Microscopy

We propose a novel computational toolbox that integrates Topological Data Analysis (TDA), Differential Box Counting (DBC), Multifractal Partition (MFP), and Local Binary Patterns (LBP), applied to time-lapse super-resolution STED microscopy images of sodium caseinate gelation induced by glucono-delta-lactone (GDL) at 30 °C and 40 °C and two GDL concentrations (1.8% and 3.5% w/v). TDA tracked topological loops, closed ring-like structures reflecting protein network interconnectivity, via max-Betti-1 curves, which revealed a lag phase of dispersed aggregates, a sharp decay coinciding with network percolation and the rheologically observed sol-gel transition, and a post-gelation increase corresponding to network rearrangements. These topological transitions were corroborated by DBC and MFP as these methods were able to resolve changes in structural complexity and spatial heterogeneity. The toolbox was validated on simulated fractal images prior to experimental application. Together, these descriptors provided sensitivity to subtle microstructural transitions that bulk rheology captured as averaged bulk mechanical responses. This integrated approach provides a robust quantitative tool for characterizing complex microstructure in food and material science with evolving microstructural dynamics. Code is available at https://github.com/Zahratabatabaei/Delifood_CV_paper.git

Multiplexed fluorescence microscopy improves tissue segmentation by providing complementary channels including nuclear (DAPI) and membrane (E-cadherin), that together encode richer spatial context than single-channel imaging alone. However, multiplexed models require all channels at inference, limiting deployment where only a subset is available. This work proposes a cross-modal knowledge distillation framework that transfers semantic information from a frozen foundation model teacher processing multiplexed input to a lightweight student operating on the nuclear channel only. The distillation objective combines MSE-based probability matching, boundary-aware supervision, and learnable uncertainty weighting. SAM ViT-H and CellSAM are evaluated as teachers across four U-Net students: Swin-Tiny (27M), ResNet18 (11M), EfficientNet-B0 (5.3M), and MobileNetV3 (1.5M), on TissueNet and BBBC038. On TissueNet, the SAM-distilled Swin-Tiny student achieves Dice 78.36 (plus or minus 1.44), a 13.05-point improvement over the no-KD baseline (65.31 plus or minus 1.35) and 87.9% recovery of teacher oracle performance (89.12 plus or minus 1.21) at a 23x parameter reduction. KD consistently improves all four students by approximately 12 Dice points, confirming architecture-agnostic distillation. SAM ViT-H outperforms CellSAM as teacher across all settings. Cross-dataset evaluation on BBBC038 shows consistent gains without teacher retraining.

This work presents MLLM-Microscope, a novel system designed for analyzing the hidden representations within Multimodal Large Language Models (MLLMs). Our system evaluates the linearity, intrinsic dimension, and anisotropy of multimodal token embeddings across transformer layers. Utilizing the ScienceQA dataset, we evaluate two state-of-the-art MLLMs, LLaVA-NeXT and OmniFusion. We find that both the main and residual streams for tokens of both modalities exhibit highly linear behaviors across transformer layers. However, LLaVA-NeXT's image tokens reveal a slight decline in linearity, whereas OmniFusion's remain consistent. Image token dimensions in OmniFusion remain consistently higher across layers compared to LLaVA-NeXT. Also, the OmniFusion's anisotropy is observed to stay consistently low throughout the layers. These findings suggest that the inner workings of MLLMs highly depend on the nature of modality fusion performed before passing the token sequence into LLM. This and other new potential insights obtainable from our system are surely capable of enhancing our understanding of the inner workings of MLLMs, informing future model design and optimization.

Image Scanning Microscopy (ISM) is a fluorescence imaging technique that combines detector-array acquisition and computational reconstruction to achieve the theoretical resolution of an ideal confocal microscope, i.e., one operating with an infinitesimally small pinhole, while maintaining high signal-to-noise ratio. Among the reconstruction methods for obtaining the super-resolved image, multi-image deconvolution (MID) and its extension aimed at preserving the optical sectioning capability of confocal microscopy, known as super-resolution sectioning ISM (s$^2$ISM), are among the most widely used approaches. Both methods rely on Richardson--Lucy-type iterative schemes, whose semi-convergent behavior requires early stopping and often leads to noise amplification and reconstruction artifacts. In this work, we introduce a self-tuning explicit regularization framework for both MID and s$^2$ISM reconstruction. Within a Bayesian maximum a posteriori formulation, we combine a multi-frame Poisson data fidelity term with explicit regularization, considering $\ell_1$ and smoothed total variation penalties as representative examples. We further develop an automatic and ground-truth-free strategy for regularization parameter selection by adapting the residual whiteness principle to the multi-frame Poisson setting and introducing a spectral high-pass extension tailored to s$^2$ISM. The resulting framework enables stable reconstructions without empirical stopping rules. To demonstrate the proposed framework, we consider first-order optimization schemes based on proximal gradient and mirror descent methods with adaptive backtracking strategies. Experiments on simulated and real fluorescence ISM datasets demonstrate improved reconstruction stability and image quality with respect to unregularized approaches, while enabling robust super-resolution and optical sectioning in low-photon conditions.

The morphological analysis of mitochondria in fluorescence microscopy (FM) is crucial for understanding cellular health, energy production, and metabolic regulation. While foundation models like the Segment Anything Model (SAM) have revolutionized natural image segmentation, their direct application to FM is hindered by a significant domain shift characterized by diffraction-limited resolution, low contrast, and complex overlapping organelle networks. Furthermore, the development of robust models is bottlenecked by a severe lack of high-quality, manually annotated instance segmentation datasets for mitochondria. In this paper, we propose a scalable solution to this data scarcity by finetuning SAM exclusively on synthetically generated FM data. We simulate realistic mitochondria data and emulate the optical properties of fluorescence microscopes to create a large-scale annotated dataset. We evaluate our fine-tuned model on a curated dataset of real, manually annotated FM images. Qualitative and quantitative analyses demonstrate that our synthetically fine-tuned model improves precision and average dice score over strong baselines. This work establishes the potential of simulation-assisted training for FM instance segmentation.

