ArticleLaboratory investigation; a journal of technical methods and pathology2021
Large-scale, three-dimensional tissue cytometry of the human kidney: a complete and accessible pipeline.
Article in Laboratory investigation; a journal of technical methods and pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Computational design of artificial supply networks for engineered human tissue.Scientific reports · 2026Article
- Distributed and networked analysis of volumetric image data for remote collaboration of microscopy image analysis.Journal of medical imaging (Bellingham, Wash.) · 2025Article
- Acute kidney injury results in long-term alterations of kidney lymphatics in mice.American journal of physiology. Renal physiology · 2024Article
- Validation of an organ mapping antibody panel for cyclical immunofluorescence microscopy on normal human kidneys.American journal of physiology. Renal physiology · 2024Article
- Precision Medicine in Nephrology: An Integrative Framework of Multidimensional Data in the Kidney Precision Medicine Project.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024Article
- Article
- Integrated Cytometry With Machine Learning Applied to High-Content Imaging of Human Kidney Tissue for In Situ Cell Classification and Neighborhood Analysis.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Defining protein expression in the kidney at large scale: from antibody validation to cytometry analysis.American journal of physiology. Renal physiology · 2023Article
- Collagen fibrils and cell nuclei are entrapped within Randall's plaques but not in CaOx matrix overgrowth: A microscopic inquiry into Randall's plaque stone pathogenesis.Anatomical record (Hoboken, N.J. : 2007) · 2022Article
- Cellular and molecular interrogation of kidney biopsy specimens.Current opinion in nephrology and hypertension · 2022Review
- Label-free imaging of non-deparaffinized sections of the human kidney to determine tissue quality and signatures of disease.Physiological reports · 2022Article
- The new era of quantitative cell imaging-challenges and opportunities.Molecular cell · 2022Review
- Machine learning analyses of highly-multiplexed immunofluorescence identifies distinct tumor and stromal cell populations in primary pancreatic tumors.Cancer biomarkers : section A of Disease markers · 2022Article
- Tissue Cytometry With Machine Learning in Kidney: From Small Specimens to Big Data.Frontiers in physiology · 2022Review
- Quantitative 3-dimensional imaging and tissue cytometry reveals lymphatic expansion in acute kidney injury.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- The Indiana O'Brien Center for Advanced Renal Microscopic Analysis.American journal of physiology. Renal physiology · 2021Review
- Digital Image Analysis Tools Developed by the Indiana O'Brien Center.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 20 institutions in 2 countries.
Funding
Abstract
The advent of personalized medicine has driven the development of novel approaches for obtaining detailed cellular and molecular information from clinical tissue samples. Tissue cytometry is a promising new technique that can be used to enumerate and characterize each cell in a tissue and, unlike flow cytometry and other single-cell techniques, does so in the context of the intact tissue, preserving spatial information that is frequently crucial to understanding a cell's physiology, function, and behavior. However, the wide-scale adoption of tissue cytometry as a research tool has been limited by the fact that published examples utilize specialized techniques that are beyond the capabilities of most laboratories. Here we describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues. In this workflow, multiphoton microscopy of unlabeled tissue is first conducted to collect autofluorescence and second-harmonic images. The tissue is then labeled with eight fluorescent probes, and imaged using spectral confocal microscopy. The raw 16-channel images are spectrally deconvolved into 8-channel images, and analyzed using the Volumetric Tissue Exploration and Analysis (VTEA) software developed by our group. We applied this workflow to analyze millimeter-scale tissue samples obtained from human nephrectomies and from renal biopsies from individuals diagnosed with diabetic nephropathy, generating a quantitative census of tens of thousands of cells in each. Such analyses can provide useful insights that can be linked to the biology or pathology of kidney disease. The approach utilizes common laboratory techniques, is compatible with most commercially-available confocal microscope systems and all image and data analysis is conducted using the VTEA image analysis software, which is available as a plug-in for ImageJ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.