Ming Li

Accurately diagnosing chronic kidney disease requires pathologists to assess the structure of multiple tissues under different stains, a process that is timeconsuming and labor-intensive. Current AI-based methods for automatic structure assessment, like segmentation, often demand extensive manual annotation and focus on single stain domain. To address these challenges, we introduce MSMTSeg, a generative self-supervised meta-learning framework for multi-stained multi-tissue segmentation in renal biopsy whole slide images (WSIs). MSMTSeg incorporates multiple stain transform models for style translation of inter-stain domains, a self-supervision module for obtaining pre-trained models with the domain-specific feature representation, and a meta-learning strategy that leverages generated virtual data and pre-trained models to learn the domain-invariant feature representation across multiple stains, thereby enhancing segmentation performance. Experimental results demonstrate that MSMTSeg achieves superior and robust performance, with mDSC of 0.836 and mIoU of 0.718 for multiple tissues under different stains, using only one annotated training sample for each stain. Our ablation study confirms the effectiveness of each component, positioning MSMTSeg ahead of classic advanced segmentation networks, recent few-shot segmentation methods, and unsupervised domain adaptation methods. In conclusion, our proposed few-shot cross-domain technology offers a feasible and cost-effective solution for multi-stained renal histology segmentation, providing convenient assistance to pathologists in clinical practice. The source code and conditionally accessible data are available at https://github.com/SnowRain510/MSMTSeg.

Membranous nephropathy is one of the most prevalent conditions responsible for nephrotic syndrome in adults. It is clinically nonspecific and mainly diagnosed by kidney biopsy pathology, with three prevalent techniques: light microscopy, electron microscopy, and immunofluorescence microscopy. Manual observation of glomeruli one by one under the microscope is very time-consuming, and there are certain differences in the observation results between physicians. This study makes use of whole-slide images scanned by a light microscope as well as immunofluorescence images to classify patients with membranous nephropathy. The framework mainly includes a glomerular segmentation module, a confidence coefficient extraction module, and a multi-modal fusion module. This framework first identifies and segments the glomerulus from whole-slide images and immunofluorescence images, and then a glomerular classifier is trained to extract the features of each glomerulus. The results are then combined to produce the final diagnosis. The results of the experiments show that the F1-score of image classification results obtained by combining two kinds of features, which can reach 97.32%, is higher than those obtained by using only light-microscopy-observed images or immunofluorescent images, which reach 92.76% and 93.20%, respectively. Experiments demonstrate that considering both WSIs and immunofluorescence images is effective in improving the diagnosis of membranous nephropathy.

Background and Objective: Detecting urine red blood cells (U-RBCs) is an important operation in diagnosing nephropathy. Existing U-RBC detection methods usually employ single-focus images to implement such tasks, which inevitably results in false positives and missed detections due to the abundance of defocused U-RBCs in the single-focus images. Meanwhile, the current diabetic nephropathy diagnosis methods heavily rely on artificially setting a threshold to detect the U-RBC proportion, whose accuracy and robustness are still supposed to be improved. Methods: To overcome these limitations, a novel multi-focus video dataset in which the typical shape of all U-RBCs can be captured in one frame is constructed, and an accurate U-RBC detection method based on multi-focus video fusion (D-MVF) is presented. The proposed D-MVF method consists of multi-focus video fusion and detection stages. In the fusion stage, D-MVF first uses the frame-difference data of multi-focus video to separate the U-RBCs from the background. Then, a new key frame extraction method based on the three metrics of information entropy, edge gradient, and intensity contrast is proposed. This method is responsible for extracting the typical shapes of U-RBCs and fusing them into a single image. In the detection stage, D-MVF utilizes the high-performance deep learning model YOLOv4 to rapidly and accurately detect U-RBCs based on the fused image. In addition, based on U-RBC detection results from D-MVF, this paper applies the K-nearest neighbor (KNN) method to replace artificial threshold setting for achieving more accurate diabetic nephropathy diagnosis. Results: A series of controlled experiments are conducted on the self-constructed dataset containing 887 multi-focus videos, and the experimental results show that the proposed D-MVF obtains a satisfactory mean average precision (mAP) of 0.915, which is significantly higher than that of the existing method based on single-focus images (0.700). Meanwhile, the diabetic nephropathy diagnosis accuracy and specificity of KNN reach 0.781 and 0.793, respectively, which significantly exceed the traditional threshold method (0.719 and 0.759). Conclusions: The research in this paper intelligently assists microscopists to complete U-RBC detection and diabetic nephropathy diagnosis. Therefore, the work load of microscopists can be effectively relieved, and the urine test demands of nephrotic patients can be met.

Communications in Computational Physics (CiCP) publishes original research and survey papers of high scientific value in computational modeling of physical problems. Results in multi-physics and multi-scale innovative computational methods and modeling in all physical sciences will be featured. CiCP is a refereed, interdisciplinary journal edited by a group of world-wide leading scientists in diverse fields to guarantee its highest standard. The journal is published in a timely fashion in printed and electronic forms.

Membranous nephropathy (MN) is a frequent type of adult nephrotic syndrome, which has a high clinical incidence and can cause various complications. In the biopsy microscope slide of membranous nephropathy, spikelike projections on the glomerular basement membrane is a prominent feature of the MN. However, due to the whole biopsy slide contains large number of glomeruli, and each glomerulus includes many spike lesions, the pathological feature of the spikes is not obvious. It thus is time-consuming for doctors to diagnose glomerulus one by one and is difficult for pathologists with less experience to diagnose. In this paper, we establish a visualized classification model based on the multi-scale annotation multi-instance learning (MSA-MIL) to achieve glomerular classification and spikes visualization. The MSA-MIL model mainly involves three parts. Firstly, U-Net is used to extract the region of the glomeruli to ensure that the features learned by the succeeding algorithm are focused inside the glomeruli itself. Secondly, we use MIL to train an instance-level classifier combined with MSA method to enhance the learning ability of the network by adding a location-level labeled reinforced dataset, thereby obtaining an example-level feature representation with rich semantics. Lastly, the predicted scores of each tile in the image are summarized to obtain glomerular classification and visualization of the classification results of the spikes via the usage of sliding window method. The experimental results confirm that the proposed MSA-MIL model can effectively and accurately classify normal glomeruli and spiked glomerulus and visualize the position of spikes in the glomerulus. Therefore, the proposed model can provide a good foundation for assisting the clinical doctors to diagnose the glomerular membranous nephropathy.