Zero-shot Volumetric CT Super-Resolution using 3D Gaussian Splatting with Upsampled 2D X-ray Projection Priors

Computed tomography (CT) is widely used in clinical diagnosis, but acquiring high-resolution (HR) CT is limited by radiation exposure risks. Deep learning-based super-resolution (SR) methods have been studied to reconstruct HR from low-resolution (LR) inputs. While supervised SR approaches have shown promising results, they require large-scale paired LR-HR volume datasets that are often unavailable. In contrast, zero-shot methods alleviate the need for paired data by using only a single LR input, but typically struggle to recover fine anatomical details due to limited internal information. To overcome these, we propose a novel zero-shot 3D CT SR framework that leverages upsampled 2D X-ray projection priors generated by a diffusion model. Exploiting the abundance of HR 2D X-ray data, we train a diffusion model on large-scale 2D X-ray projection and introduce a per-projection adaptive sampling strategy. It selects the generative process for each projection, thus providing HR projections as strong external priors for 3D CT reconstruction. These projections serve as inputs to 3D Gaussian splatting for reconstructing a 3D CT volume. Furthermore, we propose negative alpha blending (NAB-GS) that allows negative values in Gaussian density representation. NAB-GS enables residual learning between LR and diffusion-based projections, thereby enhancing high-frequency structure reconstruction. Experiments on two datasets show that our method achieves superior quantitative and qualitative results for 3D CT SR.

Virtual Multiplex Staining for Histological Images using a Marker-wise Conditioned Diffusion Model

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 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.

Co-synthesis of Histopathology Nuclei Image-Label Pairs using a Context-Conditioned Joint Diffusion Model

In multi-class histopathology nuclei analysis tasks, the lack of training data becomes a main bottleneck for the performance of learning-based methods. To tackle this challenge, previous methods have utilized generative models to increase data by generating synthetic samples. However, existing methods often overlook the importance of considering the context of biological tissues (e.g., shape, spatial layout, and tissue type) in the synthetic data. Moreover, while generative models have shown superior performance in synthesizing realistic histopathology images, none of the existing methods are capable of producing image-label pairs at the same time. In this paper, we introduce a novel framework for co-synthesizing histopathology nuclei images and paired semantic labels using a context-conditioned joint diffusion model. We propose conditioning of a diffusion model using nucleus centroid layouts with structure-related text prompts to incorporate spatial and structural context information into the generation targets. Moreover, we enhance the granularity of our synthesized semantic labels by generating instance-wise nuclei labels using distance maps synthesized concurrently in conjunction with the images and semantic labels. We demonstrate the effectiveness of our framework in generating high-quality samples on multi-institutional, multi-organ, and multi-modality datasets. Our synthetic data consistently outperforms existing augmentation methods in the downstream tasks of nuclei segmentation and classification.

Controllable and Efficient Multi-Class Pathology Nuclei Data Augmentation using Text-Conditioned Diffusion Models

In the field of computational pathology, deep learning algorithms have made significant progress in tasks such as nuclei segmentation and classification. However, the potential of these advanced methods is limited by the lack of available labeled data. Although image synthesis via recent generative models has been actively explored to address this challenge, existing works have barely addressed label augmentation and are mostly limited to single-class and unconditional label generation. In this paper, we introduce a novel two-stage framework for multi-class nuclei data augmentation using text-conditional diffusion models. In the first stage, we innovate nuclei label synthesis by generating multi-class semantic labels and corresponding instance maps through a joint diffusion model conditioned by text prompts that specify the label structure information. In the second stage, we utilize a semantic and text-conditional latent diffusion model to efficiently generate high-quality pathology images that align with the generated nuclei label images. We demonstrate the effectiveness of our method on large and diverse pathology nuclei datasets, with evaluations including qualitative and quantitative analyses, as well as assessments of downstream tasks.

Evaluation and improvement of Segment Anything Model for interactive histopathology image segmentation

With the emergence of the Segment Anything Model (SAM) as a foundational model for image segmentation, its application has been extensively studied across various domains, including the medical field. However, its potential in the context of histopathology data, specifically in region segmentation, has received relatively limited attention. In this paper, we evaluate SAM's performance in zero-shot and fine-tuned scenarios on histopathology data, with a focus on interactive segmentation. Additionally, we compare SAM with other state-of-the-art interactive models to assess its practical potential and evaluate its generalization capability with domain adaptability. In the experimental results, SAM exhibits a weakness in segmentation performance compared to other models while demonstrating relative strengths in terms of inference time and generalization capability. To improve SAM's limited local refinement ability and to enhance prompt stability while preserving its core strengths, we propose a modification of SAM's decoder. The experimental results suggest that the proposed modification is effective to make SAM useful for interactive histology image segmentation. The code is available at \url{https://github.com/hvcl/SAM_Interactive_Histopathology}

Scribble-supervised Cell Segmentation Using Multiscale Contrastive Regularization

Current state-of-the-art supervised deep learning-based segmentation approaches have demonstrated superior performance in medical image segmentation tasks. However, such supervised approaches require fully annotated pixel-level ground-truth labels, which are labor-intensive and time-consuming to acquire. Recently, Scribble2Label (S2L) demonstrated that using only a handful of scribbles with self-supervised learning can generate accurate segmentation results without full annotation. However, owing to the relatively small size of scribbles, the model is prone to overfit and the results may be biased to the selection of scribbles. In this work, we address this issue by employing a novel multiscale contrastive regularization term for S2L. The main idea is to extract features from intermediate layers of the neural network for contrastive loss so that structures at various scales can be effectively separated. To verify the efficacy of our method, we conducted ablation studies on well-known datasets, such as Data Science Bowl 2018 and MoNuSeg. The results show that the proposed multiscale contrastive loss is effective in improving the performance of S2L, which is comparable to that of the supervised learning segmentation method.

DiffMix: Diffusion Model-based Data Synthesis for Nuclei Segmentation and Classification in Imbalanced Pathology Image Datasets

Nuclei segmentation and classification is a significant process in pathology image analysis. Deep learning-based approaches have greatly contributed to the higher accuracy of this task. However, those approaches suffer from the imbalanced nuclei data composition, which shows lower classification performance on the rare nuclei class. In this paper, we propose a realistic data synthesis method using a diffusion model. We generate two types of virtual patches to enlarge the training data distribution, which is for balancing the nuclei class variance and for enlarging the chance to look at various nuclei. After that, we use a semantic-label-conditioned diffusion model to generate realistic and high-quality image samples. We demonstrate the efficacy of our method by experiment results on two imbalanced nuclei datasets, improving the state-of-the-art networks. The experimental results suggest that the proposed method improves the classification performance of the rare type nuclei classification, while showing superior segmentation and classification performance in imbalanced pathology nuclei datasets.