MAdam: Metric-Aware Multi-Objective Adam

Multi-objective optimization (MOO) underlies many machine learning problems, yet MOO solvers across the loss-balancing, gradient-balancing, and Pareto-based families almost universally hand their reconciled directions to Adam~\cite{kingma2015adam}. We show this coupling introduces two systematic gaps between the solver's intent and the optimizer's execution. The first is a \emph{weighting mismatch}: Adam's second-moment denominator entangles the time-varying preference vector with gradient statistics, marginalizing the preference into a history average and collapsing distinct Pareto trade-offs toward a near-uniform mixture. The second is a \emph{geometric mismatch}: Adam's adaptive metric distorts the Euclidean geometry MOO solvers assume, turning aligned objectives into apparent conflicts. To resolve both jointly, we introduce \textbf{MAdam} (Metric-Aware Multi-Objective Adam), a drop-in wrapper that leaves both solver and optimizer unchanged. MAdam preconditions the reconciled direction by the preference-conditioned curvature of the scalarized objective; on this whitened input, Adam's second moment collapses to identity, so the realized update is governed by the preference-conditioned metric. Across multi-task learning, Pareto-front recovery, physics-informed neural networks, and medical imaging, MAdam consistently improves over Adam for every solver family.

A Multimodal 3D Foundation Model for Light Sheet Fluorescence Microscopy Enables Few-Shot Segmentation, Classification, and Deblurring

Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computational challenges and the complexity of volumetric representation learning. In this work, we introduce a 3D foundation model for LSM data, pretrained on a large curated collection of 3D images spanning multiple organisms, stains, and imaging protocols. We learn transferable volumetric representations by jointly optimizing for masked reconstruction and image-text alignment. The pretrained backbone drastically reduces the annotation burden, enabling efficient, few-shot adaptation for varied downstream tasks. We evaluate this approach on downstream segmentation, classification, and deblurring. Our results demonstrate consistent improvements over baselines, (1) when measured using standard evaluation metrics and (2) when rigorously assessed by domain experts. This highlights the potential of foundation model pretraining to reduce annotation requirements while improving performance across diverse LSM analysis tasks. Pretrained model weights and code for pretraining and finetuning are publicly available: https://github.com/AdinaScheinfeld/lsm_fm_public_repo.git.

Synthetic Vasculature and Pathology Enhance Vision-Language Model Reasoning

Vision-Language Models (VLMs) offer a promising path toward interpretable medical diagnosis by allowing users to ask about clinical explanations alongside predictions and across different modalities. However, training VLMs for detailed reasoning requires large-scale image-text datasets. In many specialized domains, for example in reading Optical Coherence Tomography Angiography (OCTA) images, such precise text with grounded description of pathologies is scarce or even non-existent. To overcome this bottleneck, we introduce Synthetic Vasculature Reasoning (SVR), a framework that controllably synthesizes images and corresponding text, specifically: realistic retinal vasculature with Diabetic Retinopathy (DR) features: capillary dropout, microaneurysms, neovascularization, and tortuosity, while automatically generating granular reasoning texts. Based on this we curate OCTA-100K-SVR, an OCTA image-reasoning dataset with 100,000 pairs. Our experiments show that a general-purpose VLM (Qwen3-VL-8b) trained on the dataset achieves a zero-shot balanced classification accuracy of 89.67% on real OCTA images, outperforming supervised baselines. Through human expert evaluation we also demonstrate that it significantly enhances explanation quality and pathology localization on clinical data.

