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Biomarkers and Early Detection: Imaging

In situ assessment of neoplastic progression in a rodent model of esophageal adenocarcinoma using angle-resolved low-coherence interferometry.

Duke University, Durham, NC; The Ohio State University, Columbus, OH

Abstract

B11

We have developed an optical spectroscopic technique for probing nuclear morphology in situ, Angle-Resolved Low Coherence Interferometry (a/LCI). The a/LCI technique has been previously utilized to monitor neoplastic transformation in a rodent model of NMBA-induced esophageal squamous cell cancer and in MNU-induced tracheal lesions of the Syrian golden hamster. The purpose of the present pilot study is to assess whether this imaging technique can detect early changes in a rodent model of esophageal adenocarcinoma (EAC) development. The rodent model utilized is known as the esophagogastroduodenal anastomosis (EGDA) model. Briefly, a surgical anastomosis is performed between the gastroesophageal junction and duodenum resulting in reflux of gastric and duodenal contents which in turn leads to the early development of metaplastic columnar lined epithelium and esophageal adenocarcinoma at 40 weeks post-surgery. In this pilot study, one 9 week old Sprague Dawley rat was treated surgically by performing an EDGA and two age matched rats remained untreated. Animals were sacrificed 14 weeks following the EGDA date and imaging immediately performed. Each esophagus was scanned at three different points: one 2-3 mm from proximal end (the end closest to the throat), one halfway between the distal and proximal ends, and one 2-3 mm from distal end. There was a total of nine points scanned with the a/LCI system. The data from each point was analyzed using the a/LCI technique. The nuclear size was determined for cells at depths where interesting structure was indicated. Interesting structure (as determined by exhibiting discernible oscillations in the scattering profile) was found at three different depths: the esophageal surface epithelium, one subsurface layer 80-100 microns beneath the epithelial layer, and a deeper layer 150-200 microns beneath the surface, likely corresponding to the underlying a muscle layer. For both the epithelial layer and the subsurface layer, larger nuclear sizes were measured in the EGDA rodent versus the control animals by the a/LCI technique. Specifically, a non-significant reduction in nuclear size in the epithelial layer was detected between the EGDA rodent and untreated controls. A statistically significant reduction in nuclear size for the subsurface layer was detected between the EGDA rodent versus non-surgical controls (p< 0.01). In conclusion, this pilot study supports that the a/LCI technique can detect early changes in subsurface nuclear size and to a lesser extent changes in epithelial nuclear size and detection of these changes occurred in parallel with the appearance metaplastic glandular structures in the rodent esophagus. A larger study needs to be conducted to validate the pilot study findings; however, this application may be particularly useful for assessing the potential of various chemopreventive agents in this model.