A deep learning framework for glomeruli segmentation with boundary attention

Fine-grained evaluation of glomerular pathology must distinguish normal glomeruli from abnormalities such as global and segmental glomerulosclerosis, obsolescent, ischemic, solidified, disappearing, and atubular glomeruli. Supervised classification requires labeled examples of every category, which is impractical when subtypes are rare or absent from the training cohort. One-class anomaly detection offers an alternative by modeling normal data and scoring deviations, allowing previously unseen abnormalities to be detected. We use the frozen residual U-Net backbone of Omni-Seg, pretrained to segment structurally normal renal primitives without abnormal-subtype labels. We propose NoRDeC (Normal-Reference Detection and Characterization), a framework combining Mahalanobis normal-reference scoring with layer-wise representation analysis to determine whether and where glomerular pathology is encoded, how spatial aggregation affects detection, and whether abnormalities alter inter-layer relationships differently. Using glomerular images from two institutions, we evaluate backbone layers and aggregation strategies, compare NoRDeC with PaDiM and PatchCore, and analyze representations using centered kernel alignment (CKA). Layer 4 with Center-70 aggregation achieved a pooled AUROC of $0.926\pm0.013$. NoRDeC achieved the highest AUROC in six of seven abnormality categories and in the pooled analysis, while CKA suggested subtype-dependent changes in inter-layer relationships not captured by anomaly scores alone. The normal-reference model is fitted using only normal glomeruli; abnormality labels are used for configuration selection, evaluation, and grouping in the representation analysis. These results show that a frozen renal feature extractor can support both detection and representation-level characterization of glomerular abnormalities without using abnormal examples to fit the detector.

Glomerular pathology is central to the diagnosis and prognosis of renal diseases, yet the heterogeneity of glomerular morphology and fine-grained lesion patterns remain challenging for current AI approaches. We present GloPath, an entity-centric foundation model trained on over one million glomeruli extracted from 14,049 renal biopsy specimens using multi-scale and multi-view self-supervised learning. GloPath addresses two major challenges in nephropathology: glomerular lesion assessment and clinicopathological insights discovery. For lesion assessment, GloPath was benchmarked across three independent cohorts on 52 tasks, including lesion recognition, grading, few-shot classification, and cross-modality diagnosis-outperforming state-of-the-art methods in 42 tasks (80.8%). In the large-scale real-world study, it achieved an ROC-AUC of 91.51% for lesion recognition, demonstrating strong robustness in routine clinical settings. For clinicopathological insights, GloPath systematically revealed statistically significant associations between glomerular morphological parameters and clinical indicators across 224 morphology-clinical variable pairs, demonstrating its capacity to connect tissue-level pathology with patient-level outcomes. Together, these results position GloPath as a scalable and interpretable platform for glomerular lesion assessment and clinicopathological discovery, representing a step toward clinically translatable AI in renal pathology.

For accurate glaucoma diagnosis and monitoring, reliable retinal layer segmentation in OCT images is essential. However, existing 2D segmentation methods often suffer from slice-to-slice inconsistencies due to the lack of contextual information across adjacent B-scans. 3D segmentation methods are better for capturing slice-to-slice context, but they require expensive computational resources. To address these limitations, we propose a 2.5D segmentation framework that incorporates a novel cross-slice feature fusion (CFF) module into a U-Net-like architecture. The CFF module fuses inter-slice features to effectively capture contextual information, enabling consistent boundary detection across slices and improved robustness in noisy regions. The framework was validated on both a clinical dataset and the publicly available DUKE DME dataset. Compared to other segmentation methods without the CFF module, the proposed method achieved an 8.56% reduction in mean absolute distance and a 13.92% reduction in root mean square error, demonstrating improved segmentation accuracy and robustness. Overall, the proposed 2.5D framework balances contextual awareness and computational efficiency, enabling anatomically reliable retinal layer delineation for automated glaucoma evaluation and potential clinical applications.