Journal
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Volume 61, Issue 5, Pages 362-371Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1369/0022155413482926
Keywords
digital slide quantitation; image analysis; immunohistochemistry; preclinical evaluation
Categories
Funding
- Roche Pharmaceuticals
Ask authors/readers for more resources
Preclinical evaluation of a new compound, RO2910, identified a hypertrophic response in liver, thyroid gland, and pituitary gland (pars distalis). We aimed to develop and validate automated image analysis methods to quantify and refine the interpretation of semi-quantitative histology. Wistar-Han rats were administered RO2910 for 14 days. Liver, thyroid, and pituitary gland tissues were processed for routine histology and immunolabeled with anti-thyroid stimulating hormone (TSH) antibody (pituitary) and anti-topoisomerase II antibody (thyroid). Glass slides were scanned, image analysis methods were developed and applied to whole-slide images, and numerical results were compared with histopathology, circulating hormone levels, and liver enzyme mRNA expression for validation. Quantitative analysis of slides had strong individual correlation with semi-quantitative histological evaluation of all tissues studied. Hepatocellular hypertrophy quantification also correlated strongly with liver enzyme mRNA expression. In the pars distalis, measurement of TSH weak-staining areas correlated with both hypertrophy scores and circulating TSH levels. Whole-slide image analysis enabled automated quantification of semi-quantitative histopathology findings and a more refined interpretation of these data. The analysis also enabled a direct correlation with non-histological parameters using straightforward statistical analysis to provide a more refined dose-and sex-response relationship and integration among affected parameters. These findings demonstrate the utility of our image analysis to support preclinical safety evaluations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available