Retrieval-Augmented Visual Prompting: Guiding Foundation Models in Two-Photon Imaging

Two-photon calcium imaging presents a challenging setting for foundation models: image appearance varies substantially across recordings and experimental conditions, annotations are scarce, and rapid adaptation is often needed. Rather than adapting model weights through fine-tuning, we ask whether a foundation model can be guided at inference time by injecting external visual memory directly into its input. We implement this idea with SAM 3 and introduce Retrieval-Augmented Visual Prompting (RAVP), a framework in which each target tile is augmented with a retrieved annotated exemplar whose bounding box is used as a concept prompt. RAVP turns retrieval into a form of visual prompting and enables adaptation through input design alone. We study multiple exemplar selection strategies, including fluorescence-guided heuristics and a lightweight recall predictor trained to estimate which exemplar is most informative for a target tile. Experiments on the Allen Brain Observatory show that exemplar-augmented inference consistently strengthens zero-shot neuron detection and instance segmentation. Ablation studies further show that a single carefully selected exemplar is more effective than prompting with multiple retrieved examples. These results position inference-time visual memory injection as a simple and effective alternative to parameter adaptation for foundation models in specialized biomedical imaging.

LoRSA: Toward Generalizable Parameter-Efficient Fine-Tuning for Biomedical Downstream Tasks

Parameter-efficient fine-tuning enables the adaptation of vision foundation models to biomedical tasks under limited computational resources, but a single low-rank update can constrain all task-specific changes to one narrow parameter subspace. This restriction may prevent the model from simultaneously representing globally shared task structure and localized residual directions required for generalization to unseen imaging domains. We introduce LoRSA, a global--residual adaptation framework that jointly learns a dense low-rank component and a dynamically structured-sparse low-rank component. The dense component captures globally coordinated task adaptation, while the structured component provides complementary residual corrections whose support evolves during training. We characterize the representational capacity, approximation properties, rank structure, and singular-subspace complementarity of this decomposition. We evaluate LoRSA for four-class breast-density classification using DINOv3-Base, with VinDr-Mammo as the source domain and MammosighTR and RSNA as unseen external domains. LoRSA remains competitive on the internal validation set and achieves the best external macro-F1 on both target datasets, improving upon the strongest competing method by 2.15 percentage points on MammosighTR and 3.09 percentage points on RSNA. Weight-matrix analysis further shows that approximately $92\%$ of the energy of each adaptation component lies outside the bilateral singular subspace of the other, indicating that the two components learn largely complementary update directions. These results suggest that organizing adaptation capacity into distinct global and residual paths can improve the external-domain generalization of parameter-efficiently adapted biomedical vision models.

OPERA: Offline Policy-guided Expert Routing and Adaptation for Universal Biomedical Image Analysis

Biomedical image analysis spans diverse modalities and tasks, yet real-world deployment is hindered by severe distribution shifts across scanners, protocols, and patient populations. High-performing models consequently require repeated domain-specific fine-tuning, which is a costly cycle that becomes impractical when labels are scarce or privacy constraints limit data sharing. We propose OPERA (Offline Policy-guided Expert Routing and Adaptation), a multi-agent ensemble framework that addresses this deployment bottleneck by treating expert weight assignment as an offline policy learning problem: a routing policy is learned from a small validation set without gradient updates to any expert agent, then deployed with test-time adaptation to handle distribution shift. OPERA coordinates heterogeneous specialist agents through complementary mechanisms. The expert profiling module learns selection policies offline, enabling informed allocation of expertise. Each agent undergoes confidence calibration through temperature adjustment, ensuring more reliable probabilistic outputs. OPERA also incorporates distribution aware adaptation, where class weights are dynamically adjusted at the batch level using statistics derived from unlabeled test data. Instance level routing assigns each sample to the most suitable expert by leveraging inter model agreement and predictive entropy. We evaluate OPERA on 9 datasets covering fundus photography, chest X-ray, CT, MRI, and multimodal diagnostic benchmarks, comparing against 30+ baselines across classification, segmentation, and multimodal settings. OPERA consistently improves performance and calibration quality, demonstrating that offline policy-guided expert agents coordination is a practical path to deployable biomedical AI without retraining. Code is on \href{https://github.com/HUANGLIZI/OPERA}{GitHub}.

BioMedVR: Confusion-Aware Mixture-of-Prompt Experts for Biomedical Visual Reprogramming

Recent advances in vision-language models (VLMs) such as CLIP have demonstrated strong generalization across natural-image domains. However, adapting these models to biomedical imaging is non-trivial: full-model fine-tuning is computationally expensive, while medical data are often scarce and exhibit subtle, fine-grained inter-class differences, making parameter-efficient adaptation particularly critical. Visual Reprogramming (VR) offers a parameter-efficient alternative by injecting learnable perturbations into the input space, but existing VR approaches for VLMs mainly focus on positive class prompts and overlook confusing negatives, leading to miscalibrated predictions in fine-grained medical scenarios. We present BioMedVR, the first VR-based framework for biomedical imaging, enabling few-shot adaptation of pretrained VLMs through compact learnable VR modules. To mitigate class confusion, we introduce a Confusion Minimization Mechanism that leverages LLM-generated confusion-aware attributes together with a Confusion-Suppression Loss to explicitly reduce false-positive alignment. Moreover, the designed Mixture-of-Prompt Experts combines a positive expert for main-class discrimination and a negative expert for confusion suppression, balanced via adaptive gating. Extensive experiments on 18 datasets, including 11 biomedical datasets and 7 natural image benchmarks, demonstrate that BioMedVR achieves superior accuracy and generalization, effectively bridging VR and VLMs in biomedical domains.

