Quantitative grading of rat esophageal carcinogenesis using computer-assisted image tile analysis

Our objective was to grade, by computer-assisted quantitative image tile an alysis, the intraepithelial neoplasia (also called dysplasia) that develops in esophagi of rats given N-nitrosomethybenzylamine (NMBA) for 5 weeks. To perform image tile analysis, the computer divides the video image of the n eoplastic epithelium into a row of contiguous small rectangular images, or "tiles," 84 x 292 mu m in size, and quantitatively measures four selected t issue features within each image tile, The computer then calculates a tile grade for each image tile as the weighted sum of the four feature measureme nts, transformed into statistical Z-scores, the weights being determined by Fisher linear discriminant analysis of 300 tile grades of the neoplastic e pithelium referenced to the mean tile grade (MTG) of 300 image tiles of nor mal epithelium. The two grading parameters, MTG and the percentage of tile grades exceeding the MTG of normal epithelium by >4 SD units (%TG>4SD), wer e validated as endpoints for screening chemopreventive agents in the rat NM BA-induced esophageal carcinogenesis model in two ways: (a) after NMBA trea tment, %TG>4SD developed in parallel with tumor incidence and tumor multipl icity (number of papillomas/tumor-bearing rat); and (b) placing the chemopr eventive phenethylisothiocyanate in the food of NMBA-treated rats produced parallel reductions in MTG, tumor incidence, and tumor multiplicity. Both M TG and %TG>4SD, measured by quantitative image tile analysis, are sensitive and objective continuous parametric response variables expressed to three significant figures, with wide dynamic range, that may be evaluated by t te sts to compare tissue neoplastic changes before and after treatment with a chemopreventive agent.