Risk stratification of colon carcinogenesis through enhanced backscattering spectroscopy analysis of the uninvolved colonic mucosa

Introduction: Our group has been interested in applying advances in biomedical optics to colorectal cancer risk stratification. Through a recent technological breakthrough, we have been able to harness information from enhanced backscattering spectroscopy, an optics phenomenon that allows quantitative, depth-selective analysis of the epithelial microscale/nanoscale architecture. In the present study, we investigated the ability of enhanced backscattering analysis of the preneoplastic mucosa to predict risk of colon carcinogenesis. Methods: Enhanced backscattering analysis was done on intestinal mucosa at preneoplastic time points from two experimental models of colorectal cancer: the azoxymethane-treated rat and the multiple intestinal neoplasia (MIN) mouse. Data were analyzed using two previously validated spectral markers: spectral slope and principle components. We then did a pilot study on mucosal biopsies from 63 subjects undergoing screening colonoscopy. Results: In the azoxymethane-treated rat, when compared with saline-treated controls, significant changes in the enhanced backscattering markers were observed as early as 2 weeks after azoxymethane treatment (before the development of aberrant crypt foci and adenomas). Enhanced backscattering markers continued to progress over time in a manner consonant with future neoplasia. These data were replicated in the preneoplastic MIN mouse mucosa. In humans, spectral slopes in the endoscopically normal cecum, midtransverse colon, and rectum were markedly reduced in patients harboring adenomas when compared with those who were neoplasia free. Conclusions: We show, for the first time, that enhanced backscattering analysis of an aliquot of uninvolved mucosa has the potential for predicting neoplastic risk throughout the colon in both experimental colorectal cancer models and humans.