthermore, we propose a novel patch-wise ranking loss in MIL to better exploit these hard negative samples. Experiments on two public datasets demonstrate the efficacy of these proposed ideas. Our codes are available at https://github.com/winston52/HNM-WSI

Semi-Supervised Contrastive VAE for Disentanglement of Digital Pathology Images

Despite the strong prediction power of deep learning models, their interpretability remains an important concern. Disentanglement models increase interpretability by decomposing the latent space into interpretable subspaces. In this paper, we propose the first disentanglement method for pathology images. We focus on the task of detecting tumor-infiltrating lymphocytes (TIL). We propose different ideas including cascading disentanglement, novel architecture, and reconstruction branches. We achieve superior performance on complex pathology images, thus improving the interpretability and even generalization power of TIL detection deep learning models. Our codes are available at https://github.com/Shauqi/SS-cVAE.