Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue
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Abstract (arXiv)
Histological analysis of tissue samples is one of the most widely used methods for disease diagnosis. After taking a sample from a patient, it goes through a lengthy and laborious preparation, which stains the tissue to visualize different histological features under a microscope. Here, we demonstrate a label-free approach to create a virtually-stained microscopic image using a single wide-field auto-fluorescence image of an unlabeled tissue sample, bypassing the standard histochemical staining process, saving time and cost. This method is based on deep learning, and uses a convolutional neural network trained using a generative adversarial network model to transform an auto-fluorescence image of an unlabeled tissue section into an image that is equivalent to the bright-field image of the stained-version of the same sample. We validated this method by successfully creating virtually-stained microscopic images of human tissue samples, including sections of salivary gland, thyroid, kidney, liver and lung tissue, also covering three different stains. This label-free virtual-staining method eliminates cumbersome and costly histochemical staining procedures, and would significantly simplify tissue preparation in pathology and histology fields.
Key facts. Cited by 70 papers in the map (data through 7 Oct 2026). First posted on arXiv 30 Mar 2018.
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Citing papers per year: 2021: 4; 2022: 8; 2023: 16; 2024: 17; 2025: 15; 2026: 10.
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- 2022Deep Learning-enabled Virtual Histological Staining of Biological Samplescited by 42
- 2024Multistain Pretraining for Slide Representation Learning in Pathologycited by 27
- 2023Uncertainty Quantification via Neural Posterior Principal Componentscited by 16
- 2022Self-supervised learning of hologram reconstruction using physics consistencycited by 14
- 2022Virtual stain transfer in histology via cascaded deep neural networkscited by 13
- 2023Hierarchical discriminative learning improves visual representations of biomedical microscopycited by 12
- 2022Virtual staining of defocused autofluorescence images of unlabeled tissue using deep neural networkscited by 11
- 2023Virtual histological staining of unlabeled autopsy tissuecited by 11
- 2024StainDiffuser: MultiTask Dual Diffusion Model for Virtual Stainingcited by 11
- 2023Deep Learning in Breast Cancer Imaging: A Decade of Progress and Future Directionscited by 10
- 2023Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Coloncited by 10
- 2024VIMs: Virtual Immunohistochemistry Multiplex staining via Text-to-Stain Diffusion Trained on Uniplex Stainscited by 10
38 more
- 2021Is Image-to-Image Translation the Panacea for Multimodal Image Registration? A Comparative Studycited by 9
- 2024Virtual birefringence imaging and histological staining of amyloid deposits in label-free tissue using autofluorescence microscopy and deep learningcited by 8
- 2024Pixel super-resolved virtual staining of label-free tissue using diffusion modelscited by 8
- 2021Improving Unsupervised Stain-To-Stain Translation using Self-Supervision and Meta-Learningcited by 7
- 2022Few-shot Transfer Learning for Holographic Image Reconstruction using a Recurrent Neural Networkcited by 7
- 2023Digital staining in optical microscopy using deep learning -- a reviewcited by 7
- 2023A comparative evaluation of image-to-image translation methods for stain transfer in histopathologycited by 7
- 2024HEMIT: H&E to Multiplex-immunohistochemistry Image Translation with Dual-Branch Pix2pix Generatorcited by 7
- 2022Diffractive Interconnects: All-Optical Permutation Operation Using Diffractive Networkscited by 6
- 2024A robust and scalable framework for hallucination detection in virtual tissue staining and digital pathologycited by 6
- 2024Unpaired Multi-Domain Histopathology Virtual Staining using Dual Path Prompted Inversioncited by 6