Object counting remains fragmented across domain-specific datasets and task formulations, despite rapid progress in generalist vision models. Existing counting models are often tailored to scenarios such as crowds, vehicles, cells, crops, or remote-sensing objects, and thus struggle to generalize across categories, visual domains, object scales, and density distributions. In this paper, we study text-guided object counting across domains, where a model takes an image and a natural-language query as input and returns an instance-grounded set of target points whose cardinality gives the count. This formulation unifies category-conditioned counting with interpretable spatial localization. To support this setting, we construct CLOC, a Cross-domain Large-scale Object Counting dataset that reorganizes diverse public data sources into a unified benchmark. CLOC covers six visual domains: General Scene, Remote Sensing, Histopathology, Cellular Microscopy, Agriculture, and Microbiology, with about 220K images, 619 categories, and 15M object instances. Based on CLOC, we propose Count Anything, a generalist model for text-guided object counting. Unlike density-map-based methods, which dominate counting models, Count Anything adopts discrete instance points and performs dual-granularity instance enumeration. A Region-level Sparse Counter provides object-level anchors for large and sparse targets, while a Pixel-level Dense Counter handles small, crowded, and weakly bounded targets via dense point prediction. A point-centric supervision strategy enables learning from heterogeneous annotations, and Complementary Count Fusion combines both counters in a parameter-free manner. Extensive experiments show that Count Anything achieves strong accuracy and multi-domain generalization, outperforming existing open-world counting methods. Code is available at: https://github.com/Mengqi-Lei/count-anything.

Tracking the dynamics of non-canonical biological systems in microscopy videos remains a persistent challenge. Both classical and learning-based trackers depend on expert-reviewed data to be evaluated and adapted, yet exhaustive manual annotation rarely scales to the videos where these tools are needed most. We developed RIPPLE (Refinement Interpolation Platform for Point Location Estimation), which recasts annotation as sparse correction: a user clicks a starting point, RIPPLE proposes a full trajectory, and the user intervenes only where the trajectory drifts. We tested RIPPLE on five challenging microscopy datasets from our laboratories, four from the transparent jellyfish Clytia hemisphaerica and one tracking landmarks on rapidly moving sperm. Across these, RIPPLE matched the quality of exhaustive manual annotation while reducing manual clicks by 3 to 25 times across datasets. RIPPLE thereby fills a missing layer between manual annotation and fully automated tracking, enabling immediate quantification of biological dynamics, method benchmarking, and the production of the gold-standard data needed to adapt future automated microscopy trackers.

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

Existing score-based methods for inverse problems often resort to approximate minimization of the KL divergence between the inversion distribution and the Bayesian posterior. Such an approximation leads to severe mode collapse and unreliable uncertainty quantification. In this paper, we propose Principled Posterior Matching (PPM), a framework that returns to the fundamentals of variational inference, rather than using tricky approximations. Instead of relying on heuristic approximations, we rigorously formulate the exact optimization of the KL divergence via the integration of Fisher divergence. We derive a tractable, equivalent gradient form of this integral, enabling precise optimization without the biases introduced by prior approximations. Our analysis clearly reveals that the mode collapse in previous methods stems directly from this approximation gap. Supported by our theoretical solution, PPM unifies two complementary paradigms: (1) In variational inference, PPM adopts mass-covering divergences that significantly improve the inversion diversity and uncertainty quantification; (2) In amortized inference, it enables the training of an efficient reconstruction network for rapid, single-step reconstruction. Furthermore, our formulation naturally extends to a broader family of divergence measures by generalizing the integral of the Fisher divergence. We validate PPM across challenging computational imaging tasks, including inpainting, super-resolution fluorescent microscopy, and radio interferometric black-hole imaging. In all experiments, PPM achieves superior reconstruction fidelity, faithful multimodal posterior recovery, and well-calibrated uncertainty estimates, establishing a robust framework for scientific imaging.

Light-field microscopy (LFM) enables single-shot capture of multi-angular information from biological samples, supporting real-time volumetric imaging. However, traditional physics-based algorithms often suffer from limited spatial resolution, severe artifacts, and high computational costs. Existing learning-based methods improve inference efficiency but still face limitations in reconstruction accuracy and generalization capability. To address these challenges, this paper proposes a high-fidelity Three-Step Conditional Diffusion (TCD) 3D reconstruction method for LFM. Although conventional diffusion models have achieved remarkable success in generative modeling, their slow sampling process and the inherent trade-off between quality and efficiency hinder their application in real-time 3D imaging. We redesign the diffusion process through a deterministic three-step sampling strategy coupled with a lightweight conditional U-Net, establishing a new paradigm for fast and accurate volumetric reconstruction. Furthermore, an Inter-Class Detection (ICD) module is incorporated to identify out-of-distribution or anomalous inputs during inference, thereby enhancing model stability and reliability. Extensive experiments and cross-dataset evaluations demonstrate that TCD significantly outperforms state-of-the-art methods in both reconstruction fidelity and generalization, providing an efficient and practical 3D reconstruction solution for light-field microscopy.

Self-driving laboratories or autonomous experimentation are emerging as transformative platforms for accelerating scientific discovery. Bayesian optimization (BO) is among the most widely used machine learning frameworks for these purposes, but these BO-based frameworks rely on predefined scalar descriptors to guide experimentation. In many situations, the determination of an appropriate scalar descriptor can be challenging, and may fail to capture subtle yet scientifically important phenomena apparent to experts with interdisciplinary insight. To overcome this limitation, here we develop deep-kernel pairwise learning (DKPL), an approach for autonomous microscopy experiments which incorporates human expertise and interdisciplinary scientific knowledge into an active learning loop. Instead of relying on explicit scalar objectives, DKPL enables experts to directly evaluate which experimental output is more promising using interdisciplinary knowledge. DKPL then learns a latent utility function from these expert judgements to guide subsequent autonomous microscopy experiments. We demonstrate DKPL's performance in learning physically meaningful nanoscale structures while effectively prioritizing high-information measurement regions using an experimental model dataset with known ground truth. We further apply DKPL to analyze the character of ferroelectric domain walls, where we find DKPL capable of distinguishing between high and low characteristic domain-wall angles in bismuth ferrite, and able to discover both head-to-head and tail-to-tail domain-wall character in erbium manganite. This development establishes an approach to integrate expert knowledge into autonomous microscopy experiments and demonstrates a pathway toward expert-guided self-driving laboratories capable of addressing scientific problems beyond the limits of scalar-metrics-driven learning.

