🏫 主要单位：Department of Pathology, Systems Pathology Research Group, Leiden University Medical Center, Leiden University, Leiden, Netherlands ｜ 主要作者：Jesper Kers、Buzzanca, G.
Accurate, reproducible interpretation of kidney allograft biopsies is critical for diagnosis of graft injury to guide prognosis and management. The international Banff classification is a consensus diagnostic system based on semiquantitative histological lesion scoring on either extent or severity of kidney transplant biopsies. However, pathologist scoring is limited by substantial interobserver variability, constrained scalability, and the inherent nature of the scoring system itself. Here we present BanffNET, a weakly supervised, probabilistic deep learning framework that combines self-supervised feature extraction with a novel Bayesian multiple-instance learning framework to predict (continuously) the full spectrum of Banff lesion scores directly from whole-slide images (WSIs). Using lesion-specific aggregation functions tailored to localized (modeling lesion severity) and diffuse pathologies (modeling lesion extent), BanffNET generates interpretable, patch-level probability maps and calibrated slide-level scores. BanffNET's performance was assessed relative to consensus, biological correlates of rejection and clinical outcome, demonstrating superior consistency, transportability and generalization. Trained on 7,249 WSIs from three cohorts, BanffNET demonstrates consistent performance on 11,028 WSIs across five external test sets, performing on par or exceeding expert consensus across lesions. BanffNET scores align more closely than pathologist Banff scores with molecular profiles of rejection, offering a transparent, biologically grounded framework for computational pathology with relevance beyond transplantation.
主要作者：Leonhard F. Feiner、Manuel Nickel、Martin Menten
提出了一种新的方法来联合处理高维输出空间中的随机和认知不确定性，适用于医学图像分割等任务。
💡 为医学图像分割中的不确定性量化提供了新的思路。
Uncertainty Quantification (UQ) plays a vital role in enhancing the reliability of deep learning model predictions, especially in scenarios with high-dimensional output spaces. This paper addresses the dual nature of uncertainty -- aleatoric and epistemic -- focusing on their joint integration in high-dimensional regression tasks. For example, in applications like medical image segmentation or restoration, aleatoric uncertainty captures inherent data noise, while epistemic uncertainty quantifies the model's confidence in unfamiliar conditions. Modeling both jointly enables more reliable predictions by reflecting both unavoidable variability and knowledge gaps, whereas modeling only one limits transparency and robustness. We propose a novel approach that approximates the resulting joint uncertainty using a low-rank plus diagonal covariance structure, capturing essential output correlations while avoiding the computational burdens of full covariance matrices. Unlike prior work, our method explicitly combines aleatoric and epistemic uncertainties into a unified second-order distribution that supports robust downstream analyses like sampling and log-likelihood evaluation. We further introduce stabilization strategies for efficient training and inference, achieving superior UQ in the tasks of image inpainting, colorization, optical flow, and depth estimation.
Accurate brain tumor segmentation from magnetic resonance imaging (MRI) is essential for diagnosis, treatment planning, surgical guidance, and disease monitoring. However, developing automated segmentation models that generalize across diverse tumor characteristics, imaging protocols, acquisition sites, and patient populations remains challenging. Variations in tumor morphology and imaging distributions can substantially degrade performance outside the training domain. Consequently, improving the robustness and generalization of deep learning-based segmentation models has become a key objective in medical image analysis. To improve segmentation robustness, we propose Multi-Stage Dynamic Prompt nnU-Net, a prompt-conditioned extension of nnU-Net. Three independent dynamic prompt modules are inserted into the deepest encoder stages. Each module contains a learnable bank of ten 256-dimensional prompt vectors and uses globally pooled encoder features to generate image-specific prompt representations. These representations are projected into feature-wise scaling $(γ)$ and shifting $(β)$ parameters that modulate encoder feature maps through Feature-wise Linear Modulation (FiLM), enabling adaptive feature conditioning at multiple semantic levels. Evaluation on the BraTS GOAT validation dataset demonstrated that the proposed Multi-Stage Dynamic Prompt nnU-Net outperformed the baseline nnU Net across the majority of evaluated metrics and tumor subregions. The proposed model achieved average lesion-wise Dice scores of 76.16% (ET), 80.04% (TC), and 86.42% (WT), compared with 74.38%, 78.14% and 84.01% for the baseline model. The results demonstrate that multi-stage dynamic prompt conditioning improves segmentation accuracy and boundary delineation for brain tumor segmentation.
Segmentation of curvilinear anatomical structures in 3D medical images remains challenging due to complex topology, severe class imbalance, weak contrast, and large variations in structure morphology. While deep learning approaches for 3D curvilinear segmentation have been proposed, they are often tailored to specific anatomies or modalities, limiting generalization across clinical settings and leaving room for improvement. Recent generative models have shown the benefits of iterative prediction for structured segmentation tasks, yet diffusion-based methods suffer from computationally expensive sampling, hindering their use on high-resolution 3D volumes. We present 3D-CurvSegFlow, a flow matching-based model for 3D curvilinear structure segmentation. The model learns a continuous transformation from a simple source distribution to the target vascular representation, enabling progressive refinement of complex curvilinear geometries with efficient inference. We evaluate our method on Three public challenging datasets covering distinct anatomies and modalities: portal vein, cerebral vessel, and coronary arteries. Using a common architecture and training strategy across all tasks, our method outperforms general-purpose and vessel-specific approaches, with strong preservation of thin branches and vascular continuity. This work not only advances the state-of-the-art in 3D curvilinear segmentation but also opens new avenues for efficient, generalizable, and clinically applicable methods in medical image analysis.
Uncertainty estimation is critical for the safe clinical deployment of deep learning in medical image segmentation, with aleatoric uncertainty theoretically designed to capture irreducible data ambiguity. However, whether entropy-based measures reflect clinically meaningful ambiguity, i.e. case-level disagreement about whether a pathology is present at all, remains poorly understood. Contrary to most prior work, which focused on pixel-wise boundary disagreement, we systematically evaluate how well aleatoric uncertainty captures presence ambiguity. Our evaluation spans 3D lung nodule segmentation across four architectures with Monte Carlo dropout and deep ensembles, on LIDC-IDRI and an external validation cohort (LNDb). We find that entropy-based uncertainty maps align with boundary noise and minor drawing variation but carry insufficient discriminative signal for presence ambiguity. In contrast, a lightweight supervised ambiguity head trained on frozen segmentation features substantially outperforms all entropy-aggregation-based baselines across architectures, metrics, and both cohorts, and matches or exceeds methods that explicitly model ambiguity under disagreement supervision (Probabilistic U-Net, Annotator-Confusion 3D-UNet). A qualitative feature-space analysis shows that presence ambiguity is already encoded in the frozen encoder features of pixel-wise-trained networks, only to be discarded by the segmentation output and its entropy aggregation. Our findings expose a fundamental mismatch between the theoretical promise of aleatoric uncertainty and its practical behavior, and suggest that practitioners should not rely on entropy-based uncertainty as a proxy for clinical ambiguity in safety-critical applications.
Purpose: Deep learning-based medical image segmentation has achieved remarkable success, yet purely data-driven approaches often fail to exploit the rich mathematical structure inherent in medical images. We investigate whether explicit mathematical inductive biases, specifically matrix spectral analysis and vector calculus operators, can enhance segmentation beyond data-driven learning alone. Methods: We propose M-Net (Math-Augmented Network), which integrates three complementary mathematical priors into U-Net: (1) continuous spectral features derived from the condition number of centered local pixel matrices, providing a differentiable measure of texture ill-conditioning; (2) physical field operators (divergence and a discrete curl-like boundary irregularity operator) computed from image gradient fields, capturing focal intensity extrema and edge non-smoothness; and (3) a Math-Attention Gate (MAG) that adaptively fuses mathematical features with CNN-extracted deep features at skip connections. Results: Experiments on three benchmarks (LiTS, KiTS, and BraTS) show that M-Net achieves Dice scores of 78.42%, 76.15%, and 83.67%, outperforming baseline U-Net by 12.37%, 3.52%, and 5.55% on liver, kidney, and brain tumor segmentation, respectively. Ablations reveal that the condition-number feature contributes a 2.14% gain over binary invertibility features, while MAG adds 1.45% over simple concatenation. Conclusion: M-Net establishes that mathematical inductive biases provide effective complementary information for medical image segmentation. The continuous condition-number feature offers superior gradient information over discrete alternatives, and MAG preserves these priors throughout the network. This work opens avenues for integrating linear algebra and vector calculus into deep architectures for medical imaging.
Sparse keypoint extraction and matching underpin core tasks in geometric computer vision, including structure-from-motion, visual SLAM, augmented reality, and medical image registration. Learning robust local feature representations, however, typically requires accurate camera poses or depth supervision, which are often unavailable in real-world settings. Reinforcement learning (RL) has recently emerged as a promising alternative, requiring only the information if two images show the same scene or not. However, existing RL formulations such as RIPE rely on coarse binary rewards and carefully constructed negative training pairs, limiting training stability and descriptor discriminability. In this paper, we revisit RL-based keypoint learning and propose a reward that fully exploits the geometric consistency signal, deriving both reward and penalty from a single positive pair without contrasting against negatives. This richer signal provides sufficient supervisory contrast to learn discriminative detectors and descriptors from positive image pairs alone, enabling representation learning under extremely limited supervision. Furthermore, we show that the same RL objective can be extended to the matching stage by adapting LightGlue, raising AUC@5 on MegaDepth1500 from 56.58 to 59.65 and enabling weakly-supervised training of the full sparse matching pipeline from image pairs with partial visual overlap. We validate our approach on established benchmarks, demonstrating competitive results compared to fully-supervised methods. We further show that the method can be even trained on low texture medical video sequences, where camera poses are usually unavailable and standard SfM pipelines often fail. Code and data are available at https://github.com/fraunhoferhhi/RIPEpp .
Registration-based Few-shot medical image segmentation (RFMIS) aims to generate pseudo-labels for unlabeled images by warping a labeled image through registration. However, existing methods primarily perform pixel-level optimization and inference in Euclidean space, treating anatomical structures as flat and disjoint. This neglect of inherent hierarchies degrades pseudo-label quality and weakens the discrimination of ambiguous regions, limiting the segmentation performance. To overcome this challenge, we propose a Hyperbolic Hierarchy-aware Aggregative Learning framework for RFMIS, termed H2AL, that enhances both deformation plausibility and anatomical discrimination for dual-task learning. Specifically, we introduce a Hyperbolic Hierarchy-aware Infusion (H2I) module, which leverages the hierarchical modeling capability of hyperbolic space to learn precise hierarchy-aware representations via transformation-guided supervised hyperbolic contrastive learning, and injects such hierarchical priors into Euclidean space through a gated infusion block while preserving semantic richness. Furthermore, we propose an end-to-end joint optimization algorithm by gradient aggregation, where the gradients from the registration and segmentation decoders, embedding semantic and hierarchical cues, are aggregated to update the shared encoder to promote collaborative learning across tasks. Extensive experiments on two anatomical regions, with five experimental settings, demonstrate the effectiveness and efficiency of our method in both registration and segmentation. The code is publicly available at https://github.com/JiamingCai469/H2AL.