- 2023Cycle Consistency-based Uncertainty Quantification of Neural Networks in Inverse Imaging Problemscited by 4
- 2024Hierarchical Uncertainty Exploration via Feedforward Posterior Treescited by 4
- 2021A generative adversarial approach to facilitate archival-quality histopathologic diagnoses from frozen tissue sectionscited by 3
- 2022Image Translation Based Nuclei Segmentation for Immunohistochemistry Imagescited by 3
- 2023Uncertainty Visualization via Low-Dimensional Posterior Projectionscited by 3
- 2024AV-GAN: Attention-Based Varifocal Generative Adversarial Network for Uneven Medical Image Translationcited by 3
- 2025USIGAN: Unbalanced Self-Information Feature Transport for Weakly Paired Image IHC Virtual Stainingcited by 3
- 2023Automated Whole Slide Imaging for Label-Free Histology using Photon Absorption Remote Sensing Microscopycited by 2
- 2024Multi-scale Conditional Generative Modeling for Microscopic Image Restorationcited by 2
- 2024Virtual Staining of Label-Free Tissue in Imaging Mass Spectrometrycited by 2
- 2025Digital Staining with Knowledge Distillation: A Unified Framework for Unpaired and Paired-But-Misaligned Datacited by 2
- 2025From Pixels to Pathology: Restoration Diffusion for Diagnostic-Consistent Virtual IHCcited by 2
- 2025Generative AI for Misalignment-Resistant Virtual Staining to Accelerate Histopathology Workflowscited by 2
- 2023Unsupervised Deep Digital Staining For Microscopic Cell Images Via Knowledge Distillationcited by 1
- 2023AGMDT: Virtual Staining of Renal Histology Images with Adjacency-Guided Multi-Domain Transfercited by 1
- 2023Super resolution of histopathological frozen sections via deep learning preserving tissue structurecited by 1
- 2023A Polarization and Radiomics Feature Fusion Network for the Classification of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinomacited by 1
- 2024Single color digital H&E staining with In-and-Out Netcited by 1
- 2024Label-free evaluation of lung and heart transplant biopsies using tissue autofluorescence-based virtual stainingcited by 1
- 2025MIPHEI-ViT: Multiplex Immunofluorescence Prediction from H&E Images using ViT Foundation Modelscited by 1
- 2025Foreground-aware Virtual Staining for Accurate 3D Cell Morphological Profilingcited by 1
- 2025Deep learning-enabled virtual multiplexed immunostaining of label-free tissue for vascular invasion assessmentcited by 1
- 2026PRISM: Distribution-Gated Flow Matching for Controllable Unpaired Image Translationcited by 1
- 2021spectrai: A deep learning framework for spectral datacited by 0
- 2022Deep Learning-Assisted Co-registration of Full-Spectral Autofluorescence Lifetime Microscopic Images with H&E-Stained Histology Imagescited by 0
- 2023Learning with minimal effort: leveraging in silico labeling for cell and nucleus segmentationcited by 0
- 2023Quantification of cardiac capillarization in single-immunostained myocardial slices using weakly supervised instance segmentationcited by 0
50 most cited of 70 All 70 (JSON)
- 2026Seamless Whole Slide Label-Free Virtual Staining9 Sep 2026
- 2026Semi-Supervised Virtual Staining via Morphology Preservation and Histopathological Realism Constraints1 Sep 2026
- 2026PRISM: Distribution-Gated Flow Matching for Controllable Unpaired Image Translation6 Aug 2026
- 2026Physics-Informed Deep Learning Model for Cross-Modality Super-Resolution in Fluorescence Microscopy23 Jul 2026
- 2026Building artificial intelligence virtual tissue (AIVT) for tissue state representation, feature prediction, and dynamic simulation29 Jun 2026
- 2026Virtual 3D H&E Staining from Phase-contrast Back-illumination Interference Tomography21 May 2026
- 2026Continuous quantification of viral plaque dynamics using ultra-large-area label-free imaging enables rapid antiviral susceptibility testing3 May 2026
- 2026CAFlow: Adaptive-Depth Single-Step Flow Matching for Efficient Histopathology Super-Resolution19 Mar 2026
- 2026Segmentation-before-Staining Improves Structural Fidelity in Virtual IHC-to-Multiplex IF Translation17 Mar 2026
