A dual-aperture fluorescence ratio approach to minimize optical property heterogeneities for direct applications in intraoperative fluorescence-guided surgery

Oral squamous cell carcinomas represent a significant number of cancers diagnosed globally. Of these cancers, surgical resection of the primary tumor is the standard treatment. Conventional methods of assessing completeness of resection are time-consuming, laborious, and cannot be used to evaluate the entire margin of a resected tumor. As such, widefield fluorescence molecular imaging is being explored as an intraoperative technique to guide resections. The widely used single-view, wide aperture techniques have had high success in identifying positive margins (those with thickness < 1mm), but limited success in identifying close margins (1-5 mm). Here a dual aperture fluorescence ratio is presented as a means of improved detection of close margins, with evidence that this technique may be highly useful for future intraoperative fluorescence molecular imaging applications. Monte Carlo simulations are conducted to assess the technique's ability to minimize optical property heterogeneities across regions with varying absorption and scattering characteristics.