Yonatan Urman, Mark Nishimura, Daniel Abraham, Xiaozhi Cao, Kawin Setsompop
Magnetic Resonance Fingerprinting (MRF) enables fast quantitative imaging, yet reconstructing high-resolution 3D data remains computationally demanding. Non-Cartesian reconstructions require repeated non-uniform FFTs, and the commonly used Locally Low Rank (LLR) prior adds computational overhead and becomes insufficient at high accelerations. Learned 3D priors could address these limitations, but training them at scale is challenging due to memory and runtime demands. We propose SPUR-iG, a fully 3D deep unrolled subspace reconstruction framework that integrates efficient data consistency with a progressive training strategy. Data consistency leverages implicit GROG, which grids non-Cartesian data onto a Cartesian grid with an implicitly learned kernel, enabling FFT-based updates with minimal artifacts. Training proceeds in three stages: (1) pretraining a denoiser with extensive data augmentation, (2) greedy per-iteration unrolled training, and (3) final fine-tuning with gradient checkpointing. Together, these stages make large-scale 3D unrolled learning feasible within a reasonable compute budget. On a large in vivo dataset with retrospective undersampling, SPUR-iG improves subspace coefficient maps quality and quantitative accuracy at 1-mm isotropic resolution compared with LLR and a hybrid 2D/3D unrolled baseline. Whole-brain reconstructions complete in under 15-seconds, with up to $times$111 speedup for 2-minute acquisitions. Notably, $T_1$ maps with our method from 30-second scans achieve accuracy on par with or exceeding LLR reconstructions from 2-minute scans. Overall, the framework improves both accuracy and speed in large-scale 3D MRF reconstruction, enabling efficient and reliable accelerated quantitative imaging.
{"title":"Fully 3D Unrolled Magnetic Resonance Fingerprinting Reconstruction via Staged Pretraining and Implicit Gridding.","authors":"Yonatan Urman, Mark Nishimura, Daniel Abraham, Xiaozhi Cao, Kawin Setsompop","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Magnetic Resonance Fingerprinting (MRF) enables fast quantitative imaging, yet reconstructing high-resolution 3D data remains computationally demanding. Non-Cartesian reconstructions require repeated non-uniform FFTs, and the commonly used Locally Low Rank (LLR) prior adds computational overhead and becomes insufficient at high accelerations. Learned 3D priors could address these limitations, but training them at scale is challenging due to memory and runtime demands. We propose SPUR-iG, a fully 3D deep unrolled subspace reconstruction framework that integrates efficient data consistency with a progressive training strategy. Data consistency leverages implicit GROG, which grids non-Cartesian data onto a Cartesian grid with an implicitly learned kernel, enabling FFT-based updates with minimal artifacts. Training proceeds in three stages: (1) pretraining a denoiser with extensive data augmentation, (2) greedy per-iteration unrolled training, and (3) final fine-tuning with gradient checkpointing. Together, these stages make large-scale 3D unrolled learning feasible within a reasonable compute budget. On a large in vivo dataset with retrospective undersampling, SPUR-iG improves subspace coefficient maps quality and quantitative accuracy at 1-mm isotropic resolution compared with LLR and a hybrid 2D/3D unrolled baseline. Whole-brain reconstructions complete in under 15-seconds, with up to $times$111 speedup for 2-minute acquisitions. Notably, $T_1$ maps with our method from 30-second scans achieve accuracy on par with or exceeding LLR reconstructions from 2-minute scans. Overall, the framework improves both accuracy and speed in large-scale 3D MRF reconstruction, enabling efficient and reliable accelerated quantitative imaging.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12869386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohsen Nakhaei, Alison M Pouch, Silvani Amin, Matthew Daemer, Christian Herz, Natalie Yushkevich, Lourdes Al Ghofaily, Nimesh Desai, Joseph Bavaria, Matthew A Jolley, Wensi Wu
Purpose: Aortic valve (AV) biomechanics play a critical role in maintaining normal cardiac function. Pathological variations, particularly in bicuspid aortic valves, alter leaflet loading, increase strain, and accelerate disease progression. Accurate patient-specific characterization of valve geometry and deformation is therefore essential for predicting disease progression and guiding durable repair. However, existing imaging and computational methods often fail to capture rapid valve motion and complex patient-specific features, limiting precise biomechanical assessment.