Deep-learning pipelines for microscopy image classification often require expensive, labor- and time-intensive expert annotation to produce high-quality ground truth for training. Recent work has shown that prompt tuning of vision-language models (VLMs) can reduce manual annotation by constructing a small prompt set of expert-verified image-caption exemplars that is reused as few-shot context to classify all remaining images at inference time. To further reduce effort, the VLM can draft captions for candidate exemplars, which experts then verify and lightly edit instead of writing text de novo. However, two practical questions remain unaddressed: (1) which unlabeled images should be prioritized for verification, and (2) how many verified exemplars are needed to reach a performance target. In this work, we address these questions by formulating prompt-set construction as a target-driven active learning problem that prioritizes which images to annotate. We study three complementary selection criteria under strict low-resource constraints with small unlabeled pools. Experiments show that our methods reach the target performance with substantially fewer expert-verified images than random selection, achieving 100% test accuracy with as few as 20 annotated images on average. More broadly, our human-in-the-loop framework demonstrates a human-centered use of generative AI in biomedical image analysis, where experts remain actively involved in verifying and refining model output while significantly reducing annotation cost. Code and data will be publicly available.

Microscopy images contain rich information about how cells respond to perturbations, making them essential to applications like drug screening. To quantify images, researchers often use representation extraction methods, and recent years have seen a proliferation of deep learning methods. While measuring the quality of these representations is essential, evaluation remains fragmented, with each proposed model evaluated on different tasks and datasets, using custom pipelines and metrics, making it difficult to fairly compare models. Here, we introduce MorphoHELM, a comprehensive open benchmark for evaluating feature extraction methods for Cell Painting, the most widely-used morphological profiling assay. MorphoHELM consolidates evaluation standards in the field, extends and corrects them to be more robust, and evaluates on the widest range of methods to date. A defining feature of the benchmark is that each task is evaluated at different degrees of batch effects (or technical noise), directly quantifying how the ability of methods to detect biological signal degrades as noise increases. Together, these properties enable MorphoHELM to detect trade-offs between methods, and we demonstrate that models that excel at certain kinds of biological signal are weaker at others. We show that no existing model outperforms classic computer vision analytic strategies across all settings, which remain the strongest general use-case representations. All datasets, code, and evaluation tools are publicly available at https://github.com/microsoft/MorphoHELM.

Analyzing microscopy images to extract biological object properties (e.g., their morphological organization, temporal dynamics, and population density) is fundamental to various biomedical research. Yet conducting this manually is costly and time-consuming. Though deep learning-based approaches have been explored to automate this process, the substantial diversity of microscopy analysis settings in practice (including variations of biological object types, sample processing protocols, imaging equipment, and analysis tasks, etc.) often renders them ineffective. As a result, these approaches typically require extensive adaptation for different settings, which, however, can impose burdens that are often practically unsustainable for laboratories, forcing biomedical researchers to still commonly rely on manual analysis, thereby severely bottlenecking the pace of biomedical research progress. This situation has created a pressing and long-standing need for a reliable and broadly applicable microscopy image analysis tool, yet such a tool is still missing. To address this gap, we present the first ready-to-use microscopy image analysis framework, MicroscopyMatching, that can reliably perform key analysis tasks (including segmentation, tracking, and counting) across diverse microscopy analysis settings. From a fundamentally different perspective, MicroscopyMatching reformulates diverse microscopy image analysis tasks as a unified matching problem, effectively handling this problem by exploiting the robust matching capability from pre-trained latent diffusion models.

Extended depth of field microscopy encodes axial information into a single acquisition through engineered point spread functions, but conventional and deep optics approaches are subject to degradation in scattering tissue. We introduce DeepFilters, a scattering-aware deep optics framework that jointly optimizes a parameterized pupil filter and a digital-filter-based reconstruction network through a calibrated differentiable forward model to achieve broad generalization without retraining. Incorporating empirical scattering kernels, physics-guided regularization, and a hybrid genetic-gradient initialization strategy, DeepFilters extends the PSF from 16 micron to >400 micron in clear media and enables signal recovery beyond 120 micron deep in biological tissues, validated across fixed brain slices and sea urchin embryos.

Synapses are densely packed submicron structures that dynamically reorganize during learning and memory formation. Longitudinal \textit{in vivo} imaging of fluorescently tagged synaptic receptors offers a promising opportunity to study large-scale synaptic dynamics and how these processes are disrupted in neurological disease. However, in vivo imaging with 2-photon microscopy uses low laser power and therefore suffers from low signal-to-noise ratio (SNR) and high shot noise, nonlinear tissue motion between days, nonstationary fluctuations in synaptic fluorescence, and significant blur induced by the microscope point spread function (PSF). Together, these factors make it challenging to detect and track synapses, especially in regions with high synaptic density. This paper presents a novel template-based framework for modeling synapses as varying luminance point sources that move under a nonlinear tissue deformation. Taking a unified Bayesian approach, we apply this model to microscopy data by deriving a posterior that incorporates a diffeomorphic mapping for domain warping, a Gaussian point spread function for the imaging process, and a Poisson observation model for raw photon counts. The Bayesian solution simultaneously: (1) Constructs a probabilistic template of synapse locations, (2) denoises and deconvolves the image data, (3) infers fluorescence intensities, (4) performs diffeomorphic image registration to correct for tissue motion, and (5) provides confidence regions for these parameter estimates. We demonstrate the framework on both a 2D+t simulated dataset and a 3D+t longitudinal \textit{in vivo} microscopy dataset of fluorescent synapses imaged in a mouse over two weeks.

Chemical imaging enables label-free visualization of cells, tissues and living systems while providing direct biochemical information that is difficult to obtain with conventional fluorescence microscopy. Despite its promise in applications ranging from intraoperative diagnosis to drug-response analysis, its broader use remains limited by slow data acquisition, particularly for three-dimensional imaging. Here we present MicroDiffuse3D, a pretrained foundation model for 3D microscopy image restoration that recovers high-quality volumetric structure from degraded low-resolution measurements acquired at substantially higher throughput. We evaluated MicroDiffuse3D across three challenging restoration settings, including 3D super-resolution under 16-fold volumetric sparsity, joint degradation in resolution and noise, and 3D denoising in the low signal-to-noise ratio (SNR) regime, where the model delivered clear gains over strong baselines. Under the sparse 3D super-resolution setting, MicroDiffuse3D produced clearer continuity across depth with fewer artifacts and improved segmentation quality by 10.58% and line-profile concordance by 15.59%. Together, our results establish pretrained 3D restoration as a broadly applicable strategy for overcoming the throughput and SNR limitations in volumetric chemical imaging, enabling high-resolution analysis at scales and speeds that were previously difficult to achieve.