- 2026Illumination Angular Spectrum Encoding for Controlling the Functionality of Diffractive Networks8 Jan 2026
- 2025Pixel Super-Resolved Fluorescence Lifetime Imaging Using Deep Learning18 Dec 2025
- 2025Autonomous labeling of surgical resection margins using a foundation model27 Nov 2025
38 more
- 2025Building Trust in Virtual Immunohistochemistry: Automated Assessment of Image Quality6 Nov 2025
- 2025Generative AI for Misalignment-Resistant Virtual Staining to Accelerate Histopathology Workflows17 Sep 2025
- 2025Deep learning-enabled virtual multiplexed immunostaining of label-free tissue for vascular invasion assessment22 Aug 2025
- 2025Cross-Domain Image Synthesis: Generating H&E from Multiplex Biomarker Imaging5 Aug 2025
- 2025From Pixels to Pathology: Restoration Diffusion for Diagnostic-Consistent Virtual IHC4 Aug 2025
- 2025USIGAN: Unbalanced Self-Information Feature Transport for Weakly Paired Image IHC Virtual Staining8 Jul 2025
- 2025Foreground-aware Virtual Staining for Accurate 3D Cell Morphological Profiling7 Jul 2025
- 2025Detecting immune cells with label-free two-photon autofluorescence and deep learning17 Jun 2025
- 2025From Fibers to Cells: Fourier-Based Registration Enables Virtual Cresyl Violet Staining From 3D Polarized Light Imaging16 May 2025
- 2025MIPHEI-ViT: Multiplex Immunofluorescence Prediction from H&E Images using ViT Foundation Models15 May 2025
- 2025Digital Staining with Knowledge Distillation: A Unified Framework for Unpaired and Paired-But-Misaligned Data14 Apr 2025
- 2025An ensemble deep learning approach to detect tumors on Mohs micrographic surgery slides7 Apr 2025
- 2025Adaptive H&E-IHC information fusion staining framework based on feature extra27 Feb 2025
- 2024Unpaired Multi-Domain Histopathology Virtual Staining using Dual Path Prompted Inversion15 Dec 2024
- 2024Virtual Staining of Label-Free Tissue in Imaging Mass Spectrometry20 Nov 2024
- 2024Pixel super-resolved virtual staining of label-free tissue using diffusion models26 Oct 2024
- 2024Label-free evaluation of lung and heart transplant biopsies using tissue autofluorescence-based virtual staining9 Sep 2024
- 2024Novel Methods for Analyzing Cellular Interactions in Deep Learning-Based Image Cytometry: Spatial Interaction Potential and Co-Localization Index14 Aug 2024
- 2024Multistain Pretraining for Slide Representation Learning in Pathology5 Aug 2024
- 2024VIMs: Virtual Immunohistochemistry Multiplex staining via Text-to-Stain Diffusion Trained on Uniplex Stains26 Jul 2024
- 2024Virtual Gram staining of label-free bacteria using darkfield microscopy and deep learning17 Jul 2024
- 2024Multi-scale Conditional Generative Modeling for Microscopic Image Restoration7 Jul 2024
- 2024Imitating the Functionality of Image-to-Image Models Using a Single Example2 Jun 2024
- 2024Hierarchical Uncertainty Exploration via Feedforward Posterior Trees24 May 2024
- 2024Single color digital H&E staining with In-and-Out Net22 May 2024
- 2024A robust and scalable framework for hallucination detection in virtual tissue staining and digital pathology29 Apr 2024
- 2024AV-GAN: Attention-Based Varifocal Generative Adversarial Network for Uneven Medical Image Translation16 Apr 2024
- 2024HEMIT: H&E to Multiplex-immunohistochemistry Image Translation with Dual-Branch Pix2pix Generator27 Mar 2024
- 2024StainDiffuser: MultiTask Dual Diffusion Model for Virtual Staining17 Mar 2024
- 2024Virtual birefringence imaging and histological staining of amyloid deposits in label-free tissue using autofluorescence microscopy and deep learning14 Mar 2024
- 2023A Polarization and Radiomics Feature Fusion Network for the Classification of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma27 Dec 2023
- 2023Uncertainty Visualization via Low-Dimensional Posterior Projections12 Dec 2023
- 2023Quantification of cardiac capillarization in single-immunostained myocardial slices using weakly supervised instance segmentation30 Nov 2023
