Map3D: Registration Based Multi-Object Tracking on 3D Serial Whole Slide Images

There has been a long pursuit for precise and reproducible glomerular quantification on renal pathology to leverage both research and practice. When digitizing the biopsy tissue samples using whole slide imaging (WSI), a set of serial sections from the same tissue can be acquired as a stack of images, similar to frames in a video. In radiology, the stack of images (e.g., computed tomography) is naturally used to provide 3D context for organs, tissues, and tumors. In pathology, it is appealing to do a similar 3D assessment for glomeruli using a stack of serial WSI sections. However, the 3D identification and association of large-scale glomeruli on renal pathology is challenging due to large tissue deformation, missing tissues, and artifacts from WSI. Therefore, existing 3D quantitative assessments of glomeruli are still largely operated by manual or semi-automated methods, leading to labor costs, low-throughput processing, and inter-observer variability. In this paper, we propose a novel Multi-Object Association for Pathology in 3D (Map3D) method for automatically identifying and associating large-scale cross-sections of 3D objects from routine serial sectioning and WSI. The innovations of the Map3D method are three-fold: (1) the large-scale glomerular association is principled from a new multi-object tracking (MOT) perspective; (2) the quality-aware whole series registration is proposed to not only provide affinity estimation but also offer automatic kidney-wise quality assurance (QA) for registration; (3) a dual-path association method is proposed to tackle the large deformation, missing tissues, and artifacts during tracking. To the best of our knowledge, the Map3D method is the first approach that enables automatic and large-scale glomerular association across 3D serial sectioning using WSI.

Neural Network Segmentation of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis in Renal Biopsies

Glomerulosclerosis, interstitial fibrosis, and tubular atrophy (IFTA) are histologic indicators of irrecoverable kidney injury. In standard clinical practice, the renal pathologist visually assesses, under the microscope, the percentage of sclerotic glomeruli and the percentage of renal cortical involvement by IFTA. Estimation of IFTA is a subjective process due to a varied spectrum and definition of morphological manifestations. Modern artificial intelligence and computer vision algorithms have the ability to reduce inter-observer variability through rigorous quantitation. In this work, we apply convolutional neural networks for the segmentation of glomerulosclerosis and IFTA in periodic acid-Schiff stained renal biopsies. The convolutional network approach achieves high performance in intra-institutional holdout data, and achieves moderate performance in inter-intuitional holdout data, which the network had never seen in training. The convolutional approach demonstrated interesting properties, such as learning to predict regions better than the provided ground truth as well as developing its own conceptualization of segmental sclerosis. Subsequent estimations of IFTA and glomerulosclerosis percentages showed high correlation with ground truth.