Mask-guided cross-image attention for zero-shot in-silico histopathologic image generation with a diffusion model

Creating in-silico data with generative AI promises a cost-effective alternative to staining, imaging, and annotating whole slide images in computational pathology. Diffusion models are the state-of-the-art solution for generating in-silico images, offering unparalleled fidelity and realism. Using appearance transfer diffusion models allows for zero-shot image generation, facilitating fast application and making model training unnecessary. However current appearance transfer diffusion models are designed for natural images, where the main task is to transfer the foreground object from an origin to a target domain, while the background is of insignificant importance. In computational pathology, specifically in oncology, it is however not straightforward to define which objects in an image should be classified as foreground and background, as all objects in an image may be of critical importance for the detailed understanding the tumor micro-environment. We contribute to the applicability of appearance transfer diffusion models to immunohistochemistry-stained images by modifying the appearance transfer guidance to alternate between class-specific AdaIN feature statistics matchings using existing segmentation masks. The performance of the proposed method is demonstrated on the downstream task of supervised epithelium segmentation, showing that the number of manual annotations required for model training can be reduced by 75%, outperforming the baseline approach. Additionally, we consulted with a certified pathologist to investigate future improvements. We anticipate this work to inspire the application of zero-shot diffusion models in computational pathology, providing an efficient method to generate in-silico images with unmatched fidelity and realism, which prove meaningful for downstream tasks, such as training existing deep learning models or finetuning foundation models.

ReStainGAN: Leveraging IHC to IF Stain Domain Translation for in-silico Data Generation

The creation of in-silico datasets can expand the utility of existing annotations to new domains with different staining patterns in computational pathology. As such, it has the potential to significantly lower the cost associated with building large and pixel precise datasets needed to train supervised deep learning models. We propose a novel approach for the generation of in-silico immunohistochemistry (IHC) images by disentangling morphology specific IHC stains into separate image channels in immunofluorescence (IF) images. The proposed approach qualitatively and quantitatively outperforms baseline methods as proven by training nucleus segmentation models on the created in-silico datasets.

Novel Deep Learning Approach to Derive Cytokeratin Expression and Epithelium Segmentation from DAPI

Generative Adversarial Networks (GANs) are state of the art for image synthesis. Here, we present dapi2ck, a novel GAN-based approach to synthesize cytokeratin (CK) staining from immunofluorescent (IF) DAPI staining of nuclei in non-small cell lung cancer (NSCLC) images. We use the synthetic CK to segment epithelial regions, which, compared to expert annotations, yield equally good results as segmentation on stained CK. Considering the limited number of markers in a multiplexed IF (mIF) panel, our approach allows to replace CK by another marker addressing the complexity of the tumor micro-environment (TME) to facilitate patient selection for immunotherapies. In contrast to stained CK, dapi2ck does not suffer from issues like unspecific CK staining or loss of tumoral CK expression.