Abstract: SA-PO1049
Semiautomated Pipeline for Quantitative Analysis of Uremic Cardiomyopathy
Session Information
- Pathology and Lab Medicine - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Droste, Patrick, Universitatsklinikum Aachen Klinik fur Nieren- und Hochdruckkrankheiten rheumatologische und immunologische Erkrankungen, Aachen, Germany
- Wong, Dickson WL, Universitatsklinikum Aachen Institut fur Pathologie, Aachen, Germany
- Hohl, Mathias, Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes, Homburg, Saarland, Germany
- von Stillfried, Saskia, Universitatsklinikum Aachen Institut fur Pathologie, Aachen, Germany
- Klinkhammer, Barbara Mara, Universitatsklinikum Aachen Institut fur Pathologie, Aachen, Germany
- Boor, Peter, Universitatsklinikum Aachen Institut fur Pathologie, Aachen, Germany
Group or Team Name
- Laboratory of Nephropathology.
Background
Cardiac remodeling in patients with chronic kidney disease, also called uremic cardiomyopathy, is a leading cause of high mortality in these patients. The histological changes include cardiomyocyte hypertrophy and capillary rarefaction, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology.
Methods
We generated macros in ImageJ, a broadly used, open-source, java-based software. We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis, e.g., of nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis.
Results
In both animals and humans, ImageJ-based histology quantification revealed significant hypertrophy of cardiomyocytes and enabled the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease. The number of capillaries relative to the size of the cardiomyocytes indicates a rarefaction of microvasculature.
Conclusion
The pipeline enables a rapid analysis not feasible by manual methods and facilitates quantitative histology analyses in preclinical and clinical samples. The software requires few hardware requirements and is freely available.
Funding
- Government Support – Non-U.S.