Abstract
SUMMARYThe DSS (dextran sulfate sodium) model of colitis is a mouse model of inflammatory bowel disease. Microscopic symptoms include loss of crypt cells from the gut lining and infiltration of inflammatory cells into the colon. An experienced pathologist requires several hours per study to score histological changes in selected regions of the mouse gut. In order to increase the efficiency of scoring, Definiens Developer software was used to devise an entirely automated method to quantify histological changes in the whole H&E slide. When the algorithm was applied to slides from historical drug-discovery studies, automated scores classified 88% of drug candidates in the same way as pathologists’ scores. In addition, another automated image analysis method was developed to quantify colon-infiltrating macrophages, neutrophils, B cells and T cells in immunohistochemical stains of serial sections of the H&E slides. The timing of neutrophil and macrophage infiltration had the highest correlation to pathological changes, whereas T and B cell infiltration occurred later. Thus, automated image analysis enables quantitative comparisons between tissue morphology changes and cell-infiltration dynamics.
Highlights
Inflammatory bowel disease (IBD) is a disorder of the digestive tract and affects more than 1 million people in the United States alone (Abraham and Cho, 2009)
In ulcerative colitis (UC), a type of IBD, inflammation occurs primarily in the mucosa of the large intestines, leading to debilitating conditions including diarrhea, rectal bleeding and weight loss. Both genetic and non-genetic factors are associated with the disease, it is thought that UC is largely caused by an inappropriate inflammatory response by the host to intestinal microbes penetrating through a damaged epithelial barrier (Xavier and Podolsky, 2007)
Mouse models of colitis are routinely used to screen for potential therapeutics, but the screening time required for a pathologist to score their colon slides manually is a major bottleneck in the drug-discovery process
Summary
Inflammatory bowel disease (IBD) is a disorder of the digestive tract and affects more than 1 million people in the United States alone (Abraham and Cho, 2009). In ulcerative colitis (UC), a type of IBD, inflammation occurs primarily in the mucosa of the large intestines, leading to debilitating conditions including diarrhea, rectal bleeding and weight loss Both genetic and non-genetic factors are associated with the disease, it is thought that UC is largely caused by an inappropriate inflammatory response by the host to intestinal microbes penetrating through a damaged epithelial barrier (Xavier and Podolsky, 2007). The enormous variety of gut flora contributes to the heterogeneity of the disease This complexity might explain why currently available therapies for UC have only a 50% chance of positive outcome for patients (Pastorelli et al, 2009). Colitis is a highly debilitating disease that affects over a million people in the United States alone Half of these patients do not respond well to available therapies, highlighting a serious, unmet medical need. Few attempts have been made to analyze H&E slides far, even though it is one of the most common stains used by pathologists for a wide variety of applications
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