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Register a new userNuclei Grading of Clear Cell Renal Cell Carcinoma in Histopathological Image by Composite High-Resolution Network
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The grade of clear cell renal cell carcinoma (ccRCC) is a critical prognostic factor, making ccRCC nuclei grading a crucial task in RCC pathology analysis. Computer-aided nuclei grading aims to improve pathologists work efficiency while reducing their misdiagnosis rate by automatically identifying the grades of tumor nuclei within histopathological images. Such a task requires precisely segment and accurately classify the nuclei. However, most of the existing nuclei segmentation and classification methods can not handle the inter-class similarity property of nuclei grading, thus can not be directly applied to the ccRCC grading task. In this paper, we propose a Composite High-Resolution Network for ccRCC nuclei grading. Specifically, we propose a segmentation network called W-Net that can separate the clustered nuclei. Then, we recast the fine-grained classification of nuclei to two cross-category classification tasks, based on two high-resolution feature extractors (HRFEs) which are proposed for learning these two tasks. The two HRFEs share the same backbone encoder with W-Net by a composite connection so that meaningful features for the segmentation task can be inherited for the classification task. Last, a head-fusion block is applied to generate the predicted label of each nucleus. Furthermore, we introduce a dataset for ccRCC nuclei grading, containing 1000 image patches with 70945 annotated nuclei. We demonstrate that our proposed method achieves state-of-the-art performance compared to existing methods on this large ccRCC grading dataset.
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Histological subtype of papillary (p) renal cell carcinoma (RCC), type 1 vs. type 2, is an essential prognostic factor. The two subtypes of pRCC have a similar pattern, i.e., the papillary architecture, yet some subtle differences, including cellular and cell-layer level patterns. However, the cellular and cell-layer level patterns almost cannot be captured by existing CNN-based models in large-size histopathological images, which brings obstacles to directly applying these models to such a fine-grained classification task. This paper proposes a novel instance-based Vision Transformer (i-ViT) to learn robust representations of histopathological images for the pRCC subtyping task by extracting finer features from instance patches (by cropping around segmented nuclei and assigning predicted grades). The proposed i-ViT takes top-K instances as input and aggregates them for capturing both the cellular and cell-layer level patterns by a position-embedding layer, a grade-embedding layer, and a multi-head multi-layer self-attention module. To evaluate the performance of the proposed framework, experienced pathologists are invited to selected 1162 regions of interest from 171 whole slide images of type 1 and type 2 pRCC. Experimental results show that the proposed method achieves better performance than existing CNN-based models with a significant margin.
Obtaining a large amount of labeled data in medical imaging is laborious and time-consuming, especially for histopathology. However, it is much easier and cheaper to get unlabeled data from whole-slide images (WSIs). Semi-supervised learning (SSL) is an effective way to utilize unlabeled data and alleviate the need for labeled data. For this reason, we proposed a framework that employs an SSL method to accurately detect cancerous regions with a novel annotation method called Minimal Point-Based annotation, and then utilize the predicted results with an innovative hybrid loss to train a classification model for subtyping. The annotator only needs to mark a few points and label them are cancer or not in each WSI. Experiments on three significant subtypes of renal cell carcinoma (RCC) proved that the performance of the classifier trained with the Min-Point annotated dataset is comparable to a classifier trained with the segmentation annotated dataset for cancer region detection. And the subtyping model outperforms a model trained with only diagnostic labels by 12% in terms of f1-score for testing WSIs.
Renal cell carcinoma (RCC) is the most common renal cancer in adults. The histopathologic classification of RCC is essential for diagnosis, prognosis, and management of patients. Reorganization and classification of complex histologic patterns of RCC on biopsy and surgical resection slides under a microscope remains a heavily specialized, error-prone, and time-consuming task for pathologists. In this study, we developed a deep neural network model that can accurately classify digitized surgical resection slides and biopsy slides into five related classes: clear cell RCC, papillary RCC, chromophobe RCC, renal oncocytoma, and normal. In addition to the whole-slide classification pipeline, we visualized the identified indicative regions and features on slides for classification by reprocessing patch-level classification results to ensure the explainability of our diagnostic model. We evaluated our model on independent test sets of 78 surgical resection whole slides and 79 biopsy slides from our tertiary medical institution, and 69 randomly selected surgical resection slides from The Cancer Genome Atlas (TCGA) database. The average area under the curve (AUC) of our classifier on the internal resection slides, internal biopsy slides, and external TCGA slides is 0.98, 0.98 and 0.99, respectively. Our results suggest that the high generalizability of our approach across different data sources and specimen types. More importantly, our model has the potential to assist pathologists by (1) automatically pre-screening slides to reduce false-negative cases, (2) highlighting regions of importance on digitized slides to accelerate diagnosis, and (3) providing objective and accurate diagnosis as the second opinion.
Segmentation and accurate localization of nuclei in histopathological images is a very challenging problem, with most existing approaches adopting a supervised strategy. These methods usually rely on manual annotations that require a lot of time and effort from medical experts. In this study, we present a self-supervised approach for segmentation of nuclei for whole slide histopathology images. Our method works on the assumption that the size and texture of nuclei can determine the magnification at which a patch is extracted. We show that the identification of the magnification level for tiles can generate a preliminary self-supervision signal to locate nuclei. We further show that by appropriately constraining our model it is possible to retrieve meaningful segmentation maps as an auxiliary output to the primary magnification identification task. Our experiments show that with standard post-processing, our method can outperform other unsupervised nuclei segmentation approaches and report similar performance with supervised ones on the publicly available MoNuSeg dataset. Our code and models are available online to facilitate further research.
Cell detection and counting in the image-based ELISPOT and Fluorospot immunoassays is considered a bottleneck. The task has remained hard to automatize, and biomedical researchers often have to rely on results that are not accurate. Previously proposed solutions are heuristic, and data-based solutions are subject to a lack of objective ground truth data. In this paper, we analyze a partial differential equations model for ELISPOT, Fluorospot, and assays of similar design. This leads us to a mathematical observation model for the images generated by these assays. We use this model to motivate a methodology for cell detection. Finally, we provide a real-data example that suggests that this cell detection methodology and a human expert perform comparably.
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