# Virtual 3D H&E Staining from Phase-contrast Back-illumination Interference Tomography

arXiv: https://arxiv.org/abs/2605.22000 · HTML: https://mlsanity.com/paper/2605.22000/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 4 of its 25 references that are in the map.
- First posted on arXiv 21 May 2026.

## Builds on (most cited first, 4 of 4)

- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [A Style-Based Generator Architecture for Generative Adversarial Networks](https://mlsanity.com/paper/1812.04948/) (2018)
- [Arbitrary Style Transfer in Real-time with Adaptive Instance Normalization](https://mlsanity.com/paper/1703.06868/) (2017)
- [Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue](https://mlsanity.com/paper/1803.11293/) (2018)

## Abstract (arXiv)

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.
