Null-Space Diffusion Restoration with Adaptive Uncertainty-Guided Fusion for Ultrasound Speckle Reduction

Ultrasound B-mode imaging commonly suffers from speckle noise and artifacts, requiring a delicate balance between contrast, resolution, and preservation of anatomical structures. Although recently developed despeckling methods have achieved some progress, supervised learning approaches remain fundamentally limited by the ground truth paradox, which arises from the absence of noise-free, ground truth reference images in in vivo scenarios. Existing unsupervised diffusion-based methods typically enforce data consistency directly in the nonlinear log-compressed domain, which can disproportionately amplify background artifacts when mapped back to the envelope domain. To overcome these limitations, we propose an uncertainty-guided null-space diffusion (UGNS) framework, a novel label-free solution that enforces consistency correction on a stabilized positive-envelope proxy obtained via inverse log compression. The proposed UGNS introduces several technical novelties: (a) extraction of a structural prior in the stabilized envelope domain to produce a robust signal envelope that preserves anatomical structure, (b) development of an adaptive range-null reconstruction mechanism that uses an adaptive weight mask to preserve tissue regions via range-space projection, and (c) introduction of uncertainty-guided fusion in an adaptive way to mitigate sampling variability. Extensive and comparative experiments were conducted using the PICMUS benchmark and in vivo datasets. The results demonstrate that UGNS achieves competitive generalized contrast-to-noise ratio (gCNR) values across diverse datasets. In addition, it is successfully validated that UGNS effectively suppresses speckle noise while preserving fine spatial resolution. Code is available at https://github.com/yousirong/UGNS.git.

Low-Rank Velocity Fields as a Structural Prior for Unsupervised 4D Medical Image Interpolation

Endpoint-only unsupervised 4D medical image interpolation synthesizes intermediate volumes from sparsely sampled sequences with only the start and end volumes available for training; however, this weakly constrained setting often yields intermediates with unstable boundaries and non-physiological motion, limiting interpretability and downstream analysis. We propose low-rank velocity fields as a structural prior, constraining motion to a structured Tucker low-rank velocity field space that decomposes motion into globally shared spatial bases and a compact sample-specific core, thereby encouraging spatially correlated, anatomy-consistent deformation while suppressing voxel-wise high-frequency artifacts. To capture global coordination and local non-rigid details, we model motion in a coarse-to-fine multi-scale scheme and compose scale-wise deformations at inference to synthesize volumes at arbitrary times. We further provide a theoretical analysis showing that, under Tucker parameterization, low-rank parameters control the smoothness energy of the velocity field, explaining why low-rank modeling promotes smoother motion. Experiments on ACDC and 4D-Lung demonstrate state-of-the-art performance, remaining competitive with methods trained with intermediate-frame supervision, and producing intermediates with improved structural coherence and more stable anatomical contours.

Primitive Representation Learning for Unsupervised Dynamic Contrast Enhanced MRI Reconstruction

Reliable quantitative analysis of dynamic contrast-enhanced MRI requires high-quality spatiotemporal reconstructions at high undersampling rates. Scan-specific reconstructions using Gaussian and Gabor primitives have shown promising results without the need for large training datasets, but have not addressed the additional dimension of dynamic contrast. We propose a multi-dimensional, primitive based framework for dynamic contrast-enhanced MRI reconstruction that disentangles the underlying anatomy, the dynamic contrast enhancement, and residual motion into separate temporal basis functions, thereby enabling a geometrical interpretation of the representation. We show that this architecture achieves performance competitive with conventional reconstruction methods, both in reconstruction quality and in the accuracy of extracted aorta and kidney enhancement curves. The modular tier design extends naturally to additional dynamic factors and higher acceleration rates. Code available at https://github.com/compai-lab/ 2026-GaborDCE-spieker.

Unsupervised Learning of Cell Instances with Generative Routing Pyramids

Identifying and representing object instances such as cells or nuclei is a common task in microscopy image analysis. Established machine learning workflows typically use supervised detection or segmentation followed by feature extraction or classification, which requires manual annotations and treats instance segmentation and cell representation as separate stages. We describe a new unsupervised method for cell instance segmentation and phenotypic classification from unlabeled microscopy images. Our method is based on reconstructing each image using a coarse-to-fine routing pyramid that associates pixels with spatially sparse latent sources. The resulting pixel-to-latent associations yield instance masks, while the source latents encode cell morphology. We demonstrate competitive performance in instance segmentation across diverse cell morphologies and imaging modalities, as well as generative modeling of cellular phenotypes under perturbations. Source code and checkpoints are available at https://github.com/weigertlab/routing-pyramids.

