Tissue Architecture

Organoids are three-dimensional tissue models whose morphology provides important insights into tumor development, disease progression, and drug testing. Extracting these morphological features relies heavily on manual segmentation, which is time-consuming and labor-intensive. Furthermore, performing quantitative statistical analysis typically requires custom coding skills and a mathematical background, presenting a major barrier for experimental biologists. To address these challenges, we introduce MorphoOrgaAgent, a multi-agent framework that achieves zero-shot organoid segmentation, automated data analysis, and report generation based on natural language input. The framework consists mainly of three core components: a TaskUnderstandingAgent that identifies requested measurements and visualization types; a hybrid segmentation module that combines Cellpose-derived geometric prompts with text prompts to guide SAM3 for zero-shot organoid instance segmentation; and a ReportAgent that computes quantitative metrics and compiles them alongside generated visualizations into a structured report. We further introduce MorphoOrgaVQA, a benchmark designed for quantitative evaluation of agent systems in organoid morphology analysis. Experimental results demonstrate that MorphoOrgaAgent handles both explicit and descriptive user requests, produces measurements closely matching ground truth, and generates complete analysis reports without requiring manual programming. The complete source code and MorphoOrgaVQA benchmark are publicly available at https://github.com/peng-lab/MorphoOrgaAgent.

Functional tissue units (FTUs), including tertiary lymphoid structures (TLSs), blood vessels, and glands, encode localized immune, vascular, and epithelial organization in histopathology. Accurate quantification of these structures is important for studying tissue architecture and disease-associated tissue organization. However, FTUs are frequently sparse, heterogeneous, and surrounded by large amounts of morphologically similar background tissue, making automated segmentation in whole-slide images (WSIs) challenging. We therefore developed FTU-Seek, a pathology foundation model-guided framework that treats morphology-aware negative-patch selection as a key component of sparse FTU segmentation. FTU-Seek uses frozen multi-depth features from the UNI pathology foundation model to train a patch-level classifier that distinguishes FTU-containing from FTU-absent tissue. Target-absent patches are subsequently ranked according to their predicted target-containing probabilities, and the highest-scoring hard negatives are selected through a static Top$K$ strategy to construct compact segmentation training sets. The framework was evaluated using five-fold cross-validation and internal test cohorts across TLS, blood-vessel, and gland segmentation tasks, with an additional independent 30-WSI held-out cohort for TLS. Positive-only, all-tissue, random-negative, and matched random Top$K$ sampling strategies served as comparators. Segmentation-derived phenotypes were further explored in external TCGA cohorts.

Background and Objective: Quality control is a prerequisite for whole-slide image analysis, yet the benchmarks on which quality-control methods are compared share four properties that make their reported differences hard to interpret: few independent slides, annotation concentrated in a minority of them, pooled ratio metrics with no closed-form standard error, and a single inherited train/test partition. We propose a reliability protocol for such benchmarks. Methods: The protocol quantifies four sources of variability - test-set sampling, training stochasticity, partition composition, and undocumented preprocessing - a claim is reportable only if it survives all four; three of the four cost minutes of compute. We apply it to an independent reconstruction of a published diffusion-based artifact detector, evaluated on the original 24-slide partition and against a supervised baseline. Results: The method's central mechanism reproduces: the auxiliary contrastive term improves pooled F1 from 0.673 to 0.688 and replicates under a second seed (+0.0156, p = 0.031; +0.0190, p = 0.005), although it acts on pen marking rather than the artifact types cited to motivate it. Its comparative claims do not: differences between design variants, and against the supervised baseline, fall inside the uncertainty of the evaluation. Four of 24 slides carry 70% of scored annotated pixels, giving an effective sample size of 6.2, and the inherited partition sits at the 7th percentile. An unreported tissue-restriction step excludes 41.4% of out-of-focus annotation against 2.6% of air bubble; such a gate is confounded with blur by construction. Conclusions: Small-cohort benchmarks support far weaker conclusions than current reporting implies. The four checks are cheap enough to accompany any evaluation on such a resource and separate reproducible effects from differences the evaluation cannot resolve.

Automating the analysis of whole-slide images has high clinical value, since characterizing cancers requires examining them in detail. Such analysis increasingly relies on vision-language models that provide patch-level zero-shot predictions. However, these predictions remain noisy and must be refined with a few annotations. A promising paradigm for this refinement is few-shot transduction. Rather than treating each patch independently, these methods leverage the relations between patches, together with a few annotations, to refine all predictions jointly. However, current transductive methods are evaluated under conditions that overlook key properties of whole-slide images: (i) datasets consist of independent patches extracted from multiple slides, ignoring the complex tissue organization; (ii) datasets are mostly balanced, whereas a single whole-slide image exhibits severe class imbalance, with several classes absent; and (iii) annotations are sampled at random, without reflecting how a pathologist annotates a limited number of regions. To align the transduction paradigm to realistic whole-slide settings, we introduce the following contributions. First, we propose SlideCRF, which adapts conditional random fields for whole-slide images by combining spatial and biological cues while accounting for classes that may be absent from a given slide. Second, we provide a set of realistic annotation protocols, based on spatially localized clicks and scribbles, modeling different pathologist interactions, such as the iterative correction of model errors. Across four datasets, we show that SlideCRF outperforms current transductive methods in macro F1, improving over the zero-shot predictions by +24.2% and +37.5% with one and 16 clicks per present class, respectively.

In this paper, we introduce a novel framework for 4D plant growth modeling that reconstructs the continuous geometric and topological evolution of plants from sparse temporal observations. Existing methods mainly rely on dense registration, yet reliable dense sequences are hard to obtain due to scanning constraints and self-occlusions, leaving these approaches struggling under large temporal gaps where rapid organ emergence violates local rigidity. To overcome this, we bridge these gaps by formulating plant morphogenesis as a continuous procedural process on a structure-aware Riemannian growth field; this jointly models topology evolution and geometric deformation, preserving botanical hierarchies and stable spatio-temporal correspondences across distant timepoints. Our key idea is to ground symbolic growth rules within a continuous geodesic flow, where organ development follows biologically modulated trajectories that preserve structural coherence under topological changes. We further contribute a 10-day dual-species dataset with dense geometric and semantic annotations. Experiments demonstrate that our method accurately tracks individual organ growth over time and significantly outperforms state-of-the-art baselines in both geometric accuracy and correspondence consistency.

Quantitative MRI (qMRI) provides standardised tissue parameter maps, but the reliability of deep learning-based qMRI mapping methods is often not explicitly characterised. In this work we systematically evaluate uncertainty maps for quantitative MRI derived from multiple inferences of a data-consistent diffusion model-based qMRI framework. Evaluation on synthetic test data assessed error-awareness, high-error detection, selective prediction, and Gaussian interval calibration. Diffusion model-derived uncertainty was positively associated with the mapping error, while risk-coverage analysis showed that excluding high-uncertainty voxels reduced the retained error. However, the raw uncertainty was poorly calibrated for quantitative interval interpretation. Calibration was substantially improved using a post-hoc procedure combining prediction-value-dependent bias correction with scalar uncertainty scaling. Qualitative evaluation on a healthy volunteer showed spatially meaningful uncertainty patterns. These results indicate that diffusion model-derived uncertainty is informative for reliability assessment and selective prediction, but requires calibration for quantitative interval interpretation.

