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Liver toxicology study aided with automated image analysis

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The Hamner Institutes for Health Sciences, North Carolina, USA, is utilising image analysis software to develop an application that automatically analyses images of liver tissue slides as part of a liver toxicology study. The application, using Definiens TissueStudio and Definiens Developer XD software, will identify and quantify apoptotic nuclei in hundreds of whole-slide liver tissue section images, expediting the image analysis process.

'The use of automated image acquisition and analysis technologies greatly expands our ability to identify and quantify low-frequency adverse events resulting from chemical exposure,' said Dr Russell Thomas, senior investigator and director of genomic biology and bioinformatics at The Hamner Institutes. 'We are using Definiens digital pathology software to measure small changes in the background rate of apoptosis. This capability allows us to assess the effects of chemicals at environmentally-relevant doses. Initial studies demonstrated that Definiens' software delivers highly accurate and reproducible analysis results.'

Staining liver tissues with terminal transferase and biotin-16-dUTP antibodies (TUNEL fluorescent staining), researchers at The Hamner Institutes aim to measure changes in the background rate of apoptosis following chemical treatment. The goal of the study, which includes 1,680 slide sections from 168 animals and is projected to conclude in the spring of 2011, is to better understand whether changes in the background rate of apoptosis contribute to the tumour-promoting effects of the chemicals studied.

The Hamner Institutes is an independent, nonprofit research and development organisation trying to improve public health through better predictive assessments of chemical and drug safety. The addition of Definiens TissueStudio and Definiens Developer XD provides The Hamner Institutes with the ability to analyse large numbers of histological and cell-based images to study these chemical effects. Definiens image analysis software was chosen for the study because it provides the flexibility to generate and modify algorithm rule-sets to identify and measure rare occurrences, such as apoptosis in liver tissue sections.

After successfully measuring the background rates of apoptosis in the control animals, the researchers at The Hamner Institutes plan to conduct a pilot study to statistically detect changes in the background apoptosis rate following chemical treatment and, eventually, measure the change in background rates of apoptosis in a full-time course and dose-response study.