Autonomous experimentation has transformed microscopy and materials discovery by enabling closed-loop optimization including imaging and spectroscopy tuning, strucutre property relationship discovery, and exploration of combinatorial libraries. However, most current workflows remain limited to selecting measurements within fixed objective or hypothesis spaces, rather than generating new physical models from experimental data. Here, we introduce an open hypothesis-learning framework that combines symbolic regression with large-language-model-based physical evaluation and implement it for autonomous scanning probe microscopy. Symbolic regression generates candidate analytical relationships directly from sparse measurements, while the language-model evaluator ranks these candidates according to physical plausibility, scaling behavior, and consistency with known mechanisms. We demonstrate the approach on autonomous piezoresponse force microscopy measurements of ferroelectric domain switching in a PZT thin film. Starting from five seed measurements, the workflow evolves from physically incomplete candidate expressions toward interpretable voltage-time growth laws consistent with kinetic domain-wall motion. This work extends autonomous microscopy from closed-loop optimization toward open hypothesis discovery, where candidate physical laws emerge from the experiment itself rather than being specified in advance. More broadly, the framework establishes a route for integrating symbolic regression, physical reasoning, and adaptive experimentation into hierarchical autonomous scientific workflows.

Fluorescent protein quantum yield (QY) is governed by the mature chromophore and its three-dimensional microenvironment rather than sequence identity alone. Protein language models and emission-band averages capture global trends, but do not model how local physical signals act on specific chromophore regions. We present a chromophore-centred mechanism graph algorithm for QY prediction. Each PDB structure is converted into a typed 3D residue graph, registered to a mature-CRO state, partitioned into phenolate, bridge and imidazolinone regions, and transformed by channel-signal-region propagation. The representation contains 121 enrichment features; after removing identity shortcuts, 52 non-identity features are used for band-specific ExtraTrees regression. Because each feature encodes a contact channel, seed signal and target CRO region, interpretation is intrinsic rather than post hoc. On a 531-protein benchmark, the method achieved the best random-CV performance among model-based baselines (R = 0.772 +/- 0.008, MAE = 0.131 +/- 0.002), exceeding Band mean (R = 0.632), ESM-C (R = 0.734) and SaProt (R = 0.731), and ranked first in bright screening (Bright P@5 = 0.704). Under homology control, the advantage was clearest in the remote bucket (<50% similarity; R = 0.697 versus 0.633, 0.575 and 0.408), with the strongest overall bright/dark Top-K screening. Stable selected features recovered band-specific mechanisms: aromatic packing and clamp asymmetry in GFP-like proteins, charge/clamp balance in Red proteins, and flexibility-risk/bulky-contact features in Far-red proteins. Source code, feature tables and evaluation scripts are available from the first author upon request. Contact: yuchenak05@gmail.com

Understanding the neural mechanisms underlying visual computation has long been a central challenge in neuroscience. Recent alignment based approaches have improved the accuracy of decoding visual stimuli from brain activity, yet they provide limited insight into the neural computations that give rise to these improvements. To address this gap, we propose Dual-Tower Image-Neural Alignment (DINA), an interpretable contrastive framework for analyzing population level visual computations in primary visual cortex (V1). DINA jointly trains a biologically motivated dual-tower architecture that aligns visual stimuli and corresponding V1 population responses in a shared latent space at the level of intermediate feature maps, enabling both accurate decoding and direct access to interpretable feature maps. Evaluated on large-scale two-photon calcium imaging data from mouse V1, DINA achieves accurate neural-based decoding while revealing that decoding performance is primarily supported by coarse, low-level visual structure, rather than semantic category information or fine-grained details. Further analysis reveals that alignable feature maps emerge from multiple spatially distributed image regions, capturing both shape and texture cues, and are predominantly reconstructed by sparse subsets of strongly responsive neurons and their functional interactions. Together, these results confirm that, beyond enabling accurate decoding, DINA provides a principled framework for probing the computational mechanisms underlying visual processing in V1.

Lissajous confocal laser endomicroscopy (CLE) is a promising solution for high speed in vivo optical biopsy for handheld scenarios. However, Lissajous scanning traces a resonant trajectory and samples only the visited pixels per frame; at high frame rates, many pixels remain unvisited, creating structured holes. In this work, we introduce the first benchmark for high-rate Lissajous CLE, consisting of low-quality video clips paired with high-quality reference images. The reference images are wide-FOV mosaics obtained by stitching stabilized, slow-scan frames of the same tissue, enabling temporally aligned supervision. Using this dataset, we propose MIRA, a lightweight recurrent framework for Lissajous CLE restoration that iteratively aggregates temporal context through feature reuse and displacement alignment. Our experiments demonstrate that MIRA outperforms both lightweight and high-complexity baselines in restoration quality while maintaining a favorable computational efficiency suitable for clinical deployment.

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

Accurate intraoperative assessment of glioma infiltration is essential for maximizing tumor resection while preserving functional brain tissue. Fluorescence lifetime imaging (FLIm) offers real-time, label-free biochemical contrast, but its clinical utility is challenged by biological heterogeneity, class imbalance, and variability in histopathological labeling. We present a data-centric AI (DC-AI) framework that integrates confident learning (CL), class refinement, and targeted label evaluation to develop a robust multi-class FLIm classifier for glioblastoma (GBM) resection margins. FLIm data were collected from 192 tissue margins across 31 newly diagnosed IDH-wildtype GBM patients and initially labeled into seven tumor cellularity classes by an expert neuropathologist. CL was applied to quantify FLIm point-level confidence, identify label inconsistencies, and guide iterative class merging into a three-class scheme ("low", "moderate", "high"). The resulting high-fidelity dataset enabled training a model that achieved 96% accuracy in the three-class task. SHAP analysis revealed class-specific FLIm feature importance, highlighting distinct optical signatures across the infiltration spectrum. Targeted FLIm analysis further identified biological (e.g., gray matter composition) and acquisition-related (e.g., blood contamination) contributors to low-confidence predictions. Blinded re-evaluation of margins flagged by CL demonstrated intra-pathologist variability, underscoring the value of selective relabeling rather than exhaustive review. Together, these findings demonstrate that a DC-AI framework can systematically improve data reliability, enhance model robustness, and refine biological interpretation of FLIm signals, supporting the development of clinically actionable optical tools for real-time glioma margin assessment.