Reconstruction-Shift Discrimination via Mask-Guided Latent Diffusion for Medical Anomaly Detection

Unsupervised medical anomaly detection learns normal anatomical patterns from healthy training images and identifies deviations at test time. Reconstruction-based and diffusion-based methods commonly use the difference between an input image and its reconstruction as anomaly evidence. However, this residual can be ambiguous. Expressive models may preserve pathological structures, while benign anatomical variation, imaging noise, and acquisition differences may also produce large reconstruction errors. We propose discriminative mask-guided diffusion (DMD), a medical anomaly detection framework that complements residual-based localization with reconstruction-shift discrimination. DMD first learns a compact quantized latent representation of normal images. Localized masks then perturb selected latent regions, and a latent diffusion model reconstructs the perturbed representations. The resulting reconstructions are paired with their original normal images to define a self-supervised classification task. At inference, the classifier provides a learned image-level anomaly score, while the residual between the input and its diffusion-based reconstruction yields a pixel-level anomaly map. Experiments on five datasets spanning brain MRI, breast ultrasound, and chest radiography show that DMD achieves the best overall performance among the state-of-the-art baseline methods.

Panda: Unsupervised Pelvic Anomaly Detection for Real-Time MR Imaging

Female pelvic diseases remain an under researched area characterized by often delayed diagnosis. While pelvic MRI offers superior soft-tissue contrast for diagnosis and image-guided procedures, real-time anomaly detection remains challenging due to physiological motion, tissue deformation, and instrument artifacts. Existing supervised approaches are impractical, as adverse events are rare, heterogeneous, and difficult to annotate. We present a Dinomaly-based unsupervised anomaly detection framework adapted for pelvic MRI that learns normative representations from healthy cases and flags deviations without requiring labels. Our approach leverages a frozen DINOv3 Vision Transformer encoder combined with a noisy MLP bottleneck and Linear Attention decoder to prevent identity mapping while maintaining computational efficiency. Anomalies are localized via per-token cosine distance between encoder and decoder representations, yielding spatial anomaly maps that provide immediate feedback at the scanner to support radiologist decision-making and adaptive protocol adjustment. Evaluated on a curated subset of the Uterine Myoma Dataset, the framework achieves a pixel-level AUROC of 88.06% and high specificity (95.45%) at frame level at 40.5 slices/s, meeting real-time clinical deployment requirements. The spatial anomaly maps and frame-level scores provide immediate, localized feedback at the scanner to support radiologist decision-making and adaptive protocol adjustment during active procedures.

A novel unsupervised machine learning strategy to handle multimodal cardiac PET/MRI data

Arrhythmogenic left ventricular cardiomyopathy is a genetic myocardial disease difficult to diagnose due to the lack of gold standard criteria. Simultaneous PET/MR imaging, combined with multiparametric quantitative analysis, could facilitate the identification of different profiles related to the phenotype and progression of cardiomyopathy. This preliminary study focuses on a methodological strategy for dealing with PET/MRI data, including inter-patient data linkage and regional analysis. Two-step clustering was applied to T1 and T2 maps, LGE, and 18F-FDG-PET images of 99 patients genetically diagnosed with arrhythmogenic left ventricular cardiomyopathy. Each patient's images were independently z-scored and summed into a single volume, which was clustered into supervoxels. Thirty-two inter-patient groups of supervoxels were obtained by spectral clustering. An "abnormality" score was assigned to each cluster and modality, and used to visualise abnormal regions likely associated with disease. They enabled the generation of automated textual and bullseye health reports for each patient, which were compared with cardiac imager assessments using balanced accuracy in repeated nested cross-validation. This approach was further validated on a larger cohort of 167 numerical phantoms. The reports generated by clustering accurately identified most of the cardiac physicians' observations (BA = 0.76 $\pm$ 0.04 in repeated nested cross-validation on patients, and BA $\ge$ 0.8 on phantoms). Furthermore, the identified abnormal clusters closely matched their visual observations, facilitating the identification of varying degrees of fibrosis or inflammation on the images. This approach enables a more systematic handling of multimodal PET/MRI data to characterise myocardial heterogeneity in arrhythmogenic left ventricular cardiomyopathy patients.

Enhancing Implicit Neural Representations with Image Feature Embedding for Unsupervised Cardiac Cine MRI Reconstruction

Cardiac cine Magnetic Resonance Imaging (MRI) is a critical diagnostic tool that provides dynamic insights for radiologists. To accelerate acquisition, under-sampled k-space data is often used, requiring reconstruction methods that combine coil sensitivity encoding with prior information to recover missing data. Deep learning approaches have gained more attention for leveraging data-adaptive priors. While supervised learning approaches are a common choice, they depend on fully sampled reference data, which is not always available. Unsupervised methods eliminate the need for fully sampled reference data, which can be advantageous in cardiac cine MRI reconstruction. Among them, implicit neural representations (INRs) have shown great potential due to their simple architecture and good quality reconstructions. In this work, we propose an image-domain dual-branch INR framework, termed I-FP-INR, which extends the original INR design by introducing an additional feature-processing branch. This design aims to extract complementary feature embeddings to enhance the overall representation, thereby benefiting reconstruction. Extensive evaluations on both public datasets and in-house data show consistent improvements over baseline methods in reconstruction quality, with strong robustness across varied scenarios.