Methods: To address these limitations, we developed an image registration framework coupled with the finite element method (FEM) to improve AV tracking and biomechanical evaluation. Patient-specific valve geometries derived from 4D echocardiography and CT were used to simulate AV closure and generate intermediate deformation states. These FEM-generated states facilitated leaflet tracking, while image registration corrected misalignment between simulations and imaging data.
Results: In 20 patients, FEM-augmented registration improved tracking accuracy by 40% compared with direct registration. This improvement enabled more reliable strain estimation by measuring leaflet deformation directly from imaging and reducing uncertainties associated with boundary conditions and material assumptions. Using the improved tracking results, areal, Green-Lagrange, and deviatoric strains were quantified in adult trileaflet and bicuspid valves, as well as pediatric patients, revealing distinct deformation patterns across valve groups. Convergence in mean deviatoric strain between adult trileaflet and pediatric valves suggests volumetric deformation underlies age- and size-related differences in AV mechanics.
Conclusion: Overall, this FEM-augmented registration framework enhances geometric tracking and biomechanical evaluation accuracy, providing clinically relevant insights into patient-specific AV deformation to support individualized medical and intervention planning.
{"title":"Biomechanically Informed Image Registration for Patient-Specific Aortic Valve Strain Analysis.","authors":"Mohsen Nakhaei, Alison M Pouch, Silvani Amin, Matthew Daemer, Christian Herz, Natalie Yushkevich, Lourdes Al Ghofaily, Nimesh Desai, Joseph Bavaria, Matthew A Jolley, Wensi Wu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Aortic valve (AV) biomechanics play a critical role in maintaining normal cardiac function. Pathological variations, particularly in bicuspid aortic valves, alter leaflet loading, increase strain, and accelerate disease progression. Accurate patient-specific characterization of valve geometry and deformation is therefore essential for predicting disease progression and guiding durable repair. However, existing imaging and computational methods often fail to capture rapid valve motion and complex patient-specific features, limiting precise biomechanical assessment.</p><p><strong>Methods: </strong>To address these limitations, we developed an image registration framework coupled with the finite element method (FEM) to improve AV tracking and biomechanical evaluation. Patient-specific valve geometries derived from 4D echocardiography and CT were used to simulate AV closure and generate intermediate deformation states. These FEM-generated states facilitated leaflet tracking, while image registration corrected misalignment between simulations and imaging data.</p><p><strong>Results: </strong>In 20 patients, FEM-augmented registration improved tracking accuracy by 40% compared with direct registration. This improvement enabled more reliable strain estimation by measuring leaflet deformation directly from imaging and reducing uncertainties associated with boundary conditions and material assumptions. Using the improved tracking results, areal, Green-Lagrange, and deviatoric strains were quantified in adult trileaflet and bicuspid valves, as well as pediatric patients, revealing distinct deformation patterns across valve groups. Convergence in mean deviatoric strain between adult trileaflet and pediatric valves suggests volumetric deformation underlies age- and size-related differences in AV mechanics.</p><p><strong>Conclusion: </strong>Overall, this FEM-augmented registration framework enhances geometric tracking and biomechanical evaluation accuracy, providing clinically relevant insights into patient-specific AV deformation to support individualized medical and intervention planning.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Integrating multi-omics data, such as DNA methylation, mRNA expression, and microRNA (miRNA) expression, offers a comprehensive view of the biological mechanisms underlying disease. However, the high dimensionality of multi-omics data, the heterogeneity across modalities, and the lack of reliable biological interaction networks make meaningful integration challenging. In addition, many existing models rely on handcrafted similarity graphs, are vulnerable to class imbalance, and often lack built-in interpretability, limiting their usefulness in biomedical applications. We propose Multi-Omics integration with Tree-generated Graph Neural Network (MOTGNN), a novel and interpretable framework for binary disease classification. MOTGNN employs eXtreme Gradient Boosting (XGBoost) for omics-specific supervised graph construction, followed by modality-specific Graph Neural Networks (GNNs) for hierarchical representation learning, and a deep feedforward network for cross-omics integration. Across three real-world disease datasets, MOTGNN outperforms state-of-the-art baselines by 5-10% in accuracy, ROC-AUC, and F1-score, and remains robust to severe class imbalance. The model maintains computational efficiency through the use of sparse graphs and provides built-in interpretability, revealing both top-ranked biomarkers and the relative contributions of each omics modality. These results highlight the potential of MOTGNN to improve both predictive accuracy and interpretability in multi-omics disease modeling.
