Nuclei classification is a critical step in computer-aided diagnosis with histopathology images. In the past, various methods have employed graph neural networks (GNN) to analyze cell graphs that model inter-cell relationships by considering nuclei as vertices. However, they are limited by the GNN mechanism that only passes messages among local nodes via fixed edges. To address the issue, we develop a cell graph transformer (CGT) that treats nodes and edges as input tokens to enable learnable adjacency and information exchange among all nodes. Nevertheless, training the transformer with a cell graph presents another challenge. Poorly initialized features can lead to noisy self-attention scores and inferior convergence, particularly when processing the cell graphs with numerous connections. Thus, we further propose a novel topology-aware pretraining method that leverages a graph convolutional network (GCN) to learn a feature extractor. The pre-trained features may suppress unreasonable correlations and hence ease the finetuning of CGT. Experimental results suggest that the proposed cell graph transformer with topology-aware pretraining significantly improves the nuclei classification results, and achieves the state-of-the-art performance. Code and models are available at https://github.com/lhaof/CGT
The recognition of multi-class cell nuclei can significantly facilitate the process of histopathological diagnosis. Numerous pathological datasets are currently available, but their annotations are inconsistent. Most existing methods require individual training on each dataset to deduce the relevant labels and lack the use of common knowledge across datasets, consequently restricting the quality of recognition. In this paper, we propose a universal cell nucleus classification framework (UniCell), which employs a novel prompt learning mechanism to uniformly predict the corresponding categories of pathological images from different dataset domains. In particular, our framework adopts an end-to-end architecture for nuclei detection and classification, and utilizes flexible prediction heads for adapting various datasets. Moreover, we develop a Dynamic Prompt Module (DPM) that exploits the properties of multiple datasets to enhance features. The DPM first integrates the embeddings of datasets and semantic categories, and then employs the integrated prompts to refine image representations, efficiently harvesting the shared knowledge among the related cell types and data sources. Experimental results demonstrate that the proposed method effectively achieves the state-of-the-art results on four nucleus detection and classification benchmarks. Code and models are available at https://github.com/lhaof/UniCell
In the field of biomedical image analysis, the quest for architectures capable of effectively capturing long-range dependencies is paramount, especially when dealing with 3D image segmentation, classification, and landmark detection. Traditional Convolutional Neural Networks (CNNs) struggle with locality respective field, and Transformers have a heavy computational load when applied to high-dimensional medical images. In this paper, we introduce nnMamba, a novel architecture that integrates the strengths of CNNs and the advanced long-range modeling capabilities of State Space Sequence Models (SSMs). nnMamba adds the SSMs to the convolutional residual-block to extract local features and model complex dependencies. For diffirent tasks, we build different blocks to learn the features. Extensive experiments demonstrate nnMamba's superiority over state-of-the-art methods in a suite of challenging tasks, including 3D image segmentation, classification, and landmark detection. nnMamba emerges as a robust solution, offering both the local representation ability of CNNs and the efficient global context processing of SSMs, setting a new standard for long-range dependency modeling in medical image analysis. Code is available at https://github.com/lhaof/nnMamba
Cell segmentation for multi-modal microscopy images remains a challenge due to the complex textures, patterns, and cell shapes in these images. To tackle the problem, we first develop an automatic cell classification pipeline to label the microscopy images based on their low-level image characteristics, and then train a classification model based on the category labels. Afterward, we train a separate segmentation model for each category using the images in the corresponding category. Besides, we further deploy two types of segmentation models to segment cells with roundish and irregular shapes respectively. Moreover, an efficient and powerful backbone model is utilized to enhance the efficiency of our segmentation model. Evaluated on the Tuning Set of NeurIPS 2022 Cell Segmentation Challenge, our method achieves an F1-score of 0.8795 and the running time for all cases is within the time tolerance.
Nuclei segmentation is a fundamental but challenging task in the quantitative analysis of histopathology images. Although fully-supervised deep learning-based methods have made significant progress, a large number of labeled images are required to achieve great segmentation performance. Considering that manually labeling all nuclei instances for a dataset is inefficient, obtaining a large-scale human-annotated dataset is time-consuming and labor-intensive. Therefore, augmenting a dataset with only a few labeled images to improve the segmentation performance is of significant research and application value. In this paper, we introduce the first diffusion-based augmentation method for nuclei segmentation. The idea is to synthesize a large number of labeled images to facilitate training the segmentation model. To achieve this, we propose a two-step strategy. In the first step, we train an unconditional diffusion model to synthesize the Nuclei Structure that is defined as the representation of pixel-level semantic and distance transform. Each synthetic nuclei structure will serve as a constraint on histopathology image synthesis and is further post-processed to be an instance map. In the second step, we train a conditioned diffusion model to synthesize histopathology images based on nuclei structures. The synthetic histopathology images paired with synthetic instance maps will be added to the real dataset for training the segmentation model. The experimental results show that by augmenting 10% labeled real dataset with synthetic samples, one can achieve comparable segmentation results with the fully-supervised baseline.
