Seeing Abnormal from Normal: Glomerular Abnormality in Representations of Normal Renal Morphology
Authors: Greta Hasko, Rachit Saluja, Tianyu Shi, Leiyue Zhao, Yuechen Yang, Daniel Reisenbuechler, Tianyuan Yao, Zhenhao Guo, +8 more
Abstract
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±0.013. 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.
Deploying AI-based anomaly detection across diverse clinical imaging settings remains challenging because most existing methods rely on modality-specific architectures, anatomical priors, or extensive retraining, limiting their use as general-purpose screening tools. One-class classification (OCC) offers a label-efficient alternative by training exclusively on normal data, but conventional two-stage pipelines fit a density estimator directly on raw pretrained embeddings, leaving substantial discriminative structure in the latent space unexploited. We introduce a training-free, modality-agnostic framework that inserts an explicit manifold-refinement stage between feature extraction and anomaly scoring. Empirical density weights, estimated via a UMAP-derived neighborhood graph, guide an iterative shift of embeddings toward locally dense regions, compacting normal samples, leaving anomalies relatively isolated prior to Gaussian density estimation and Mahalanobis-based scoring. This refinement introduces no additional trainable parameters and no architectural modification, allowing it to be layered onto any pretrained encoder. Evaluated on the MedIAnomaly benchmark across seven datasets spanning five imaging modalities (X-ray, MRI, fundus, dermatoscopy, histopathology), the framework achieves the best AUC on four datasets and the best Average Precision on five datasets among methods evaluated in the benchmark, outperforming specialized reconstruction and diffusion-based methods with a single fixed hyperparameter configuration across all modalities. These results demonstrate that meaningful gains can be achieved through post-hoc geometric refinement of existing representations rather than bespoke encoders, offering a practical and scalable AI screening framework for real-world, multi-modality clinical workflows where retraining and abnormal-case annotation are costly or infeasible.
The rapid proliferation of open-source medical foundation models (FMs) raises a practical question: how well do their pre-trained representations transfer to clinically relevant but data-scarce classification tasks? Particularly in CT-based renal lesion classification, a push toward greater generalizability would be meaningful, as the field is constrained by inherently limited training data. We addressed this through a benchmark of three medical FMs on this specific task. This six-class problem spans common entities like cysts and clear cell renal cell carcinoma, alongside rare subtypes. Using a frozen feature-probing protocol, we compared FM embeddings against a handcrafted radiomics classifier and a 3D ResNet-50 trained from scratch. Models were trained on a composite dataset of 2,854 lesions and evaluated on an external test set of 234 lesions from The Cancer Imaging Archive. Our results reveal two key findings. First, FM performance (AUC 0.70-0.77) matched the from-scratch ResNet (AUC 0.72) while drastically reducing hardware demand, requiring only seconds on a CPU after feature extraction. However, the conventional radiomics baseline significantly outperformed all deep learning approaches, achieving an AUC of 0.88 (all p ≤ 0.002). This suggests that current generalist FM embeddings do not yet capture the fine-grained texture and shape heterogeneity driving histological subtype discrimination. Despite their potential in data-scarce settings, medical FMs did not surpass established models for renal lesion stratification, leaving radiomics as the current state-of-the-art.
Reliable automated analysis of Optical Coherence Tomography (OCT) imaging is crucial for diagnosing retinal disorders but faces a critical barrier: the need for expensive, labor-intensive expert annotations. Supervised deep learning models struggle to generalize across diverse pathologies, imaging devices, and patient populations due to their restricted vocabulary of annotated abnormalities. We propose an unsupervised anomaly detection framework that learns the normative distribution of healthy retinal anatomy without lesion annotations, directly addressing annotation efficiency challenges in clinical deployment. Our approach leverages a discrete latent model trained on normal B-scans to capture OCT-specific structural patterns. To enhance clinical robustness, we incorporate retinal layer-aware supervision and structured triplet learning to separate healthy from pathological representations, improving model reliability across varied imaging conditions. During inference, anomalies are detected and localized via reconstruction discrepancies, enabling both image and pixel-level identification without requiring disease-specific labels. On the Kermany dataset (AUROC: 0.799), our method substantially outperforms VAE, VQVAE, VQGAN, and f-AnoGAN baselines. Critically, cross-dataset evaluation on Srinivasan achieves AUROC 0.884 with superior generalization, demonstrating robust domain adaptation. On the external RETOUCH benchmark, unsupervised anomaly segmentation achieves competitive Dice (0.200) and mIoU (0.117) scores, validating reproducibility across institutions.