# F2FLDM: Latent Diffusion Models with Histopathology Pre-Trained Embeddings for Unpaired Frozen Section to FFPE Translation

arXiv: https://arxiv.org/abs/2404.12650 · HTML: https://mlsanity.com/paper/2404.12650/

## Key facts

- Cited by 6 papers in the map (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 21 of its 26 references that are in the map.
- First posted on arXiv 19 Apr 2024.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)

## Builds on (most cited first, 21 of 21)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Image-to-Image Translation with Conditional Adversarial Networks](https://mlsanity.com/paper/1611.07004/) (2016)
- [SDXL: Improving Latent Diffusion Models for High-Resolution Image Synthesis](https://mlsanity.com/paper/2307.01952/) (2023)
- [Improved Training of Wasserstein GANs](https://mlsanity.com/paper/1704.00028/) (2017)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Contrastive Learning for Unpaired Image-to-Image Translation](https://mlsanity.com/paper/2007.15651/) (2020)
- [Scaling up GANs for Text-to-Image Synthesis](https://mlsanity.com/paper/2303.05511/) (2023)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Dual Diffusion Implicit Bridges for Image-to-Image Translation](https://mlsanity.com/paper/2203.08382/) (2022)
- [Exposing flaws of generative model evaluation metrics and their unfair treatment of diffusion models](https://mlsanity.com/paper/2306.04675/) (2023)
- [Benchmarking Self-Supervised Learning on Diverse Pathology Datasets](https://mlsanity.com/paper/2212.04690/) (2022)
- [Unpaired Image-to-Image Translation via Neural Schr"odinger Bridge](https://mlsanity.com/paper/2305.15086/) (2023)
- [Improving Tuning-Free Real Image Editing with Proximal Guidance](https://mlsanity.com/paper/2306.05414/) (2023)
- [A Morphology Focused Diffusion Probabilistic Model for Synthesis of Histopathology Images](https://mlsanity.com/paper/2209.13167/) (2022)
- [Unifying Diffusion Models' Latent Space, with Applications to CycleDiffusion and Guidance](https://mlsanity.com/paper/2210.05559/) (2022)
- [UVCGAN: UNet Vision Transformer cycle-consistent GAN for unpaired image-to-image translation](https://mlsanity.com/paper/2203.02557/) (2022)
- [Rotation-Agnostic Image Representation Learning for Digital Pathology](https://mlsanity.com/paper/2311.08359/) (2023)
- [Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Colon](https://mlsanity.com/paper/2308.13182/) (2023)

## Built on by (most cited first, 6 of 6)

- [Content Generation Models in Computational Pathology: A Comprehensive Survey on Methods, Applications, and Challenges](https://mlsanity.com/paper/2505.10993/) (2025)
- [LadderMIL: Multiple Instance Learning with Coarse-to-Fine Self-Distillation](https://mlsanity.com/paper/2502.02707/) (2025)
- [IMPLICITSTAINER: Resolution Agnostic Data-Efficient Virtual Staining Using Neural Implicit Functions](https://mlsanity.com/paper/2505.09831/) (2025)
- [Building Trust in Virtual Immunohistochemistry: Automated Assessment of Image Quality](https://mlsanity.com/paper/2511.04615/) (2025)
- [Layout-Guided Controllable Pathology Image Generation with In-Context Diffusion Transformers](https://mlsanity.com/paper/2603.13386/) (2026)
- [Towards Reliable AI-Based Histological Staining: A Systematic Study of Scaling and Uncertainty in Unpaired Generative Models](https://mlsanity.com/paper/2608.24626/) (2026)

## Abstract (arXiv)

The Frozen Section (FS) technique is a rapid and efficient method, taking only 15-30 minutes to prepare slides for pathologists' evaluation during surgery, enabling immediate decisions on further surgical interventions. However, FS process often introduces artifacts and distortions like folds and ice-crystal effects. In contrast, these artifacts and distortions are absent in the higher-quality formalin-fixed paraffin-embedded (FFPE) slides, which require 2-3 days to prepare. While Generative Adversarial Network (GAN)-based methods have been used to translate FS to FFPE images (F2F), they may leave morphological inaccuracies with remaining FS artifacts or introduce new artifacts, reducing the quality of these translations for clinical assessments. In this study, we benchmark recent generative models, focusing on GANs and Latent Diffusion Models (LDMs), to overcome these limitations. We introduce a novel approach that combines LDMs with Histopathology Pre-Trained Embeddings to enhance restoration of FS images. Our framework leverages LDMs conditioned by both text and pre-trained embeddings to learn meaningful features of FS and FFPE histopathology images. Through diffusion and denoising techniques, our approach not only preserves essential diagnostic attributes like color staining and tissue morphology but also proposes an embedding translation mechanism to better predict the targeted FFPE representation of input FS images. As a result, this work achieves a significant improvement in classification performance, with the Area Under the Curve rising from 81.99% to 94.64%, accompanied by an advantageous CaseFD. This work establishes a new benchmark for FS to FFPE image translation quality, promising enhanced reliability and accuracy in histopathology FS image analysis. Our work is available at https://minhmanho.github.io/f2f_ldm/.