In practical settings, medical image segmentation models are often developed with limited annotated data rather than fully labeled datasets. Training frequently begins in ultra-low labeled regimes where only a small number of volumes are annotated. In such scenarios, practitioners must simultaneously decide which cases to annotate and how to best use the remaining unlabeled data. Although active learning (AL) and semi-supervised learning (SSL) both target annotation scarcity, they are typically designed and optimized independently, resulting in objective mismatch and unstable training during early-stage "cold start" conditions. We propose RegAL, a unified active semi-supervised framework governed by a shared topology-aware Pareto optimization that couples sample acquisition with unlabeled data utilization. RegAL evaluates images along three complementary axes, voxel-wise uncertainty, feature diversity, and a novel topological consistency metric, to select anatomically informative edge cases for annotation. On the other hand, the same criteria are used to identify geometrically stable atlas candidates for diffeomorphic registration-guided augmentation to train a self-supervised Mean Teacher segmentation network. Across BraTS 2021, dHCP, and ProstateX, RegAL remains stable with few labeled volumes and consistently outperforms state-of-the-art AL, SSL, and active semi-supervised baselines across Dice and boundary-distance (ASD, HD95) metrics under extreme annotation scarcity.
The nnU-Net has demonstrated continuous success in medical segmentation tasks, which heavily rely on the availability and diversity of annotated biomedical data. However, assembling medical imaging cohorts remains challenging due to numerous factors such as privacy regulations and annotation costs. As a result, data augmentation plays a crucial role in increasing data availability while maintaining anatomical feasibility. Hence, we propose the ++nnU-Net, a novel data augmentation module based on image registration that operates prior to preprocessing and training take place. Our framework was evaluated across five different 2D datasets. In this workflow, image data go through a two-stage registration process, generating new warped images. The transformations are then applied to the respective segmentation. In addition, the pipeline computes available disk space, generates supplementary binary synthetic masks and generates checkpoints. We demonstrate that the ++nnU-Net outperforms the nnU-Net baseline, yielding improvements in Dice Similarity Coefficient scores. In the most prominent cases, we observe performance gains of approximately 22\%. These findings highlight the effectiveness of registration-based data augmentation, particularly for 2D medical imaging datasets and suggest that the ++nnU-Net provides a practical and scalable approach for enhancing segmentation performance in data-limited settings. The source code for the ++nnU-Net is available at: https://github.com/sofia-adelie/plusplusnnunet.git
Accurate 3D medical image segmentation requires the integration of long-range anatomical context with fine boundary detail. Existing methods often model global and local features in separate modules or feature levels and perform channel recalibration independently. This may cause semantic mismatch between global context and local boundaries, insufficient channel relationship modeling, weak spatial-channel interaction, and redundant representations. We propose CDGC-Net, a 3D medical image segmentation network that combines cooperative dual-scale spatial attention with grouped hierarchical channel modeling. With-in each CDGC block, Cooperative Dual-Scale Self-Attention (CDSA) assigns attention heads to parallel local-window and global-sparse branches. The two branches capture fine spatial details and long-range anatomical context at the same feature level. Their outputs are concatenated into an $N\times C$ spatial representation and directly passed to Grouped Hierarchical Channel Attention (GHCA). GHCA organizes the channels into $r$ groups and models both within-group and cross-group dependencies. CDSA and GHCA reuse a shared key projection to maintain a consistent feature reference. Residual feature alignment subsequently integrates the refined features with the original representation. On the Synapse, ACDC, BraTS, and LA datasets, CDGC-Net achieved mean DSC values of 86.96\%, 92.91\%, 82.56\%, and 93.52\%, respectively, exceeding the next-highest reported values by 0.39, 0.47, 0.17, and 0.32 percentage points. CDGC-Net contains 25.83M parameters and 28.62G FLOPs for an input size of $64\times128\times128$, reducing these quantities by 39.87\% and 40.30\%, respectively, relative to UNETR++. These results indicate a favorable trade-off between segmentation accuracy and computational complexity.
Self-supervised pretraining enables transferable representations for medical imaging, yet most CT encoders remain biased toward coarse semantic understanding, limiting their sensitivity to fine-grained anatomical structures such as vessels or small tumors. In this paper, we introduce Biased Masked Image Modeling (B-MIM), a modification of the iBOT objective that stochastically reduces global semantic alignment to prioritize local patch reconstruction. This bias encourages the encoder to capture high-frequency morphological details and structural continuity. We curate a multi-institutional CT abdominal dataset of 9,955 filtered studies from 17 public sources and pretrain a 3D Swin Transformer backbone using B-MIM. Across inter-dataset experiments on liver vessel segmentation, the proposed encoder improves topological fidelity (clDice) and achieves competitive Dice scores in tumor segmentation, compared to fully fine-tuned baselines, despite updating only a fraction of the parameters. Our results suggest that reducing global semantic pressure during pretraining enhances generalization to intricate anatomical structures.
主要作者：Alexis Ivan Escamilla-Lopez、Gilberto Ochoa-Ruiz、Salvador Hinojosa
提出LUX，一种病变感知的图条件视觉-语言架构，用于解释性内窥镜图像字幕生成。
💡 通过图条件视觉-语言架构，提高了内窥镜图像字幕生成的准确性和可解释性。
The interpretation of endoscopic imagery in ulcerative colitis is complex and subjective, with variability in human assessment and subtle mucosal inflammation. Although deep learning has advanced automated analysis, most vision-language models rely on global visual embeddings that overlook the localized and relational nature of pathological evidence, limiting clinical reliability and interpretability. We introduce LUX (Lesion-aware Unified eXplainable captioning), a graph-conditioned vision-language architecture for explainable endoscopic image captioning. LUX constructs a lesion-centric scene graph from Grad-CAM and CBAM activation maps, representing pathological regions as nodes and encoding their spatial and clinical relationships. These graph embeddings are integrated into the cross-attention layers of a T5 decoder, enabling generated words to attend to specific lesion nodes rather than only to global image features. This provides direct alignment between linguistic content and pathological evidence, supporting token-level interpretability and relational reasoning. LUX outperforms strong baseline and state-of-the-art medical captioning models across BLEU, METEOR, ROUGE-L, and CIDEr, with particularly strong gains in CIDEr. It also reduces hallucinated clinical findings and improves lesion-level grounding through stronger correspondence between generated tokens and localized pathological regions.
Acquiring pixel-level annotations for medical image segmentation is a severe bottleneck. Traditional U-Net architectures, while effective, learn local texture patterns and lack awareness of global anatomical structures, leading to boundary delineation failures in low-data regimes. This research paper proposes utilizing unsupervised Denoising Diffusion Probabilistic Models (DDPMs) to extract anatomical features. We train a DDPM on 21 unlabeled abdominal CT scans to learn structural representations, transferring the encoder weights to a downstream segmentation task evaluated on the BTCV multi-organ dataset. Diffusion pretraining significantly improved liver segmentation: Dice increased from $0.75\pm0.36$ to $0.93\pm0.16$ ($p < 5.33\times10^{-26}$, 0.529 Cohen's d), Average Surface Distance (ASD) decreased by 66%, and 95th-percentile Hausdorff Distance (HD95) reduced by 45%. For kidney segmentation, Dice improved from $0.90\pm0.19$ to $0.95\pm0.10$ ($p < 4.01\times10^{-11}$). Multi-organ pooled performance showed a 68% variance reduction and a 74% improvement in boundary precision (Dice $0.95\pm0.07$). Crucially, frozen encoder models retained > 80% of fine-tuned performance without exposure to segmentation labels, proving the existence of learned anatomical priors. In low-data scenarios, diffusion-pretrained models maintained robust performance with only 50% (Dice: 0.92 liver, 0.94 kidney), 25%, and even 10% (Dice: 0.89 liver, 0.71 kidney) of labeled data. Using unlabeled images for diffusion-based pretraining successfully embeds robust anatomical features prior to human supervision, transforming U-Nets into anatomy-aware systems.
🏫 主要单位：The Lyon Hepatology Institute IHU EVEREST ｜ 主要作者：Barbara Testoni、Roca Suarez, A. A.
评估了精确切割肝切片作为评估针对乙型和丁型肝炎病毒治疗剂的模型。
💡 为乙型和丁型肝炎病毒的治疗研究提供了新的体外模型。
Background: Developing new therapeutic strategies against hepatitis B virus (HBV) and hepatitis delta virus (HDV) is essential to cure these infections. Yet evaluation of host-targeting agents (HTAs) with in vitro/in vivo models remains challenging. Therefore, we assessed precision-cut liver slices (PCLS) as an HBV/HDV co-infection model to study virus-host interactions and HTAs. Methods: We generated PCLS from human liver resections and infected them ex vivo with HBV and HDV. Tissue viability and architecture were monitored by intracellular ATP, secreted albumin, and multiplexed immunofluorescence. Viral markers were assessed by quantitative PCR, western blot, and light-sheet microscopy in infected slices following treatment with a sodium taurocholate co-transporting polypeptide (NTCP)-targeting peptide, lonafarnib, or the Toll-like receptor 8 agonist selgantolimod (SLGN). Single-cell RNA sequencing was performed to characterize the cellular responses to SLGN. Results: Here we show that our ex vivo infection protocol allows the establishment of HBV and HDV infection within the liver's three-dimensional architecture. Treatment with three well-characterized HTAs produced distinct antiviral effects consistent with each mechanism: an NTCP-targeting peptide blocked entry; lonafarnib induced intracellular hepatitis delta antigen accumulation; SLGN showed anti-HBV activity not previously seen in cultured hepatocytes, indicating cross-talk between immune and infected cells within liver slices. Conclusion: These results provide the characterization of PCLS as an ex vivo model of HBV/HDV co-infection and antiviral testing. In the future, PCLS could contribute to expediting pre-clinical characterization of HTAs and to exploring alternatives to animal experimentation.
🏫 主要单位：Hong Kong Polytechnic University ｜ 主要作者：Yao Zhongping、Liu, C.
研究了SARS-CoV-2主要蛋白酶的抑制机制，包括二聚化促进和破坏。
💡 为抗病毒药物的开发提供了新的思路。
The SARS-CoV-2 main protease (Mpro) is a key target for antiviral drugs. Given its conserved sequence across coronaviruses and essential role in viral replication, numerous inhibitors have been developed to target its active site. Mpro exists in equilibrium between the active dimer and inactive monomer, rendering targeting dimerization as a promising alternative strategy for drug development. This study investigates the monomer-dimer equilibrium and conformational changes of Mpro induced by inhibitor binding. We utilized 13C labeling combined with native mass spectrometry to assess how different inhibitors, including peptidomimetic inhibitors (PF-07321332, PF-00835231, GC376, and boceprevir), and non-peptidomimetic inhibitors (carmofur, ebselen, MR6-31-2, AT7519 and pelitinib), influence Mpro dimerization and subunit exchange. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was further employed to investigate the conformational dynamics of Mpro and its interactions with these inhibitors. Key findings revealed divergent mechanisms: peptidomimetic inhibitors significantly shifted the equilibrium towards the dimeric state, suppressing subunit exchange dynamics and rigidifying the dimer interface. In contrast, ebselen impaired the dimer form and increased the flexibility of the dimer interface. Notably, we identified a novel covalent binding site for ebselen at C300 by tandem mass spectrometry, with molecular dynamics simulations further indicating that this modification allosterically altered the hydrogen bond network of the Mpro dimer interface. Importantly, C300 mutational analyses demonstrated that C300 contributes to ebselen-mediated dimer disruption and enzymatic inhibition. Overall, this study reveals distinct inhibitory modes between peptidomimetic inhibitors and ebselen, highlighting the potential of targeting allosteric sites at the dimer interface for the design of next-generation Mpro inhibitors.
