用神经隐式函数实现无需高数据量的高分辨率虚拟染色
IMPLICITSTAINER: Resolution Agnostic Data-Efficient Virtual Staining Using Neural Implicit Functions
- 将染色转换建模为连续空间映射,取代传统分块处理
- 在低数据量下仍保持高性能,且生成结果稳定可复现
- 适合病理诊断中需要精准、一致染色图像的研究者
苏木精-伊红(H&E)染色是癌症诊断的核心,能展现组织结构和细胞形态,但缺乏分子特异性,难以区分细胞状态。免疫组织化学(IHC)等抗体染色可识别特定表型(如CD3⁺ T细胞或HER2阳性肿瘤细胞),但成本高、耗时长且不普及。基于深度学习的虚拟染色方法可从H&E图像生成虚拟IHC图像,作为替代方案。然而,现有方法多为分块处理,固定分辨率,需大量数据,并常依赖后处理超分辨模型;生成对抗网络(GAN)与扩散模型引入随机性,导致幻觉和结构失真,影响临床可靠性。本文提出IMPLICITSTAINER,一种确定性框架,将虚拟染色重构为连续像素级翻译问题。该方法采用神经隐式深度学习模型,通过源域H&E像素及其局部邻域、显式坐标信息的高维嵌入,预测目标域(IHC)像素。相比传统方法,该框架支持分辨率无关推理,在低数据条件下更稳健,且输出确定、可复现。在超过二十种基线模型上,IMPLICITSTAINER在虚拟染色任务(包括IHC与mIF)中均达到当前最优性能。
原文摘要 · Abstract (English)
Hematoxylin and eosin (H&E)-stained slides are central to cancer diagnosis and monitoring, visualizing tissue architecture and cellular morphology. However, H&E lacks the molecular specificity needed to distinguish cell states and functional activation. Antibody-based stains, such as immunohistochemistry (IHC), are therefore required to identify specific phenotypes (e.g., CD3$^+$ T cells or HER2-positive tumor cells) but are costly, time-consuming, and not universally available. Deep learning-based image translation methods, often termed virtual staining, offer a complementary alternative by generating virtual immunostains directly from H&E images. Most existing virtual staining methods are patch-based and operate at fixed resolutions, often requiring large datasets and additional post-hoc super-resolution models to generate high-resolution images. Furthermore, GAN- and diffusion-based approaches introduce stochasticity into generated stains which, although beneficial for visual realism in natural images, can lead to hallucinations and structural distortions that affect the accuracy and reliability required for clinical use. We propose IMPLICITSTAINER, a deterministic framework that reformulates virtual staining as a continuous pixel-level translation problem. In contrast to existing patch-based approaches, IMPLICITSTAINER formulates image translation as a continuous spatial mapping using neural implicit deep learning models. Each target-domain (IHC) pixel is predicted from a high-dimensional embedding of the corresponding source-domain H&E pixel, its local spatial neighborhood, and explicit coordinate information. IMPLICITSTAINER enables resolution-agnostic inference, improves robustness in low-data regimes, and yields deterministic, reproducible outputs. Across more than twenty baselines, IMPLICITSTAINER achieves SOTA performance on virtual staining tasks, including IHC and mIF.
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