Meyke Hermsen

Scattered tubular cells (STCs) are a phenotypically distinct cell population in the proximal tubule that increase in number after acute kidney injury. We aimed to characterize the human STC population. Three‐dimensional human tissue analysis revealed that STCs are preferentially located within inner bends of the tubule and are barely present in young kidney tissue (+CD24⁻CD133⁻ proximal tubule epithelial cells (PTECs) and CD13⁺CD24+ and CD13⁺CD133⁺ STCs were analyzed using RNA sequencing. Transcriptome analysis revealed an upregulation of nuclear factor κB, tumor necrosis factor alpha, and inflammatory pathways in STCs, whereas metabolism, especially the tricarboxylic acid cycle and oxidative phosphorylation, was downregulated, without showing signs of cellular senescence. Using immunostaining and a publicly available single‐cell sequencing database of human kidneys, we demonstrate that STCs represent a heterogeneous population in a transient state. In conclusion, STCs are dedifferentiated PTECs showing a metabolic shift toward glycolysis, which could facilitate cellular survival after kidney injury. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Examination of a kidney biopsy is frequently required to diagnose the type and stage of a kidney disease or to determine the cause of kidney transplant dysfunction. Using various (immuno)histochemical stainings, biopsy slides are visually assessed by the pathologist for the recognition of distinctive patterns leading to a diagnosis. In addition, grading systems are used to express the severity of pathological changes, e.g. the extent of inflammation in (un)scarred renal parenchyma [ 1]. Although pathologists are very well trained in this type of pattern recognition and quantification, the resulting scores remain semi-quantitative, are not always reproducible and have limited predictive value in clinical practice. Moreover, the scoring of tissue slides in large research settings can be a tedious task. As a result, there is a need for tools that facilitate objective, quantitative scoring in renal pathology, possibly leading to the discovery of hallmarks that can (better) predict the course of the renal disease or evaluate the response to treatment. Artificial intelligence (AI) has the potential to yield such tools [ 2, 3].

Significance Statement: Histopathologic assessment of kidney tissue currently relies on manual scoring or traditional image-processing techniques to quantify and classify tissue features, time-consuming approaches that have limited reproducibility. The authors present an alternative approach, featuring a convolutional neural network for multiclass segmentation of kidney tissue in sections stained by periodic acid–Schiff. Their findings demonstrate applicability of convolutional neural networks for tissue from multiple centers, for biopsies and nephrectomy samples, and for the analysis of both healthy and pathologic tissues. In addition, they validated the network’s results with components from the Banff classification system. Their convolutional neural network may have utility for quantitative studies involving kidney histopathology across centers and potential for application in routine diagnostics. Background: The development of deep neural networks is facilitating more advanced digital analysis of histopathologic images. We trained a convolutional neural network for multiclass segmentation of digitized kidney tissue sections stained with periodic acid–Schiff (PAS). Methods: We trained the network using multiclass annotations from 40 whole-slide images of stained kidney transplant biopsies and applied it to four independent data sets. We assessed multiclass segmentation performance by calculating Dice coefficients for ten tissue classes on ten transplant biopsies from the Radboud University Medical Center in Nijmegen, The Netherlands, and on ten transplant biopsies from an external center for validation. We also fully segmented 15 nephrectomy samples and calculated the network’s glomerular detection rates and compared network-based measures with visually scored histologic components (Banff classification) in 82 kidney transplant biopsies. Results: The weighted mean Dice coefficients of all classes were 0.80 and 0.84 in ten kidney transplant biopsies from the Radboud center and the external center, respectively. The best segmented class was “glomeruli” in both data sets (Dice coefficients, 0.95 and 0.94, respectively), followed by “tubuli combined” and “interstitium.” The network detected 92.7% of all glomeruli in nephrectomy samples, with 10.4% false positives. In whole transplant biopsies, the mean intraclass correlation coefficient for glomerular counting performed by pathologists versus the network was 0.94. We found significant correlations between visually scored histologic components and network-based measures. Conclusions: This study presents the first convolutional neural network for multiclass segmentation of PAS-stained nephrectomy samples and transplant biopsies. Our network may have utility for quantitative studies involving kidney histopathology across centers and provide opportunities for deep learning applications in routine diagnostics.