🏫 主要单位：University of Wisconsin-Madison ｜ 主要作者：Lila E. Hoachlander-Hobby、Hoachlander-Hobby, L. E.
研究了Rho GTPase在细胞修复过程中的时空动态，揭示了细胞骨架重塑的分子机制。
💡 为细胞骨架重塑提供了新的见解。
Cells generate dynamic patterns of Rho GTPase activation to direct the subsequent patterning of Rho GTPase effectors needed to remodel the cell cortex during processes ranging from cell division to cell repair. To understand how such patterns arise, we used live cell imaging, time-resolved Rho GTPase manipulations, and a novel computational tool to study the spatiotemporal dynamics of Rho, Cdc42 and several downstream Cdc42 targets in wounded Xenopus laevis oocytes. We find that the characteristic wound-induced segregation of Rho and Cdc42 activity into concentric zones is followed by polarization of the Cdc42 zone such that Toca-1 progressively concentrates at the back of the Cdc42 zone while Arp2/3, cofilin, cortactin, and the Rho GAP p190RhoGAP progressively concentrate at the front of the Cdc42 zone, where it overlaps the Rho zone. Remarkably, the juxtaposition of Rho activity to Cdc42 is required for the polarization of p190RhoGAP, while p190RhoGAP is responsible for establishing the boundary between the Cdc42 and Rho zones. The results indicate that the characteristic segregation of the Rho and Cdc42 zones, as well as the polarization of the Cdc42 zone, arise from cortical self-organization. Further, these findings reveal a simple mechanism for hierarchical establishment of cortical patterns: recruitment of new proteins to regions of signaling compartment overlap.
Neuromesodermal progenitors (NMPs) sustain vertebrate body-axis elongation by generating both neural and paraxial mesodermal tissues. Although signaling and metabolic pathways regulate NMP states, whether intercellular communication contributes to the coordination of progenitor behaviour and developmental timing remains unclear. Here, we identify GJA1, encoding connexin-43 (Cx43), as a gene dynamically enriched within the neuromesodermal competent domain of the chick embryo. Cx43-associated channels and hemichannels accumulate preferentially within the NMP population, and a photoactivatable tracer assay demonstrates enhanced connexin-mediated exchange within the posterior growth zone. Pharmacological inhibition of hemichannels or gap junctions revealed distinct contributions of these communication modes to transcriptional regulation across the NMP continuum. Gap-junction inhibition primarily altered SOX2 expression within progenitor populations, whereas hemichannel inhibition selectively affected TBXT expression in mesodermal cells. Connexin inhibition also reduced the relative size of the progenitor compartment and altered the spatial organization of newly formed somites. Strikingly, disruption of connexin-mediated communication impaired segmentation dynamics, leading to increased frequencies of off-pace segmentation events, accelerated segmentation timing and progressive deviation from the expected segmentation program. These defects emerged rapidly and accumulated over successive segmentation cycles, indicating a requirement for connexin activity in maintaining developmental robustness. Together, our findings identify connexin-43 as a regulator of neuromesodermal progenitor states and reveal a previously unrecognized link between intercellular communication and segmentation clock robustness during vertebrate axis elongation.
主要作者：Pedro R. A. S. Bassia、Wenxuan Li、Jakob Wasserthal
提出利用报告监督肿瘤分割的新框架，显著提高分割性能。
💡 为肿瘤分割提供了新的思路，有望提高临床诊断的准确性。
Segmentation models can surpass radiologists, classification models, and vision-language models in tumor detection. Importantly, segmentation models outline tumors, allowing radiologists to better verify and trust the AI output. Their main limitation is the scarcity of tumor masks: creating one 3D tumor mask takes up to 30 minutes, so most public CT datasets contain only a few hundred masks, and even the largest private datasets contain only a couple of thousand. Tumor masks are not produced in clinical routine, but radiology reports are. Public datasets contain tens of thousands of CT-Report pairs, and hospitals contain hundreds of thousands. These reports describe tumors in detail, providing large-scale, informative training data. Here, we introduce Report Supervision (R-Super), a training framework that uses reports to directly supervise and improve tumor segmentation. R-Super introduces new loss functions that teach segmentation models to segment tumors that match report descriptions of tumor count, sizes, and locations. Reports are only used for training. We evaluated R-Super on kidney and pancreatic tumor segmentation, exploring diverse training data sizes, up to 41,418 CT-Report plus 3,488 pancreatic tumor CT-Mask pairs. On external validation, R-Super increased tumor detection F1-Score and segmentation DSC by up to +15% with respect to mask-only training. It also surpassed alternative methods such as CLIP and multi-task learning. Leveraging numerous readily available reports to supplement scarce masks, R-Super strongly improves AI performance when very few training masks are available (e.g., 50), and when many masks are available (e.g., 3,488), unlocking scale in tumor segmentation.
Diabetic retinopathy (DR) is a major cause of preventable blindness, creating a need for accurate and trustworthy automated screening. This study investigates an explainable DR classification framework using vision foundation models and multiple transfer learning strategies. Three backbones, DINOv2, CLIP, and Vision Transformer (ViT), were evaluated using full fine-tuning, linear probing, and Low-Rank Adaptation (LoRA). Models were trained and internally evaluated on the ODIR dataset and externally evaluated on APTOS to assess generalization. DINOv2-LoRA achieved the highest internal AUROC of 0.758, while DINOv2 full fine-tuning and ViT full fine-tuning achieved the highest external AUROC of 0.920. Calibration was further assessed using reliability analysis after isotonic regression. For explainability, Grad-CAM and HiResCAM were evaluated against expert-annotated lesion masks from the IDRiD dataset using Dice, Intersection over Union (IoU), and Pointing Game metrics. The results demonstrate that foundation models, particularly DINOv2, can provide strong predictive performance, while LoRA offers a parameter-efficient alternative to full fine-tuning. Quantitative evaluation of explanation maps further supports the assessment of whether model attention corresponds to clinically relevant retinal lesions.
主要作者：Huseyin Umut Isik、Mehmet Alp Ozaydin、Sila Kurugol
提出针对3D胸部CT的解剖路由对比视觉语言学习框架，有效提高异常检测性能。
💡 为胸部CT的异常检测提供了新的技术手段。
Contrastive vision-language learning uses paired chest CT volumes and radiology reports to learn abnormality classifiers without manually annotated labels. However, two characteristics of chest CT challenge conventional global contrastive learning. First, many critical abnormalities are small or anatomically localized, and pooling an en- tire volume into a single embedding may dilute their visual evidence. Second, the standard contrastive objective treats every other scan in a batch as a negative. Because many chest CTs share abnormalities, this objective incorrectly pushes co-positive pairs apart. We propose Anatomy-Routed Contrastive Learning for 3D Chest CT (ARC-CT), a region-aware framework that addresses these limitations using only la- bels extracted from reports by an LLM, with no manual annotations or bounding boxes. ARC-CT combines three components: (1) an Anato- myQFormer localizing evidence via queries constrained by automatically generated organ masks; (2) a label-Jaccard soft InfoNCE objective in- tegrating the standard one-hot target with the label-set overlap of each pair, which reduces false-negative penalties between studies that share clinical findings; and (3) an organ-level alignment loss connecting mask- pooled visual features to organ-specific report text extracted offline with a large language model. ARC-CT achieves a 0.86 mask-free macro AUC across 18 abnormalities using a compact 3D ResNet-18 backbone. Over- all, ARC-CT outperforms both comparable efficient baselines and sev- eral larger transformer models. Our code and weights are available at https://github.com/arc-ct/arc-ct.
Human-in-the-loop active learning (AL) can identify key phrases to facilitate biomedical ontology development, maintenance, and other curation tasks. However, determining which documents to annotate by humans is not straightforward. We explored new strategies to make the document selection process transparent, reproducible, and effective. Our AL pipeline modified a BiLSTM-CRF model using PubMed abstracts. We tested four novel document-level uncertainty aggregation strategies: KPSum, KPAvg, DocSum, and DocAvg, that operate over standard token-level uncertainty scores: Minimum Token Probability (MTP), Token Entropy (TE), and Margin. All strategies show significant improvement in early active learning cycles ({theta} to {theta}2) for recall and F1. The systematic evaluations show that KPSum (actual order) shows consistent improvement in both recall and F1. The weighted F1 ({beta} = 5, 10) provided complementary results to raw recall and F1 ({beta} = 1). Our work advances uncertainty sampling by introducing document-level uncertainty aggregation and shows promise in automating ontology curation.
Texture image classification plays a significant role in computer vision applications, including industrial inspection, medical image analysis, remote sensing, and object recognition. Handcrafted features can capture local texture characteristics but may have limited capability to represent complex visual patterns. In contrast, deep learning models automatically learn discriminative representations but may not fully exploit the multiscale spatial-frequency information inherent in texture images. This paper proposes a hybrid feature fusion framework, termed DWT_AlexNet_DNN, which combines Discrete Wavelet Transform (DWT) features with deep features extracted using AlexNet for texture image classification.
Translating electroencephalography (EEG) into functional magnetic resonance imaging (fMRI) is important for medical neuroimaging, clinical brain-state monitoring, and multimodal neural decoding, because it aims to infer spatially organized hemodynamic activity from fast and accessible electrophysiological recordings. Existing EEG-to-fMRI studies mainly pursue stronger decoders, but the problem is also constrained by a representation-interface mismatch: fMRI responses are delayed, temporally integrated, and spatially distributed, whereas generic EEG encodings often entangle temporal lag, channel identity, and frequency-band structure. We propose Multi-band EEG Latent-state Tokenization (MEL), a coordinate-preserving EEG representation framework that anchors each target fMRI response to its preceding EEG history and organizes it into lag-channel-frequency neural-state tokens. By explicitly capturing hemodynamic latency and spectral-spatial dynamics, MEL aligns fMRI-pertinent EEG representations with capacity-controlled readouts without depending entirely on model scaling. Experiments on VU EEG-fMRI benchmarks and external Oddball data show that MEL improves prediction over strong NeuroBOLT baselines. Ablations and controls further indicate that the gains come from structured EEG representation rather than leakage, shortcut statistics, or decoder capacity.