{"title":"MOTGNN: Interpretable Graph Neural Networks for Multi-Omics Disease Classification.","authors":"Tiantian Yang, Zhiqian Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Integrating multi-omics data, such as DNA methylation, mRNA expression, and microRNA (miRNA) expression, offers a comprehensive view of the biological mechanisms underlying disease. However, the high dimensionality of multi-omics data, the heterogeneity across modalities, and the lack of reliable biological interaction networks make meaningful integration challenging. In addition, many existing models rely on handcrafted similarity graphs, are vulnerable to class imbalance, and often lack built-in interpretability, limiting their usefulness in biomedical applications. We propose Multi-Omics integration with Tree-generated Graph Neural Network (<b>MOTGNN</b>), a novel and interpretable framework for binary disease classification. MOTGNN employs eXtreme Gradient Boosting (XGBoost) for omics-specific supervised graph construction, followed by modality-specific Graph Neural Networks (GNNs) for hierarchical representation learning, and a deep feedforward network for cross-omics integration. Across three real-world disease datasets, MOTGNN outperforms state-of-the-art baselines by 5-10% in accuracy, ROC-AUC, and F1-score, and remains robust to severe class imbalance. The model maintains computational efficiency through the use of sparse graphs and provides built-in interpretability, revealing both top-ranked biomarkers and the relative contributions of each omics modality. These results highlight the potential of MOTGNN to improve both predictive accuracy and interpretability in multi-omics disease modeling.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Universal approximation theorems establish the expressive capacity of neural network architectures. For dynamical systems, existing results are limited to finite time horizons or systems with a globally stable equilibrium, leaving multistability and limit cycles unaddressed. We prove that Neural ODEs achieve closeness-trajectories within error except for initial conditions of measure -over the infinite time horizon for three target classes: (1) Morse-Smale systems (a structurally stable class) with hyperbolic fixed points, (2) Morse-Smale systems with hyperbolic limit cycles via exact period matching, and (3) systems with normally hyperbolic continuous attractors via discretization. We further establish a temporal generalization bound: closeness implies error for all , bridging topological guarantees to training metrics. These results provide the first universal approximation framework for multistable infinite-horizon dynamics.
{"title":"Universal Approximation Theorems for Dynamical Systems with Infinite-Time Horizon Guarantees.","authors":"Ábel Ságodi, Il Memming Park","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Universal approximation theorems establish the expressive capacity of neural network architectures. For dynamical systems, existing results are limited to finite time horizons or systems with a globally stable equilibrium, leaving multistability and limit cycles unaddressed. We prove that Neural ODEs achieve <math><mi>ε</mi> <mo>-</mo> <mi>δ</mi></math> closeness-trajectories within error <math><mi>ε</mi></math> except for initial conditions of measure <math><mo><</mo> <mi>δ</mi></math> -over the <i>infinite</i> time horizon <math><mo>[</mo> <mn>0</mn> <mo>,</mo> <mi>∞</mi> <mo>)</mo></math> for three target classes: (1) Morse-Smale systems (a structurally stable class) with hyperbolic fixed points, (2) Morse-Smale systems with hyperbolic limit cycles via exact period matching, and (3) systems with normally hyperbolic continuous attractors via discretization. We further establish a temporal generalization bound: <math><mi>ε</mi> <mo>-</mo> <mi>δ</mi></math> closeness implies <math> <msup><mrow><mi>L</mi></mrow> <mrow><mi>p</mi></mrow> </msup> </math> error <math><mo>≤</mo> <msup><mrow><mi>ε</mi></mrow> <mrow><mi>p</mi></mrow> </msup> <mo>+</mo> <mi>δ</mi> <mo>⋅</mo> <msup><mrow><mi>D</mi></mrow> <mrow><mi>p</mi></mrow> </msup> </math> for all <math><mi>t</mi> <mo>≥</mo> <mn>0</mn></math> , bridging topological guarantees to training metrics. These results provide the first universal approximation framework for multistable infinite-horizon dynamics.