Quantitative histological assessment of xenobiotic-induced liver enzyme induction and pituitary-thyroid axis stimulation in rats using whole-slide automated image analysis.

Rosario Garrido, Tanja S Zabka, Jianhua Tao, Mark Fielden, Adrian Fretland, Mudher Albassam

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2013 May

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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.

Citation

Rosario Garrido, Tanja S Zabka, Jianhua Tao, Mark Fielden, Adrian Fretland, Mudher Albassam. Quantitative histological assessment of xenobiotic-induced liver enzyme induction and pituitary-thyroid axis stimulation in rats using whole-slide automated image analysis. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2013 May;61(5):362-71