用H&E图像生成18种标记物的虚拟多路染色,提升病理分析效率。
Virtual Multiplex Staining for Histological Images using a Marker-wise Conditioned Diffusion Model
- 基于条件扩散模型,逐标记生成多路染色图像。
- 可生成最多18种标记物,远超此前2-3种的限制。
- 适用于已有H&E数据集的回顾性研究与大规模分析。
多路成像正推动病理学发展,实现组织样本中多个生物标志物的同时可视化,提供传统苏木精-伊红(H&E)染色无法获得的分子级信息。然而,多路数据获取的复杂性和高昂成本阻碍了其广泛应用。此外,大多数现有的H&E图像库缺乏对应的多路图像,限制了多模态分析机会。为此,我们利用潜在扩散模型(LDMs)在建模复杂数据分布方面的优势,通过其强大先验对目标领域进行微调。本文提出一种新型虚拟多路染色框架,利用预训练的LDM参数,通过条件扩散模型从H&E图像生成多路图像。该方法采用逐标记条件化策略,共享同一架构生成所有标记物。为应对不同标记染色间像素值分布差异并提升推理速度,我们对模型进行单步采样微调,通过像素级损失函数提升颜色对比度保真度与推理效率。我们在两个公开数据集上验证框架,显著证明其生成多达18种标记物的能力,准确率显著优于此前仅支持2-3种标记物的方法。该工作首次实现高效虚拟多路染色,弥合了H&E与多路成像之间的鸿沟,有望推动现有H&E图像库的回顾性研究与大规模分析。
原文摘要 · Abstract (English)
Multiplex imaging is revolutionizing pathology by enabling the simultaneous visualization of multiple biomarkers within tissue samples, providing molecular-level insights that traditional hematoxylin and eosin (H&E) staining cannot provide. However, the complexity and cost of multiplex data acquisition have hindered its widespread adoption. Additionally, most existing large repositories of H&E images lack corresponding multiplex images, limiting opportunities for multimodal analysis. To address these challenges, we leverage recent advances in latent diffusion models (LDMs), which excel at modeling complex data distributions by utilizing their powerful priors for fine-tuning to a target domain. In this paper, we introduce a novel framework for virtual multiplex staining that utilizes pretrained LDM parameters to generate multiplex images from H&E images using a conditional diffusion model. Our approach enables marker-by-marker generation by conditioning the diffusion model on each marker, while sharing the same architecture across all markers. To tackle the challenge of varying pixel value distributions across different marker stains and to improve inference speed, we fine-tune the model for single-step sampling, enhancing both color contrast fidelity and inference efficiency through pixel-level loss functions. We validate our framework on two publicly available datasets, notably demonstrating its effectiveness in generating up to 18 different marker types with improved accuracy, a substantial increase over the 2-3 marker types achieved in previous approaches. This validation highlights the potential of our framework, pioneering virtual multiplex staining. Finally, this paper bridges the gap between H&E and multiplex imaging, potentially enabling retrospective studies and large-scale analyses of existing H&E image repositories.
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