Unsupervised Susceptibility Distortion Correction of EPI without Calibration Scans via Image Translation-Based Registration

Functional magnetic resonance imaging (fMRI) utilizes echo-planar imaging (EPI) to capture blood-oxygen-level-dependent (BOLD) signals with high temporal resolution. However, EPI is inherently sensitive to magnetic field inhomogeneities, resulting in susceptibility-induced geometric distortions along the phase-encoding (PE) direction. To correct these distortions, conventional approaches rely on additional calibration scans, such as field maps or reverse PE acquisitions, which are not always available in practice. To overcome this limitation, we propose SACRED, a calibration scan-free susceptibility distortion correction framework that corrects geometric distortions via image translation-based registration using only a routinely acquired anatomical T1-weighted (T1w) image and a unidirectional PE BOLD image. SACRED employs an invertible neural network as the image translation backbone to bridge the contrast gap between BOLD and T1w images while enforcing structural consistency through a modality independent neighborhood descriptor. This design enables the use of a mono-contrast similarity objective to train the registration network in an unsupervised manner without requiring distortion-corrected BOLD images. In addition, we incorporate test-time adaptation (TTA) to further enhance performance on out-of-distribution (OOD) data at inference time. SACRED was evaluated on one in-distribution (ID) dataset and two OOD datasets, and was compared with representative fMRI distortion correction methods. The results demonstrate that SACRED significantly outperforms competing methods on both ID and OOD datasets, exhibiting robustness to scanner and population shifts, partly enabled by TTA. The code will be made publicly available upon acceptance.

Memory-Augmented LSTM Autoencoder for Unsupervised Activity Recognition with IMU Sensor Fusion

HAR using Inertial Measurement Unit (IMU) sensors is vital for healthcare monitoring and rehabilitation. Despite deep learning advancements, major challenges remain: reliance on labeled data, multi-sensor fusion complexity, and the limited ability of unsupervised methods to capture spatiotemporal dependencies. These issues are pronounced in real-world scenarios with noisy data, overlapping activities, and missing labels. We propose a fully unsupervised spatiotemporal feature fusion framework using a memory-augmented autoencoder. It enhances activity representations via short temporal windows of multi-sensor IMU data, enabling real-time applications. Our framework extracts hierarchical static features via a Stacked Autoencoder, fusing them within and across sensors. A sequence-to-sequence LSTM Autoencoder then temporally refines these features, incorporating historical motion patterns without labels. We analyze key hyperparameters to identify configurations that maximize feature separability under short-window constraints. Evaluated on DaLiAc and PAMAP2 using realistic inter-class window segmentation, our method achieves 96.6% and 98.4% accuracy, respectively, surpassing supervised baselines and unsupervised approaches. Our method improves feature separability by up to 9% despite shorter temporal windows. While our realistic inter-class segmentation reduces accuracy by ~7%, it was intentionally adopted to better reflect real-world activity transitions and practical relevance.

On-Manifold Variational Learning with Heat-Kernel Priors

Learning unsupervised representations of medical imaging cohorts can reveal clinically meaningful prototypes without expert labels, which are often noisy and fail to capture true pathological heterogeneity. However, existing deep latent-variable models estimate Gaussian mixture priors via Euclidean averaging, producing prototypes that drift off the curved data manifold and degenerate as the number of sub-populations grows. We propose a manifold-anchored variational framework built on a geometry-aware Expectation-Maximization (EM) algorithm, whose M-step selects each sub-population prototype as the graph medoid with the highest diffusion centrality on a heat-kernel-weighted latent graph, ensuring that every prototype remains on-manifold. A Dirichlet energy regularizer enforces geometric smoothness of the latent space, and a per-sub-population uncertainty score enables label-free quality assessment. \rev{The manifold-anchored EM is a general-purpose geometric tool that extends standard EM and applies readily to other latent-variable models beyond this setting.} On cardiac scar and brain MRI benchmarks, our framework attains the highest accuracy among all compared methods, produces the sharpest prototypes reported to date, and remains stable at large sub-population counts where all baselines degenerate.