Graph Conditioned Diffusion for Controllable Histopathology Image Generation

Recent advances in Diffusion Probabilistic Models (DPMs) have set new standards in high-quality image synthesis. Yet, controlled generation remains challenging, particularly in sensitive areas such as medical imaging. Medical images feature inherent structure such as consistent spatial arrangement, shape or texture, all of which are critical for diagnosis. However, existing DPMs operate in noisy latent spaces that lack semantic structure and strong priors, making it difficult to ensure meaningful control over generated content. To address this, we propose graph-based object-level representations for Graph-Conditioned-Diffusion. Our approach generates graph nodes corresponding to each major structure in the image, encapsulating their individual features and relationships. These graph representations are processed by a transformer module and integrated into a diffusion model via the text-conditioning mechanism, enabling fine-grained control over generation. We evaluate this approach using a real-world histopathology use case, demonstrating that our generated data can reliably substitute for annotated patient data in downstream segmentation tasks. The code is available here.

Topology Optimization in Medical Image Segmentation with Fast Euler Characteristic

Deep learning-based medical image segmentation techniques have shown promising results when evaluated based on conventional metrics such as the Dice score or Intersection-over-Union. However, these fully automatic methods often fail to meet clinically acceptable accuracy, especially when topological constraints should be observed, e.g., continuous boundaries or closed surfaces. In medical image segmentation, the correctness of a segmentation in terms of the required topological genus sometimes is even more important than the pixel-wise accuracy. Existing topology-aware approaches commonly estimate and constrain the topological structure via the concept of persistent homology (PH). However, these methods are difficult to implement for high dimensional data due to their polynomial computational complexity. To overcome this problem, we propose a novel and fast approach for topology-aware segmentation based on the Euler Characteristic ($\chi$). First, we propose a fast formulation for $\chi$ computation in both 2D and 3D. The scalar $\chi$ error between the prediction and ground-truth serves as the topological evaluation metric. Then we estimate the spatial topology correctness of any segmentation network via a so-called topological violation map, i.e., a detailed map that highlights regions with $\chi$ errors. Finally, the segmentation results from the arbitrary network are refined based on the topological violation maps by a topology-aware correction network. Our experiments are conducted on both 2D and 3D datasets and show that our method can significantly improve topological correctness while preserving pixel-wise segmentation accuracy.

From Pixels to Histopathology: A Graph-Based Framework for Interpretable Whole Slide Image Analysis

The histopathological classification of whole-slide images (WSIs) is a fundamental task in digital pathology; yet it requires extensive time and expertise from specialists. While deep learning methods show promising results, they typically process WSIs by dividing them into artificial patches, which inherently prevents a network from learning from the entire image context, disregards natural tissue structures and compromises interpretability. Our method overcomes this limitation through a novel graph-based framework that constructs WSI graph representations. The WSI-graph efficiently captures essential histopathological information in a compact form. We build tissue representations (nodes) that follow biological boundaries rather than arbitrary patches all while providing interpretable features for explainability. Through adaptive graph coarsening guided by learned embeddings, we progressively merge regions while maintaining discriminative local features and enabling efficient global information exchange. In our method's final step, we solve the diagnostic task through a graph attention network. We empirically demonstrate strong performance on multiple challenging tasks such as cancer stage classification and survival prediction, while also identifying predictive factors using Integrated Gradients. Our implementation is publicly available at https://github.com/HistoGraph31/pix2pathology

Fine-tuning Vision Language Models with Graph-based Knowledge for Explainable Medical Image Analysis

Accurate staging of Diabetic Retinopathy (DR) is essential for guiding timely interventions and preventing vision loss. However, current staging models are hardly interpretable, and most public datasets contain no clinical reasoning or interpretation beyond image-level labels. In this paper, we present a novel method that integrates graph representation learning with vision-language models (VLMs) to deliver explainable DR diagnosis. Our approach leverages optical coherence tomography angiography (OCTA) images by constructing biologically informed graphs that encode key retinal vascular features such as vessel morphology and spatial connectivity. A graph neural network (GNN) then performs DR staging while integrated gradients highlight critical nodes and edges and their individual features that drive the classification decisions. We collect this graph-based knowledge which attributes the model's prediction to physiological structures and their characteristics. We then transform it into textual descriptions for VLMs. We perform instruction-tuning with these textual descriptions and the corresponding image to train a student VLM. This final agent can classify the disease and explain its decision in a human interpretable way solely based on a single image input. Experimental evaluations on both proprietary and public datasets demonstrate that our method not only improves classification accuracy but also offers more clinically interpretable results. An expert study further demonstrates that our method provides more accurate diagnostic explanations and paves the way for precise localization of pathologies in OCTA images.