Automatic nuclei detection and classification can produce effective information for disease diagnosis. Most existing methods classify nuclei independently or do not make full use of the semantic similarity between nuclei and their grouping features. In this paper, we propose a novel end-to-end nuclei detection and classification framework based on a grouping transformer-based classifier. The nuclei classifier learns and updates the representations of nuclei groups and categories via hierarchically grouping the nucleus embeddings. Then the cell types are predicted with the pairwise correlations between categorical embeddings and nucleus features. For the efficiency of the fully transformer-based framework, we take the nucleus group embeddings as the input prompts of backbone, which helps harvest grouping guided features by tuning only the prompts instead of the whole backbone. Experimental results show that the proposed method significantly outperforms the existing models on three datasets.
Automatic tissue segmentation of fetal brain images is essential for the quantitative analysis of prenatal neurodevelopment. However, producing voxel-level annotations of fetal brain imaging is time-consuming and expensive. To reduce labeling costs, we propose a practical unsupervised domain adaptation (UDA) setting that adapts the segmentation labels of high-quality fetal brain atlases to unlabeled fetal brain MRI data from another domain. To address the task, we propose a new UDA framework based on Appearance and Structure Consistency, named ASC. We adapt the segmentation model to the appearances of different domains by constraining the consistency before and after a frequency-based image transformation, which is to swap the appearance between brain MRI data and atlases. Consider that even in the same domain, the fetal brain images of different gestational ages could have significant variations in the anatomical structures. To make the model adapt to the structural variations in the target domain, we further encourage prediction consistency under different structural perturbations. Extensive experiments on FeTA 2021 benchmark demonstrate the effectiveness of our ASC in comparison to registration-based, semi-supervised learning-based, and existing UDA-based methods.
Deep learning (DL) has been used in the automatic diagnosis of Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with brain imaging data. However, previous methods have not fully exploited the relation between brain image and clinical information that is widely adopted by experts in practice. To exploit the heterogeneous features from imaging and tabular data simultaneously, we propose the Visual-Attribute Prompt Learning-based Transformer (VAP-Former), a transformer-based network that efficiently extracts and fuses the multi-modal features with prompt fine-tuning. Furthermore, we propose a Prompt fine-Tuning (PT) scheme to transfer the knowledge from AD prediction task for progressive MCI (pMCI) diagnosis. In details, we first pre-train the VAP-Former without prompts on the AD diagnosis task and then fine-tune the model on the pMCI detection task with PT, which only needs to optimize a small amount of parameters while keeping the backbone frozen. Next, we propose a novel global prompt token for the visual prompts to provide global guidance to the multi-modal representations. Extensive experiments not only show the superiority of our method compared with the state-of-the-art methods in pMCI prediction but also demonstrate that the global prompt can make the prompt learning process more effective and stable. Interestingly, the proposed prompt learning model even outperforms the fully fine-tuning baseline on transferring the knowledge from AD to pMCI.
Multi-class cell nuclei detection is a fundamental prerequisite in the diagnosis of histopathology. It is critical to efficiently locate and identify cells with diverse morphology and distributions in digital pathological images. Most existing methods take complex intermediate representations as learning targets and rely on inflexible post-refinements while paying less attention to various cell density and fields of view. In this paper, we propose a novel Affine-Consistent Transformer (AC-Former), which directly yields a sequence of nucleus positions and is trained collaboratively through two sub-networks, a global and a local network. The local branch learns to infer distorted input images of smaller scales while the global network outputs the large-scale predictions as extra supervision signals. We further introduce an Adaptive Affine Transformer (AAT) module, which can automatically learn the key spatial transformations to warp original images for local network training. The AAT module works by learning to capture the transformed image regions that are more valuable for training the model. Experimental results demonstrate that the proposed method significantly outperforms existing state-of-the-art algorithms on various benchmarks.
Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyperparameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods, but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.