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Automatic instance segmentation of glomeruli within kidney Whole Slide Imaging (WSI) is essential for clinical research in renal pathology. In computer vision, the end-to-end instance segmentation methods (e.g., Mask-RCNN) have shown their advantages relative to detect-then-segment approaches by performing complementary detection and segmentation tasks simultaneously. As a result, the end-to-end Mask-RCNN approach has been the de facto standard method in recent glomerular segmentation studies, where downsampling and patch-based techniques are used to properly evaluate the high resolution images from WSI (e.g., >10,000x10,000 pixels on 40x). However, in high resolution WSI, a single glomerulus itself can be more than 1,000x1,000 pixels in original resolution which yields significant information loss when the corresponding features maps are downsampled via the Mask-RCNN pipeline. In this paper, we assess if the end-to-end instance segmentation framework is optimal for high-resolution WSI objects by comparing Mask-RCNN with our proposed detect-then-segment framework. Beyond such a comparison, we also comprehensively evaluate the performance of our detect-then-segment pipeline through: 1) two of the most prevalent segmentation backbones (U-Net and DeepLab_v3); 2) six different image resolutions (from 512x512 to 28x28); and 3) two different color spaces (RGB and LAB). Our detect-then-segment pipeline, with the DeepLab_v3 segmentation framework operating on previously detected glomeruli of 512x512 resolution, achieved a 0.953 dice similarity coefficient (DSC), compared with a 0.902 DSC from the end-to-end Mask-RCNN pipeline. Further, we found that neither RGB nor LAB color spaces yield better performance when compared against each other in the context of a detect-then-segment framework. Detect-then-segment pipeline achieved better segmentation performance compared with End-to-end method.
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 t he 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) are naturally used to provide 3D context for organs, tissues, and tumors. In pathology, it is appealing to do a similar 3D assessment. 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. 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 formed as 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. Our proposed method Map3D achieved MOTA= 44.6, which is 12.1% higher than the non deep learning benchmarks.
Object detection networks are powerful in computer vision, but not necessarily optimized for biomedical object detection. In this work, we propose CircleNet, a simple anchor-free detection method with circle representation for detection of the ball-s haped glomerulus. Different from the traditional bounding box based detection method, the bounding circle (1) reduces the degrees of freedom of detection representation, (2) is naturally rotation invariant, (3) and optimized for ball-shaped objects. The key innovation to enable this representation is the anchor-free framework with the circle detection head. We evaluate CircleNet in the context of detection of glomerulus. CircleNet increases average precision of the glomerulus detection from 0.598 to 0.647. Another key advantage is that CircleNet achieves better rotation consistency compared with bounding box representations.
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