Data augmentation is a cornerstone of deep learning pipelines, yet existing strategies treat it as a static, model-agnostic preprocessing step, either relying on expensive dataset-specific policy search or applying transformations uniformly at random, regardless of what the model has already learned. We introduce ActiveAugment, a unified framework that treats augmentation selection as an online active learning problem. For each training minibatch, ActiveAugment generates a pool of candidate augmented views and scores each candidate using a combination of the model's predictive uncertainty and the feature discrepancy induced by the augmentation. The augmentation under which the current model is most fragile is selected per sample, and the model is then trained with a joint supervised classification and supervised contrastive objective that enforces intra-class invariance to the selected augmentations while maintaining inter-class separation. We evaluate ActiveAugment on eight benchmark datasets spanning natural and medical imaging, using CNN and transformer architectures across three training regimes (training from scratch, full fine-tuning, and linear probing), and comparing eight active selection strategies for augmentation scoring. ActiveAugment outperforms AutoAugment, RandAugment, and TrivialAugment under controlled augmentation shifts across all domains and budgets, with the most pronounced gains at low labelling budgets. On medical imaging datasets, where data is scarce and domain shift relative to natural-image pretrained models is large, ActiveAugment achieves higher test F1 than all baselines, demonstrating strong cross-domain adaptability. Our analysis reveals that the augmentation selection policy evolves meaningfully during training and that strategy choice has a direct impact on generalisation. Code is available at: https://github.com/noahvide/ActiveAugment.
Perceptual losses are widely used in medical image synthesis because they encourage agreement in high-level structure beyond voxel-wise intensity similarity. In practice, most perceptual losses are still computed with natural-image backbones such as VGG16 or ResNet50, even when the target domain is magnetic resonance imaging (MRI). This mismatch may weaken supervision for anatomy, contrast enhancement, and acquisition variability. We test whether medical foundation model features provide a more suitable perceptual loss for brain MRI contrast dose simulation. The study has two stages. First, we compare RadImageNet, SegVol, and BrainIAC with ImageNet-pretrained VGG16 and ResNet50 as frozen feature extractors on four public medical imaging benchmarks: thyroid ultrasound, breast ultrasound, anterior cruciate ligament knee MRI, and meniscus knee MRI. RadImageNet achieves the lowest mean rank across the Stage I representation suite and is selected as $φ^\star$. Second, we replace only the VGG16 feature extractor in an existing iterative brain MRI dose simulation framework with $φ^\star$. The generator, reconstruction loss, adversarial loss, auxiliary losses, optimization schedule, and loss weights are kept unchanged. Standard metrics change modestly, with PSNR increasing from 41.63 to 41.74, SSIM from 0.9739 to 0.9754, RMSE decreasing from 0.1384 to 0.1369, and residual-uptake CNR from 0.0085 to 0.0082. The visual results show the main effect: RadImageNet reduces residual enhancement in marked structures, follows a more faithful dose-reduction trajectory, and remains close to the acquired 10% low-dose target. These results support domain-aligned radiology features as a practical perceptual feature space for MRI dose simulation, while leaving clinical equivalence and larger-cohort validation as future work.
Objective: Cognitive impairment is a common comorbidity among people with epilepsy (PWE) and is associated with disability and reduced quality of life. We characterized the burden of cognitive impairment and identified factors associated with cognitive performance in a large, population-based cohort of PWE living in Northern Peru, a region highly endemic for Taenia solium where neurocysticercosis (NCC) is a common cause of acquired epilepsy. Methods: PWE enrolled in a population-based cohort in Northern Peru between 2007 and 2020 completed the Mini-Mental State Examination (MMSE) at enrollment. Cognitive impairment was defined as an MMSE score <24. Demographic and clinical data, including epilepsy characteristics and NCC status, were collected. Negative binomial regression was used to identify factors associated with the number of MMSE errors. Results: Among 764 participants, the mean MMSE score was 26.4 (SD 4.2), and 16.4% met criteria for cognitive impairment. Memory and attention were the most affected domains. In multivariable analysis, older age and lower educational attainment were independently associated with poorer cognitive performance. Conclusion: In this large, community-based cohort from Northern Peru, approximately 1 in 6 PWE had abnormal global cognition on the MMSE, with memory and attention most affected. These findings underscore the importance of incorporating cognitive evaluation and management into comprehensive epilepsy care, particularly in resource-limited settings where cognitive morbidity may be underrecognized. Given the potential for cognitive difficulties to compound disability and adversely affect quality of life, identifying and addressing cognitive morbidity may be especially important in populations already facing substantial barriers to epilepsy care.
Noninvasive live-cell imaging in deep human tissues is crucial for exploring the cellular biological and pathogenic processes, but remains a significant unmet challenge. Diffusion magnetic resonance imaging (dMRI) promises to narrow this gap by noninvasively providing cellular-level microstructural information. Within a single crowded voxel containing millions of living cells, the intricate cellular-level microstructures create numerous microcompartments, each characterized by a specific diffusivity. However, conventional dMRI methods relying on voxel-averaged macroscopic parameters, merely reflect aggregate microstructural properties and fail to quantify this distribution of microcompartment-specific diffusivity within a voxel, thereby obscuring microstructural details. Here, we propose an intravoxel diffusivity probability distribution (IDPD) model to resolve a wealth of essential microstructural information via quantifying microcompartment-specific diffusivity distribution, thereby enabling direct cellular-level characterization. This exceptional capability is realized through a multi-tiered analytical workflow spanning targeted single-voxel or region of interest (ROI) analysis to global visualization using dynamic videos and statistic parametric maps. Ultimately, the IDPD model enables noninvasive cellular-level microstructure imaging, offering a promising avenue to evaluate living cell functions in vivo.
Accurate 3D abnormality segmentation in chest CT requires dense spatial supervision, but obtaining expert voxel-level labels is costly. Radiology reports, however, are routinely generated during clinical interpretation and contain instance-specific descriptions that can provide additional guidance without new dense annotation. Existing vision-language grounding methods typically require report-derived findings at inference, making localization dependent on paired text and limiting each forward pass to a queried finding. We propose Instance-Guided Report Anchoring (IGRA), a model-agnostic module that preserves the correspondence between each annotated abnormality instance and the report finding that describes it. IGRA pools each instance representation and anchors it to the corresponding finding embedding during training; all text-related components are discarded at inference. We further reformulate free-text grounding on ReXGroundingCT as multi-label volumetric segmentation by merging same-category instances, allowing all abnormality categories to be predicted in one image-only forward pass. IGRA improves Dice by 22.5% over the strongest image-only baseline (30.93 vs. 25.25) and is comparable to VoxTell on the single-finding subset (30.29 vs. 30.43). Applied unchanged to four standard 3D segmentation backbones, IGRA improves Dice and hit rate across all architectures. Zero-shot evaluation on LIDC-IDRI, PleThora, and a private in-house dataset further shows consistent gains over image-only baselines.
Recent radiology multi-modal language models have made substantial progress in chest X-ray report generation, visual question answering, and temporal reasoning. While longitudinal chest X-ray interpretation compares sequential examinations to describe change, visual grounding aims to connect clinical language with localized image evidence. Although longitudinal modeling and visual grounding have each advanced radiology language models, how localized visual evidence can support longitudinal interpretation remains under-explored. We introduce CheXGround, a region-grounded longitudinal chest X-ray language model that represents paired studies through corresponding anatomical regions. CheXGround extracts anatomical regions from current and prior radiographs, encodes them as temporally enhanced Region-of-Interest (ROI) tokens, and combines them with global temporal image context during generation. To connect these region tokens with clinical text, we propose Temporal Region--Phrase Alignment, a pretraining objective that aligns temporal anatomical representations with localized report phrases. We evaluate CheXGround on single-study and longitudinal Visual Question Answering (VQA), longitudinal findings generation, temporal grounded VQA, and anatomical grounding. Across these tasks, CheXGround improves clinical language quality, temporal reasoning, and localization accuracy over recent baselines. Our results suggest that organizing longitudinal evidence at the anatomical level is a strong representation for grounded radiology language modeling. Project page: https://adonaydem.github.io/chexground-website
Agentic workflows can coordinate modelling, but balancing predictive performance, measurement burden and reproducibility is unclear. We developed DXA Agent, an agentic workflow for dual-energy X-ray absorptiometry (DXA) outcomes integrating planning, feature-model refinement, tools, provenance and hypothesis-generating interpretation. Models were independently developed and tested in UK Biobank (5,318 participants) and the National Health and Nutrition Examination Survey (NHANES; 3,777 participants), using cost-efficient and no-limit strategies. Across 20 UK Biobank and three NHANES bone mineral density sites, cost-efficient models achieved lower RMSE and higher R2 than the best conventional comparator, with median relative RMSE reductions of 10.9% and 9.9%, respectively. Classification was task dependent: UK Biobank osteoporosis averaged AUROC 0.839 and PR-AUC 0.182, whereas NHANES performance was comparable with conventional models. Higher-burden features did not consistently improve prediction. These retrospective, cohort-internal findings position DXA Agent as an inspectable, measurement-burden-aware research workflow requiring independent prospective validation.
Chronic pain mechanisms are complex, spanning multiple brain regions and networks. We ask whether resting brain activity carries a readout of that state. From a few minutes of resting-state electroencephalography (EEG), we generate a spectrogram to represent how each region of the cortex oscillates across frequency and time and pass it through CREST (Cortical Resting-state EEG Spatial Transformer): a frozen image-recognition network that reads each region as an image--here, a spectrogram--paired with a graph model that weighs the 56 cortical regions together to classify chronic-pain status. Across 125 people (74 with chronic pain, 51 healthy controls), evaluated through a leave-one-subject-out cross-validation, CREST separates the two groups with an area under the receiver operating characteristic curve (AUROC) = 0.782 (permutation p < 0.005). Control experiments implicate each persons individual alpha rhythm. Clinical relevanceA resting-state EEG readout of chronic MSK pain could clarify pathophysiology and inform treatment.
The development of deep learning over the past decade has revolutionized medical imaging segmentation, allowing the extraction of precise descriptors from large volumes to characterize pathologies. Data augmentation is a technique widely regarded as a way to improve model training. It includes simple transformations like spatial operations or intensity modifications, but also more advanced synthesis techniques. Their goal is to generate new realistic samples from an existing dataset to diversify the images used during training. Among them, several propose different mixing strategies to combine real samples. However, one of their major shortcomings is to yield limited variability in terms of generated lesion shapes and locations. In this work, we introduce a novel image synthesis method, called OTLesMix, that leverages Wasserstein barycenter and optimal transport plan to generate realistic and diverse samples. We evaluated our method on three brain lesion segmentation tasks, on which it improves the Dice score compared to a model trained without synthetic data by 2.9 to 6.6 points, and outperforms state-of-the-art mix-based methods.
Current 3D generative models mostly produce a final surface: a visually strong but largely opaque mesh. Interactive 3D worlds need more than a surface. They need named parts, an assembly hierarchy, measurable constraints, local edit handles, and joints for articulation. We present Nova3D, a system that generates 3D assets as executable Blender source code; the compiled mesh, a binary glTF (GLB), is treated as the artifact, not the asset. Because the output is a program, semantic handles exist at generation time rather than being recovered afterward by segmentation or rigging. We evaluate on Nova3D-Bench, a frozen, spec-grounded benchmark of 54 items across six domains and three difficulty levels with text and image inputs, against eleven baselines in four families (mesh-native, part-structured, code-native, and CAD) plus a same-LLM ablation. Nova3D produces an executable program and a valid artifact for 54/54 items. Every asset exposes named parts organized in a parent-child assembly tree; no mesh-native, CAD, or segmentation baseline exposes either. It satisfies 51/52 prompt-stated numeric and count constraints (best baseline: 11/52), passes 14/18 blinded local edits with locality preserved in 18/18, and articulates 59 joints across 12 assets at 98.3% geometric validity, where every baseline exposes zero native joints. Its geometry is competitive: it wins the structured domains in a pairwise shape-quality tournament and is second only to the strongest mesh-native model, while conceding texture realism to baked-PBR systems. The central result is representational: code-native generation turns a generated 3D object from an opaque surface into a programmable asset that downstream systems can inspect, measure, edit, and animate.
