This study explores the application of supervised and unsupervised autoencoders (AEs) to automate nuclei classification in clear cell renal cell carcinoma (ccRCC) images, a diagnostic task traditionally reliant on subjective visual grading by pathologists. We evaluate various AE architectures, including standard AEs, contractive AEs (CAEs), and discriminative AEs (DAEs), as well as a classifier-based discriminative AE (CDAE), optimized using the hyperparameter tuning tool Optuna. Bhattacharyya distance is selected from several metrics to assess class separability in the latent space, revealing challenges in distinguishing adjacent grades using unsupervised models. CDAE, integrating a supervised classifier branch, demonstrated superior performance in both latent space separation and classification accuracy. Given that CDAE-CNN achieved notable improvements in classification metrics, affirming the value of supervised learning for class-specific feature extraction, F1 score was incorporated into the tuning process to optimize classification performance. Results show significant improvements in identifying aggressive ccRCC grades by leveraging the classification capability of AE through latent clustering followed by fine-grained classification. Our model outperforms the current state of the art, CHR-Network, across all evaluated metrics. These findings suggest that integrating a classifier branch in AEs, combined with neural architecture search and contrastive learning, enhances grading automation in ccRCC pathology, particularly in detecting aggressive tumor grades, and may improve diagnostic accuracy.
In pathology, accurate and efficient analysis of Hematoxylin and Eosin (H\&E) slides is crucial for timely and effective cancer diagnosis. Although many deep learning solutions for nuclei instance segmentation and classification exist in the literature, they often entail high computational costs and resource requirements, thus limiting their practical usage in medical applications. To address this issue, we introduce a novel convolutional neural network, NuLite, a U-Net-like architecture designed explicitly on Fast-ViT, a state-of-the-art (SOTA) lightweight CNN. We obtained three versions of our model, NuLite-S, NuLite-M, and NuLite-H, trained on the PanNuke dataset. The experimental results prove that our models equal CellViT (SOTA) in terms of panoptic quality and detection. However, our lightest model, NuLite-S, is 40 times smaller in terms of parameters and about 8 times smaller in terms of GFlops, while our heaviest model is 17 times smaller in terms of parameters and about 7 times smaller in terms of GFlops. Moreover, our model is up to about 8 times faster than CellViT. Lastly, to prove the effectiveness of our solution, we provide a robust comparison of external datasets, namely CoNseP, MoNuSeg, and GlySAC. Our model is publicly available at https://github.com/CosmoIknosLab/NuLite
This paper introduces a new technique to measure the feature dependency of neural network models. The motivation is to better understand a model by querying whether it is using information from human-understandable features, e.g., anatomical shape, volume, or image texture. Our method is based on the principle that if a model is dependent on a feature, then removal of that feature should significantly harm its performance. A targeted feature is "removed" by collapsing the dimension in the data distribution that corresponds to that feature. We perform this by moving data points along the feature dimension to a baseline feature value while staying on the data manifold, as estimated by a deep generative model. Then we observe how the model's performance changes on the modified test data set, with the target feature dimension removed. We test our method on deep neural network models trained on synthetic image data with known ground truth, an Alzheimer's disease prediction task using MRI and hippocampus segmentations from the OASIS-3 dataset, and a cell nuclei classification task using the Lizard dataset.
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
Simultaneous segmentation and classification of nuclei in digital histology play an essential role in computer-assisted cancer diagnosis; however, it remains challenging. The highest achieved binary and multi-class Panoptic Quality (PQ) remains as low as 0.68 bPQ and 0.49 mPQ, respectively. It is due to the higher staining variability, variability across the tissue, rough clinical conditions, overlapping nuclei, and nuclear class imbalance. The generic deep-learning methods usually rely on end-to-end models, which fail to address these problems associated explicitly with digital histology. In our previous work, DAN-NucNet, we resolved these issues for semantic segmentation with an end-to-end model. This work extends our previous model to simultaneous instance segmentation and classification. We introduce additional decoder heads with independent weighted losses, which produce semantic segmentation, edge proposals, and classification maps. We use the outputs from the three-head model to apply post-processing to produce the final segmentation and classification. Our multi-stage approach utilizes edge proposals and semantic segmentations compared to direct segmentation and classification strategies followed by most state-of-the-art methods. Due to this, we demonstrate a significant performance improvement in producing high-quality instance segmentation and nuclei classification. We have achieved a 0.841 Dice score for semantic segmentation, 0.713 bPQ scores for instance segmentation, and 0.633 mPQ for nuclei classification. Our proposed framework is generalized across 19 types of tissues. Furthermore, the framework is less complex compared to the state-of-the-art.
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.
Nuclei classification provides valuable information for histopathology image analysis. However, the large variations in the appearance of different nuclei types cause difficulties in identifying nuclei. Most neural network based methods are affected by the local receptive field of convolutions, and pay less attention to the spatial distribution of nuclei or the irregular contour shape of a nucleus. In this paper, we first propose a novel polygon-structure feature learning mechanism that transforms a nucleus contour into a sequence of points sampled in order, and employ a recurrent neural network that aggregates the sequential change in distance between key points to obtain learnable shape features. Next, we convert a histopathology image into a graph structure with nuclei as nodes, and build a graph neural network to embed the spatial distribution of nuclei into their representations. To capture the correlations between the categories of nuclei and their surrounding tissue patterns, we further introduce edge features that are defined as the background textures between adjacent nuclei. Lastly, we integrate both polygon and graph structure learning mechanisms into a whole framework that can extract intra and inter-nucleus structural characteristics for nuclei classification. Experimental results show that the proposed framework achieves significant improvements compared to the state-of-the-art methods.