CellNet -- Localizing Cells using Sparse and Noisy Point Annotations

Counting living cells is an important step in many biological research workflows. Our collaborators at the Wellcome Sanger Institute study vital genes in humans via large scale saturation genome editing screening, which requires repeatedly counting cells a great number of times. Computer Vision based automation is crucial for high throughput and resource efficiency. In this work, we develop a regression-based deep learning computer vision algorithm to detect and count cells in phase-contrast microscopy images. To reduce annotation effort, which in practice often becomes a bottleneck, we focus on counting cells only using sparse point annotations, which are fast and easy to acquire. By comparison to state-of-the-art 0-shot methods, we show that regression-based counting is a promising alternative in low data regimes. Through developing methods to automatically count living cells in microscopy images, we contribute to valuable research on the human genome. The code is available at https://github.com/beijn/cellnet.

MMBU: A Massive Multi-modal Biomedical Understanding Benchmark to Probe the Perception Capabilities of Vision-Language Models

Vision and language models (VLMs) hold immense promise to transform biomedical imaging workflows, from detecting lesions in chest X-rays to profiling cellular features in microscopy. Realizing this potential, however, requires robust and fine-grained visual perception. Models need to correctly interpret subtle features in images, and they must do so across diverse biomedical modalities, scales, and contexts. Nevertheless, current benchmarks remain limited. To address these gaps, we introduce the Massive Multimodal Biomedical Understanding (MMBU) benchmark. It is the largest biomedical vision and language benchmark to date, covering 35 submodalities with rich structured metadata. It includes both open and closed versions of ungrounded classification, grounded classification, and object detection, enabling systematic evaluation of model performance across biological scales, clinical settings, and imaging modalities. Evaluating 15 open-weight and 2 frontier VLMs, we find that while medical adaptation provides measurable gains for some models, the high accuracy often reported on established benchmarks can mask deficiencies in visual perception and domain generalization.

Cell Phantom Video Generation in Elliptical Fourier Descriptor Domain

Training Deep Neural Networks for tracking individual cells in biomedical videos requires a large amount of annotated data. The annotation of videos for cell tracking is very time consuming and often requires domain expertise; this explains the limited availability of public annotated data to address important medical problems like tissue repair or cancer treatment. Generating synthetic videos along with their Ground Truth annotations is a promising solution that relies, as a foundational first step, on the synthesis of single cell annotations (or phantoms). Phantoms need to be time consistent, as they have to replicate biological processes that are specific to the cell types. In this work, we propose a novel framework for generating videos of cell phantoms in the Elliptical Fourier Descriptors (EFDs) domain, a compact and geometrically interpretable representation for 2D closed contours. We represent the cell phantom evolution as a multivariate time series of EFD coefficients, introducing a strong prior for cell morphology and enabling the efficient generation of sequences that evolve coherently in time. Our experimental validation proves that modelling the temporal evolution in EFD space enables the generation of biologically plausible phantom videos. Our method can be used in generative pipelines for synthesizing annotated data for cell tracking, thus strongly mitigating the annotation effort for creating new datasets. Our code is available for download here: https://github.com/FrancescoBenedetto99/efd-cell-video-gen.

MTCurv: Deep learning for direct microtubule curvature mapping in noisy fluorescence microscopy images

Accurate quantification of the geometry of curvilinear biological structures is essential for understanding cellular mechanics and disease-related morphological alterations. Microtubule curvature is a key descriptor of filament rigidity and mechanical perturbations. However, reliable curvature extraction from fluorescence microscopy images remains challenging due to noise, low contrast, and partial filament visibility. Existing approaches rely on segmentation pipelines with pre or post-processing, which are highly sensitive to segmentation errors and often fail under adverse imaging conditions. In this work, we propose MTCurv, a deep learning framework for direct, segmenta-tion-free regression of microtubule curvature maps from noisy microscopy images. Leveraging a synthetic dataset with pixel-wise curvature annotations, we reformulated curvature estimation as a regression problem and adapted an attention-based residual U-Net. To reduce hallucinations and enforce spatial coherence, we introduced a gradient-aware loss combining Mean Squared Error with a gradient consistency term. Beyond model and loss design, we evaluated commonly used regression and image quality metrics, revealing that many perceptual and blind metrics are poorly suited for curvature estimation. Correlation-based metrics, particularly Spearman correlation, emerged as more reliable indicators of curvature prediction quality. Experiments on two datasets of increasing difficulty demonstrated that MTCurv accurately recovers local microtubule curvatures, even in the presence of background fluorescence. Ablation studies highlighted the contribution of both residual encoding and attention-based decoding. Overall, this work provides a practical tool for filament curvature analysis and methodological insights for geometry-aware regression in biomedical imaging. Datasets and code are made available.