Whole slide images (WSIs) in digital histopathology are acquired at discrete magnification levels encoding complementary diagnostic information from global tissue architecture to fine-grained cellular morphology. Yet, deep learning models remain sensitive to scale variation. Existing magnification-invariant methods rely on multi-scale architectures at predefined discrete resolutions, while in clinical deployment the acquisition magnification varies continuously, rarely aligns with a model's fixed training resolution, and intermediate scales are common, so robust coverage otherwise demands a costly ensemble of magnification-specific models. We propose Conditional Layer Normalization (CLN), a lightweight mechanism that generates affine normalization parameters from input pixel size via a small MLP, integrated into standard CNN architectures for both WSI classification and segmentation. Trained on patches sampled continuously across a range of pixel sizes, the model decouples inference from scanner-dependent magnification and generalizes to arbitrary, previously unseen scales at test time. On the PANDA prostate cancer dataset, our approach on average matches or exceeds independently trained single-magnification models and ranks among the top three performers at every evaluated magnification, including those unseen during training. This collapses a five-model ensemble into a single network and reduces training, and inference cost roughly 4-5 times, while leaving the multiply-accumulate count unchanged. The code is available at: https://github.com/aflorkowska/OneModelToMagnifyThemAll.

Robotic neural-thread placement requires regulating the insertion-tool tip relative to tissue that moves with cardiac and respiratory pulsation. This paper develops a preview-based relative-motion controller that estimates latency-delayed periodic surface motion, predicts it over a short horizon, and uses offset-free model predictive control to regulate relative placement while limiting actuator effort and lateral relative velocity. In MuJoCo, the 1-DOF controller achieves 12.0\um\ free-space and 1.9\um\ contact RMS relative-placement error, versus 18.3/176.8\um\ for delayed-feedback impedance and 286.1/275.5\um\ for lab-frame PD, at the cost of higher peak contact force (3.43 versus 2.00mN) since offset-free tracking drives the tip fully to the commanded depth rather than yielding against the tissue. In 3 DOF, coupled preview reduces contact lateral shear from 1.34 to 0.50mm/s with 2.1\um\ lateral RMS error. A feasibility-restored octagonal shear formulation keeps the QP solvable under degraded sensing by adding a bounded shared slack: at 10\um\ RMS per-axis sensing noise, where a matched cost-only controller violates the 0.80mm/s budget in all 10 seeds (mean/maximum 0.988/1.175mm/s), the soft-octagon controller completes all 10 seeds with no fallback and no measured violation (0.653/0.712~mm/s), with its operating envelope characterized up to 15\um\ RMS. A two-vertex Lyapunov certificate for the controller's actual finite-horizon error-feedback gain holds over $-40\%/{+}50\%$ reflected-mass mismatch. The modeled tip is a rigid contact point, and the study is simulation-only: flexible-thread and carrier-needle mechanics, a validated transient-force constraint, biological damage thresholds, and hardware-realistic sensing and timing remain required before deployment.

Confocal microscopy of optically cleared and swelled tissue resolves complex biological structures in 3D, but such acquisitions are highly anisotropic: along the under-sampled axial direction the structure can appear discontinuous, hampering reconstruction and automated quantitative analysis. The usual remedy upsamples the axial dimension to an isotropic volume before training a segmentation model, which requires dense annotations in the upsampled space, a prohibitive labeling burden. We present an end-to-end, GPU-accelerated framework that overcomes this without additional annotations. The model is trained on the native acquisition volume; random rotation of training patches leverages the well-resolved lateral plane to supply the missing axial information, and a z-axis continuity loss keeps neighboring slices consistent. We adapt both a convolutional (3D U-Net) and a transformer (SwinUNETR) backbone, aggregate overlapping patches by Gaussian consensus, and compute point-spread-function-corrected membrane thickness by ray-surface intersection on the GPU. We apply the method to the glomerular basement membrane (GBM), a thin, highly convoluted part of the kidney's filtration barrier that grows more irregular in disease. Segmentation accuracy matches inter-expert agreement. Continuity-aware training improves reconstruction smoothness and suppresses a periodic terracing artifact at minimal accuracy cost. We quantify GBM thickness across the reconstructed 3D surface and capture disease-related thickening, enabling fully automated anisotropic 3D morphometry of biological structures without dense volumetric labels or image restoration.

Engineered Skeletal Muscle Tissues (ESMs) have become a key structure for biomedical disease modeling and pharmacological screening, yet their functional characterization often relies on simplistic metrics like peak force, discarding critical kinetic information. This is partially due to the high level of mathematical complexity which mechanistic models introduce to capture these dynamics. Hence, exactly the complexity prevents scalable application and widespread adaptation in the field. Here we present a Physics-Flavored Neural Network (PFNN) that automates the kinetic phenotyping of ESMs. Our architecture integrates a stretched-exponential physical model into a CNN-Transformer, enabling the extraction of physically meaningful parameters directly from force-time profiles. To address the scarcity of labeled biological data, we employ a hybrid training paradigm: the model develops a "physical intuition" on synthetic data before undergoing unsupervised self-alignment on unlabeled real-world measurements. Our results demonstrate that this physics-flavored approach achieves high-fidelity parameterization across diverse contractile phenotypes and cell lines, including Duchenne Muscular Dystrophy models. Our scalable, self-improving pipeline bridges the gap between idealized biophysics and noisy \emph{in vitro} data, providing a robust tool for high-throughput biophysical research.

Uterine peristalsis is a key physiological phenomenon responsible for various functions across the menstrual cycle, intimately linked to uterine wall microstructure. Alterations in uterine motion and tissue properties are implicated in the etiology of gynecological diseases, yet these processes have been studied in isolation. We introduce a dynamic multi-echo gradient echo EPI framework for simultaneous characterization and correlation of uterine peristaltic activity and time-resolved T2* changes at 0.55T. Inherent susceptibility artifacts, reduced resolution, and burden of manual uterine layer annotation are addressed by an unsupervised adversarial domain adaptation framework, transferring segmentation knowledge from labeled cine MRI to unlabeled dynamic EPI. We implemented Unet-LSTM with multi-scale domain discriminators that exploits temporal layer dynamics. A Dice score of 0.88 and Jaccard index of 0.80 was achieved. Mean T2* values were 108ms, 76ms, and 124ms for the myometrium, junctional zone, and endometrium. A negative correlation between junctional zone area and T2* was observed in 14/39 cases, providing first insights into oxygenation patterns associated with junctional zone contraction and motion, demonstrating feasibility of assessing the interplay between contractility and dynamic T2* changes.

Vision Transformers (ViTs) and their hierarchical variants have achieved strong performance in Computational Pathology (CPath). However, most are pre-trained on single-resolution Whole Slide Images (WSIs), limiting their generalization across arbitrary resolutions. Gigapixel WSIs inherently contain diagnostic patterns at multiple scales, including cellular morphologies, tissue architectures, and global context, mirroring how expert pathologists examine WSIs. We introduce Multi-Resolution Pyramid Transformer (MRPT), a model that hierarchically aggregates multi-resolution information from cellular to tissue and WSI levels. MRPT employs a biologically meaningful Consecutive Cross-Resolution Attention (CCRA) mechanism to capture scale-independent interactions and enforces multi-resolution semantic consistency by aligning embeddings across resolutions, yielding robust and generalizable WSI representations. Pre-trained in a multi-resolution self-supervised manner on 624M patches, 2.4M regions, and 36K WSIs, MRPT learns rich coarse-to-fine histopathology features. Extensive experiments on 34 diverse datasets show that MRPT surpasses recent foundation models and Multimodal Large Language Models (MLLMs) in cancer subtype classification, tissue phenotyping, and Visual Question Answering (VQA) for WSI understanding.