Medical Visual Question Answering (Med-VQA) holds significant promise for clinical decision support, yet faces challenges due to limited annotated data and the high computational demands of existing large vision-language models. We propose MedFG-VQA, a lightweight framework that leverages a memory bank to augment DCT-based low-frequency features and employs graph-enhanced cross-attention for effective visual-textual alignment. Specifically, our approach features two key components: Frequency-Memory Fusion (FMF), which enhances low-frequency features by retrieving from a learnable memory bank built on DCT decomposition, and Graph-Aware Cross-Attention (GACA), which aligns visual-textual features via cross-attention and refines them through graph-convolutional aggregation. To address data scarcity, we construct SynMed-VQA, a large-scale synthetic dataset comprising over 2 million question-answer pairs across 9 imaging modalities and 10 major organs, generated with GPT-4o. Extensive experiments on SynMed-VQA and three other standard biomedical VQA benchmarks demonstrate that MedFG-VQA achieves competitive or superior performance compared to much larger models while maintaining significantly lower computational costs, highlighting its efficiency and potential for clinical deployment.
Synthetic image generation is a promising strategy to address data scarcity and the underrepresentation of clinically important phenotypes in medical imaging, yet generating images that faithfully reflect meaningful patient characteristics remains challenging. In this work, we investigate metadata-conditioned cardiac magnetic resonance (CMR) synthesis using a pretrained latent diffusion model, encoding structured clinical metadata and slice position as textual prompts to guide CMR generation. To improve metadata adherence and address the imbalance of clinical attributes, we integrate three strategies: Metadata-Free Classifier-Free Guidance (CFG), Contrastive Batching, and Inverse-Frequency Sampling. The framework was fine-tuned and evaluated on 59,058 short-axis CMR from the UK Biobank using paired image similarity, distributional fidelity, and subgroup-level analyses. The combined approach achieved a Fréchet Inception Distance (FID) of 37.47, improving by 57.04\% over the same model fine-tuned without these strategies and by 28.68\% over a previous text-conditioned CMR diffusion baseline requiring cardiac geometry as additional input, while relying solely on patient metadata. This distributional gain, driven mainly by Metadata-Free CFG, came with a modest reduction in paired similarity, suggesting that the model prioritizes population-level realism over exact image reproduction. Subgroup analyses demonstrated improved alignment across demographic and acquisition-related metadata, with disease-specific conditioning being the most challenging task. These findings demonstrate the potential of generative foundation models for clinically meaningful CMR synthesis while highlighting the need for more effective metadata-aware conditioning strategies. Our code is available at https://github.com/rodriguezmarc/conditional-cmr.
3D brain MRI generation has made significant advances in medical imaging, simulation, and controllable anatomical analysis. However, existing generative models typically synthesize 3D volumes monolithically, often overlooking regional anatomical structures and limiting local controllability. To address these limitations, we introduce AnaDiffusion, an anatomically compositional latent diffusion framework that factorizes the generation process into distinct, anatomically meaningful regions, followed by part-to-whole assembly and global refinement. Our approach first trains part diffusion models to capture local structural priors. We then inject an assembled anatomical composite of the parts into the whole-brain latent representation and continue denoising. This mechanism enables the model to resolve global context while preserving the injected anatomy. As a result, AnaDiffusion produces both explicit part assets and a globally coherent volume, thereby enabling controllable part editing without requiring subject-specific dense segmentation maps at inference time while maintaining consistent part-to-whole brain structure. On the subject-disjoint ADNI test split, AnaDiffusion achieves the lowest FID across the whole brain, left and right hemispheres, cerebellar-brainstem complex, and seam regions. It also achieves the best cerebellar and second-best ventricular and brainstem absolute Cohen's d values among the evaluated methods. In localized editing experiments, paired MS-SSIM demonstrates high target transfer and off-target preservation, supporting controllable part replacement with minimal unintended anatomical alterations.
Automated radiological report generation can alleviate clinical workloads and eliminate observer variability. However, standard free-text generation models pose hallucination risks in dense regions and fail under data scarcity. We address these challenges in Head and Neck Cancer (HNC) from contrast-enhanced CT (CECT) imaging. To enforce factual safety, we reformulate report generation as an anatomically grounded, multi-label, structured reporting task, predicting localized tumor involvement across a hierarchical clinical schema. To bridge the visual gap from missing metabolic imaging (e.g., PET), we introduce SGRNet (Spatially Guided Radiology Network), incorporating two low-cost spatial priors: automated organ segmentations and weakly supervised tumor localization maps modeled via 3D Gaussian heatmaps. These priors are dynamically integrated via spatial feature modulation to guide the network toward subtle tumor-induced structural alterations. Evaluated on a multi-centric dataset of 184 paired HNC CECT volumes and reports, on five clinically salient, densely packed anatomical subsites, SGRNet achieves a mean Average Precision (mAP) of 0.60, an 8.8 percentage-point absolute improvement over strong volume-only 3D baselines.
Large language models (LLMs) have demonstrated considerable promise in program generation for small-scale and conventional application development; however, they remain limited when applied to complex, domain-specific tasks such as medical image processing. General-purpose models lack explicit domain knowledge and robust validation mechanisms to ensure correctness, often requiring substantial human intervention to produce reliable processing pipelines. To address these limitations, we propose AutoMedImg, a multi-agent framework for fully automated medical image processing code generation. AutoMedImg orchestrates specialised agents across two phases: a Planning Phase that performs dataset analysis and architecture design with semantic and formal verification, and a Coding Phase that generates modules in parallel with static checking, execution testing, and assembly validation. This multi-stage validation mitigates error propagation throughout generation, while comprehensive auto-context engineering combining domain-specific knowledge bases, shared memory, and validation feedback automates context construction without manual prompting. A cross-project adaptive pipeline synthesis mechanism further accumulates validated pipelines and retrieves proven components for new tasks based on project similarity, enhancing generation efficiency through cross-project learning. Extensive evaluation across six diverse and well-established medical imaging datasets with five backbone LLMs demonstrates that AutoMedImg achieves zero human intervention, with Dice scores of up to 0.90 for segmentation tasks and 99% accuracy for classification.
Large-scale, publicly available datasets have driven advances in deep learning, but privacy and legal restrictions often limit data sharing in medical imaging. Synthetic data generation offers a privacy-friendly alternative to enable the training of high-performance models on health data. While most state-of-the-art generative models produce high-quality images, they remain computationally expensive, which limits their applicability on resource-constrained hardware. We propose StyleGANCA, the first lightweight general-purpose NCA-based generative adversarial network. The architecture integrates a StyleGAN-inspired mapping network and adaptive style modulation into a multi-scale NCA synthesis process, enabling latent-controlled image generation through iterative local interactions. We evaluate StyleGANCA on BloodMNIST and PathMNIST against adversarial, variational, diffusion, and NCA-based baselines. Experimental results demonstrate that StyleGANCA achieves competitive image quality with substantially fewer parameters than baseline architectures, achieving the best FID and KID scores on PathMNIST with only 617k parameters. Furthermore, downstream experiments show that the generated images preserve class-specific information and effectively support the training of multi-class classifiers. Our code is publicly available at: https://github.com/MECLabTUDA/StyleGANCA
Joint-embedding predictive architectures (JEPAs) have primarily been developed for self-supervised representation learning. Denoising JEPA (D-JEPA) recently demonstrated strong generative capabilities on natural images, yet the applicability to 3D medical imaging remains unexplored. Building on the D-JEPA framework, we present Med-D-JEPA, a systematic adaptation and evaluation of joint-embedding predictive generation for 3D brain MRI. Med-D-JEPA operates on continuous latent tokens produced by a 3D KL-regularized adversarial variational autoencoder, and combines masked context prediction, representation-level alignment, per-token diffusion, and iterative next-set-of-token sampling. We evaluate unconditional and class-conditional generation quality on BraTS2019 and OASIS-1 datasets; downstream classification utility; and preliminary whole-tumor segmentation on BraTS2020. Across different generation settings, Med-D-JEPA achieves superior or competitive performance compared to several strong baselines on fidelity and diversity metrics. Compared to training with real samples, Med-D-JEPA-based synthetic pretraining improves classification AUC from 0.63 to 0.85 on BraTS2019 and from 0.78 to 0.87 on OASIS-1. In the segmentation study, pretraining on Med-D-JEPA samples improves Dice from 0.74 to 0.80 and reduces HD95 from 13.40 to 9.56 mm. These findings establish joint-embedding predictive generation as a promising direction for 3D medical image synthesis and encourage further research in this direction.
Streptococcus pneumoniae asymptomatically colonizes the nasopharynx but can invade the lower respiratory tract to cause life-threatening disease, particularly in older adults. However, whether the initial site of bacterial deposition following intranasal inoculation determines disease progression has not been directly examined. Here, we developed a near-infrared (NIR) fluorescence imaging approach using indocyanine green (ICG)-labeled S. pneumoniae TIGR4 to visualize early bacterial distribution in real time. ICG labeling by simple mixing, without genetic or chemical modification, neither impaired bacterial growth at 33 or 37{degrees}C, nor altered acid tolerance. Continuous video imaging during the first 10 min of infection resolved two distinct patterns: bacteria confined to the nasopharynx (colonization) and those aspirated into the lower respiratory tract (aspiration). Kaplan-Meier analysis revealed markedly higher mortality in the aspiration group in both young (hazard ratio = 7.9) and aged (hazard ratio = 8.4) mice, despite a 10-fold lower inoculum used for aged animals, with deaths beginning on day 3. Systemic profiling of blood at 24 h by RNA sequencing and plasma proteomics revealed that early aspiration in aged mice was associated with the activation of inflammatory and hematopoietic programs, enrichment of complement and coagulation cascades, and phagocytic pathways. Together, these findings establish aspiration into the lower respiratory tract as a trigger of severe pneumococcal disease and introduce real-time NIR imaging as a technique for linking early infection dynamics to systemic host responses.
Objective and scalable approaches for detecting subtle motor impairment in isolated REM sleep behavior disorder (iRBD), a prodromal stage of Parkinson's disease, remain limited. We investigated whether markerless motion capture from single RGB-camera videos can identify gait abnormalities in people living with iRBD and provide interpretable digital biomarkers. We retrospectively analyzed 93 standardized walking videos from three clinical sites. Human pose estimation extracted 12 body markers and 14 kinematic time series. Thirty-five machine learning approaches classified healthy controls (HC) and people with iRBD. The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS III) served as the clinical baseline. The best-performing model (tsfresh+XGBoost) achieved an AUROC of 0.739, significantly outperforming the MDS-UPDRS III sum score when trained on data from all three sites. Harmonized multi-site training improved performance. SHAP identified hip-related temporal features as key contributors, which differed between groups and showed stronger associations with regional dopaminergic deficits than clinical scores. Single-camera gait analysis may provide scalable digital biomarkers for low-cost screening and monitoring of prodromal PD.