Automated nuclei segmentation and classification are the keys to analyze and understand the cellular characteristics and functionality, supporting computer-aided digital pathology in disease diagnosis. However, the task still remains challenging due to the intrinsic variations in size, intensity, and morphology of different types of nuclei. Herein, we propose a self-guided ordinal regression neural network for simultaneous nuclear segmentation and classification that can exploit the intrinsic characteristics of nuclei and focus on highly uncertain areas during training. The proposed network formulates nuclei segmentation as an ordinal regression learning by introducing a distance decreasing discretization strategy, which stratifies nuclei in a way that inner regions forming a regular shape of nuclei are separated from outer regions forming an irregular shape. It also adopts a self-guided training strategy to adaptively adjust the weights associated with nuclear pixels, depending on the difficulty of the pixels that is assessed by the network itself. To evaluate the performance of the proposed network, we employ large-scale multi-tissue datasets with 276349 exhaustively annotated nuclei. We show that the proposed network achieves the state-of-the-art performance in both nuclei segmentation and classification in comparison to several methods that are recently developed for segmentation and/or classification.
Computer-aided histopathological image analysis for cancer detection is a major research challenge in the medical domain. Automatic detection and classification of nuclei for cancer diagnosis impose a lot of challenges in developing state of the art algorithms due to the heterogeneity of cell nuclei and data set variability. Recently, a multitude of classification algorithms has used complex deep learning models for their dataset. However, most of these methods are rigid and their architectural arrangement suffers from inflexibility and non-interpretability. In this research article, we have proposed a hybrid and flexible deep learning architecture OLConvNet that integrates the interpretability of traditional object-level features and generalization of deep learning features by using a shallower Convolutional Neural Network (CNN) named as $CNN_{3L}$. $CNN_{3L}$ reduces the training time by training fewer parameters and hence eliminating space constraints imposed by deeper algorithms. We used F1-score and multiclass Area Under the Curve (AUC) performance parameters to compare the results. To further strengthen the viability of our architectural approach, we tested our proposed methodology with state of the art deep learning architectures AlexNet, VGG16, VGG19, ResNet50, InceptionV3, and DenseNet121 as backbone networks. After a comprehensive analysis of classification results from all four architectures, we observed that our proposed model works well and perform better than contemporary complex algorithms.
Due to cellular heterogeneity, cell nuclei classification, segmentation, and detection from pathological images are challenging tasks. In the last few years, Deep Convolutional Neural Networks (DCNN) approaches have been shown state-of-the-art (SOTA) performance on histopathological imaging in different studies. In this work, we have proposed different advanced DCNN models and evaluated for nuclei classification, segmentation, and detection. First, the Densely Connected Recurrent Convolutional Network (DCRN) model is used for nuclei classification. Second, Recurrent Residual U-Net (R2U-Net) is applied for nuclei segmentation. Third, the R2U-Net regression model which is named UD-Net is used for nuclei detection from pathological images. The experiments are conducted with different datasets including Routine Colon Cancer(RCC) classification and detection dataset, and Nuclei Segmentation Challenge 2018 dataset. The experimental results show that the proposed DCNN models provide superior performance compared to the existing approaches for nuclei classification, segmentation, and detection tasks. The results are evaluated with different performance metrics including precision, recall, Dice Coefficient (DC), Means Squared Errors (MSE), F1-score, and overall accuracy. We have achieved around 3.4% and 4.5% better F-1 score for nuclei classification and detection tasks compared to recently published DCNN based method. In addition, R2U-Net shows around 92.15% testing accuracy in term of DC. These improved methods will help for pathological practices for better quantitative analysis of nuclei in Whole Slide Images(WSI) which ultimately will help for better understanding of different types of cancer in clinical workflow.
Efficient and precise classification of histological cell nuclei is of utmost importance due to its potential applications in the field of medical image analysis. It would facilitate the medical practitioners to better understand and explore various factors for cancer treatment. The classification of histological cell nuclei is a challenging task due to the cellular heterogeneity. This paper proposes an efficient Convolutional Neural Network (CNN) based architecture for classification of histological routine colon cancer nuclei named as RCCNet. The main objective of this network is to keep the CNN model as simple as possible. The proposed RCCNet model consists of only 1,512,868 learnable parameters which are significantly less compared to the popular CNN models such as AlexNet, CIFARVGG, GoogLeNet, and WRN. The experiments are conducted over publicly available routine colon cancer histological dataset "CRCHistoPhenotypes". The results of the proposed RCCNet model are compared with five state-of-the-art CNN models in terms of the accuracy, weighted average F1 score and training time. The proposed method has achieved a classification accuracy of 80.61% and 0.7887 weighted average F1 score. The proposed RCCNet is more efficient and generalized terms of the training time and data over-fitting, respectively.
Accurate and robust cell nuclei classification is the cornerstone for a wider range of tasks in digital and Computational Pathology. However, most machine learning systems require extensive labeling from expert pathologists for each individual problem at hand, with no or limited abilities for knowledge transfer between datasets and organ sites. In this paper we implement and evaluate a variety of deep neural network models and model ensembles for nuclei classification in renal cell cancer (RCC) and prostate cancer (PCa). We propose a convolutional neural network system based on residual learning which significantly improves over the state-of-the-art in cell nuclei classification. Finally, we show that the combination of tissue types during training increases not only classification accuracy but also overall survival analysis.