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Integration and analysis of multi-omics data provide valuable insights for improving cancer subtype classification. However, such data are inherently heterogeneous, high-dimensional, and exhibit complex intra- and inter-modality dependencies. Graph neural networks (GNNs) offer a principled framework for modeling these structures, but existing approaches often rely on prior knowledge or predefined similarity networks that produce undirected or unweighted graphs and fail to capture task-specific directionality and interaction strength. Interpretability at both the modality and feature levels also remains limited. To address these challenges, we propose TF-DWGNet, a novel Graph Neural Network framework that combines tree-based Directed Weighted graph construction with Tensor Fusion for multiclass cancer subtype classification. TF-DWGNet introduces two key innovations: (i) a supervised tree-based strategy that constructs directed, weighted graphs tailored to each omics modality, and (ii) a tensor fusion mechanism that captures unimodal, bimodal, and trimodal interactions using low-rank decomposition for computational efficiency. Experiments on three real-world cancer datasets demonstrate that TF-DWGNet consistently outperforms state-of-the-art baselines across multiple metrics and statistical tests. In addition, the model provides biologically meaningful insights through modality-level contribution scores and ranked feature importance. These results highlight that TF-DWGNet is an effective and interpretable solution for multi-omics integration in cancer research.
{"title":"TF-DWGNet: A Directed Weighted Graph Neural Network with Tensor Fusion for Multi-Omics Cancer Subtype Classification.","authors":"Tiantian Yang, Zhiqian Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Integration and analysis of multi-omics data provide valuable insights for improving cancer subtype classification. However, such data are inherently heterogeneous, high-dimensional, and exhibit complex intra- and inter-modality dependencies. Graph neural networks (GNNs) offer a principled framework for modeling these structures, but existing approaches often rely on prior knowledge or predefined similarity networks that produce undirected or unweighted graphs and fail to capture task-specific directionality and interaction strength. Interpretability at both the modality and feature levels also remains limited. To address these challenges, we propose <b>TF-DWGNet</b>, a novel <b>G</b>raph Neural <b>N</b>etwork framework that combines tree-based <b>D</b>irected <b>W</b>eighted graph construction with <b>T</b>ensor <b>F</b>usion for multiclass cancer subtype classification. TF-DWGNet introduces two key innovations: (i) a supervised tree-based strategy that constructs directed, weighted graphs tailored to each omics modality, and (ii) a tensor fusion mechanism that captures unimodal, bimodal, and trimodal interactions using low-rank decomposition for computational efficiency. Experiments on three real-world cancer datasets demonstrate that TF-DWGNet consistently outperforms state-of-the-art baselines across multiple metrics and statistical tests. In addition, the model provides biologically meaningful insights through modality-level contribution scores and ranked feature importance. These results highlight that TF-DWGNet is an effective and interpretable solution for multi-omics integration in cancer research.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osho Rawal, Rex Lu, Edgar Gonzalez-Kozlova, Sacha Gnjatic, Zeynep H Gümüş
Tabular datasets are commonly visualized as heatmaps, where data values are represented as color intensities in a matrix to reveal patterns and correlations. However, modern omics technologies increasingly generate matrices so large that existing visual exploration tools require downsampling or filtering, risking loss of biologically important patterns. Additional barriers arise from tools that require command-line expertise, or fragmented workflows for downstream biological interpretation. We present ClusterChirp, a web-based platform for real-time, interactive exploration of large-scale data matrices enabled by GPU-accelerated rendering and parallelized hierarchical clustering using multiple CPU cores. Built on deck.gl and multi-threaded clustering algorithms, ClusterChirp supports on-the-fly clustering, multi-metric sorting, feature search, and adjustable visualization parameters for interactive explorations. Uniquely, a natural language interface powered by a Large Language Model helps users perform complex operations and build reproducible workflows from conversational commands. Furthermore, users can select clusters to explore interactive within-cluster correlation networks in 2D or 3D, or perform functional enrichment through biological knowledge bases. Developed with iterative user feedback and adhering to FAIR4S principles, ClusterChirp empowers researchers to extract insights from high-dimensional omics data with unprecedented ease and speed. This website is freely available at clusterchirp.mssm.edu, with no login required.
