# Building Trust in Virtual Immunohistochemistry: Automated Assessment of Image Quality

arXiv: https://arxiv.org/abs/2511.04615 · HTML: https://mlsanity.com/paper/2511.04615/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 41 of its 76 references that are in the map.
- First posted on arXiv 6 Nov 2025.

## Builds on (most cited first, 30 of 41)

- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [Image-to-Image Translation with Conditional Adversarial Networks](https://mlsanity.com/paper/1611.07004/) (2016)
- [Zero-Shot Text-to-Image Generation](https://mlsanity.com/paper/2102.12092/) (2021)
- [Going Deeper with Convolutions](https://mlsanity.com/paper/1409.4842/) (2014)
- [UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction](https://mlsanity.com/paper/1802.03426/) (2018)
- [Demystifying MMD GANs](https://mlsanity.com/paper/1801.01401/) (2018)
- [Improved Precision and Recall Metric for Assessing Generative Models](https://mlsanity.com/paper/1904.06991/) (2019)
- [Unsupervised Image-to-Image Translation Networks](https://mlsanity.com/paper/1703.00848/) (2017)
- [BBDM: Image-to-image Translation with Brownian Bridge Diffusion Models](https://mlsanity.com/paper/2205.07680/) (2022)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [ControlNeXt: Powerful and Efficient Control for Image and Video Generation](https://mlsanity.com/paper/2408.06070/) (2024)
- [Virchow: A Million-Slide Digital Pathology Foundation Model](https://mlsanity.com/paper/2309.07778/) (2023)
- [Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue](https://mlsanity.com/paper/1803.11293/) (2018)
- [BCI: Breast Cancer Immunohistochemical Image Generation through Pyramid Pix2pix](https://mlsanity.com/paper/2204.11425/) (2022)
- [SynthRAD2023 Grand Challenge dataset: generating synthetic CT for radiotherapy](https://mlsanity.com/paper/2303.16320/) (2023)
- [UVCGAN: UNet Vision Transformer cycle-consistent GAN for unpaired image-to-image translation](https://mlsanity.com/paper/2203.02557/) (2022)
- [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)
- [One Model to Synthesize Them All: Multi-contrast Multi-scale Transformer for Missing Data Imputation](https://mlsanity.com/paper/2204.13738/) (2022)
- [QS-Attn: Query-Selected Attention for Contrastive Learning in I2I Translation](https://mlsanity.com/paper/2203.08483/) (2022)
- [Adaptive Supervised PatchNCE Loss for Learning H&E-to-IHC Stain Translation with Inconsistent Groundtruth Image Pairs](https://mlsanity.com/paper/2303.06193/) (2023)
- [StainNet: a fast and robust stain normalization network](https://mlsanity.com/paper/2012.12535/) (2020)
- [Multistain Pretraining for Slide Representation Learning in Pathology](https://mlsanity.com/paper/2408.02859/) (2024)
- [A study of why we need to reassess full reference image quality assessment with medical images](https://mlsanity.com/paper/2405.19097/) (2024)
- [Vector Quantized Image-to-Image Translation](https://mlsanity.com/paper/2207.13286/) (2022)
- [Virtual stain transfer in histology via cascaded deep neural networks](https://mlsanity.com/paper/2207.06578/) (2022)
- [StainDiffuser: MultiTask Dual Diffusion Model for Virtual Staining](https://mlsanity.com/paper/2403.11340/) (2024)
- [Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Colon](https://mlsanity.com/paper/2308.13182/) (2023)
- [VIMs: Virtual Immunohistochemistry Multiplex staining via Text-to-Stain Diffusion Trained on Uniplex Stains](https://mlsanity.com/paper/2407.19113/) (2024)

## Abstract (arXiv)

Deep learning models can generate virtual immunohistochemistry (IHC) stains from hematoxylin and eosin (H&E) images, offering a scalable and low-cost alternative to laboratory IHC. However, reliable evaluation of image quality remains a challenge as current texture- and distribution-based metrics quantify image fidelity rather than the accuracy of IHC staining. Here, we introduce an automated and accuracy grounded framework to determine image quality across sixteen paired or unpaired image translation models. Using color deconvolution, we generate masks of pixels stained brown (i.e., IHC-positive) as predicted by each virtual IHC model. We use the segmented masks of real and virtual IHC to compute stain accuracy metrics (Dice, IoU, Hausdorff distance) that directly quantify correct pixel - level labeling without needing expert manual annotations. Our results demonstrate that conventional image fidelity metrics, including Frechet Inception Distance (FID), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM), correlate poorly with stain accuracy and pathologist assessment. Paired models such as PyramidPix2Pix and AdaptiveNCE achieve the highest stain accuracy, whereas unpaired diffusion- and GAN-based models are less reliable in providing accurate IHC positive pixel labels. Moreover, whole-slide images (WSI) reveal performance declines that are invisible in patch-based evaluations, emphasizing the need for WSI-level benchmarks. Together, this framework defines a reproducible approach for assessing the quality of virtual IHC models, a critical step to accelerate translation towards routine use by pathologists.