Object detection and segmentation in three-dimensional medical images is a very active area of research. However, most proposed deep learning models carry a high computational cost, and only few aim to be broadly applicable, achieve high detection performance, and remain fast to execute on resource-constrained hardware. To address this gap, we present RadYOLO, a 3D extension of YOLO11 tailored to medical images. We compare it with nnU-Net and nnDetection on five datasets comprising CT and MRI data with varying object sizes and prevalence. RadYOLO's detection performance surpasses that of nnDetection on four of five datasets and is comparable on one. Compared to nnU-Net, RadYOLO performs better on lesion detection tasks, while nnU-Net excels at detecting large organs when precise localization is required. When rough object localization is sufficient, RadYOLO matches or outperforms nnU-Net on all five datasets. Regarding inference time, RadYOLO is 8-46x faster than nnU-Net on a GPU. Compared to nnDetection the speedup is even higher. When executed on a CPU, RadYOLO's inference runs within seconds (still faster than nnU-Net on a GPU) offering a significant advantage for clinical and edge-device deployment. RadYOLO repository: https://github.com/FraunhoferMEVIS/RadYOLO
Despite years of methodological progress, how far AI has come in liver fibrosis staging has never been systematically evaluated under the heterogeneous, multi-center conditions that define clinical practice. To address this gap, we introduce LiFS, a large-scale dataset and benchmark derived from the MICCAI 2025 CARE-Liver challenge, comprising 610 patients across multiple centers and scanners with multi-sequence MRI. To the best of our knowledge, LiFS is the first benchmark providing complete gadoxetic acid-enhanced sequences with histopathology-confirmed annotations from diverse real-world scanners. Through systematic evaluation of 9 independently developed methods selected from 96 registered teams against in-cohort radiologist reference results, our findings address how far current AI has progressed toward clinical-level liver fibrosis staging from three complementary perspectives. First, against radiologists, the best AI methods were broadly comparable to the senior radiologist and significantly exceeded the junior radiologist in selected settings, while median AI performance generally approached junior-radiologist levels. Second, from a data perspective, cross-center heterogeneity, label imbalance, and contrast-enhanced sequence variability emerge as the dominant challenges for AI methods. Third, from a technical perspective, methodological design choices, including spatial registration, input dimensionality, multi-modal fusion strategy, and backbone architecture, appear to modulate cross-center robustness, although no single choice alone closes the gap. Overall, LiFS provides a rigorous real-world benchmark for positioning the current state of AI in liver fibrosis staging and for enabling future research on the key challenges that limit clinically reliable deployment.
Volumetric medical VQA requires reasoning over long and redundant 3D visual token sequences, especially in multi-sequence MRI where complementary modalities provide diverse diagnostic cues but expose the decoder to many repeated anatomical regions. To investigate reasoning under multi-sequence visual redundancy, we first introduce BreMRIs-VQA, a clinically curated breast MRI benchmark with 1.19M QA pairs from 71.0K sequences and 12.9K patients, covering both free-text and multiple-choice questions. We further propose SeVeR, a selective visual exposure framework that compresses dense volumes into modality-wise prototypes and retrieves complementary multi-level evidence with change-aware gated attention during decoding, trained with a marginal-utility self-consistency objective that suppresses unhelpful retrieval. Experiments on BreMRIs-VQA and public benchmarks show that SeVeR improves both discriminative and generative performance while exposing substantially fewer visual tokens.
Reducing annotation requirements remains a key challenge in developing robust medical object detectors. To address this, Vision-Language (VL) object detection methods leverage grounding text information to enable powerful zero-shot and few-shot object detectors in the natural image domain [1, 2, 3, 4]. However, transferring these methods to the medical domain is challenging due to the absence of comparable quality and quantity of the grounding data. Regardless, significant contextual and non-imaging information exists in medical images that remains underutilized. Few-shot learning (FSL) techniques partially address this limitation but struggle to general ize to unseen medical findings and require extensive retraining when new findings are introduced [5, 6]. To overcome these challenges, we extend our prior EM-DETR framework [7] and introduce a scalable FS detection approach designed for efficient abnormality detection in Chest X-Ray (CXR) images under minimal supervision. The proposed architecture incorporates exemplar-based feature generation and domain-aware contrastive optimization, enabling effective adaptation to novel disease findings without exhaustive retraining. Our method achieves near state-of-the-art (SOTA) detection performance using less than 10% of the annotated data, demonstrating its potential for practical, annotation-efficient clinical deployment across both proprietary and public CXR datasets.
As artificial intelligence is increasingly integrated into chest X-ray (CXR) interpretation, triage, and clinical decision support, understanding its vulnerability to adversarial manipulation is critical for safe deployment. Existing robustness evaluations, however, predominantly rely on pixel-space attacks that introduce numerically constrained perturbations but may not represent plausible radiographic variation. This limitation is particularly important in multi-disease CXR classification, where models simultaneously evaluate multiple overlapping pathologies and adversarial failures may alter several diagnostic predictions. We propose a text-guided diffusion-based adversarial framework that optimizes learnable text conditioning while keeping the diffusion generator and target classifier frozen, enabling adversarial generation through a learned image prior rather than direct pixel manipulation. We evaluate the framework across multiple classifier architectures in both binary atelectasis and multi-disease CXR classification and compare it with FGSM, PGD, and Carlini-Wagner attacks. Our approach consistently produced the greatest degradation in classifier performance, reducing AUROC to 0.3885-0.5646 in binary classification and 0.4441-0.4878 in the multi-disease setting, while achieving superior image fidelity (SSIM 0.9080, LPIPS 0.1670, FID 51.23). Importantly, clinician interpretation remained unchanged for 95.9% of binary and 73.8% of multi-disease adversarial images despite substantial changes in model predictions. These findings reveal a clinically important discrepancy between human and machine interpretation and demonstrate the need to extend medical AI robustness evaluation beyond conventional pixel-space attacks toward generative threat models that can expose failures under visually and clinically plausible image variations.
Psychosis as a symptom manifests in schizophenia and bipolar disorder, two highly heterogeneous psychiatric illnesses with overlapping clinical manifestations. Resting-state functional Magnetic Resonance Imaging (rsfMRI), represents a promising tool for identifying objective biomarkers of functional brain alterations to aid differential diagnosis. In this work, we comparatively evaluate multiple rs-fMRI representations for differentiating schizophrenia and bipolar disorder using intrinsic connectivity network (ICN) temporal profiles and several functional network connectivity (FNC) approaches, including static, dynamic, and high-order connectivity analyses. The study was conducted on a cohort of 371 subjects with psychosis, while evaluation was performed using a separate held-out cohort of 315 subjects. We investigated convolutional neural network architectures applied to ICN temporal profiles, spectrograms, and scalograms, alongside classical machine learning models trained on connectivity-derived features. Across the evaluated approaches, ICN temporal profiles provided the most consistent discriminative performance, with a 1D convolutional neural network achieving the strongest overall results under the benchmark protocol. Among connectivity-based methods, static functional connectivity generally outperformed dynamic and high-order representations, suggesting that increased representational complexity did not necessarily translate into improved generalization. Although the obtained classification performance remained modest, the results highlight the challenges of robust psychosis differentiation using rs-fMRI while emphasizing the relative stability of low-order connectivity representations and temporal ICN features. These findings contribute to ongoing efforts toward reproducible and interpretable neuroimaging biomarkers for psychiatric disorders.
Errors in radiology reports can adversely affect patient treatment, yet automated report quality assurance remains challenging because errors are often subtle and require domain expertise to detect. Although large language models (LLMs) have recently been proposed for radiology report verification, their ability to detect clinically meaningful errors beyond chest X-ray datasets remains under-explored. To this end, we present the first systematic evaluation of language models for PET/CT report error detection, comparing compact domain-specific models with SOTA open-weight LLMs. We collected 30,633 oncology FDG PET/CT reports from 23 radiologists over 10 years. We trained domain-specific BERT models to detect clinically motivated synthetic reporting errors and evaluated alongside zero-/few-shot Qwen3-32B, Gemma-3-27B and Llama-3.3-70B on a held-out benchmark of 11,500 reports. A 15M-parameter model achieved 94.4% balanced accuracy with a 5.8% false-positive rate, compared with 84.0% for the strongest prompted LLM. Task-specific adaptation of Llama-3.3-70B closed this performance gap (94.4%) but retained substantially greater computational requirements. Our results suggest that domain-specific training matters more than model scale for PET/CT report error detection, supporting compact models as an accurate and computationally efficient approach to automated radiology report quality assurance.
Developing competitive deep learning baselines for medical imaging remains a highly iterative process requiring literature review, implementation, experimentation, and expert refinement. Existing automation approaches typically optimize isolated components, such as architecture search or hyperparameter tuning, rather than the complete baseline development process. We present an agentic AI Scientist workflow that combines literature-guided reasoning, automated code generation, and hypothesis-driven experimentation to generate competitive baseline models for medical imaging challenges. The framework is evaluated on four public benchmarks spanning segmentation, classification, and detection. Across all tasks, the Experimentation Pipeline consistently improves validation performance, achieving competitive leaderboard results, including 6th place on both PUMA tracks (15 teams) and 31st place on MILK10k (125 teams). On MIDOG25, the resulting model also demonstrates strong domain generalization across scanners, tumor types, and species. Using the same workflow across all challenges without task-specific redesign, we demonstrate that skill-based, literature-guided agentic workflows can substantially reduce the engineering effort required to develop competitive medical imaging baselines.
Large language models (LLMs) show promise in medical image interpretation but suffer from hallucination, limited accuracy, and run-to-run inconsistency. We developed and validated an agentic AI framework integrating LLMs with specialized deep learning tools for glaucoma detection from fundus photography. The workflow had three steps: (1) LLM initial assessment; (2) function calling to invoke specialized tools for image quality (QAModel, FundaQ-8), glaucoma classification (SwinV2-Tiny), and optic disc/cup segmentation (SegFormer-B0); and (3) LLM reflection integrating the initial impression with tool outputs. Two LLMs (Gemini 2.5 Flash, GPT-5.4 mini) were evaluated on two public datasets (ORIGA, n=100; RIM-ONE-v3, n=100) under uncropped and cropped fields of view; all images were independently graded by a masked fellowship-trained glaucoma specialist. The agentic workflow improved classification accuracy by 16 to 47 percentage points across all conditions, reaching within 6 points of the specialist; on RIM-ONE-v3 the best configurations matched the specialist accuracy of 88%. LLM-alone approaches failed in two ways: GPT-5.4 mini showed positive bias (sensitivity 95-100%, specificity 0-5%), while Gemini 2.5 Flash varied stochastically between runs; the agentic workflow corrected both. Cup-to-disc ratio error fell 15-50% (MAE 0.156-0.228 to 0.104-0.132), and correlation with specialist grading rose from weak (r=0.12-0.39) to moderate-strong (r=0.59-0.84). Run-to-run consistency rose from near-random (kappa as low as -0.01) to near-perfect (kappa up to 0.96). Integrating LLMs with specialized tools addressed key limitations of LLM-alone approaches, including over-diagnosis and run-to-run variability. Gains held for both LLMs, suggesting generalizability across backbones, and may signal a shift from monolithic models toward orchestrated multi-agent systems in medical AI.