{"title":"ClusterChirp: A GPU-accelerated Web Server for Natural Language-Guided Interactive Visualization and Analysis of Large Omics Data.","authors":"Osho Rawal, Rex Lu, Edgar Gonzalez-Kozlova, Sacha Gnjatic, Zeynep H Gümüş","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tabular datasets are commonly visualized as heatmaps, where data values are represented as color intensities in a matrix to reveal patterns and correlations. However, modern omics technologies increasingly generate matrices so large that existing visual exploration tools require downsampling or filtering, risking loss of biologically important patterns. Additional barriers arise from tools that require command-line expertise, or fragmented workflows for downstream biological interpretation. We present ClusterChirp, a web-based platform for real-time, interactive exploration of large-scale data matrices enabled by GPU-accelerated rendering and parallelized hierarchical clustering using multiple CPU cores. Built on deck.gl and multi-threaded clustering algorithms, ClusterChirp supports on-the-fly clustering, multi-metric sorting, feature search, and adjustable visualization parameters for interactive explorations. Uniquely, a natural language interface powered by a Large Language Model helps users perform complex operations and build reproducible workflows from conversational commands. Furthermore, users can select clusters to explore interactive within-cluster correlation networks in 2D or 3D, or perform functional enrichment through biological knowledge bases. Developed with iterative user feedback and adhering to FAIR4S principles, ClusterChirp empowers researchers to extract insights from high-dimensional omics data with unprecedented ease and speed. This website is freely available at clusterchirp.mssm.edu, with no login required.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shabeeb Ameen, Kyungeun Kim, Ligesh Theeyancheri, Minh Thanh, Mingming Wu, Alison E Patteson, J M Schwarz, Tao Zhang
Understanding how cells escape from embedded spheroids requires a mechanical framework linking stress generation within cells, across cells, and between cells and the surrounding extracellular matrix (ECM). We develop such a framework by coupling a 3D vertex model of a spheroid to a fibrous ECM network and deriving a 3D Cauchy stress tensor for deformable polyhedral cells, enabling direct cell-level stress quantification in three dimensions. We analyze maximum shear stress in solid-like and fluid-like spheroids: solid-like spheroids exhibit broader stress distributions and radial stress gradients, while fluid-like spheroids show lower stresses with weak spatial organization. Cell shape anisotropy is not generically aligned with principal stress directions, indicating that morphology alone is an unreliable proxy for mechanical state. We further demonstrate strain stiffening at the single-cell level, where elongation produces nonlinear increases in maximum shear stress, allowing boundary cells in otherwise low-stress, fluid-like spheroids to transiently generate forces sufficient to remodel the matrix. To connect strain-induced stress amplification to invasion modes, we introduce an extended 3D vertex model with explicit, tunable cell-cell adhesion springs. In this minimal mechanical framework, single-cell breakout results from strain stiffening combined with reduced adhesion, whereas multi-cell streaming additionally requires anisotropic adhesion strengthened along the elongation axis and weakened orthogonally. Together, these results identify distinct mechanical pathways coupling cell strain, stress amplification, and adhesion organization to spheroid invasion.