Accurate whole-cell and nuclear segmentation is essential for precision pathology and spatial omics, yet routine hematoxylin and eosin (H&E) staining provides limited cytoplasmic contrast, restricting analyses to nuclei. Multiplex immunofluorescence (mIF) facilitates precise whole-cell delineation but remains constrained by cost and accessibility. We introduce VitaminP, a cross-modal learning framework enabling whole cell segmentation from H&E images. By learning from paired H&E-mIF data, VitaminP transfers molecular boundary information from mIF to overcome cytoplasmic contrast in H&E, establishing cross-modal supervision as a general strategy for recovering missing biological structure. We train VitaminP on 14 public datasets covering 34 cancer types and over 7 million instances, integrating publicly available labels with extensive annotations generated in this study, forming one of the largest resources for segmentation. VitaminP outperforms four state-of-the-art methods and generalizes to unseen datasets, including an in-house dataset spanning 24 rare cancer types. We further developed VitaminPScope, an open-source platform providing an interface for scalable inference and enabling broad adoption.

In spite of the utility of 3-D electron back-scattered diffraction (EBSD) microscopy, the data collection process can be time-consuming with serial-sectioning. Hence, it is natural to look at other modalities, such as polarized light (PL) data, to accelerate EBSD data collection, supplemented with shared information. Complementarily, features in chaotic PL data could even be enriched with a handful of EBSD measurements. To inherently learn the complex dynamics between EBSD and PL to solve these inverse problems, we use an unconditional multimodal diffusion model, motivated by progress in diffusion models for inverse problems. Although trained solely on synthetic data once, our model has strong generalizable capabilities on real data which can be low-resolution, noisy, corrupted, and misregistered. With inference-time scaling, we show gains in performance on a variety of objectives including grain boundary prediction, super-resolution, and denoising. With our model, we demonstrate that there is little difference from full resolution performance with only 25% (1/4 the resolution) of EBSD data and corrupted PL data.

We present S1-VL, a multimodal reasoning model for scientific domains that natively supports two complementary reasoning paradigms: Scientific Reasoning, which relies on structured chain-of-thought, and Thinking-with-Images, which enables the model to actively manipulate images through Python code execution during reasoning. In the Thinking-with-Images mode, the model generates and executes image-processing code in a sandbox environment, obtains intermediate visual results, and continues reasoning in a multi-turn iterative manner. This design is particularly effective for challenging scenarios such as high-resolution scientific chart interpretation, microscopic image understanding, and geometry-assisted reasoning. To construct the training data, we collect scientific multimodal datasets spanning six disciplines: mathematics, physics, chemistry, astronomy, geography, and biology. We further develop a six-dimensional quality filtering framework for reasoning trajectories. To mitigate redundant, ineffective, and erroneous visual operations commonly found in existing datasets, we propose a multi-stage filtering pipeline together with an adaptive data routing strategy. This strategy converts samples with low visual information gain into pure Reasoning-mode data, enabling the model to learn when image operations are truly necessary. S1-VL is trained through a four-stage progressive pipeline: scientific multimodal SFT, Thinking-with-Images cold-start SFT, and two stages of reinforcement learning with SAPO. We build S1-VL-32B on top of Qwen3-VL-32B-Thinking and evaluate it on 13 benchmarks. Experimental results show that S1-VL-32B achieves state-of-the-art performance on all five Thinking-with-Images benchmarks, including HRBench-4K, HRBench-8K, MME-RealWorld-CN, MME-RealWorld-Lite, and V*, and outperforms compared systems on scientific reasoning benchmarks such as Physics and VRSBench.

Peak picking is a fundamental preprocessing step in Mass Spectrometry Imaging (MSI), where each sample is represented by hundreds to thousands of ion images. Existing approaches require careful dataset-specific hyperparameter tuning, and often fail to generalize across acquisition protocols. We introduce IonMorphNet, a spatial-structure-aware representation model for ion images that enables fully data-driven peak picking without any task-specific supervision. We curate 53 publicly available MSI datasets and define six structural classes capturing representative spatial patterns in ion images to train standard image backbones for structural pattern classification. Once trained, IonMorphNet can assess ion images and perform peak picking without additional hyperparameter tuning. Using a ConvNeXt V2-Tiny backbone, our approach improves peak picking performance by +7 % mSCF1 compared to state-of-the-art methods across multiple datasets. Beyond peak picking, we demonstrate that spatially informed channel reduction enables a 3D CNN for patch-based tumor classification in MSI. This approach matches or exceeds pixel-wise spectral classifiers by up to +7.3 % Balanced Accuracy on three tumor classification tasks, indicating meaningful ion image selection. The source code and model weights are available at https://github.com/CeMOS-IS/IonMorphNet.

Extracting standardized metallurgical metrics from microscopy images remains challenging due to complex grain morphology and the data demands of supervised segmentation. To bridge foundational computer vision with practical metallurgical evaluation, we propose an automated pipeline for dense instance segmentation and grain size estimation that adapts Cellpose-SAM to microstructures and integrates its topology-aware gradient tracking with an ASTM E112 Jeffries planimetric module. We systematically benchmark this pipeline against a classical convolutional network (U-Net), an adaptive-prompting vision foundation model (MatSAM) and a contemporary vision-language model (Qwen2.5-VL-7B). Our evaluations reveal that while the out-of-the-box vision-language model struggles with the localized spatial reasoning required for dense microscopic counting and MatSAM suffers from over-segmentation despite its domain-specific prompt generation, our adapted pipeline successfully maintains topological separation. Furthermore, experiments across progressively reduced training splits demonstrate exceptional few-shot scalability; utilizing only two training samples, the proposed system predicts the ASTM grain size number (G) with a mean absolute percentage error (MAPE) as low as 1.50%, while robustness testing across varying target grain counts empirically validates the ASTM 50-grain sampling minimum. These results highlight the efficacy of application-level foundation model integration for highly accurate, automated materials characterization. Our project repository is available at https://github.com/mueez-overflow/ASTM-Grain-Size-Estimator.