Towards a Pseudo-Labeling Workflow for Celltype-Classification from Explanted Brain Slice Recordings

This paper proposes an unsupervised workflow to pseudo-label extracellular spikes from human brain slice MEA recordings into two putative cell types: pyramidal cells and interneurons. Here, the raw data from the data acquisition system is used and processed. The pipeline for pre-processing includes bandpass filtering, threshold--based spike detection, frame alignment and normalization. In the ML workflow, dimensionality reduction (PCA, t-SNE, UMAP), clustering (GMM, k-means). To achieve an online system, template matching and OSort under varying curation strictness is also considered. All pipelines are evaluated by different cluster quality with within-cluster Pearson correlation, Silhouette score, and Calinski-Harabasz index. Applying stricter curation improves separation at some cost to inclusivity.

AUCp: Pseudo-AUC for Inference Model Selection with Unlabeled Validation Data in Abnormality Detection

Abnormality detection is a crucial yet challenging task in medical image analysis. Distinguishing abnormalities from normal data by learning to reconstruct normal-only data alleviates the reliance on labeled datasets. However, many studies, even if unsupervised, rely on a labeled validation set to select the best model for inference from multiple training iterations. For many diseases labeled data are unavailable and substantially time consuming to obtain. To address this, AUCp - a novel metric that supports abnormality detection for unsupervised and self-supervised methods is proposed. Instead of evaluating the realism of reconstructed images to select the best of model for inference, it focuses on actual detection performance and without requiring an annotated test set. Assuming the pseudo ground truth of all unannotated samples in the test set as abnormal/positive and using traditional AUC calculation, AUCp scores are derived. Given a large and representative training set of normal samples, we show mathematical and empirical evidence that model selection using AUCp scores improves disease detection in terms of unsupervised and self-supervised methods over conventional metrics. Using two unsupervised methods for neurologic disease detection and self-supervised methods on diverse datasets, our results demonstrate that the AUCp score effectively identifies the optimal model for inference, significantly enhancing abnormality and disease detection. The corresponding implementations are available in https://github.com/mahfuzmohammad/AUCp.

Unsupervised Pattern Analysis in Japanese Veterinary Toxicology: A Regulatory-Compliant Framework for Cross-Species Risk Assessment

Veterinary pharmacovigilance systems are essential for monitoring adverse drug events (ADEs), yet existing approaches often fail to capture region-specific toxicity patterns shaped by local biological and regulatory contexts. In Japan, these challenges are amplified by species-specific metabolic differences and reporting practices defined by the Ministry of Agriculture, Forestry, and Fisheries (MAFF). Most prior work relies on prediction-oriented models, limiting mechanistic interpretability. This study proposes a regulatory-integrated unsupervised framework for pattern discovery using the National Veterinary Assay Laboratory (NVAL) database. ADEs are encoded into organ system-aligned representations and adjusted for species-specific reporting biases, enabling cross-species comparison. Similarity-based clustering and dimensionality reduction are applied to identify latent toxicity structures. Analysis of 4,120 high-confidence ADE reports (9,080 drug-ADE combinations) identified three significant species clusters (p < 0.01), including hepatic-dominant patterns in companion animals (0.42 $\pm$ 0.06), renal toxicity in ruminants (0.39 $\pm$ 0.07), and dermatological sensitivity in sheep (0.35 $\pm$ 0.07). Drug-level clustering achieved 83% alignment with pharmacological classes, while cosine similarity outperformed alternative metrics (silhouette score: 0.48; cluster precision: 87%). Regulatory validation showed strong agreement with established classifications. These findings demonstrate that regulation-aligned unsupervised analysis can uncover biologically meaningful, region-specific toxicity patterns, providing an interpretable and scalable framework for veterinary drug safety assessment.

Local-sensitive connectivity filter (ls-cf): A post-processing unsupervised improvement of the frangi, hessian and vesselness filters for multimodal vessel segmentation

A retinal vessel analysis is a procedure that can be used as an assessment of risks to the eye. This work proposes an unsupervised multimodal approach that improves the response of the Frangi filter, enabling automatic vessel segmentation. We propose a filter that computes pixel-level vessel continuity while introducing a local tolerance heuristic to fill in vessel discontinuities produced by the Frangi response. This proposal, called the local-sensitive connectivity filter (LS-CF), is compared against a naive connectivity filter to the baseline thresholded Frangi filter response and to the naive connectivity filter response in combination with the morphological closing and to the current approaches in the literature. The proposal was able to achieve competitive results in a variety of multimodal datasets. It was robust enough to outperform all the state-of-the-art approaches in the literature for the OSIRIX angiographic dataset in terms of accuracy and 4 out of 5 works in the case of the IOSTAR dataset while also outperforming several works in the case of the DRIVE and STARE datasets and 6 out of 10 in the CHASE-DB dataset. For the CHASE-DB, it also outperformed all the state-of-the-art unsupervised methods.