Fine-grained understanding of surgical activity is essential for context-aware assistance in the operating room, including safety monitoring, adverse event identification, and skill assessment. Surgical action triplets, defined as tuples of the form <instrument, verb, target>, provide a structured description of instrument-tissue interactions. A key open problem, however, is how to learn triplet representations that remain reliable across institutions, where surgical video varies in acquisition conditions, surgeon style, tool usage, and tissue handling, while existing triplet datasets do not support explicit evaluation of center-wise transfer. To address this problem, we propose \textbf{SPIRIT}, a structured framework for surgical action triplet recognition designed to learn interaction representations that transfer more reliably across centers. Instead of treating each triplet as a flat class label, SPIRIT first learns spatio-temporal representations for instruments, verbs, and targets, then models their pairwise relations, and finally composes them into coherent triplet predictions, with multi-head distillation used to stabilize learning. To evaluate this setting, we establish \textbf{MultiBypass-4C-T40}, a multi-centric dataset for dense surgical action triplet recognition in Roux-en-Y gastric bypass across four geographically distinct centers, with auxiliary phase and step annotations. Across multiple evaluation protocols, SPIRIT consistently outperforms strong recent baselines, highlighting the value of explicit relational reasoning for multi-centric triplet recognition. Code will be available at https://github.com/CAMMA-public/multibypass-4c-t40.

Pathology foundation models are reported to encode molecular programmes in tissue morphology, but the evidence is usually a cohort-wide ranked gene list rather than a prediction for a held-out patient. We rebuild such an analysis with the patient as the unit of evidence and ask which pipeline component carries signal. Across 11 frozen backbones, four pre-specified gene programmes and 285 TCGA-BRCA patients with paired slides and RNA-seq (44 cells; GroupKFold by patient, all preprocessing fitted inside the fold), ridge regression on mean-pooled embeddings predicts held-out programme scores at Spearman rho = 0.25-0.56, UNI2 strongest on all four (immune 0.556). A matched permutation null gives raw p ~ 1e-4 at 10,000 permutations for every cell; Holm-adjusted p = 0.0044. The signal is real but not uniformly morphological. Against competing models on the same patients and folds, embeddings beat tissue composition for ER/luminal, proliferation and immune (+0.280, +0.284, +0.479; p <= 0.003) but not basal, where compartment fractions alone reach 0.469 against the embedding's 0.493 (p = 0.77). Fifty-four interpretable cell-count features come within 0.043-0.085 on every programme. The geometric machinery contributes nothing measurable, and we identify why: the geodesic graph selects neighbours by Euclidean nearest-neighbour search and only reweights edges already chosen, so the topology is Euclidean by construction (Riemannian minus Euclidean = +0.0010, 95% CI [-0.0007, +0.0029]). Applied consistently the geometry is worse (-0.0117). Ridge regression beats the graph-and-metric decoder by +0.097 (CI [+0.069, +0.127]). The driver-count metric common in this literature is near-uninformative here: 91.8% of random six-gene panels recover >=5/6 drivers.

We present a novel technique for predicting the imaging quality of anomalies such as cancer cells located inside organic tissues. This technique is useful for evaluating and designing RF tomography sensors.

Single-cell perturbation atlases rarely measure every intervention in every cellular context: a query perturbation is often observed in one or more source contexts but missing in the recipient context where its effect is needed. Ignoring those measured responses discards query-specific experimental evidence, whereas copying or weakly calibrating them across contexts risks transferring the wrong signal. We propose PerturbMap, which predicts a missing recipient-context effect by combining a recipient-local low-rank base with accepted proposals that transport the same perturbation's measured source responses through source-to-recipient ridge experts fit on paired training perturbations, with proposal weights determined by route reliability estimated on validation anchors. On the Perturb-CITE-seq melanoma cohort, PerturbMap improves full-effect MSE by 4.1% over a recipient-local low-rank base and achieves lower MSE than FedAvg, zero-response, raw-copy, calibrated-copy, and identity-shuffled affine controls. It remains within $2.82\times10^{-6}$ MSE of our centralized token-matched pooled reference, which uses a stronger training interface. A condition-mean specificity diagnostic shows the same direction: same-recipient top-10 counterpart retrieval by cosine increases from 74.5% for the low-rank base to 80.5% for PerturbMap.

Human cortical organoids provide an experimentally accessible model of early neural circuit formation, yet whether their activity reflects structured information processing rather than spontaneous synchronization is unclear. We developed a graph-computational framework to quantify stimulus-evoked propagation. This includes stimulus-conditioned functional graphs, a graph-constrained dynamical (graph-neural-network) model used as a system-identification tool, a biological message-passing principle bounding integration depth by observable propagation depth, and a suite of graph-level metrics. We carried this program out in full on longitudinal HD-MEA recordings from three organoids. Once the true acquisition sampling rate and stimulus timing were recovered, the evoked response proved to be a fast, near-synchronous network burst with no measurable outward propagation (peak-latency vs. distance slope = 0). The propagation/integration-depth metrics (Deff ,reachability index, dmax) therefore do not apply, and per-day connectivity graphs were not reliably estimable at the available trial count, a negative result with methodological consequences for applying such metrics to organoid data. Reframing around synchrony, response-population size and shared variability revealed a control-validated phenomenon, i.e., repeated daily stimulation progressively depressed and spatially contracted the evoked response. That repeated stimulation reshapes organoid networks is established, but longitudinal designs in which every preparation is stimulated cannot separate this from developmental maturation. We break that confound with a developmentally-matched, stimulation-naive control, where at day 7, an organoid receiving its first-ever stimulation engaged 93% of the array, whereas organoids with five prior sessions engaged 10%.

Understanding tissue organisation in multiplexed imaging requires modelling both cellular phenotypes and their spatial context. Existing approaches typically rely on handcrafted features, such as marker intensity statistics or cell-type proportions, which often fail to scale or generalise across cohorts with heterogeneous marker panels. We introduce MUL-T, a lightweight transformer framework that reframes tissue architecture as a masked contextual prediction task over discrete cell tokens. By learning contextualised [CLS] embeddings without task-specific supervision, the model captures higher-order cellular interactions while remaining computationally efficient. We evaluate MUL-T on several clinically relevant downstream tasks, including core-level tumour pattern classification, patient-level grading, PD-L1 positivity prediction, and cross-dataset treatment response prediction. Across tasks, MUL-T consistently outperforms classical feature-based baselines and achieves performance comparable to a foundation ViT model, despite substantially fewer parameters and lower training cost.

