Glo-MMF: A modular multi-model framework for automated morphometry of glomerular ultrastructural features

Automated morphological analysis of glomerular ultrastructures facilitates diagnosis by reducing pathologists' burden and improving efficiency and accuracy. However, the inherent heterogeneity of different ultrastructural quantification processes hinders the ability of existing single-model studies to fulfill the clinical demand for the simultaneous achievement of multiple analytical objectives, including structure measurement, state assessment, and lesion localization. To address this, we developed Glo-MMF, a modular framework that integrates automated analysis, incorporating segmentation, classification, and detection. This framework aims to jointly quantify key ultrastructural features within the glomerulus, offering strong support for renal pathology research and diagnostic assistance.

Glo-MMF decomposes the quantification task of glomerular ultrastructural morphological features by constructing three dedicated deep learning models: an ultrastructural segmentation model, a glomerular filtration barrier (GFB) region classification model, and an electron-dense deposits (EDD) detection model. The outputs of these models are systematically integrated through a post-processing workflow comprising four computer vision modules, enabling the measurement of multiple ultrastructural features. Key operations include adaptive cropping of GFB regions and screening of suitable measurement locations. This approach significantly enhances measurement reliability, overcomes the limitations of traditional grading descriptions, and provides more thorough and interpretable quantitative results for glomerular pathological analysis.

Trained on 372 renal biopsy electron microscopy images, the Glo-MMF framework enables simultaneous quantification of the thickness of glomerular basement membrane (GBM), the degree of foot process effacement (FPE), and the location of EDD. In 115 test cases spanning 9 renal pathological types, the automated quantification results for these three features demonstrated strong agreement with descriptions in pathological reports. Processing and analysis per case in a CPU environment, including measurement of GBM thickness, quantification of FPE degree, and location of EDD, required an average time of 4.23 ± 0.48 s.

The modular design of Glo-MMF enables a certain degree of flexible extensibility, supporting the joint quantification of multiple key glomerular ultrastructural features. This framework ensures robust performance and clinical applicability across various renal pathological types, demonstrating significant potential to play an efficient auxiliary role in glomerular pathological analysis.