{"title":"Cell strain-stiffening drives cell breakout from embedded spheroids.","authors":"Shabeeb Ameen, Kyungeun Kim, Ligesh Theeyancheri, Minh Thanh, Mingming Wu, Alison E Patteson, J M Schwarz, Tao Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Understanding how cells escape from embedded spheroids requires a mechanical framework linking stress generation within cells, across cells, and between cells and the surrounding extracellular matrix (ECM). We develop such a framework by coupling a 3D vertex model of a spheroid to a fibrous ECM network and deriving a 3D Cauchy stress tensor for deformable polyhedral cells, enabling direct cell-level stress quantification in three dimensions. We analyze maximum shear stress in solid-like and fluid-like spheroids: solid-like spheroids exhibit broader stress distributions and radial stress gradients, while fluid-like spheroids show lower stresses with weak spatial organization. Cell shape anisotropy is not generically aligned with principal stress directions, indicating that morphology alone is an unreliable proxy for mechanical state. We further demonstrate strain stiffening at the single-cell level, where elongation produces nonlinear increases in maximum shear stress, allowing boundary cells in otherwise low-stress, fluid-like spheroids to transiently generate forces sufficient to remodel the matrix. To connect strain-induced stress amplification to invasion modes, we introduce an extended 3D vertex model with explicit, tunable cell-cell adhesion springs. In this minimal mechanical framework, single-cell breakout results from strain stiffening combined with reduced adhesion, whereas multi-cell streaming additionally requires anisotropic adhesion strengthened along the elongation axis and weakened orthogonally. Together, these results identify distinct mechanical pathways coupling cell strain, stress amplification, and adhesion organization to spheroid invasion.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Zhang, Arkadiusz Sitek, Lisa Blackberg, Matthew Kupinski, Lars Furenlid, Hamid Sabet
This study demonstrates the feasibility of a novel fabrication technique for high spatial resolution CsI: Tl scintillation detectors tailored for single photon emission computed tomography (SPECT) systems. Building upon our previously developed laser induced optical barrier (LIOB) method, which achieved high spatial resolution, excellent sensitivity, and 100% fabrication yield in CsI: Tl detectors, we extend this approach to a converging-pixel architecture. A CsI: Tl crystal array with converging pixels was designed and fabricated, featuring entrance-face pixels of 1.6x1.6 mm2 and photodetector side pixels of 2x2 mm2. To localize gamma-ray interactions, both the center of gravity (CoG) algorithm and a maximum-likelihood (ML) based decoding method were implemented. A custom built four axis motion platform was developed to deliver a finely collimated pencil beam at precisely controlled positions and angles across the array, enabling generation of a comprehensive dataset for prior knowledge and validation. The results demonstrate an energy resolution of 11.79+/-0.53% (collimated experiment) and a position localization accuracy of 1.00+/-0.42 mm (nearest neighbor interpolation), confirming that the proposed converging-pixel architecture, combined with statistical decoding algorithms, provides a promising path toward the development of high-performance SPECT detectors.
{"title":"Maximum-Likelihood--Based Position Decoding of Laser Processed Converging Pixel CsI: Tl Detectors for High-Resolution SPECT.","authors":"Xi Zhang, Arkadiusz Sitek, Lisa Blackberg, Matthew Kupinski, Lars Furenlid, Hamid Sabet","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study demonstrates the feasibility of a novel fabrication technique for high spatial resolution CsI: Tl scintillation detectors tailored for single photon emission computed tomography (SPECT) systems. Building upon our previously developed laser induced optical barrier (LIOB) method, which achieved high spatial resolution, excellent sensitivity, and 100% fabrication yield in CsI: Tl detectors, we extend this approach to a converging-pixel architecture. A CsI: Tl crystal array with converging pixels was designed and fabricated, featuring entrance-face pixels of 1.6x1.6 mm2 and photodetector side pixels of 2x2 mm2. To localize gamma-ray interactions, both the center of gravity (CoG) algorithm and a maximum-likelihood (ML) based decoding method were implemented. A custom built four axis motion platform was developed to deliver a finely collimated pencil beam at precisely controlled positions and angles across the array, enabling generation of a comprehensive dataset for prior knowledge and validation. The results demonstrate an energy resolution of 11.79+/-0.53% (collimated experiment) and a position localization accuracy of 1.00+/-0.42 mm (nearest neighbor interpolation), confirming that the proposed converging-pixel architecture, combined with statistical decoding algorithms, provides a promising path toward the development of high-performance SPECT detectors.