# Virtual histological staining of unlabeled autopsy tissue

arXiv: https://arxiv.org/abs/2308.00920 · HTML: https://mlsanity.com/paper/2308.00920/

## Key facts

- Cited by 11 papers in the map (data through 14 Oct 2026).
- Builds on 16 of its 77 references that are in the map.
- First posted on arXiv 2 Aug 2023.

## Builds on (most cited first, 16 of 16)

- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [Image-to-Image Translation with Conditional Adversarial Networks](https://mlsanity.com/paper/1611.07004/) (2016)
- [TransUNet: Transformers Make Strong Encoders for Medical Image Segmentation](https://mlsanity.com/paper/2102.04306/) (2021)
- [Attention U-Net: Learning Where to Look for the Pancreas](https://mlsanity.com/paper/1804.03999/) (2018)
- [VoxelMorph: A Learning Framework for Deformable Medical Image Registration](https://mlsanity.com/paper/1809.05231/) (2018)
- [Deeper Depth Prediction with Fully Convolutional Residual Networks](https://mlsanity.com/paper/1606.00373/) (2016)
- [Attention Gated Networks: Learning to Leverage Salient Regions in Medical Images](https://mlsanity.com/paper/1808.08114/) (2018)
- [Recent advances and clinical applications of deep learning in medical image analysis](https://mlsanity.com/paper/2105.13381/) (2021)
- [Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue](https://mlsanity.com/paper/1803.11293/) (2018)
- [Deep learning-based transformation of the H&E stain into special stains](https://mlsanity.com/paper/2008.08871/) (2020)
- [Deep Learning-enabled Virtual Histological Staining of Biological Samples](https://mlsanity.com/paper/2211.06822/) (2022)
- [PhaseStain: Digital staining of label-free quantitative phase microscopy images using deep learning](https://mlsanity.com/paper/1807.07701/) (2018)
- [Digital synthesis of histological stains using micro-structured and multiplexed virtual staining of label-free tissue](https://mlsanity.com/paper/2001.07267/) (2020)
- [Label-free virtual HER2 immunohistochemical staining of breast tissue using deep learning](https://mlsanity.com/paper/2112.05240/) (2021)
- [Virtual staining of defocused autofluorescence images of unlabeled tissue using deep neural networks](https://mlsanity.com/paper/2207.02946/) (2022)
- [Virtual Histological Staining of Label-Free Total Absorption Photoacoustic Remote Sensing (TA-PARS)](https://mlsanity.com/paper/2203.02584/) (2022)

## Built on by (most cited first, 11 of 11)

- [Virtual birefringence imaging and histological staining of amyloid deposits in label-free tissue using autofluorescence microscopy and deep learning](https://mlsanity.com/paper/2403.09100/) (2024)
- [Pixel super-resolved virtual staining of label-free tissue using diffusion models](https://mlsanity.com/paper/2410.20073/) (2024)
- [A robust and scalable framework for hallucination detection in virtual tissue staining and digital pathology](https://mlsanity.com/paper/2404.18458/) (2024)
- [Virtual Staining of Label-Free Tissue in Imaging Mass Spectrometry](https://mlsanity.com/paper/2411.13120/) (2024)
- [Generative AI for Misalignment-Resistant Virtual Staining to Accelerate Histopathology Workflows](https://mlsanity.com/paper/2509.14119/) (2025)
- [Label-free evaluation of lung and heart transplant biopsies using tissue autofluorescence-based virtual staining](https://mlsanity.com/paper/2409.05255/) (2024)
- [Deep learning-enabled virtual multiplexed immunostaining of label-free tissue for vascular invasion assessment](https://mlsanity.com/paper/2508.16209/) (2025)
- [Virtual Gram staining of label-free bacteria using darkfield microscopy and deep learning](https://mlsanity.com/paper/2407.12337/) (2024)
- [PRINTER:Deformation-Aware Adversarial Learning for Virtual IHC Staining with In Situ Fidelity](https://mlsanity.com/paper/2509.01214/) (2025)
- [K-Stain: Keypoint-Driven Correspondence for H&E-to-IHC Virtual Staining](https://mlsanity.com/paper/2511.06709/) (2025)
- [Deep Learning for Generating Computational PIN-4 Immunohistochemistry Staining from Prostate Biopsy H&E Images](https://mlsanity.com/paper/2606.01871/) (2026)

## Abstract (arXiv)

Histological examination is a crucial step in an autopsy; however, the traditional histochemical staining of post-mortem samples faces multiple challenges, including the inferior staining quality due to autolysis caused by delayed fixation of cadaver tissue, as well as the resource-intensive nature of chemical staining procedures covering large tissue areas, which demand substantial labor, cost, and time. These challenges can become more pronounced during global health crises when the availability of histopathology services is limited, resulting in further delays in tissue fixation and more severe staining artifacts. Here, we report the first demonstration of virtual staining of autopsy tissue and show that a trained neural network can rapidly transform autofluorescence images of label-free autopsy tissue sections into brightfield equivalent images that match hematoxylin and eosin (H&E) stained versions of the same samples, eliminating autolysis-induced severe staining artifacts inherent in traditional histochemical staining of autopsied tissue. Our virtual H&E model was trained using >0.7 TB of image data and a data-efficient collaboration scheme that integrates the virtual staining network with an image registration network. The trained model effectively accentuated nuclear, cytoplasmic and extracellular features in new autopsy tissue samples that experienced severe autolysis, such as COVID-19 samples never seen before, where the traditional histochemical staining failed to provide consistent staining quality. This virtual autopsy staining technique can also be extended to necrotic tissue, and can rapidly and cost-effectively generate artifact-free H&E stains despite severe autolysis and cell death, also reducing labor, cost and infrastructure requirements associated with the standard histochemical staining.