Skelite: Compact Neural Networks for Efficient Iterative Skeletonization

Skeletonization extracts thin representations from images that compactly encode their geometry and topology. These representations have become an important topological prior for preserving connectivity in curvilinear structures, aiding medical tasks like vessel segmentation. Existing compatible skeletonization algorithms face significant trade-offs: morphology-based approaches are computationally efficient but prone to frequent breakages, while topology-preserving methods require substantial computational resources. We propose a novel framework for training iterative skeletonization algorithms with a learnable component. The framework leverages synthetic data, task-specific augmentation, and a model distillation strategy to learn compact neural networks that produce thin, connected skeletons with a fully differentiable iterative algorithm. Our method demonstrates a 100 times speedup over topology-constrained algorithms while maintaining high accuracy and generalizing effectively to new domains without fine-tuning. Benchmarking and downstream validation in 2D and 3D tasks demonstrate its computational efficiency and real-world applicability

Interpretable Retinal Disease Prediction Using Biology-Informed Heterogeneous Graph Representations

Interpretability is crucial to enhance trust in machine learning models for medical diagnostics. However, most state-of-the-art image classifiers based on neural networks are not interpretable. As a result, clinicians often resort to known biomarkers for diagnosis, although biomarker-based classification typically performs worse than large neural networks. This work proposes a method that surpasses the performance of established machine learning models while simultaneously improving prediction interpretability for diabetic retinopathy staging from optical coherence tomography angiography (OCTA) images. Our method is based on a novel biology-informed heterogeneous graph representation that models retinal vessel segments, intercapillary areas, and the foveal avascular zone (FAZ) in a human-interpretable way. This graph representation allows us to frame diabetic retinopathy staging as a graph-level classification task, which we solve using an efficient graph neural network. We benchmark our method against well-established baselines, including classical biomarker-based classifiers, convolutional neural networks (CNNs), and vision transformers. Our model outperforms all baselines on two datasets. Crucially, we use our biology-informed graph to provide explanations of unprecedented detail. Our approach surpasses existing methods in precisely localizing and identifying critical vessels or intercapillary areas. In addition, we give informative and human-interpretable attributions to critical characteristics. Our work contributes to the development of clinical decision-support tools in ophthalmology.

SELMA3D challenge: Self-supervised learning for 3D light-sheet microscopy image segmentation

Recent innovations in light sheet microscopy, paired with developments in tissue clearing techniques, enable the 3D imaging of large mammalian tissues with cellular resolution. Combined with the progress in large-scale data analysis, driven by deep learning, these innovations empower researchers to rapidly investigate the morphological and functional properties of diverse biological samples. Segmentation, a crucial preliminary step in the analysis process, can be automated using domain-specific deep learning models with expert-level performance. However, these models exhibit high sensitivity to domain shifts, leading to a significant drop in accuracy when applied to data outside their training distribution. To address this limitation, and inspired by the recent success of self-supervised learning in training generalizable models, we organized the SELMA3D Challenge during the MICCAI 2024 conference. SELMA3D provides a vast collection of light-sheet images from cleared mice and human brains, comprising 35 large 3D images-each with over 1000^3 voxels-and 315 annotated small patches for finetuning, preliminary testing and final testing. The dataset encompasses diverse biological structures, including vessel-like and spot-like structures. Five teams participated in all phases of the challenge, and their proposed methods are reviewed in this paper. Quantitative and qualitative results from most participating teams demonstrate that self-supervised learning on large datasets improves segmentation model performance and generalization. We will continue to support and extend SELMA3D as an inaugural MICCAI challenge focused on self-supervised learning for 3D microscopy image segmentation.