Cross-Domain Image Synthesis: Generating H&E from Multiplex Biomarker Imaging

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Main Authors: Saurav, Jillur Rahman, Nasr, Mohammad Sadegh, Luber, Jacob M.
Format: Preprint
Published: 2025
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author Saurav, Jillur Rahman
Nasr, Mohammad Sadegh
Luber, Jacob M.
author_facet Saurav, Jillur Rahman
Nasr, Mohammad Sadegh
Luber, Jacob M.
contents While multiplex immunofluorescence (mIF) imaging provides deep, spatially-resolved molecular data, integrating this information with the morphological standard of Hematoxylin & Eosin (H&E) can be very important for obtaining complementary information about the underlying tissue. Generating a virtual H&E stain from mIF data offers a powerful solution, providing immediate morphological context. Crucially, this approach enables the application of the vast ecosystem of H&E-based computer-aided diagnosis (CAD) tools to analyze rich molecular data, bridging the gap between molecular and morphological analysis. In this work, we investigate the use of a multi-level Vector-Quantized Generative Adversarial Network (VQGAN) to create high-fidelity virtual H&E stains from mIF images. We rigorously evaluated our VQGAN against a standard conditional GAN (cGAN) baseline on two publicly available colorectal cancer datasets, assessing performance on both image similarity and functional utility for downstream analysis. Our results show that while both architectures produce visually plausible images, the virtual stains generated by our VQGAN provide a more effective substrate for computer-aided diagnosis. Specifically, downstream nuclei segmentation and semantic preservation in tissue classification tasks performed on VQGAN-generated images demonstrate superior performance and agreement with ground-truth analysis compared to those from the cGAN. This work establishes that a multi-level VQGAN is a robust and superior architecture for generating scientifically useful virtual stains, offering a viable pathway to integrate the rich molecular data of mIF into established and powerful H&E-based analytical workflows.
format Preprint
id arxiv_https___arxiv_org_abs_2508_04734
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Cross-Domain Image Synthesis: Generating H&E from Multiplex Biomarker Imaging
Saurav, Jillur Rahman
Nasr, Mohammad Sadegh
Luber, Jacob M.
Quantitative Methods
Artificial Intelligence
Image and Video Processing
While multiplex immunofluorescence (mIF) imaging provides deep, spatially-resolved molecular data, integrating this information with the morphological standard of Hematoxylin & Eosin (H&E) can be very important for obtaining complementary information about the underlying tissue. Generating a virtual H&E stain from mIF data offers a powerful solution, providing immediate morphological context. Crucially, this approach enables the application of the vast ecosystem of H&E-based computer-aided diagnosis (CAD) tools to analyze rich molecular data, bridging the gap between molecular and morphological analysis. In this work, we investigate the use of a multi-level Vector-Quantized Generative Adversarial Network (VQGAN) to create high-fidelity virtual H&E stains from mIF images. We rigorously evaluated our VQGAN against a standard conditional GAN (cGAN) baseline on two publicly available colorectal cancer datasets, assessing performance on both image similarity and functional utility for downstream analysis. Our results show that while both architectures produce visually plausible images, the virtual stains generated by our VQGAN provide a more effective substrate for computer-aided diagnosis. Specifically, downstream nuclei segmentation and semantic preservation in tissue classification tasks performed on VQGAN-generated images demonstrate superior performance and agreement with ground-truth analysis compared to those from the cGAN. This work establishes that a multi-level VQGAN is a robust and superior architecture for generating scientifically useful virtual stains, offering a viable pathway to integrate the rich molecular data of mIF into established and powerful H&E-based analytical workflows.
title Cross-Domain Image Synthesis: Generating H&E from Multiplex Biomarker Imaging
topic Quantitative Methods
Artificial Intelligence
Image and Video Processing
url https://arxiv.org/abs/2508.04734