Automated detection of cancer metastases in lymph nodes has the potential to improve assessment of prognosis for patients. To enable fair comparison between the algorithms for this purpose, we set up the CAMELYON17 challenge in conjunction with the IEEE International Symposium on Biomedical Imaging 2017 conference in Melbourne. Over 300 participants registered on the challenge website, of which 23 teams submitted a total of 37 algorithms before the initial deadline. Participants were provided with 899 whole-slide images for developing their algorithms. The developed algorithms were evaluated based on the test set encompassing 100 patients and 500 whole-slide images. The evaluation metric used was a quadratic weighted Cohen’s kappa. We discuss the algorithmic details of the ten best pre-conference and two post-conference submissions. All these participants used convolutional neural networks in combination with pre-and postprocessing steps. Algorithms differed mostly in neural network architecture, training strategy and pre-and postprocessing methodology. Overall, the kappa metric ranged from 0.89 to -0.13 across all submissions. The best results were obtained with pre-trained architectures such as ResNet. Confusion matrix analysis revealed that all participants struggled with reliably identifying isolated tumor cells, the smallest type of metastasis, with detection rates below 40%. Qualitative inspection of the results of the top participants showed categories of false positives, such as nerves or contamination, which could be targets for further optimization. Last, we show that simple combinations of the top algorithms result in higher kappa metric values than any algorithm individually, with 0.93 for the best combination.

Quiz Ref ID Full digitalization of the microscopic evaluation of stained tissue sections in histopathology has become feasible in recent years because of advances in slide scanning technology and cost reduction in digital storage. Advantages of digital pathology include remote diagnostics, immediate availability of archival cases, and easier consultations with expert pathologists.¹ Also, the possibility for computer-aided diagnostics may be advantageous.²

We evaluate the detection of glomerular structures in whole slide images (WSIs) of histopathological slides stained with multiple histochemical and immuno-histochemical staining using a convolutional neural network (CNN) based approach. We mutually compare the CNN performance on different stainings (Jones H&E, PAS, Sirius Red and CDIO) and we present a novel approach to improve glomeruli detection on one staining by taking into account the classification results from differently stained consecutive sections of the same tissue. Using this integrative approach, the detection rate (Fl-score) on a single stain can be improved by up to 30%.

Purpose: In breast imaging, radiological in vivo images, such as x‐ray mammography and magnetic resonance imaging (MRI), are used for tumor detection, diagnosis, and size determination. After excision, the specimen is typically sliced into slabs and a small subset is sampled. Histopathological imaging of the stained samples is used as the gold standard for characterization of the tumor microenvironment. A 3D volume reconstruction of the whole specimen from the 2D slabs could facilitate bridging the gap between histology and in vivo radiological imaging. This task is challenging, however, due to the large deformation that the breast tissue undergoes after surgery and the significant undersampling of the specimen obtained in histology. In this work, we present a method to reconstruct a coherent 3D volume from 2D digital radiographs of the specimen slabs.Methods: To reconstruct a 3D breast specimen volume, we propose the use of multiple target neighboring slices, when deforming each 2D slab radiograph in the volume, rather than performing pairwise registrations. The algorithm combines neighborhood slice information with free‐form deformations, which enables a flexible, nonlinear deformation to be computed subject to the constraint that a coherent 3D volume is obtained. The neighborhood information provides adequate constraints, without the need for any additional regularization terms.Results: The volume reconstruction algorithm is validated on clinical mastectomy samples using a quantitative assessment of the volume reconstruction smoothness and a comparison with a whole specimen 3D image acquired for validation before slicing. Additionally, a target registration error of 5 mm (comparable to the specimen slab thickness of 4 mm) was obtained for five cases. The error was computed using manual annotations from four observers as gold standard, with interobserver variability of 3.4 mm. Finally, we illustrate how the reconstructed volumes can be used to map histology images to a 3D specimen image of the whole sample (either MRI or CT).Conclusions: Qualitative and quantitative assessment has illustrated the benefit of using our proposed methodology to reconstruct a coherent specimen volume from serial slab radiographs. To our knowledge, this is the first method that has been applied to clinical breast cases, with the goal of reconstructing a whole specimen sample. The algorithm can be used as part of the pipeline of mapping histology images to ex vivo and ultimately in vivo radiological images of the breast.