Singular Value Decomposition (SVD) underlies matrix factorisation tasks across computational imaging, with medical applications increasingly demanding real-time processing. Yet SVD algorithms are inherently sequential, constraining real-time GPU throughput and limit online deployment in clinical pipelines. This study introduces Quasi-SVD, a differentiable, fully parallelized matrix factorization framework for GPUs. Rather than enforcing orthogonality on both factors, it guarantees exact orthogonality for a single Lie-parameterized factor while recovering the remaining components through soft constraints, enabling efficient parallel decomposition without iterative singular-vector optimization. This asymmetric design, provably sufficient for valid factorisation, achieves reconstruction fidelity of SSIM = 0.89-0.94 and accelerates computation by 3-20x relative to cuSOLVER and randomised SVD, enabling throughput above 25 FPS. Performance is evaluated on two medical imaging tasks spanning complementary computational regimes: (1) spatio-temporal background subtraction for ultrasound localisation microscopy, requiring high-dimensional matrix separation, and (2) Mueller matrix polarimetry for neurosurgical tissue characterisation, requiring massive batch processing of small matrices. Across both regimes and multiple imaging instruments, the proposed framework demonstrates robust domain transfer and throughput exceeding 25 FPS at clinical matrix scales, a rate sufficient for live image-guided workflows that classical solvers cannot currently support in these settings. By prioritising downstream reconstruction fidelity over exact spectral recovery, Quasi-SVD makes structured matrix factorisation practical for real-time imaging.

Predicting spatial gene expression from routine hematoxylin and eosin (H&E) images provides a practical complement to experimental spatial transcriptomics. Existing approaches focus on local or multi-scale visual features and often treat pretrained gene representations as fixed priors, although the interpretation of local morphology and the relevance of gene priors depend on tissue context. We propose HistoGPA, a context-conditioned gene-prior attention framework that uses a shared slide-level representation in two parallel pathways: one modulates local morphological features, whereas the other conditions pretrained gene embeddings and retrieves gene-prior information through cross-attention. This design enables each spatial location to retrieve context-adapted gene-prior information using its local morphology, position, and slide context. Across ten cancer types in HEST-1k, HistoGPA achieves the highest macro-averaged gene-wise Pearson correlation coefficient among the compared methods under the same evaluation protocol for both the top-50 and top-1,500 highly variable gene sets. Additional analyses show that HistoGPA better recovers the spatial expression patterns of cancer-associated genes and yields greater agreement between clusters derived independently from predicted and ground-truth expression profiles. Together, these findings motivate a context-dependent view of histology-to-expression prediction, in which local morphological representations and gene priors are jointly adapted to the broader tissue context.

Autonomous robotic craniotomy requires continuous regulation of tool-tissue interactions to mitigate mechanical overload and thermal damage while maintaining surgical efficiency. However, this process is inherently partially observable due to unknown, time-varying tissue properties and the inability to directly measure cutting temperatures under physical occlusion. To address these challenges, we propose RL-MACRO, a cybernetic closed-loop intelligence framework that couples multimodal perception, adaptive decision-making, and robotic execution. This framework empowers the surgical robot to autonomously perceive inaccessible states from partial sensory feedback and dynamically optimize its behaviors under uncertain environment. A CNN-LSTM observer first fuses force and sound feedback to reconstruct the hidden temperature state (R^2=0.939, MAE = 1.717 deg C). This reconstructed temperature, alongside multi-sensor features, forms the belief state for an offline Implicit Q-Learning (IQL) policy. A novel dual-head Actor dynamically coordinates the feed rate, spindle speed, and cutting depth to optimize efficiency within strict safety bounds. These decisions are seamlessly translated into spatial motions via online trajectory re-planning and velocity servoing. Experiments on bovine ribs and six ex vivo goat skulls validate the system's robust perception, adaptive recovery from force/temperature excursions, and smooth execution on irregular surfaces, establishing a data-driven cybernetic paradigm for safe and efficient autonomous bone cutting.

Safe navigation within the spinal subarachnoid space is constrained by its narrow, compliant, and delicate anatomy. Conventional catheters and continuum robots rely on proximal pushing, generating friction and shear along the tissue device interface that limit distal controllability and increase the risk of neural injury. Here, we present a 2 mm diameter eversion-growing robotic platform that enables friction minimised extension and steering within the human spinal subarachnoid space, validated through computational modelling, phantom experiments, and intact human cadaver studies. The robot integrates a miniature endoscope for real time intrathecal visualisation and advances by pressure driven tip eversion, localising motion to the distal tip while minimising translational sliding of the deployed body. Phantom experiments demonstrated reductions of 65.2% in mean interaction force and 48.0% in peak interaction force compared with matched push-based insertion. Physics based modelling showed that eversion based growth redistributed tissue loading, reducing local stress concentrations and interfacial shear relative to conventional insertion. In an intact human cadaver, the system achieved 150 mm of controlled intrathecal extension with concurrent fluoroscopic and endoscopic visualisation, providing access across multiple vertebral levels from a standard lumbar entry point. Postprocedural laminectomy and durotomy revealed no observable macroscopic disruption of the dura mater or surrounding neural structures. These results provide the first mechanically characterised and multimodally validated demonstration of eversion-based robotic navigation in intact human spinal anatomy, establishing a quantitative and procedural foundation for future intrathecal interventions. Further validation in larger anatomical cohorts and under physiological conditions will be required before clinical translation.

With growing surgeon shortages, automating surgical sub-tasks such as tissue dissection offers a promising step toward reducing workload and expanding patient access. Prior work has relied on hand-crafted incision policies that cannot quantify uncertainty or has relied on simulation-based methods that require strong modeling assumptions. We instead view tissue attachment identification as an inherently probabilistic problem and propose a Bayesian approach that avoids explicit tissue modeling. Our method uses a Sequential Bayesian Hilbert Map (SBHM) to represent the likelihood that each tissue point is attached to the underlying resection surface. An ensemble of learned classifiers predicts attachment likelihoods from spatial data acquired during robotic tissue retraction, with each classifier serving as a noisy information source to update the SBHM. To plan the next retraction, we devise Bayesian Retraction Optimization (BRO) to select the most informative action under safety constraints. As the SBHM refines over time, regions with high attachment likelihood are selectively incised. We validate our method in simulation across diverse tissue geometries and acquisition strategies, and demonstrate zero-shot transfer to real robotic dissection experiments.

Kirigami turns stiff sheets into compliant, shape-morphing structures, but its reliance on periodic cut patterns comes at a cost: correlated panel rotations couple extension to shear, so stretching one axis drives a parasitic shear that cannot be suppressed, and also confine anisotropic stiffness to a narrow, discrete set of responses that cannot be tuned independently. Biological tissues overcome an analogous constraint through controlled disorder, such as graded fiber orientations in skin and hierarchical anisotropy in myocardium, achieving direction-dependent mechanics unavailable to regular architectures. Here, we show that engineered disorder is a design degree of freedom for kirigami, with stochastic kirigami accessing a continuous and far broader region of mechanical response than periodic patterns. This includes programmable anisotropy with near-complete elimination of extension-shear coupling. Because disordered patterns lack a simple parameterization, we navigate this design space with a geometry-aware graph neural network (GNN) that maps cut topology to the full nonlinear, bidirectional stress-strain response, coupled to a genetic algorithm that inverse-designs patterns reproducing target responses along two perpendicular axes. The GNN trains an order of magnitude faster and more accurately than image-based models. Fabricated elastomer samples reproduce the predicted nonlinear, anisotropic responses, closing the loop from design to physical component. By turning disorder into a variable to control directional stiffness, this work develops architected materials that stretch without parasitic shear, from soft actuators to tissue-interfacing devices matched to the anisotropy of living tissue.

