Document Detail


Quantitative histological assessment of xenobiotic-induced liver enzyme induction and pituitary-thyroid axis stimulation in rats using whole-slide automated image analysis.
MedLine Citation:
PMID:  23456825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Rosario Garrido; Tanja S Zabka; Jianhua Tao; Mark Fielden; Adrian Fretland; Mudher Albassam
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-01
Journal Detail:
Title:  The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society     Volume:  61     ISSN:  1551-5044     ISO Abbreviation:  J. Histochem. Cytochem.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-06-26     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  9815334     Medline TA:  J Histochem Cytochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  362-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Animals
Automation
Enzyme Induction / drug effects
Feasibility Studies
Female
Histological Techniques / methods*
Hypertrophy / blood,  enzymology,  pathology
Image Processing, Computer-Assisted / methods*
Liver / drug effects,  enzymology*,  pathology*
Male
Pituitary Gland / drug effects,  metabolism,  pathology*
Rats
Rats, Inbred WF
Thyroid Gland / drug effects,  metabolism,  pathology*
Thyrotropin / blood
Xenobiotics / pharmacology*
Chemical
Reg. No./Substance:
0/Xenobiotics; 9002-71-5/Thyrotropin
Comments/Corrections
Comment In:
J Histochem Cytochem. 2013 Oct;61(10):759-60   [PMID:  24084867 ]
J Histochem Cytochem. 2013 Oct;61(10):761-2   [PMID:  24084868 ]

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