Rabies remains a major public health concern across many African and Asian countries, where accurate diagnosis is critical for effective epidemiological surveillance. The gold standard diagnostic methods rely heavily on fluorescence microscopy, necessitating skilled laboratory personnel for the accurate interpretation of results. Such expertise is often scarce, particularly in regions with low annual sample volumes. This paper presents an automated, AI-driven diagnostic system designed to address these challenges. We developed a robust pipeline utilizing fluorescent image analysis through transfer learning with four deep learning architectures: EfficientNetB0, EfficientNetB2, VGG16, and Vision Transformer (ViTB16). Three distinct data augmentation strategies were evaluated to enhance model generalization on a dataset of 155 microscopic images (123 positive and 32 negative). Our results demonstrate that TrivialAugmentWide was the most effective augmentation technique, as it preserved critical fluorescent patterns while improving model robustness. The EfficientNetB0 model, utilizing Geometric & Color augmentation and selected through stratified 3fold cross-validation, achieved optimal classification performance on cropped images. Despite constraints posed by class imbalance and a limited dataset size, this work confirms the viability of deep learning for automating rabies diagnosis. The proposed method enables fast and reliable detection with significant potential for further optimization. An online tool was deployed to facilitate practical access, establishing a framework for future medical imaging applications. This research underscores the potential of optimized deep learning models to transform rabies diagnostics and improve public health outcomes.

Unlike macro-expression, micro-expression does not follow a strictly consistent mapping rule between emotions and Action Units (AUs). As a result, some micro-expressions share identical AUs yet represent completely opposite emotional categories, making them highly visually similar. Existing microexpression recognition (MER) methods mostly rely on explicit facial motion cues (e.g., optical flow, frame differences, AU features) while ignoring implicit emotion information. To tackle this issue, this paper presents a Motion Emotion Feature Decoupling Network (MEDN) for MER. We design a dual-branch framework to separately extract motion and emotion features. In the motion branch, an AU-detection task restricts features to the explicit motion domain, and orthogonal loss is adopted to reduce motion emotion feature coupling. For implicit emotion modeling, we propose a Sparse Emotion Vision Transformer (SEVit) that sparsifies spatial tokens to highlight local temporal variations with multi-scale sparsity rates. A Collaborative Fusion Module (CoFM) is further developed to fuse disentangled motion and emotion features adaptively. Extensive experiments on three benchmark datasets validate that MEDN effectively decouples motion and emotion features and achieves superior recognition performance, offering a new perspective for enhancing recognition accuracy and generalization.

Breast cancer diagnosis demands rapid and precise tools, yet traditional histopathological methods often fall short in intra-operative settings. Deep Ultraviolet (DUV) fluorescence imaging emerges as a transformative approach, offering high-contrast, label-free visualization of whole-slide images (WSIs) with unprecedented detail, surpassing conventional hematoxylin and eosin (H&E) staining in speed and resolution. However, existing deep learning methods for breast cancer classification, predominantly patch-based, fragment spatial context and incur significant preprocessing overhead, limiting their clinical utility. Moreover, standard attention mechanisms, such as Spatial, Squeeze-and-Excitation, Global Context and Guided Context Gating, fail to fully exploit the rich, multi-scale regional relationships inherent in DUV-WSI data, often prioritizing generic feature recalibration over diagnostic specificity. This study introduces a novel Region-Affinity Attention mechanism tailored for DUV-WSI breast cancer classification, processing entire slides without patching to preserve spatial integrity. By modeling local neighbor distances and constructing a full affinity matrix, our method dynamically highlights diagnostically relevant regions, augmented by a contrastive loss to enhance feature discriminability. Evaluated on a dataset of 136 DUV-WSI samples, our approach achieves an accuracy of 92.67 +/- 0.73% and an AUC of 95.97%, outperforming existing attention methods.

Traditional melissopalynology is a time-consuming and subjective process, often taking 4-6 hours per sample. We present an automated, high-throughput microscopy system that integrates H_\infty robust mechanical control with advanced deep learning pipelines for the precise counting, classification, and morphological analysis of pollen grains from Bio Bio region in south central territory in Chile. Our system employs U^2-Net for salient object detection and a DINOv2 Vision Transformer backbone trained via Deep Metric Learning for classification. By integrating Gradient-Weighted Attention, the model provides human-interpretable texture and diagnostic feature annotations. The system achieves a 95.8% classification recall and at least 6x processing speedup compared to manual expert analysis.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Conventional computed tomography (CT) imaging, while essential for detection and staging, has limitations in distinguishing benign from malignant lesions and providing interpretable diagnostic insights. To address this challenge, this study proposes a dual-modal artificial intelligence framework that integrates CT radiology with hematoxylin and eosin (H&E) histopathology for lung cancer diagnosis and subtype classification. The system employs convolutional neural networks to extract radiologic and histopathologic features and incorporates clinical metadata to improve robustness. Predictions from both modalities are fused using a weighted decision-level integration mechanism to classify adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell lung cancer, and normal tissue. Explainable AI techniques including Grad-CAM, Grad-CAM++, Integrated Gradients, Occlusion, Saliency Maps, and SmoothGrad are applied to provide visual interpretability. Experimental results show strong performance with accuracy up to 0.87, AUROC above 0.97, and macro F1-score of 0.88. Grad-CAM++ achieved the highest faithfulness and localization accuracy, demonstrating strong correspondence with expert-annotated tumor regions. These results indicate that multimodal fusion of radiology and histopathology can improve diagnostic performance while maintaining model transparency, suggesting potential for future clinical decision support systems in precision oncology.

