Faster R-CNN-Based Glomerular Detection in Multistained Human Whole Slide Images

The detection of objects of interest in high-resolution digital pathological images is a key part of diagnosis and is a labor-intensive task for pathologists. In this paper, we describe a Faster R-CNN-based approach for the detection of glomeruli in multistained whole slide images (WSIs) of human renal tissue sections. Faster R-CNN is a state-of-the-art general object detection method based on a convolutional neural network, which simultaneously proposes object bounds and objectness scores at each point in an image. The method takes an image obtained from a WSI with a sliding window and classifies and localizes every glomerulus in the image by drawing the bounding boxes. We configured Faster R-CNN with a pretrained Inception-ResNet model and retrained it to be adapted to our task, then evaluated it based on a large dataset consisting of more than 33,000 annotated glomeruli obtained from 800 WSIs. The results showed the approach produces comparable or higher than average F-measures with different stains compared to other recently published approaches. This approach could have practical application in hospitals and laboratories for the quantitative analysis of glomeruli in WSIs and, potentially, lead to a better understanding of chronic glomerulonephritis

Computational Pipeline for Glomerular Segmentation and Association of the Quantified Regions with Prognosis of Kidney Function in IgA Nephropathy

The histopathological findings of the glomeruli from whole slide images (WSIs) of a renal biopsy play an important role in diagnosing and grading kidney disease. This study aimed to develop an automated computational pipeline to detect glomeruli and to segment the histopathological regions inside of the glomerulus in a WSI. In order to assess the significance of this pipeline, we conducted a multivariate regression analysis to determine whether the quantified regions were associated with the prognosis of kidney function in 46 cases of immunoglobulin A nephropathy (IgAN). The developed pipelines showed a mean intersection over union (IoU) of 0.670 and 0.693 for five classes (i.e., background, Bowman’s space, glomerular tuft, crescentic, and sclerotic regions) against the WSI of its facility, and 0.678 and 0.609 against the WSI of the external facility. The multivariate analysis revealed that the predicted sclerotic regions, even those that were predicted by the external model, had a significant negative impact on the slope of the estimated glomerular filtration rate after biopsy. This is the first study to demonstrate that the quantified sclerotic regions that are predicted by an automated computational pipeline for the segmentation of the histopathological glomerular components on WSIs impact the prognosis of kidney function in patients with IgAN

Mass spectrometry-based absolute quantification of amyloid proteins in pathology tissue specimens: Merits and limitations.

To clarify the significance of quantitative analyses of amyloid proteins in clinical practice and in research relating to systemic amyloidoses, we applied mass spectrometry-based quantification by isotope-labeled cell-free products (MS-QBIC) to formalin-fixed, paraffin-embedded (FFPE) tissues. The technique was applied to amyloid tissues collected by laser microdissection of Congo red-stained lesions of FFPE specimens. Twelve of 13 amyloid precursor proteins were successfully quantified, including serum amyloid A (SAA), transthyretin (TTR), immunoglobulin kappa light chain (IGK), immunoglobulin lambda light chain (IGL), beta-2-microglobulin (B2M), apolipoprotein (Apo) A1, Apo A4, Apo E, lysozyme, Apo A2, gelsolin, and fibrinogen alpha chain; leukocyte cell-derived chemotaxin-2 was not detected. The quantification of SAA, TTR, IGK, IGL, and B2M confirmed the responsible proteins, even when the immunohistochemical results were not decisive. Considerable amounts of Apo A1, Apo A4, and Apo E were deposited in parallel amounts with the responsible proteins. Quantification of amyloid protein by MS-QBIC is feasible and useful for the classification of and research on systemic amyloidoses