- 2023Super resolution of histopathological frozen sections via deep learning preserving tissue structure17 Oct 2023
- 2023Uncertainty Quantification via Neural Posterior Principal Components27 Sep 2023
- 2023AGMDT: Virtual Staining of Renal Histology Images with Adjacency-Guided Multi-Domain Transfer12 Sep 2023
- 2023Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Colon25 Aug 2023
- 2023Virtual histological staining of unlabeled autopsy tissue2 Aug 2023
50 newest of 70 All 70 (JSON)
- 2024VIMs: Virtual Immunohistochemistry Multiplex staining via Text-to-Stain Diffusion Trained on Uniplex Stainscited by 10
- 2024Pixel super-resolved virtual staining of label-free tissue using diffusion modelscited by 8
- 2024Multi-scale Conditional Generative Modeling for Microscopic Image Restorationcited by 2
- 2026PRISM: Distribution-Gated Flow Matching for Controllable Unpaired Image Translationcited by 1
- 2026CAFlow: Adaptive-Depth Single-Step Flow Matching for Efficient Histopathology Super-Resolutioncited by 0
- 2026PRISM: Distribution-Gated Flow Matching for Controllable Unpaired Image Translation6 Aug 2026
- 2026CAFlow: Adaptive-Depth Single-Step Flow Matching for Efficient Histopathology Super-Resolution19 Mar 2026
- 2024Pixel super-resolved virtual staining of label-free tissue using diffusion models26 Oct 2024
- 2024VIMs: Virtual Immunohistochemistry Multiplex staining via Text-to-Stain Diffusion Trained on Uniplex Stains26 Jul 2024
- 2024Multi-scale Conditional Generative Modeling for Microscopic Image Restoration7 Jul 2024
- 2022Deep Learning-enabled Virtual Histological Staining of Biological Samplescited by 42
- 2024Multistain Pretraining for Slide Representation Learning in Pathologycited by 27
- 2023Uncertainty Quantification via Neural Posterior Principal Componentscited by 16
- 2022Self-supervised learning of hologram reconstruction using physics consistencycited by 14
- 2022Virtual stain transfer in histology via cascaded deep neural networkscited by 13
- 2023Hierarchical discriminative learning improves visual representations of biomedical microscopycited by 12
- 2022Virtual staining of defocused autofluorescence images of unlabeled tissue using deep neural networkscited by 11
- 2023Virtual histological staining of unlabeled autopsy tissuecited by 11
- 2024StainDiffuser: MultiTask Dual Diffusion Model for Virtual Stainingcited by 11
- 2023Deep Learning in Breast Cancer Imaging: A Decade of Progress and Future Directionscited by 10
- 2023Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Coloncited by 10
- 2021Is Image-to-Image Translation the Panacea for Multimodal Image Registration? A Comparative Studycited by 9
12 most cited of 65 All 65 (JSON)
- 2026Seamless Whole Slide Label-Free Virtual Staining9 Sep 2026
- 2026Semi-Supervised Virtual Staining via Morphology Preservation and Histopathological Realism Constraints1 Sep 2026
- 2026Physics-Informed Deep Learning Model for Cross-Modality Super-Resolution in Fluorescence Microscopy23 Jul 2026
- 2026Building artificial intelligence virtual tissue (AIVT) for tissue state representation, feature prediction, and dynamic simulation29 Jun 2026
- 2026Virtual 3D H&E Staining from Phase-contrast Back-illumination Interference Tomography21 May 2026
- 2026Continuous quantification of viral plaque dynamics using ultra-large-area label-free imaging enables rapid antiviral susceptibility testing3 May 2026
- 2026Segmentation-before-Staining Improves Structural Fidelity in Virtual IHC-to-Multiplex IF Translation17 Mar 2026
- 2026Illumination Angular Spectrum Encoding for Controlling the Functionality of Diffractive Networks8 Jan 2026
- 2025Pixel Super-Resolved Fluorescence Lifetime Imaging Using Deep Learning18 Dec 2025
- 2025Autonomous labeling of surgical resection margins using a foundation model27 Nov 2025
- 2025Building Trust in Virtual Immunohistochemistry: Automated Assessment of Image Quality6 Nov 2025
- 2025Generative AI for Misalignment-Resistant Virtual Staining to Accelerate Histopathology Workflows17 Sep 2025
12 newest of 65 All 65 (JSON)