A low cost fluorescence-based optical system is developed for detecting the presence of certain microorganisms and molecules within a diluted sample. A specifically designed device setup compatible with conventional 96 well plates is chosen to create an ideal environment in which a smart phone camera can be used as the optical detector. In comparison with conventional microplate reading machines such as Perkin Elmer Victor Machine, the device presented in this paper is not equipped with expensive elements such as exciter filer, barrier filter and photomultiplier; instead, a phone camera is all needed to detect fluorescence within the sample. The strategy being involved is to determine the relationship between the image color of the sample in RGB color space and the molar concentration of the fluorescence specimen in that sample. This manuscript is a preprint version of work related to a publication in IEEE. The final version may differ from this manuscript.

Background: Task-specific microscopy datasets are often small, making it difficult to train deep learning models that learn robust features. While self-supervised learning (SSL) has shown promise through pretraining on large, domain-specific datasets, generalizability across datasets with differing staining protocols and channel configurations remains underexplored. We investigated the generalizability of SSL models pretrained on ImageNet-1k and HPA FOV, evaluating their embeddings on OpenCell with and without fine-tuning, two channel-mismatch strategies, and varying fine-tuning data fractions. We additionally analyzed single-cell embeddings on a labeled OpenCell subset. Result: DINO-based ViT backbones pretrained on HPA FOV or ImageNet-1k transfer well to OpenCell even without fine-tuning. Fine-tuning further improved performance to 0.704 $\pm$ 0.027 (17 classes, multi-class labels). At the single-cell level, the HPA single-cell-pretrained model achieved the highest k-nearest neighbor performance across all neighborhood sizes (macro $F_1$ $\geq$ 0.515). Conclusion: SSL methods like DINO, pretrained on large domain-relevant datasets, enable effective use of deep learning features for fine-tuning on small, task-specific microscopy datasets.

Autonomous experimental systems are increasingly used in materials research to accelerate scientific discovery, but their performance is often limited by low-quality, noisy data. This issue is especially problematic in data-intensive structure-property learning tasks such as Image-to-Spectrum (Im2Spec) and Spectrum-to-Image (Spec2Im) translations, where standard active learning strategies can mistakenly prioritize poor-quality measurements. We introduce a gated active learning framework that combines curiosity-driven sampling with a physics-informed quality control filter based on the Simple Harmonic Oscillator model fits, allowing the system to automatically exclude low-fidelity data during acquisition. Evaluations on a pre-acquired dataset of band-excitation piezoresponse spectroscopy (BEPS) data from PbTiO3 thin films with spatially localized noise show that the proposed method outperforms random sampling, standard active learning, and multitask learning strategies. The gated approach enhances both Im2Spec and Spec2Im by handling noise during training and acquisition, leading to more reliable forward and inverse predictions. In contrast, standard active learners often misinterpret noise as uncertainty and end up acquiring bad samples that hurt performance. Given its promising applicability, we further deployed the framework in real-time experiments on BiFeO3 thin films, demonstrating its effectiveness in real autonomous microscopy experiments. Overall, this work supports a shift toward hybrid autonomy in self-driving labs, where physics-informed quality assessment and active decision-making work hand-in-hand for more reliable discovery.

Deep learning underlies most modern approaches and tools in computer vision, including biomedical imaging. However, for interactive semantic segmentation (often called pixel classification in this context) and interactive object-level classification (object classification), feature-based shallow learning remains widely used. This is due to the diversity of data in this domain, the lack of large pretraining datasets, and the need for computational and label efficiency. In contrast, state-of-the-art tools for many other vision tasks in microscopy - most notably cellular instance segmentation - already rely on deep learning and have recently benefited substantially from vision foundation models (VFMs), particularly SAM. Here, we investigate whether VFMs can also improve pixel and object classification compared to current approaches. To this end, we evaluate several VFMs, including general-purpose models (SAM, SAM2, SAM3, DINOv3) and domain-specific ones ($μ$SAM, PathoSAM, KRONOS), in combination with shallow learning and attentive probing on five diverse and challenging datasets. Our results demonstrate consistent improvements over hand-crafted features and provide a clear pathway toward practical improvements. Furthermore, our study establishes a benchmark for VFMs in microscopy and informs future developments in this area.

The tortuosity of corneal nerve fibers are used as indication for different diseases. Current state-of-the-art methods for grading the tortuosity heavily rely on expensive segmentation maps of these nerve fibers. In this paper, we demonstrate that self-supervised pretrained features from ImageNet are transferable to the domain of in vivo confocal microscopy. We show that DINO should not be disregarded as a deep learning model for medical imaging, although it was superseded by two later versions. After careful fine-tuning, DINO improves upon the state-of-the-art in terms of accuracy (84,25%) and sensitivity (77,97%). Our fine-tuned model focuses on the key morphological elements in grading without the use of segmentation maps.

Biophysical diffusion MRI models like Neurite Exchange Imaging (NEXI) are essential for probing gray matter microstructure, estimating compartment diffusivities, neurite fraction, and exchange time. However, NEXI's multi-shell, multi-diffusion-time requirements cause prohibitively long acquisitions. Leveraging the Connectome 2.0 ultra-high gradient scanner, we developed a time-efficient protocol using an Explainable AI (XAI) framework. Combining XGBoost, SHAP, and Recursive Feature Elimination trained on synthetic signals, XAI identified an optimal 8-feature subset, cutting scan time from 27 to 14 minutes. Validated in vivo in seven healthy participants, the XAI protocol was benchmarked against the full 15-feature acquisition, a Cram'er-Rao Lower Bound (CRLB) theoretical optimum, and two heuristics ("Mid-Range" and "Corner"). It robustly reproduced parameter estimates and maintained test-retest reproducibility. Remarkably, the XAI selection converged to the CRLB optimum. This validates XAI's optimality while highlighting its main advantage: achieving gold-standard optimization without complex analytical Jacobians, making it easily adaptable to numerical models or complex noise where CRLB is intractable. Furthermore, XAI showed superior in vivo robustness over heuristics: "Mid-Range" sampling yielded biased exchange time estimates from insufficient temporal diversity, while "Corner" sampling gave unstable intra-neurite diffusivity estimates (5-fold higher CV) due to noise sensitivity. Ultimately, this robust 14-minute protocol accelerates exchange-sensitive microstructural mapping, establishing a model-agnostic optimization framework adaptable to future ultra-high gradient systems and existing clinical scanners.