Federated learning is used in medical imaging where privacy prohibits centralizing data. Standard federated algorithms assume homogeneous hardware, identical architectures, and centralized aggregation, which fails when hospitals have unequal compute resources. We propose capacity-aware coordination: measure each hospital's throughput, assign capacity-appropriate architectures (MobileNetV3-Small, EfficientNet-B0, ResNet-50), and combine predictions via weighted ensemble. Weak and strong hospitals can participate without forcing uniform architectures. We separate on-chain policy from off-chain learning. A Solidity contract stores hospital registration, benchmark hashes, metrics, and weights. Hospitals train locally and submit only hashes and scalars (not parameters). Weighted ensemble inference is computed off-chain. Experiments on PneumoniaMNIST and DermaMNIST (5 seeds, 3 non-IID levels) show our method achieves lower or equal calibration error versus equal-weight ensemble and competitive accuracy versus FedAvg, FedProx, and FedMD. Communication overhead is 224 bytes per round, a reduction of over 912,000x compared to FedAvg.
Although Multimodal Large Language Models (MLLMs) have demonstrated impressive performance in Medical Visual Question Answering (Med-VQA), their reliance on global image features often lacks precise pixel-level grounding, thereby limiting clinical trustworthiness. To bridge the semantic gap between high-level clinical reasoning and spatial localization, we propose \textsc{\textsc{MedREAL}} (\textbf{Med}ical \textbf{RE}asoning-driven \textbf{A}nswering and \textbf{L}ocalization), a unified framework that seamlessly aligns linguistic reasoning with spatial grounding. Specifically, \textsc{MedREAL} introduces \textbf{S}eg \textbf{A}nchored \textbf{R}easoning \textbf{P}ooling (SARP) to distill task-relevant semantic evidence directly from \texttt{[SEG]} tokens within the MLLM's hidden states. Furthermore, a \textbf{R}easoning-to-\textbf{V}isual (R2V) fusion mechanism is proposed to effectively inject these reasoning-aware features into a segmentation pipeline for accurate mask decoding. To facilitate this paradigm, we construct MedRAVS-13K, a comprehensive dataset comprising 13,824 expertly validated samples across four diverse imaging modalities. Extensive experiments demonstrate that \textsc{MedREAL} significantly outperforms state-of-the-arts, achieving 68.49\% gIoU and 70.47\% cIoU on benchmark evaluations. By generating evidence masks that are strictly consistent with textual diagnoses, \textsc{MedREAL} provides a robust, interpretable framework for reasoning-driven medical image analysis.
Vision-language models (VLMs) are increasingly used in clinical pipelines where a chest X-ray is interpreted alongside retrieved reports, preliminary notes, or prior imaging. Existing benchmarks measure whether models answer correctly in isolation, but not whether they preserve a correct image-only decision when plausible context conflicts with the image. We introduce Multi-Context Chest X-ray (MC-CXR), a benchmark of 240 cases expanded into 2,522 instances that isolates context-induced disruption through paired perturbation. Each case fixes the current image and target finding while presenting matched reliable and misleading context across text and prior CXR, with visual overlays where available. MC-CXR defines three task families and two paired metrics, the switch-to-wrong rate and the context-aligned error rate. We evaluate ten VLMs spanning open-source general, medical-domain, and closed-source systems. Image-only accuracy is necessary but insufficient. Mean switch rates range from 45.6-78.1% across misleading textual sources and 35.7-61.7% across misleading visual sources. Among switched predictions, 74.6% align with the misleading label for text versus 17.6% for visual context, a 57.0-point gap (95% CI 50.9-62.8). This text-visual asymmetry is observed under the standardized direct-answer protocol. The dataset is available on PhysioNet.
🏫 主要单位：Dartmouth College ｜ 主要作者：James V. Haxby、Zhang, Y.
研究发现，尽管功能拓扑结构存在个体差异，非人类灵长类动物在观看电影时的大脑活动存在共享表征空间。
💡 为理解大脑功能和认知提供了新的视角。
Response hyperalignment (RHA) of fMRI patterns acquired during movie-viewing in 12 rhesus monkeys revealed shared representational spaces despite idiosyncratic functional topographies. RHA greatly improved inter-subject correlation of movie response time-series in occipital, temporal, and prefrontal cortices and afforded highly accurate between-subject decoding of movie time-points and estimation of idiosyncratic functional topographies. These results demonstrate that nonhuman primates share high-dimensional, high-capacity representational spaces encoded in idiosyncratic fine-grained functional topographies.
Advances in spatiotemporal single-cell imaging have enabled detailed observations of cell population dynamics and intercellular interactions. However, translating these rich data sets into mechanistic insight remains a significant challenge. Agent-based models (ABMs) are a bottom-up computational framework for investigating the emergent behavior of cell populations that can arise from rules defining the interactions between individual neighboring cells, while topological data analysis (TDA) provides robust descriptors of spatial organization. We present TOPAZ (TOpologically-based Parameter inference for Agent-based model optimiZation), a computational pipeline that integrates TDA with approximate Bayesian computation (ABC), approximate approximate Bayesian computation (AABC), and Bayesian model selection to identify biologically plausible ABMs from spatiotemporal cellular data. TOPAZ uses persistent homology to quantify spatial features of cell trajectories and combines this topological information with parameter inference via ABC and AABC and model comparison using the Bayesian information criterion. We validate TOPAZ using simulations of collective fibroblast movement, demonstrating its ability to accurately recover model parameters and distinguish between a baseline ABM and an extended model that incorporates an alignment interaction. Our results and open-source code demonstrate the utility of TOPAZ as an extensible framework for mechanistic inference and model discrimination in spatial single-cell analysis.
🏫 主要单位：Institute for Basic Sciences ｜ 主要作者：C. Justin Lee、Kim, T. Y.
揭示了AXL-ICD/SIRT2轴在阿尔茨海默病中的关键作用，为神经炎症的治疗提供了新靶点。
💡 该研究为阿尔茨海默病的治疗提供了新的分子靶点。
Autophagy dysfunction and neuroinflammation are central to Alzheimer's disease (AD), yet how extracellular amyloid-{beta} (A{beta}) couples to impaired autophagic flux and heightened neuroinflammation remains unknown. Here, we identify the TAM receptor AXL as a molecular transducer that couples A{beta} sensing to the regulation of autophagy and neuroinflammation in astrocytes. A{beta} induces {gamma}-secretase-dependent cleavage of AXL, generating a nuclear intracellular domain (AXL-ICD) that forms phase-separated condensates and activates autophagy gene transcription through SIRT2-mediated recruitment of the RUVBL1/2-INO80 chromatin-remodeling complex. This axis is activated in astrocytes of postmortem AD brains. Concurrently, AXL-ICD binds to the SIRT2 catalytic domain and suppresses its deacetylase activity, increasing -tubulin acetylation and altering microtubule dynamics. While moderate AXL-ICD levels promote autophagic flux, excessive elevation paradoxically triggers microtubule hyperstabilization, thereby impairing autophagosome-lysosome fusion and causing pathological accumulation of autophagosomes and H2O2. The inhibitory peptide AxSBiP disrupts the AXL-ICD/SIRT2 interaction, restores autophagic flux, reduces plaque burden, and normalizes A{beta}-induced H2O2 production and astrogliosis in APP/PS1 mice. We propose the AXL-ICD/SIRT2 axis as an effective therapeutic target to reduce A{beta} burden and neuroinflammation in AD
Medical referral (directing patients to the appropriate hospital department) is a complex decision-making process requiring the synthesis of multimodal data, including patient narratives, laboratory indicators, and radiology imaging. While Large Language Models (LLMs) have advanced medical dialogue systems, they struggle with real-world referral tasks due to two primary limitations: (1) Information Overload, where models fixate on high-frequency disease terms while overlooking subtle but critical urgency indicators; and (2) Unstructured Collaboration, where existing multi-agent frameworks rely on loose dialogue that leads to semantic drift and confirmation bias. To address these challenges, we introduce MASGR (Multi-Agent Structured Graph Reasoning), a framework that treats referral not as a classification task but as a structured graph construction problem. MASGR deploys specialized agents to extract evidence from distinct modalities and coordinates them through a clinical reasoning graph. This graph forces agents to establish explicit logical connections between conflicting evidence. Furthermore, we integrate a knowledge-guided arbitration mechanism that prioritizes patient safety rules over standard diagnostic classification. Extensive experiments on real-world medical records demonstrate that MASGR significantly outperforms state-of-the-art LLMs and existing multi-agent systems, particularly in complex cases requiring the balancing of chronic disease management and emergency intervention. The AI contribution lies in the Multi-Agent Structured Graph Reasoning framework that transforms unstructured multi-agent dialogue into a verifiable logical graph construction. The engineering application is demonstrated through its deployment in a complex healthcare decision-making system to optimize the precision of complex medical referrals.
Deformable image registration (DIR) is a core problem in medical image analysis; but, unlike labeling decision problems such as classification and segmentation, registration is a problem class that involves stringent physical constraints. Although deep learning methods have made faster registration possible, the resulting models are often difficult to interpret compared to hand-crafted methods with explicit objectives and interpretable physical meaning. In this work, we show that an analytical method can still yield competitive and superior results to deep learning in a common deformable registration task. We study pTVreg as a parametric total variation based registration in that context. Observing its different implementations to perform at various degrees, we introduce here an accessible implementation of this method, together with a Bayesian optimization framework that automatically sets self-parameters for any DIR task from a set of sample examples. Experiments on Lung250M-4B show that our proposed implementation achieves state-of-the-art results in this benchmark, substantially superior to existing deep learning solutions and other pTVreg variants as baselines. The source code will be made publicly available at https://github.com/oazeybekoglu/ptvreg-python .
Deformable image registration models implicitly encode deformation priors through their parametrization and optimization. In this work, we conduct a validation study on continuous registration methods to examine how these implicit priors affect performance across different registration tasks. Classic B-Spline transformations impose locality, smoothness, and scale through their control-point structure, whereas recent INR-based methods impose different priors through neural parameterization and optimization. We compare INR-Dense (IDIR), which directly models a dense displacement field using a SIREN-based INR; INR-BSCP (SINR), which predicts B-Spline control points with an INR; D-BSCP, which directly optimizes single-scale B-Spline control points; and MR-D-BSCP, which adds a multiresolution coarse-to-fine scheme. Experiments on inter-subject brain MR registration (OASIS) and intra-subject exhale-to-inhale lung CT registration (DIR-LAB 4DCT) reveal different behavior across deformation regimes. On OASIS, where deformations are moderate but locally complex, D-BSCP matches or slightly outperforms INR-BSCP, suggesting that the B-Spline parameterization accounts for much of INR-BSCP's effectiveness. On DIR-LAB 4DCT, where respiratory motion is larger and more coherent, single-scale B-Spline methods (D-BSCP and INR-BSCP) are less suitable, while INR-Dense and MR-D-BSCP are more effective. Across both tasks, MR-D-BSCP achieves the best performance among the tested continuous parameterizations. These findings highlight that registration accuracy depends strongly on matching the induced deformation prior to the target motion pattern, and support prior-deformation matching as a practical design principle for medical image registration. Our code will be available at https://github.com/HengjieLiu/RightPriorDIR.
