Gastrointestinal neuroendocrine tumors (GI-NETs) including gastric carcinoids and duodenal neuroendocrine tumors (DNETs), represent a growing class of cancer.1 There is a strong need for intraoperative localization to facilitate diagnosis and treatment of DNETs, particularly those related to the hereditary MEN1 syndrome. However, these demands are precluded by a lack of in vivo model systems that accurately recapitulate disease heterogeneity and progression. Optical imaging markers are commonly used diagnostically to probe early tissue changes that occur with the onset of cancer. Promising techniques include autofluorescence imaging (AFI), which probes intrinsic biochemistry and metabolic markers, and optical coherence tomography (OCT), which provides a robust microstructural reference. Both have demonstrated widespread promise for non-invasive disease screening, making them potential candidates for localization of DNETs. Here we apply AFI and OCT to a mouse model of human MEN1 syndrome to identify unique optical markers associated with neuroendocrine cell reprogramming. Using Cre-lox technology, we generated a glial cell-directed Men1 knockout mouse model that exhibits enhanced neuroendocrine cell differentiation in the stomach and duodenum. We measured variations in optical imaging markers using AFI and OCT images of transgenic and wild type mice. The transgenic lines exhibit significant fluctuations in optical imaging markers compared to wild type mice, both in the scope of AFI and OCT (p<0.01). These results suggest that AFI and OCT may further inform biological and metabolic changes associated with initial neuroendocrine cell reprogramming prefacing tumor formation. Further studies are needed to fully elucidate the significance of these optical markers in GI-NET pathogenesis.