Surgical tissue retraction requires effective manipulation planning under partial and noisy perception. We study state estimation for deformable tissue retraction, where only sparse observations of the tissue surface are available at decision time. We propose a learned state estimator that reconstructs the full deformable mesh state from 40 noisy vertex observations. The estimator combines a multilayer perceptron with a low-dimensional PCA latent representation and is trained using geometry-aware regularization that encourages smooth and physically plausible deformations. We evaluate the approach in a 2D deformable sheet simulation using single-step and multi-step retraction planning. Results show that the learned estimator achieves 98.1% of oracle performance in multi-step retraction while supporting efficient inference. These results demonstrate that learned, geometry-regularized state estimation can support effective deformable manipulation under realistic perception constraints.

Background: Automated 3D segmentation of muscles and adipose tissue from CT is vital for body composition analysis, but multi-source data heterogeneity and high CPU memory demands hinder clinical deployment. Methods: We propose a coarse-to-fine hierarchical framework to segment ten tissue structures. Efficiency is optimized using Dynamic Spacing and Anisotropic Patching, a Group Inference mechanism for low-memory sliding-window processing, and Topology-Aware Asymmetric Resampling for fast post-processing. Results: The framework was trained on 1,558 CT volumes from seven public and two private datasets, and evaluated on an independent test cohort (N=105), per-structure Dice coefficients ranged from 0.924 to 0.982. Eight major structures met the +-10% relative error clinical acceptance limit. On a 12-core CPU workstation, the GPU-free pipeline averaged 44.5 seconds per volume with 4.73 GB peak memory. Conclusion: This framework balances accuracy and efficiency, enabling robust, large-scale body composition analysis on standard CPU workstations.

Quantifying plant growth dynamics from sparse longitudinal 3D observations is fundamental for agriculture and plant sciences. Yet, plants pose unique challenges: they undergo intricate non-rigid deformations, exhibit changing topology as new organs emerge, and often lack explicit temporal correspondences between consecutive data acquisitions due to newly formed tissue. Methods designed for general scenes struggle to model topology changes and asynchronous organ growth characteristic of plants. To address these challenges, we introduce GrowFields, a compositional dynamic neural field representation for organ-aware 4D plant growth modelling from point cloud time series. Our approach decomposes a plant into its constituent organs and aligns each organ into its own canonical coordinate frame, isolating intrinsic growth patterns from global plant motion. We then learn a shared continuous neural deformation field that models temporal dynamics across all organs, conditioned on learnable per-organ latent codes capturing organ identity and growth characteristics. The resulting modular yet unified representation naturally accommodates the asynchronous development of plant organs while remaining grounded in the practical setting of organ-level plant tracking. We evaluate GrowFields on growth sequences from four plant species, assessing geometric fitting and organ tracking accuracy using manually annotated leaf-tip trajectories. Results demonstrate consistent improvements in spatial precision, temporal coherence, and morphological fidelity over a range of existing representations.

Modeling tissue states and their transitions is essential for understanding tissue homeostasis in health and pathological remodeling in disease. However, conventional computational modeling approaches are inadequate to capture the complexity of tissues as spatially organized, multiscale biological systems. Artificial intelligence (AI) has shown a remarkable ability for representing intricate systems, creating new opportunities to characterize tissue states and their transitions. Here, we propose the concept of AI virtual tissue (AIVT), an AI framework grounded in spatial multimodal data for modeling tissues in health and disease. AIVT is designed to learn unified, spatially resolved, and dynamically manipulatable representations of tissue state, enabling tissue state representation and analysis, molecular and morphological feature prediction, and simulation of spatiotemporal tissue dynamics. We outline the fundamental assumptions, core capabilities, architectural components, as well as data and algorithm foundations of AIVT as a framework for AI-driven tissue modeling.

Predicting distant metastasis from the digital H & E slides of the primary tumor is a critical yet challenging task in computational pathology. Multiple Instance Learning (MIL) approaches can attend to subdomains in whole slide images (WSIs) that harbor features of pre-metastatic cancer regions. However, conventional MIL models largely treat tissue patches as unordered bags, discarding the spatial layout that defines how these regions are arranged and interact across the tissue. We propose that metastatic risk is shaped not only by local patch appearance, but also by the geometric organization of patches in the WSI and the interaction between the tissue compartments. To this end, we introduce Distance-aware Tissue Modeling for Multiple Instance Learning (DTMF-MIL), a spatial MIL framework that reinforces feature embeddings with explicit distance priors. By computing signed distance functions (SDFs) to capture regions with similar features, and representing each patch with radial-basis distance responses and local SDF statistics, DTMF-MIL learns positions of patches with respect to regional interiors and boundaries. The interactions between similar patches are contextualized across local tissue neighborhoods and used to guide slide-level attention while pooling patch feature evidence for metastasis prediction. We evaluate DTMF-MIL for prediction of distant prostate cancer metastasis in an internal prostate needle-biopsy cohort (IPC) from a large hospital system and on public TCGA-COAD and TCGA-KIRC datasets across multiple pathology foundation-model backbones. Across most dataset, backbone, and metric combinations, DTMF-MIL achieves the strongest results consistently.

Mammogram-based deep learning models have improved breast cancer risk prediction, but the learned imaging patterns remain underexplored. Existing interpretability methods rely on single-image saliency maps, failing to identify recurring mammographic phenotypes across large patient cohorts. By clustering patch embeddings from a pre-trained model, Mirai, we isolate recurring phenotypes linked to 5-year cancer risk. Analyses show risk-increasing phenotypes capture complex structures (e.g., dense tissue, microcalcifications) and shortcut artifacts (e.g., clips). These phenotypes correlate strongly with older age and higher BI-RADS density. Our framework connects tissue patterns to AI risk scores, revealing clinical signatures and potential latent model confounders.

Histopathological tissue segmentation is essential for computer-aided diagnosis, yet weakly supervised methods often suffer from noisy pseudo-labels generated by Class Activation Mapping (CAM). Existing CAM approaches tend to focus on staining-driven appearance cues rather than true causal tissue morphology, resulting in spurious localization and poor structural consistency. To address this issue, we propose C$^2$RM-Seg, a two-stage framework that integrates causal pseudo-label refinement with structure-aware semantic enhancement. For classification, we introduce a Causal Counterfactual Reasoning Module (C$^2$RM) that decomposes features into latent factors and performs counterfactual intervention via a learned causal structure matrix, suppressing confounding context and producing morphology-aligned CAMs. For segmentation, we design a Dual-Path Structural-Semantic Architecture that combines fine-grained structural features from ResNeSt with global semantic priors from a frozen DINOV3 foundation model. A cross-path gating mechanism adaptively regulates semantic injection using local structural cues to preserve boundary fidelity. To further mitigate residual pseudo-label noise, we propose an Uncertainty-Gated Margin (UGM) loss, which dynamically balances margin enforcement and confidence learning based on prediction uncertainty. Extensive experiments on two public histopathological tissue datasets show that C$^2$RM-Seg achieves state-of-the-art performance.