Quantitative microstructural characterization is fundamental to materials science, and electron micrographs (EMs) provide indispensable high-resolution insights. However, progress in deep learning-based analysis of EMs has been hampered by the scarcity of large-scale, expert-annotated public datasets. To address this issue, we introduce EM3M, a large-scale and multimodal dataset for instance-level understanding of EMs. EM3M comprises 5,091 high-quality EMs, approximately 3 million instance segmentation annotations, and image-level textual descriptions with disentangled attributes. The dataset is constructed through a rigorous multi-stage curation and validation pipeline, with comprehensive statistical analyses to ensure reliability and reproducibility. Building upon these curated image-text pairs, we further provide a text-to-image diffusion model that serves as a controllable data augmentation engine, demonstrating that synthetic augmentation consistently improves downstream segmentation performance. To establish a systematic benchmark, we evaluate representative instance segmentation methods on EM3M. Our results reveal that conventional detection-based and query-based methods struggle with the extreme instance densities and textural complexities inherent in EMs. We additionally provide an optimized flow-based baseline to facilitate fair comparison and future research. EM3M {Dataset: https://huggingface.co/datasets/UniParser/EM3M}, the generative engine {Generation: https://huggingface.co/UniParser/EM3M-Gen}, and an online demo {Segmentation demo: https://www.bohrium.com/apps/uni-aims} are publicly available to support future research in automated materials analysis.

We introduce methods to quantify how Large Language Models (LLMs) encode and store contextual information, revealing that tokens often seen as minor (e.g., determiners, punctuation) carry surprisingly high context. Notably, removing these tokens -- especially stopwords, articles, and commas -- consistently degrades performance on MMLU and BABILong-4k, even if removing only irrelevant tokens. Our analysis also shows a strong correlation between contextualization and linearity, where linearity measures how closely the transformation from one layer's embeddings to the next can be approximated by a single linear mapping. These findings underscore the hidden importance of filler tokens in maintaining context. For further exploration, we present LLM-Microscope, an open-source toolkit that assesses token-level nonlinearity, evaluates contextual memory, visualizes intermediate layer contributions (via an adapted Logit Lens), and measures the intrinsic dimensionality of representations. This toolkit illuminates how seemingly trivial tokens can be critical for long-range understanding.

Mental health problems such as stress, anxiety, and depression affect millions of people worldwide. These conditions are usually assessed using questionnaires, which rely on how people describe their own feelings. In this study, we explore whether a wearable device can help measure mental health using physical signals from the body. The device records small changes in blood flow and tissue activity from the fingertip. We collected data from 132 adults across 19 countries and compared these signals with mental health questionnaire results. We found that patterns in blood flow and tissue activity are linked to stress-related symptoms. This approach may help develop new tools for simple, non-invasive mental health monitoring in everyday life. Code and datasets are publicly available: https://github.com/leduckhai/Wearable_LDF-FS

This paper outlines the specifications and design approach used to construct a full body imaging scanner capable of capturing skin lesions at a dermatoscopic level using cameras mounted on the end-effectors of four UR10 manipulators. The system possesses a view-planning algorithm capable of appropriately selecting the best camera position to acquire images of moles, a high-level controller to allow the manipulators to work simultaneously and a collision-detector that halts the manipulators when they make contact with an object or a person. We evaluate the system through real-patient full-body scans, comparing acquired images against contact dermoscopy and an existing total-body photography system (Vectra) across clinically relevant lesion features, and quantify true optical resolving power using a USAF 1951 resolution target, yielding a smallest resolvable feature size of 22.1 microns for our scanner compared to 8.8 microns for contact dermoscopy. Results show the scanner consistently outperforms Vectra across most clinically relevant features and achieves comparable performance to contact dermoscopy for the majority of features assessed. By acquiring dermatoscopic-quality images automatically and without contact, and without requiring a separate manual dermoscopic examination, the scanner closes part of the gap between total-body photography and handheld dermoscopy, suggesting potential for future integration into screening workflows.

Ptychographic imaging at synchrotron and X-ray free-electron laser sources requires densely overlapping scans, which limits throughput and increases dose; extending coherent diffractive imaging to overlap-free operation on extended samples remains an open problem. We present a self-supervised inverse-mapping network for single-frame Fresnel coherent diffraction imaging (CDI) and overlapped ptychography with fixed, pre-estimated probes. The learned neural network reconstructs individual object patches from either one diffraction frame or several overlapping measurements at a time. In single-frame mode, the phase diversity provided by the curved-wavefront probe at the off-focus sample position removes the requirement for overlap constraints, enabling sparser scans and proportionally lower dose at fixed exposure. On synthetic line patterns, reconstructed amplitude SSIM exceeds 0.90 in single-frame mode with the curved probe and reaches 0.952-0.968 with overlap constraints. Optimization of the network via a Poisson negative log likelihood objective, rather than the more common mean absolute error, yields 10-fold improved photon-dose efficiency at doses below $10^5$ photons per image, where shot noise typically limits resolution. In addition to these synthetic studies, we demonstrate robust single-frame reconstruction of extended samples using ptychographic datasets from APS and LCLS, with end-to-end reconstruction of a 10,304-frame workload approximately $36\times$ faster than a highly optimized iterative solver. Together, these results unify single-frame Fresnel CDI and overlapped ptychography within one self-supervised framework, supporting dose-efficient, high-throughput imaging at modern light sources.

This paper proposes a fully differentiable jitter correction method for X-ray phase-contrast micro computed tomography using a deep learning-based image quality metric that estimates and compensates per-projection rigid jitter directly from the acquired projection data, without a pre-scan motion-free reference. The approach builds on a gradient-based auto-focus strategy adapted to parallel-beam geometry. A set of candidate objective functions is benchmarked in a controlled study, and the sensitivity of the visual information fidelity (VIF) metric to the jitter artifact is verified with the target phase-contrast data. To operate without a clean reference, a compact 3D convolutional neural network is trained to predict the VIF score from a single corrupted volume. A spatially selective total variation penalty applied exclusively to the image background is introduced to penalize spurious high-frequency structures that otherwise emerge during optimization. Experiments on biological specimens acquired at different synchrotron beamlines are conducted. Evaluation uses jitter motion applied to simulated and experimentally acquired projection data. The result confirms that the integrated pipeline reliably recovers fine structural detail lost due to jitter, with generalization demonstrated across morphologically distinct samples.