Head-and-neck (HN) proton therapy is highly sensitive to anatomical change over a 4-to-6-week course, as tumor shrinkage, weight loss, and setup variation can misposition the Bragg peak near critical organs such as the parotids, oral cavity, brainstem, and spinal cord, leading to target underdosing or organ-at-risk overdosing. Online adaptive proton therapy replans on the anatomy of the day, yet standard workflows rely on offline replanning that requires repeated CT acquisition and roughly a week of preparation, adding burden, cost, and delay. We investigate whether a patient's treatment-day anatomy can be predicted before image acquisition by transferring longitudinal change from a population database. We propose a digital-twin framework built on a pretrained foundation-model deformable registration network used without patient-specific training. A first registration aligns a prior patient's planning CT to the target and carries the prior's during-treatment quality assurance CT (QACT) into the target frame; a second registration estimates the prior's planning-to-QACT change, which is then applied to the target's own planning CT to synthesize predicted CTs (pdCTs) with propagated contours. Using 88 HN patients, each with a planning CT and three QACTs, we show that pdCTs better match treatment-day anatomy than the static planning CT. Compared with the planning CT alone, normalized cross-correlation improves by 22.8%, Dice for organs-at-risk by 20.2%, and CT-number error decreases by 23.4%. Gains are largest for patients with major anatomical change and negligible when anatomy is stable. This cross-patient motion transfer leverages the digital-twin concept to anticipate treatment-day anatomy, enabling personalized online adaptive proton therapy without repeated imaging.
Accurate 3D--2D liver registration, which aligns preoperative 3D models to partial, view-dependent intraoperative surface observations, is critical for AR-guided laparoscopic surgery but remains challenging due to severe occlusion, limited visibility, and the lack of 3D ground-truth supervision. Existing landmark-free approaches perform partial-to-complete geometric alignment, yet robust self-supervision under extreme partial visibility remains difficult. We propose Vis2Reg, a visibility-aware registration framework that explicitly constrains deformation using mask-consistent visible regions. We introduce a visibility-aware self-supervision that derives a visible-domain 3D supervision signal from intraoperative masks, enabled by differentiable point rasterization and mask-guided back-projection. This formulation improves robustness under severe occlusion while maintaining fully self-supervised learning. Vis2Reg combines a robust geometric rigid initialization module with an implicit neural deformation field for stable alignment. Vis2Reg achieves a Dice score of 92.6\% and a Chamfer Distance of 1.43 mm on real intraoperative datasets, with 111 ms per-frame inference time, demonstrating both accuracy and practical efficiency.
Medical image registration benefits significantly from deep learning, yet existing approaches often lack physical explainability and fine-grained deformation control. Motivated by Demons algorithms, we propose a novel DrivenMorph framework that bridges attention mechanisms with variational image registration by incorporating difference modeling as a physically inspired inductive bias. The resulting driving force, computed from local differences in the latent feature space, provides explicit semantic guidance throughout the registration process. It directly drives the registration process through a neural Demons layer that simulates force-displacement interactions to generate smooth and anatomically consistent deformation. Unlike previous methods, our approach not only integrates traditional registration principles with popular deep networks, providing an explainable and efficient solution for learning-based medical image registration, but also separates difference modeling from deformation, improving modularity and explainability. Extensive experiments on multiple 3D brain MRI datasets demonstrate superior performance over state of-the-art learning-based and optimization-based methods. Furthermore, visualizations and statistical analyses confirm that the learned driving force aligns closely with actual deformation patterns, supporting its explanatory value.
Deformable medical image registration aligns anatomical structures across images but remains computationally dense at 3D resolution. Spiking neural networks (SNNs) offer sparse event-driven computation, yet have not been systematically studied for deformable medical image registration. We introduce SpikeReg, a spiking U-Net for 3D brain MRI registration. SpikeReg is initialized from an analog ANN registration teacher, converted by layer-wise weight transfer and activation-percentile threshold calibration, and fine-tuned with a surrogate-gradient objective combining local cross-correlation, diffusion regularization, and spike-rate sparsity. On the OASIS Learn2Reg validation split ($19$ image pairs), SpikeReg reaches Dice $0.7474 \pm 0.032$, with no significant paired Dice difference from the ANN teacher ($0.7480 \pm 0.037$, $p = 0.67$), at a $12.8\%$ mean spike rate and a $55.5\times$ projected arithmetic-energy reduction under an event-sparse SynOps/MAC proxy relative to the dense-ANN baseline. We additionally report two negative findings: displacement distillation from the ANN teacher hurts performance, and ANN teachers trained with a label-Dice loss fail to transfer through rate-code conversion. Together these results show that dense geometric prediction can be performed under sparse event-driven computation, opening a path toward neuromorphic medical image registration.
Purpose: To complement 1.5-minute measurements of common tensor-valued diffusion MRI (dMRI) markers with rapid constrained fitting. Methods: Fast dMRI protocols for obtaining rotational invariants of the cumulant expansion (RICE) were paired with constrained weighted linear least squares (CWLLS) to stabilize the more fragile WLLS fit. A compact constraint set was formulated, including a novel mean-dependent upper bound on total diffusional variance. Evaluation used diffusion tensor distribution (DTD) simulations, healthy-volunteer data with a resolution-dependent SNR experiment, and a glioma patient dataset. A 5-minute q-space trajectory imaging (QTI) protocol served as a reference. Results: Across experiments, CWLLS reduced unphysical estimates and fit outliers in parameters such as microscopic FA and isotropic diffusivity variance. In simulations, it narrowed error distributions most clearly in the CSF-dominant case, while some metrics showed a bias-variance trade-off. In vivo, CWLLS removed negative variance estimates, truncated out-of-bounds tails, and reduced artifacts in fluid-contaminated voxels while preserving anatomical contrast. It also retained more stable maps than WLLS at higher resolution, although both estimators degraded in the lowest-SNR setting. Notably, the new mean-dependent variance bound was violated in 15.4% of voxels in the patient dataset, accounting for nearly half of the 32.7% that violated at least one constraint. Healthy-volunteer benchmarking showed that CWLLS completed in under 30 seconds. The constrained QTI fit required 72 minutes, making CWLLS 160 times faster. Conclusion: CWLLS for fast RICE yielded high-quality parameter maps at an online-ready computational cost. This may enhance the reliability of dMRI tissue characterization and strengthen the path toward clinical translation.
Background Timely diagnostic testing is essential for rapid diagnosis of potentially life-threatening conditions, but formal assessment of current trends and geographic variation in diagnostic delays in England is lacking. Methods We assessed recent trends in four imaging and four endoscopy tests in England using public data across 103 sub-Integrated Care Boards from 2019 to 2026. We compared the proportion of patients waiting more than 6 weeks in June 2026 versus June 2025 using mixed-effects binomial logistic regression. Changes in geographic variation (beyond that expected by chance) were quantified using random-effect variances. Local trends were examined using conditional estimates. Results Previous reductions in delays have stalled in the past year, even increasing for gastrointestinal endoscopies and MRI. From June 2025 to June 2026, delays increased for gastroscopy (24% to 29%), colonoscopy (26% to 31%), flexible sigmoidoscopy (28% to 32%), and MRI (15% to 23%). Substantial geographic variation persists, with three- to five-fold differences across the middle 50% of local areas. Local variation has increased significantly for MRI. Local trends diverged markedly, with delays falling by >50% in some areas and doubling in others. Conclusions Policy-makers should prioritise tackling deteriorating waiting times for gastrointestinal endoscopies and MRIs, and identifying local drivers of delays.
🏫 主要单位：Oregon Health and Science University ｜ 主要作者：Mariam Okhovat、Layman, C. E.
早期接触野火烟雾与长期系统性免疫重塑和表观遗传重编程相关。
💡 对公共卫生和儿童健康研究具有重要意义。
Wildfire smoke is an escalating global public health threat exposing millions of people, including children, to hazardous air pollution each year. Although wildfire smoke toxicants have been linked to a range of adverse health outcomes, including immune dysregulation, the long-term consequences of real-world pediatric wildfire smoke exposure on health and development remain largely unknown. To investigate the persistent effects of early-life exposure on immune health, here we leveraged a cohort of rhesus macaques that experienced nine consecutive days of hazardous wildfire smoke exposure in infancy during the 2020 Oregon Labor Day wildfires. By integrating ex vivo immune stimulations, multiplex cytokine profiling, single-cell transcriptomics, and genome-wide DNA methylation profiling, we identified persistent immunological consequences across molecular and functional levels. We found that a single severe postnatal exposure, in the first three months of life, was associated with persistent change in the innate immune response, including reduced pro-inflammatory cytokine response to a bacterial endotoxin, with subtle but consistent transcriptional changes in myeloid cells, particularly among males. Wildfire smoke exposure was also associated with changes in proportion of B and T/NK cells, and within the T/NK cell compartment, exposed animals exhibited an expansion of cytotoxic cells. Consistent with this, CD8+ T cells displayed extensive transcriptional remodeling and shifted toward more differentiated effector states, with the greatest differentiation observed in animals exposed at the youngest ages. Genome-wide DNA methylation profiling identified smoke-associated methylation changes consistent with acceleration of epigenetic aging, as well as persistent epigenetic alterations impacting genes involved in oxidative stress responses, innate immunity, T cell differentiation, and hematopoiesis. These findings demonstrate that a single severe wildfire smoke exposure during a critical developmental window is associated with extensive immune and epigenetic remodeling that persist years after exposure, providing new insight into the long-term biological consequences of early-life wildfire smoke exposure.
🏫 主要单位：Wuhan Institute of Virology ｜ 主要作者：Ke Peng、Fang, y.
发现凋亡caspases通过调节线粒体形态动力学促进抗病毒免疫反应，具有潜在的治疗意义。
💡 该研究揭示了凋亡在抗病毒免疫中的作用，为病毒感染的治疗提供了新的思路。
Apoptosis has been recognized as a suicidal host-defense programmed cell death pathway against invading pathogens. However, recent evidences showed that viruses can employ caspases to cleave and inactivate immune signaling molecules to facilitate infection. Whether caspases can instead promote anti-viral immune responses is currently unknown. Here, we demonstrated that the NSs protein of RVFV triggers activation of apoptotic caspases, which cleave the mitochondrial fission factor DRP1 resulting in mitochondrial elongation. Elongated mitochondria promote MAVS aggregation leading to enhanced anti-viral immunity. Apoptotic caspases, including caspase-3, -6, -7 and -8, cleave DRP1 at the motifs of D500FAD503 and/or AEAD556, suggesting that this cleavage event may occur during infection of different viruses. Indeed, infection of H1N1, SeV and HSV-1 all triggered apoptotic caspases activation to cleave DRP1 promoting anti-viral immune responses. Compared with wild-type DRP1, introduction of caspase-resistant DRP1 strongly attenuated immune responses triggered by virus infection. These results revealed a mechanism through which apoptotic caspases promote anti-viral immunity by regulating mitochondrial morphodynamics.