Spatial proteomics enables single-cell-resolution characterization of protein expression within tissue architecture, playing a critical role in understanding tumor microenvironments and guiding precision medicine. However, current analysis workflows remain fragmented, requiring expert manual orchestration of heterogeneous tools and limiting research scalability and reproducibility. We present SP-Mind, the first autonomous AI agent designed to unify the spatial proteomics analysis pipeline, from raw multiplexed tissue imaging to downstream phenotype discovery. Equipped with expert-curated biological analysis skills and specialized computational tools, SP-Mind converts natural-language queries into end-to-end analytical workflows without task-specific fine-tuning. To rigorously evaluate its capabilities, we introduce SP-Bench, a comprehensive benchmark spanning diverse tissue types, comprising 102 tasks across 18 distinct categories. Through extensive evaluation on SP-Bench and established downstream tasks, SP-Mind achieves state-of-the-art performance compared to existing open-source biomedical agent baselines.

Accurate segmentation of curvilinear structures remains challenging in biomedical imaging due to their thin geometry, complex topology, and sensitivity to noise. This is particularly critical for microscopy images of cytoskeletal network, where low signal-to-noise ratios and dense filament crossings often lead to fragmented or inaccurate segmentation. In this work, we propose CurvSegFlow, a segmentation framework based on time-conditioned flow matching. Instead of predicting a segmentation mask in a single pass, the method models segmentation as a dynamic process that progressively refines a noisy initialization into the target structure through a learned velocity field. The proposed model combines a U-Net backbone with triple-term loss function and temporal embeddings to guide the refinement process across reconstruction stages. This formulation enables gradual error correction and improves the continuity of thin structures. CurvSegFlow is evaluated on multiple synthetic and real microtubule datasets, as well as on public benchmarks of retinal vessels, corneal nerves and coronary arteries. Across datasets, the method achieves competitive or superior performance compared to established segmentation models, with consistent improvements in precision and structural continuity, particularly under low signal-to-noise conditions. These results show that flow-based iterative refinement provides a robust and general framework for curvilinear structure segmentation. Overall, the proposed approach improves segmentation quality in challenging imaging conditions and generalizes effectively across modalities without architectural changes.

Scaling robot policy learning for autonomous surgery is challenging, as expert demonstrations are expensive and in vivo exploration poses substantial safety risks. Surgical world models address this by generating realistic, action-conditioned future frames from an initial observation, but existing methods exhibit two persistent failure modes: spatial interaction incoherence, where visible instrument contact fails to induce spatially consistent tissue deformation, and temporal fidelity collapse, where prediction errors compound across autoregressive rollouts and progressively corrupt visual quality. We present SurgVista, a surgical world model that mitigates both failures through two training recipes. Deformation Consistency Regularization extracts scene-point trajectories from training videos and enforces cross-frame coherence through latent contrastive learning, strengthening physically consistent instrument-tissue dynamics. Drift Adaptation Training mitigates long-horizon drift by perturbing conditioning frames with online prediction residuals and photometric augmentations calibrated to long-horizon drift statistics, sustaining visual fidelity over extended rollouts. To enable rigorous evaluation, we further introduce SurgWorld-Bench, featuring diverse procedure types, long-range rollouts, and decoupled metrics for instrument-motion accuracy and tissue-response fidelity. Extensive experiments show that SurgVista consistently outperforms state-of-the-art methods across visual quality, temporal consistency, and interaction fidelity, with gains widening as the prediction horizon grows.

Pathological images are inherently multi-scale, requiring pathologists to integrate evidence from global tissue architecture at low magnification to cellular morphology at higher magnification for accurate diagnosis. While existing pathological datasets for vision-language models (VLMs) include various scales, they often lack explicit cross-scale reasoning objectives. This limitation prevents VLMs from capturing essential cross-scale representations and learning evidence-based reasoning. To bridge this gap, we introduce the first cross-scale training and evaluation paradigm that formulates pathology interpretation as multi-magnification reasoning. However, creating such a task reveals a critical challenge: multi-image visual question answering (VQA) is prone to text-only shortcuts, which allow models to guess answers using magnification-dependent artifacts rather than visual evidence. To address this, we propose a leakage-aware curation pipeline that combines adversarial text-only screening with constraint-guided question design. Using this pipeline, we construct Scale-VQA, a high-quality benchmark with 4,685 multiple-choice questions grounded in 2,537 pathology images across multiple magnification levels. Finally, we present ScaleReasoner-R1, a model trained via reinforcement learning to optimize performance on cross-scale VQA tasks. ScaleReasoner-R1 achieves state-of-the-art performance on our cross-scale reasoning benchmark and generalizes to SOTA performance on established single-scale benchmarks. Findings suggest that even the limited cross-scale supervision can significantly improve pathological understanding. Code is available at https://github.com/iMVR-PL/ScaleReasoner-R1.

Constitutive artificial neural networks (CANNs) provide interpretable material model discovery, but have so far been used in stress-supervised settings based on apparent stress-strain data from homogeneous tests. Because each test samples only a narrow loading path and provides homogenized rather than local stress information, robust discovery typically requires multiple loading modes to constrain the multidimensional response. This is challenging for soft biological tissues, where repeated testing, damage, and sample variability limit reliable information from a single specimen. Here, we combine CANNs with the stress-unsupervised full-field discovery framework EUCLID to identify sparse hyperelastic laws directly from displacement fields and reaction forces in one heterogeneity-inducing loading case. CANN-EUCLID minimizes equilibrium imbalance with sparsity-promoting regularization selecting compact active terms, without local stress measurements or a prescribed law. We evaluate the approach on isotropic and anisotropic benchmarks with prescribed ground-truth laws. When the ground truth is representable by the chosen CANN basis, our method recovers the correct terms with near-exact accuracy, including exponential terms with embedded parameters. When it is not contained in the basis, the method retains shared terms and approximates missing contributions using available basis functions. Generalization depends strongly on sampled deformation states: exponential strain-stiffening terms can be recovered accurately when sufficiently probed, but can produce large extrapolation errors when the stiffening regime lies outside the sampled domain. Forward FE validation simulations show that the discovered behavior accurately replicates the ground truth. These results establish stress-unsupervised CANN discovery as a promising framework for interpretable full-field constitutive model identification.

High-content imaging assays quantify cellular responses to chemical and genetic perturbations, yet continuous trajectories of individual cells are unobservable because cells are chemically fixed at acquisition. Perturbation modeling therefore reduces to inferring stochastic transport between control and treated populations observed only as separate marginals. While recent generative models achieve strong end-point alignment, boundary consistency does not determine intermediate evolution: multiple stochastic processes may connect identical marginals while traversing regions unsupported by observed single-cell morphologies. We introduce \textbf{FreeBridge}, a Schrödinger Bridge formulation for single-cell transition modeling under endpoint-only supervision. FreeBridge defines atomic states as instance-segmented single-cell representations, establishing a fixed cellular manifold, and learns stochastic transport constrained within this geometry via empirical latent support regularization. Across BBBC021, RxRx1, and JUMP, FreeBridge maintains competitive or improved endpoint fidelity and mechanism-of-action retention under a unified evaluation protocol; on BBBC021, it further reduces intermediate support violations. These findings highlight the importance of geometric grounding for biologically interpretable perturbation dynamics. Project page: https://y-research-sbu.github.io/FreeBridge/.

Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

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.