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147273359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nerea Encina-Baranda, Robert J Paneque-Yunta, Javier Lopez-Rodriguez, Edwin C Pratt, Trong Nghia Nguyen, Jan Grimm, Alejandro Lopez-Montes, Joaquin L Herraiz
Positron range (PR) limits spatial resolution and quantitative accuracy in PET imaging, particularly for high-energy positron-emitting radionuclides like 68Ga. We propose a deep learning method using 3D residual encoder-decoder convolutional neural networks (3D RED-CNNs), incorporating tissue-dependent anatomical information through a u-map-dependent loss function. Models were trained with realistic simulations and, using initial PET and CT data, generated positron range corrected images. We validated the models in simulations and real acquisitions. Three 3D RED-CNN architectures, Single-channel, Two-channel, and DualEncoder, were trained on simulated PET datasets and evaluated on synthetic and real PET acquisitions from 68Ga-FH and 68Ga-PSMA-617 mouse studies. Performance was compared to a standard Richardson-Lucy-based positron range correction (RL-PRC) method using metrics such as mean absolute error (MAE), structural similarity index (SSIM), contrast recovery (CR), and contrast-to-noise ratio (CNR). CNN-based methods achieved up to 19 percent SSIM improvement and 13 percent MAE reduction compared to RL-PRC. The Two-Channel model achieved the highest CR and CNR, recovering lung activity with 97 percent agreement to ground truth versus 77 percent for RL-PRC. Noise levels remained stable for CNN models (approximately 5.9 percent), while RL-PRC increased noise by 5.8 percent. In preclinical acquisitions, the Two-Channel model achieved the highest CNR across tissues while maintaining the lowest noise level (9.6 percent). Although no ground truth was available for real data, tumor delineation and spillover artifacts improved with the Two-Channel model. These findings highlight the potential of CNN-based PRC to enhance quantitative PET imaging, particularly for 68Ga. Future work will improve model generalization through domain adaptation and hybrid training strategies.
正电子距离(PR)限制了PET成像的空间分辨率和定量精度,特别是对于像68Ga这样的高能正电子发射放射性核素。我们提出了一种使用3D残差编码器-解码器卷积神经网络(3D red - cnn)的深度学习方法,通过u-map依赖的损失函数结合组织相关的解剖信息。模型经过真实模拟训练,并使用初始PET和CT数据生成正电子距离校正图像。我们在模拟和实际采集中验证了这些模型。我们在模拟PET数据集上训练了三种3D RED-CNN架构(单通道、双通道和双通道),并对68Ga-FH和68Ga-PSMA-617小鼠的合成和真实PET采集结果进行了评估。使用平均绝对误差(MAE)、结构相似指数(SSIM)、对比度恢复(CR)和对比噪声比(CNR)等指标,将性能与标准richardson - lucon -based正电子范围校正(RL-PRC)方法进行比较。与RL-PRC相比,基于cnn的方法实现了高达19%的SSIM改进和13%的MAE降低。双通道模型获得了最高的CR和CNR,恢复肺活动的一致性为97%,而RL-PRC为77%。CNN模型的噪声水平保持稳定(约5.9%),而RL-PRC模型的噪声水平增加了5.8%。在临床前采集中,双通道模型在保持最低噪声水平(9.6%)的同时,实现了跨组织的最高CNR。尽管没有真实数据的基础真相,但双通道模型改善了肿瘤描绘和溢出伪影。这些发现强调了基于cnn的PRC增强定量PET成像的潜力,特别是对68Ga。未来的工作将通过领域自适应和混合训练策略来改进模型泛化。
{"title":"A tissue-informed deep learning-based method for positron range correction in preclinical 68Ga PET imaging.","authors":"Nerea Encina-Baranda, Robert J Paneque-Yunta, Javier Lopez-Rodriguez, Edwin C Pratt, Trong Nghia Nguyen, Jan Grimm, Alejandro Lopez-Montes, Joaquin L Herraiz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Positron range (PR) limits spatial resolution and quantitative accuracy in PET imaging, particularly for high-energy positron-emitting radionuclides like 68Ga. We propose a deep learning method using 3D residual encoder-decoder convolutional neural networks (3D RED-CNNs), incorporating tissue-dependent anatomical information through a u-map-dependent loss function. Models were trained with realistic simulations and, using initial PET and CT data, generated positron range corrected images. We validated the models in simulations and real acquisitions. Three 3D RED-CNN architectures, Single-channel, Two-channel, and DualEncoder, were trained on simulated PET datasets and evaluated on synthetic and real PET acquisitions from 68Ga-FH and 68Ga-PSMA-617 mouse studies. Performance was compared to a standard Richardson-Lucy-based positron range correction (RL-PRC) method using metrics such as mean absolute error (MAE), structural similarity index (SSIM), contrast recovery (CR), and contrast-to-noise ratio (CNR). CNN-based methods achieved up to 19 percent SSIM improvement and 13 percent MAE reduction compared to RL-PRC. The Two-Channel model achieved the highest CR and CNR, recovering lung activity with 97 percent agreement to ground truth versus 77 percent for RL-PRC. Noise levels remained stable for CNN models (approximately 5.9 percent), while RL-PRC increased noise by 5.8 percent. In preclinical acquisitions, the Two-Channel model achieved the highest CNR across tissues while maintaining the lowest noise level (9.6 percent). Although no ground truth was available for real data, tumor delineation and spillover artifacts improved with the Two-Channel model. These findings highlight the potential of CNN-based PRC to enhance quantitative PET imaging, particularly for 68Ga. Future work will improve model generalization through domain adaptation and hybrid training strategies.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12889857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A major goal of neuroscience is to understand brain computations during visual processing in naturalistic settings. A dominant approach is to use image-computable deep neural networks trained with different task objectives as a basis for linear encoding models. However, in addition to requiring estimation of a large number of linear encoding parameters, this approach ignores the structure of the feature maps both in the brain and the models. Recently proposed alternatives factor the linear mapping into separate sets of spatial and feature weights, thus finding static receptive fields for units, which is appropriate only for early visual areas. In this work, we employ the attention mechanism used in the transformer architecture to study how retinotopic visual features can be dynamically routed to category-selective areas in high-level visual processing. We show that this computational motif is significantly more powerful than alternative methods in predicting brain activity during natural scene viewing, across different feature basis models and modalities. We also show that this approach is inherently more interpretable as the attention-routing signals for different high-level categorical areas can be easily visualized for any input image. Given its high performance at predicting brain responses to novel images, the model deserves consideration as a candidate mechanistic model of how visual information from retinotopic maps is routed in the human brain based on the relevance of the input content to different category-selective regions. Our code is available at https://github.com/Hosseinadeli/transformer_brain_encoder/.
{"title":"Transformer brain encoders explain human high-level visual responses.","authors":"Hossein Adeli, Sun Minni, Nikolaus Kriegeskorte","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A major goal of neuroscience is to understand brain computations during visual processing in naturalistic settings. A dominant approach is to use image-computable deep neural networks trained with different task objectives as a basis for linear encoding models. However, in addition to requiring estimation of a large number of linear encoding parameters, this approach ignores the structure of the feature maps both in the brain and the models. Recently proposed alternatives factor the linear mapping into separate sets of spatial and feature weights, thus finding static receptive fields for units, which is appropriate only for early visual areas. In this work, we employ the attention mechanism used in the transformer architecture to study how retinotopic visual features can be dynamically routed to category-selective areas in high-level visual processing. We show that this computational motif is significantly more powerful than alternative methods in predicting brain activity during natural scene viewing, across different feature basis models and modalities. We also show that this approach is inherently more interpretable as the attention-routing signals for different high-level categorical areas can be easily visualized for any input image. Given its high performance at predicting brain responses to novel images, the model deserves consideration as a candidate mechanistic model of how visual information from retinotopic maps is routed in the human brain based on the relevance of the input content to different category-selective regions. Our code is available at https://github.com/Hosseinadeli/transformer_brain_encoder/.</p>","PeriodicalId":93888,"journal":{"name":"ArXiv","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12889847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}