Medical video diagnosis involves inferring clinical decisions from dynamic tissue responses throughout examination processes. Existing methods rely on an end-to-end learning paradigm that i) focuses on appearance rather than pathology, ii) lacks clinical priors, and iii) reasons solely from observations without counterfactual comparison. This work introduces MedVCR, a counterfactual reasoning framework that mimics clinical diagnostic thinking. MedVCR comprises three components: a Counterfactual Generator that synthesizes tissue evolution under specified pathological states via a diffusion-based manner; a Counterfactual Representation Learning module that encodes diagnostic knowledge through clinical rules (i.e., temporal consistency, pathological separability, and counterfactual alignment); and a Dual Diagnostic Prediction strategy that integrates video-level assessment with frame-level counterfactual analysis. MedVCR is evaluated under both fully supervised (e.g., colposcopy) and weakly supervised (e.g., colonoscopy) video diagnosis settings, yielding 2.6%-10.2% performance gains compared with leading baselines. Comprehensive ablation studies further validate the effectiveness of each component. The code will be released.

Pathology foundation models (PFMs) have emerged as a core approach for learning transferable representations from whole slide images (WSIs), and they are typically benchmarked through downstream clinical endpoints. While such task level evaluations are indispensable, they offer limited insight into what the representations themselves encode, particularly whether PFM embeddings can distinguish meaningful tissue regions and capture their spatial relationships. We present SpaPath-Bench, a representation level benchmark designed to diagnose spatial representation capability in PFMs. SpaPath-Bench formulates spatial domain identification (SDI) on paired whole slide image and spatial transcriptomics (ST) data as a diagnostic task. It curates 42 public paired WSI and ST slides, enables large scale evaluation across 19 encoders and seven SDI methods, and measures partition quality using three complementary criteria: unsupervised spatial coherence, transcriptomics referenced agreement, and expert referenced agreement. Across 83K runs, SpaPath-Bench reveals that different pretraining paradigms capture distinct aspects of tissue spatial architecture, and it provides practical guidance for building the next generation of spatially aware computational pathology models. Code and data pipelines are publicly available at https://bokai-zhao.github.io/SpaPath-benchboard/.

Three-dimensional (3D) histopathology of unprocessed tissues has the potential to transform disease management by enabling volumetric characterization of tissue microarchitecture and in-vivo assessment. Back-illumination Interference Tomography (BIT) is a new phase microscopy technology that provides rapid, non-destructive volumetric imaging of unprocessed tissues. However, translating BIT volumes into clinically interpretable H&E images remains challenging, particularly due to shift-variant contrast and the absence of quantitative validation benchmarks. We introduce HistoBIT3D, the first voxel-wise paired BIT and fluorescence-labeled nuclei dataset, enabling quantitative evaluation of structural preservation in unsupervised virtual staining against ground-truth nuclear distributions. Using this dataset, we present a novel virtual staining framework that translates BIT volumes with shift-variant contrast into realistic H&E volumes by leveraging bidirectional multiscale content consistency and cross-domain style reuse to enhance structural fidelity and perceptual realism. Our method achieves state-of-the-art realism metrics while significantly improving 3D nuclei segmentation accuracy and boundary preservation under zero-shot Cellpose evaluation. Together, these contributions establish a quantitatively validated, structurally faithful, and scalable pipeline for 3D virtual H&E staining, advancing the paradigm of slide-free, volumetric computational histopathology. Our data and code are available at: https://github.com/aasong113/HistoBIT3D_VirtualStaining.

In histopathology, human experts primarily rely on color as a means of enhancing contrast to interpret tissue morphology, whereas machine vision models process color as raw statistical information. This distinction raises a fundamental question: to what extent can pixel intensity alone, independent of structural and morphological cues, support cancer classification? To address this question, we systematically evaluated the standalone discriminative power of global color features while deliberately excluding all morphological information. Specifically, we extracted statistical color moments and discretized RGB and HSV color histograms, and assessed their performance across ten diverse experimental settings using classical machine learning classifiers. Our results demonstrate that color features alone can achieve strong performance in binary diagnostic tasks (e.g., benign versus malignant), with classification accuracies reaching up to 89%. This performance is likely attributable to global chromatic shifts associated with malignancy. Importantly, these simple color-based representations consistently outperformed random baselines by a substantial margin, indicating that raw color distributions encode a non-random and diagnostically relevant signal for cancer detection. Consequently, this study suggests that simple, computationally efficient color features can serve as an effective pre-screening tool. By identifying samples with strong chromatic indicators of malignancy, these lightweight models could function as a first-pass triage system, reducing the computational burden on complex deep learning architectures.

In various surgical procedures, regions of interest (ROIs) such as organs or lesions are often occluded by overlying tissues, requiring surgeons to achieve adequate exposure for precise intervention. However, the irregular geometry, nonlinear biomechanical properties of overlying tissues, and limited intraoperative visibility of the ROI pose significant challenges to the autonomous execution of tissue retraction. To address this, we formulate a realistic model of the tissue retraction task and propose a learning-based adaptive control framework for achieving ROI exposure. The method optimizes control inputs online by monitoring changes in the visual boundary of the tissue, while leveraging a deep deformation estimation model trained on simulation data to identify the optimal grasping point and ensure the convergence and safety of the adaptive controller. Through simulations and real-world experiments on different deformable materials, it has been demonstrated that this framework exhibits zero-shot adaptation to similar tasks and can complete the autonomous retraction process, from initial grasp selection to full ROI exposure. Therefore, it has the potential to be applied in actual surgical assistance scenarios.

Whole-slide MIL models are often called context-aware once graphs, Transform ers, or state-space modules are placed above patch embeddings. We show that this label can be deceptive. On pathology tasks where tissue architecture is part of the diagnostic signal, several strong MIL baselines retain nearly unchanged slide level AUC after patch coordinates are permuted. Their predictions are accurate, but largely compositional. We refer to this failure mode as spatial blindness. Our explanation is optimization-based: dense appearance statistics are learned early under slide-level supervision, leaving weak gradients for sparse spatial relations. ResTopoMIL addresses the issue by first fitting a permutation-invariant prototype histogram and then freezing it while a lightweight graph branch learns the residual under a coordinate-shuffling constraint. The architecture is simple by design; the intervention is in how the spatial branch is trained. Across 9 public WSI bench marks, ResTopoMIL improves classification and survival prediction with 1.15M parameters, restores sensitivity to coordinate perturbation, and gives stronger lo calization evidence on CAMELYON-16.

In robot-assisted minimally invasive surgery, high-fidelity dynamic endoscopic scene reconstruction and simulation are crucial to enhancing downstream tasks and advancing surgical outcomes. However, existing methods primarily focus on visual reconstruction, lacking physics-based descriptions of the scene required for realistic simulation. We propose a unified framework that achieves physics-aware reconstruction and physical simulation of endoscopic scenes through Multi-modal Large Language Models (MLLMs)-guided Gaussian Splatting. Our approach utilizes 4D Gaussian Splatting (4DGS) integrated with pre-trained segmentation and depth estimation to represent deformable tissues and tools. To achieve automatic inference of physical properties, we introduce an object-wise material field that initializes material parameters via MLLM and refines them through a differentiable Material Point Method (MPM) under joint supervision from rendered images and optical flow. Validated on both open-source and in-house datasets, our framework achieves superior simulation fidelity and physical accuracy compared to state-of-the-art methods, underscoring its potential to advance robot-assisted surgical applications.

Haptic rendering of viscoelastic materials that exhibit creep and stress relaxation is crucial for many applications, such as medical training with realistic biological tissue models. Fractional-order viscoelastic models provide an effective means of describing intrinsically time-dependent dynamics with few parameters, as these models can naturally capture memory effects. In this study, we present analyses of passivity and rendering performance for fractional-order viscoelastic models under finite-memory discretization. We derive closed-form expressions to ensure the passivity of haptic rendering with a fractional-order (FO) standard linear solid (SLS) model based on Grunwald-Letnikov derivative under short-memory discretization. We also provide symbolic expressions for the effective stiffness and damping of such FO-SLS models. The resulting passivity conditions constitute a unified framework that generalizes previously reported results for integer-order Kelvin-Voigt, Maxwell, and SLS models, since these results are special cases of the newly derived condition. Furthermore, we provide experimental validations of the theoretical passivity bounds and human-subject evaluations of perceived realism of FO-SLS models. Overall, this study establishes a unified theoretical framework and experimental evaluations for FO viscoelastic rendering under short-memory discretization.

Accurate analysis of histopathological images is critical for disease diagnosis and treatment planning. Whole-slide images (WSIs), which digitize tissue specimens at gigapixel resolution, are fundamental to this process but require aggregating thousands of patches for slide-level predictions. Multiple Instance Learning (MIL) tackles this challenge with a two-stage paradigm, decoupling tile-level embedding and slide-level prediction. However, most existing methods implicitly embed patch representations in homogeneous Euclidean spaces, overlooking the hierarchical organization and regional heterogeneity of pathological tissues. This limits current models' ability to capture global tissue architecture and fine-grained cellular morphology. To address this limitation, we introduce a hybrid hyperbolic-Euclidean representation that embeds WSI features in dual geometric spaces, enabling complementary modeling of hierarchical tissue structures and local morphological details. Building on this formulation, we develop BatMIL, a WSI classification framework that leverages both geometric spaces. To model long-range dependencies among thousands of patches, we employ a structured state space sequence model (S4) backbone that encodes patch sequences with linear computational complexity. Furthermore, to account for regional heterogeneity, we introduce a chunk-level mixture-of-experts (MoE) module that groups patches into regions and dynamically routes them to specialized subnetworks, improving representational capacity while reducing redundant computation. Extensive experiments on seven WSI datasets spanning six cancer types demonstrate that BatMIL consistently outperforms state-of-the-art MIL approaches in slide-level classification tasks. These results indicate that geometry-aware representation learning offers a promising direction for next-generation computational pathology.

Organoids are complex, three dimensional, self-organizing cell cultures which manifest organ-like features and represent a powerful platform for studying human disease and developing treatment options. Organoid development is characterized by dynamic morphological and cellular organization, which mimic some aspects of organ development. To study these rapid changes over the course of organoid development, advanced imaging and analytical tools are critical to accurately monitor the trajectory of organoid growth and investigate disease processes. In this work, we focus on computer vision and machine learning techniques to automatically measure the size and shape of developing spheroids derived from pluripotent stem cells (iPSCs), which are typically the starting material for generating organoid cultures. To facilitate this task, we introduce a composite method that combines the Segment Anything Model (SAM), a general-purpose foundation model, with an existing domain-specific tool. This composite method is evaluated together with several existing tools by testing them on organoid image data and comparing with the results of manual image segmentation. We find that no single existing tool is able to segment the test images with sufficient accuracy across all test conditions, but the newly introduced composite method produces consistent and accurate results for all but a very small fraction of the most challenging images. Finally, we compare the accuracy of this method to the variability between manual segmentations by independent annotators (inter-observer variability) and find that by one measure it performs at the level of inter-observer variability and by others it performs very close to it.

This study proposes a transferable encoding strategy that maps tactile sensor data to electrical stimulation patterns, enabling neural organoids to perform an open-loop artificial tactile Braille classification task. Human forebrain organoids cultured on a low-density microelectrode array (MEA) are systematically stimulated to characterize the relationship between electrical stimulation parameters (number of pulse, phase amplitude, phase duration, and trigger delay) and organoid responses, measured as spike activity and spatial displacement of the center of activity. Implemented on event-based tactile inputs recorded from the Evetac sensor, our system achieved an average Braille letter classification accuracy of 61% with a single organoid, which increased significantly to 83% when responses from a three-organoid ensemble were combined. Additionally, the multi-organoid configuration demonstrated enhanced robustness against various types of artificially introduced noise. This research demonstrates the potential of organoids as low-power, adaptive bio-hybrid computational elements and provides a foundational encoding framework for future scalable bio-hybrid computing architectures.

Tissue deformation recovery based on stereo endoscopic images is crucial for tool-tissue interaction analysis and benefits surgical navigation and autonomous soft tissue manipulation. Previous research suffers from the problems raised from camera motion, occlusion, large tissue deformation, lack of tissue-specific biomechanical priors, and reliance on offline processing. Unlike previous studies where the tissue geometry and deformation are represented by 3D points and displacements, the proposed method models tissue geometry as the 3D point and derivative map and tissue deformation as the 3D displacement and local deformation map. For a single surface point, 6 parameters are used to describe its rigid motion and 3 parameters for its local deformation. The method is formulated under the camera-centric setting, where all motions are regarded as the scene motion with respect to the camera. Inter-frame alignment is realized by optimizing the inter-frame deformation, making it unnecessary to estimate camera pose. The concept of the canonical map is introduced to optimize tissue geometry and deformation in an online approach. Quantitative and qualitative experiments were conducted using in vivo and ex vivo laparoscopic datasets. With the inputs of depth and optical flow, the method stably models tissue geometry and deformation even when the tissue is partially occluded or moving outside the field of view. Results show that the 3D reconstruction accuracy in the non-occluded and occluded areas reaches 0.37$\pm$0.27 mm and 0.39$\pm$0.21 mm in terms of surface distance, respectively. The method can also estimate surface strain distribution during various manipulations as an extra modality for mechanical-based analysis.

Dense prediction is a fundamental requirement for many medical vision tasks such as medical image restoration, registration, and segmentation. The most popular vision model, Convolutional Neural Networks (CNNs), has reached bottlenecks due to the intrinsic locality of convolution operations. Recently, transformers have been widely adopted for dense prediction for their capability to capture long-range visual dependence. However, due to the high computational complexity and large memory consumption of self-attention operations, transformers are usually used at downsampled feature resolutions. Such usage cannot effectively leverage the tissue-level textural information available only at the full image resolution. This textural information is crucial for medical dense prediction as it can differentiate the subtle human anatomy in medical images. In this study, we hypothesize that Multi-layer Perceptrons (MLPs) are superior alternatives to transformers in medical dense prediction where tissue-level details dominate the performance, as MLPs enable long-range dependence at the full image resolution. To validate our hypothesis, we develop a full-resolution hierarchical MLP framework that uses MLPs beginning from the full image resolution. We evaluate this framework with various MLP blocks on a wide range of medical dense prediction tasks including restoration, registration, and segmentation. Extensive experiments on six public well-benchmarked datasets show that, by simply using MLPs at full resolution, our framework outperforms its CNN and transformer counterparts and achieves state-of-the-art performance on various medical dense prediction tasks.